Effects of glycolic acid peeling on the cutaneous manifestation of generalized acanthosis nigricans caused by FGFR3 mutation: A report of one sporadic and two familial cases

http://ift.tt/2t8PoCE

Case of autoimmune autonomic ganglionopathy manifesting anhidrosis

Abstract

Autoimmune autonomic ganglionopathy (AAG), clinically characterized by gastrointestinal dysmotility, orthostatic hypotension and tonic pupils, is an idiopathic acquired disorder of the autonomic nervous system elicited by antibodies against ganglionic acetylcholine receptor (gAChR). We encountered a 60-year-old man who presented with severe anhidrosis, difficulty in thermoregulation, orthostatic hypotension, gastrointestinal dysmotility, tonic pupils and ptosis. Histologically, an anhidrotic skin sample was normal. Routine laboratory examinations of blood, urine and cerebrospinal fluid returned no abnormal findings. Serological examination revealed antibodies against α3 and β4 subunits of gAChR. The diagnosis was AAG. As sudomotor dysfunction reflects ganglionic neuropathy in AAG, we concluded that his anhidrosis was attributable to AAG. Anhidrosis is an important clue for the diagnosis of AAG, a rare neurological disorder.

http://ift.tt/2szgx4O

Isotretinoin and tattooing: a cautionary tale

http://ift.tt/2rmxLhD

We could predict good responders to vagus nerve stimulation: a surrogate marker by slow cortical potential shift

Publication date: Available online 15 June 2017
Source:Clinical Neurophysiology
Author(s): Borgil Bayasgalan, Masao Matsuhashi, Tomoyuki Fumuro, Haruhiko Nohira, Naoki Nakano, Koji Iida, Masaya Katagiri, Akihiro Shimotake, Riki Matsumoto, Takayuki Kikuchi, Takeharu Kunieda, Amami Kato, Ryosuke Takahashi, Akio Ikeda
ObjectiveWe investigated whether vagus nerve stimulation (VNS) induces a positive shift of slow cortical potentials (SCPs) in patients with >50% seizure reduction (responders) but not in non-responders.MethodsWe analyzed routine clinical electroencephalograms (EEGs) from 24 patients who were undergoing seizure treatment by VNS. The patients were divided into 2 groups by hardware time constant (TC) of EEG: the TC 10-s group (10 patients) and TC 2-s group (14 patients). We compared SCPs at 5 electrodes (Cz and adjacent ones) between the 2 states of VNS: during stimulation and between stimulations. Seizure reduction was independently judged. Correlation between SCP (positivity or not) and seizure reduction (>50% or not) was estimated.ResultsIn the TC 10-s group, the correlation between SCP and seizure reduction was significant (p < 0.05) (i.e., both good results in 4 and both negative results in 5). In TC 2-s group, the correlation between SCP and seizure reduction was not significant (p = 0.209).ConclusionsA positive shift of SCP recorded by using a TC of 10 s could be a surrogate marker for VNS response.SignificanceSCP could be a biomarker of good responders to VNS.



http://ift.tt/2ttNCM1

Subclinical white matter lesions and medial temporal lobe atrophy are associated with EEG slowing in a memory clinic cohort

Publication date: Available online 15 June 2017
Source:Clinical Neurophysiology
Author(s): Milica G. Kramberger, Katarina Giske, Lena Cavallin, Ingemar Kåreholt, Thomas Andersson, Bengt Winblad, Vesna Jelic
ObjectiveThe aim of the study was to describe the relationship between electroencephalographic (EEG) findings obtained by standardised visual analysis, subclinical white matter lesions (WML) and brain atrophy in a large memory clinic population.MethodsPatients with Alzheimer's disease (AD, n = 58), mild cognitive impairment (MCI, n = 141), subjective cognitive impairment (SCI, n = 194) had clinical, MRI based WML severity and regional atrophy assessments, and routine resting EEG recording. Background activity (BA) and episodic and continuous abnormalities were assessed visually in EEG.ResultsWML (p = 0.006) and atrophy in medial temporal regions (MTA) (p = <0.001) were associated with slower BA in all diagnoses. WML were associated in SCI with total episodic EEG abnormalities (p = 0.03).ConclusionsEEG is associated with subclinical WML burden and cortical brain atrophy in a memory clinic population.SignificanceEven the standard visually assessed EEG can complement a memory clinic diagnostic workup.



http://ift.tt/2svyoZt

Real-world, single-centre experience of apremilast for the treatment of moderate to severe psoriasis

http://ift.tt/2rCX7qy

Real-world, single-centre experience of apremilast for the treatment of moderate to severe psoriasis

http://ift.tt/2rCX7qy

Randomised controlled trial of a baked egg intervention in young children allergic to raw egg but not baked egg

Consumption of baked egg by raw egg allergic children is associated with immune changes suggesting development of tolerance. However, causation has not been tested using a double blind randomized controlled tr...

http://ift.tt/2szfrWQ

Randomised controlled trial of a baked egg intervention in young children allergic to raw egg but not baked egg

Consumption of baked egg by raw egg allergic children is associated with immune changes suggesting development of tolerance. However, causation has not been tested using a double blind randomized controlled tr...

http://ift.tt/2szfrWQ

The extended bundle of the tensor veli palatini: Anatomic consideration of the dilating mechanism of the Eustachian tube

The aim of this study was to analyze the topographical structures of the muscles surrounding the Eustachian tube.

http://ift.tt/2rmLNQf

The extended bundle of the tensor veli palatini: Anatomic consideration of the dilating mechanism of the Eustachian tube

The aim of this study was to analyze the topographical structures of the muscles surrounding the Eustachian tube.

http://ift.tt/2rmLNQf

Metaplastic breast carcinoma with chondroid differentiation: a rare variant of infiltrative carcinoma in a 38-year-old woman

Metaplastic breast carcinoma (MBC) is a rare type of invasive breast carcinoma, and chondroid differentiation is even rarer. Here we report a case of MBC with extensive chondroid differentiation in a 38-year-old woman who presented with a lump in her left breast. Ultrasound findings were most compatible with those of giant fibroadenoma. A histopathological examination revealed a malignant lesion comprising neoplastic epithelial cells arranged in solid nests, with large areas of chondroid differentiation. Neoplastic chondroid cells exhibited a positive reaction for S-100, patchy positive reaction for pan-cytokeratin (AE1/AE3) and negative reaction for epithelial membrane antigen. Both carcinomatous and chondroid cells exhibited p53 overexpression. Sentinel lymph node biopsy revealed no tumorous involvement.

http://ift.tt/2shgNSV

It's a cod! Finding Nemo (impacted fishbone) in the emergency department

A 23-year-old woman presented to the emergency department (ED) with a sensation of a 'fish bone' stuck in her throat after eating cod. On physical examination, while she reported an uncomfortable sensation in her throat, no airway compromise was evident. Clinical examination, including ear, nose and throat (ENT) and oropharyngeal assessment, was unremarkable. A linear opacity consistent with a fishbone was visualised on a soft tissue lateral neck X-ray anterior to the vertebral body of C4–6. One attempt to visualise the fishbone on direct laryngoscopy failed in the ED. The fishbone was later removed the next day via direct visualisation with a flexible endoscope in the operating theatre by the ENT surgical team. The patient's recovery was uneventful.

http://ift.tt/2rx8Vja

Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications: An observational study in 29 countries.

BACKGROUND: Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. OBJECTIVES: To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. DESIGN: This was a prospective international 1-week observational study using the 'Assess Respiratory Risk in Surgical Patients in Catalonia risk score' (ARISCAT score) for PPC for risk stratification. PATIENTS AND SETTING: Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. MAIN OUTCOME MEASURES: The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. RESULTS: A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (VT) size was 500 ml, or 7 to 9 ml kg-1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P

http://ift.tt/2tt9Uxn

Women awaken faster than men after electroencephalogram-monitored propofol sedation for colonoscopy: A prospective observational study.

BACKGROUND: Sedation for colonoscopy using intravenous propofol has become standard in many Western countries. OBJECTIVE: Sex-specific differences have been shown for general anaesthesia in dentistry, but no such data existed for gastrointestinal endoscopy. DESIGN: A prospective observational study. SETTING: An academic teaching hospital of Hannover Medical School. PATIENTS: A total of 219 patients (108 women and 111 men) scheduled for colonoscopy. INTERVENTION: Propofol sedation using electroencephalogram monitoring during a constant level of sedation depth (D0 to D2) performed by trained nurses or physicians after a body-weight-adjusted loading dose. MAIN OUTCOME MEASURES: The primary end-point was the presence of sex-specific differences in awakening time (time from end of sedation to eye-opening and complete orientation); secondary outcome parameters analysed were total dose of propofol, sedation-associated complications (bradycardia, hypotension, hypoxaemia and apnoea), patient cooperation and patient satisfaction. Multivariate analysis was performed to correct confounding factors such as age and BMI. RESULTS: Women awakened significantly faster than men, with a time to eye-opening of 7.3 +/- 3.7 versus 8.4 +/- 3.4 min (P = 0.005) and time until complete orientation of 9.1 +/- 3.9 versus 10.4 +/- 13.7 min (P = 0.008). The propofol dosage was not significantly different, with some trend towards more propofol per kg body weight in women (3.98 +/- 1.81 mg versus 3.72 +/- 1.75 mg, P = 0.232). CONCLUSION: The effect of sex aspects should be considered when propofol is used as sedation for gastrointestinal endoscopy. That includes adequate dosing for women as well as caution regarding potential overdosing of male patients. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02687568). (C) 2017 European Society of Anaesthesiology

http://ift.tt/2sveg9X

Rocuronium is more hepatotoxic than succinylcholine in vitro.

BACKGROUND: The development of liver failure is a major problem in critically ill patients. The hepatotoxicity of many drugs, as one important reason for liver failure, is poorly screened for in human models. Rocuronium and succinylcholine are neuromuscular blocking agents used for tracheal intubation and for rapid-sequence induction. OBJECTIVE: We used an in-vitro test with a permanent cell line and compared rocuronium and succinylcholine for hepatotoxicity. DESIGN: In-vitro study. SETTING: A basic science laboratory, University Hospital Rostock, Germany. MATERIAL/(PATIENTS): The basic test compound is the permanent human liver cell line HepG2/C3A. In a standardised microtitre plate assay the toxicity of different concentrations of rocuronium, succinylcholine and plasma control was tested. INTERVENTIONS: After two incubation periods of 3 days, the viability of cells (XTT test, lactate dehydrogenase release and trypan blue staining), micro-albumin synthesis and the cytochrome 1A2 activity (metabolism of ethoxyresorufin) were measured. MAIN OUTCOME MEASURES: Differences between rocuronium and succinylcholine were assessed using the Kruskal-Wallis one-way test and two-tailed Mann-Whitney U test. RESULTS: Rocuronium, but not succinylcholine, led to a significant dose-dependent decrease of viability, albumin synthesis and cytochrome 1A2 activity of test cells. CONCLUSION: An in-vitro test with a cell line showed hepatotoxicity of rocuronium that was dose-dependent. Further studies are needed to investigate the underlying mechanisms of the effects of rocuronium on hepatic cellular integrity. TRIAL REGISTRATION: Not suitable. (C) 2017 European Society of Anaesthesiology

http://ift.tt/2tt7QoR

Doctor says you are cured, but you still feel the pain. Borrelia DNA persistence in Lyme disease

Publication date: Available online 15 June 2017
Source:Microbes and Infection
Author(s): Jorge Cervantes
Lyme disease is a zoonosis caused by infection with Borrelia burgdorferi (Bb). A great amount of research has attempted to elucidate the mechanisms by which Bb causes inflammation and chronic symptomatology in some patients. Patients often seek unconventional treatments that lack scientific evidence, as medical care is unable to effectively explain and treat their illness. Bb-DNA can persist for long periods of time in some individuals, even after antibiotic therapy. Herein, scientific rationale is presented for a new therapeutic approach against remaining bacterial DNA, and/or increasing the ability of human macrophages to remove extracellular Bb DNA.



http://ift.tt/2s7qpBi

Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications: An observational study in 29 countries.

BACKGROUND: Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. OBJECTIVES: To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. DESIGN: This was a prospective international 1-week observational study using the 'Assess Respiratory Risk in Surgical Patients in Catalonia risk score' (ARISCAT score) for PPC for risk stratification. PATIENTS AND SETTING: Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. MAIN OUTCOME MEASURES: The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. RESULTS: A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (VT) size was 500 ml, or 7 to 9 ml kg-1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P

http://ift.tt/2tt9Uxn

Women awaken faster than men after electroencephalogram-monitored propofol sedation for colonoscopy: A prospective observational study.

BACKGROUND: Sedation for colonoscopy using intravenous propofol has become standard in many Western countries. OBJECTIVE: Sex-specific differences have been shown for general anaesthesia in dentistry, but no such data existed for gastrointestinal endoscopy. DESIGN: A prospective observational study. SETTING: An academic teaching hospital of Hannover Medical School. PATIENTS: A total of 219 patients (108 women and 111 men) scheduled for colonoscopy. INTERVENTION: Propofol sedation using electroencephalogram monitoring during a constant level of sedation depth (D0 to D2) performed by trained nurses or physicians after a body-weight-adjusted loading dose. MAIN OUTCOME MEASURES: The primary end-point was the presence of sex-specific differences in awakening time (time from end of sedation to eye-opening and complete orientation); secondary outcome parameters analysed were total dose of propofol, sedation-associated complications (bradycardia, hypotension, hypoxaemia and apnoea), patient cooperation and patient satisfaction. Multivariate analysis was performed to correct confounding factors such as age and BMI. RESULTS: Women awakened significantly faster than men, with a time to eye-opening of 7.3 +/- 3.7 versus 8.4 +/- 3.4 min (P = 0.005) and time until complete orientation of 9.1 +/- 3.9 versus 10.4 +/- 13.7 min (P = 0.008). The propofol dosage was not significantly different, with some trend towards more propofol per kg body weight in women (3.98 +/- 1.81 mg versus 3.72 +/- 1.75 mg, P = 0.232). CONCLUSION: The effect of sex aspects should be considered when propofol is used as sedation for gastrointestinal endoscopy. That includes adequate dosing for women as well as caution regarding potential overdosing of male patients. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02687568). (C) 2017 European Society of Anaesthesiology

http://ift.tt/2sveg9X

Rocuronium is more hepatotoxic than succinylcholine in vitro.

BACKGROUND: The development of liver failure is a major problem in critically ill patients. The hepatotoxicity of many drugs, as one important reason for liver failure, is poorly screened for in human models. Rocuronium and succinylcholine are neuromuscular blocking agents used for tracheal intubation and for rapid-sequence induction. OBJECTIVE: We used an in-vitro test with a permanent cell line and compared rocuronium and succinylcholine for hepatotoxicity. DESIGN: In-vitro study. SETTING: A basic science laboratory, University Hospital Rostock, Germany. MATERIAL/(PATIENTS): The basic test compound is the permanent human liver cell line HepG2/C3A. In a standardised microtitre plate assay the toxicity of different concentrations of rocuronium, succinylcholine and plasma control was tested. INTERVENTIONS: After two incubation periods of 3 days, the viability of cells (XTT test, lactate dehydrogenase release and trypan blue staining), micro-albumin synthesis and the cytochrome 1A2 activity (metabolism of ethoxyresorufin) were measured. MAIN OUTCOME MEASURES: Differences between rocuronium and succinylcholine were assessed using the Kruskal-Wallis one-way test and two-tailed Mann-Whitney U test. RESULTS: Rocuronium, but not succinylcholine, led to a significant dose-dependent decrease of viability, albumin synthesis and cytochrome 1A2 activity of test cells. CONCLUSION: An in-vitro test with a cell line showed hepatotoxicity of rocuronium that was dose-dependent. Further studies are needed to investigate the underlying mechanisms of the effects of rocuronium on hepatic cellular integrity. TRIAL REGISTRATION: Not suitable. (C) 2017 European Society of Anaesthesiology

http://ift.tt/2tt7QoR

Pediatric head and neck bone sarcomas: An analysis of 204 cases

To analyze the demographics, survival, and treatment efficacy of pediatric sarcomas of the facial skeleton and skull.

http://ift.tt/2rmQLwe

A novel management of streptococcal pharyngotonsillar infections by laser-activated silver nanoparticles and methylene blue conjugate, in vitro study

Species of Streptococcus are classified based on their hemolytic properties ‏ into alpha and beta types. And, since antimicrobial drug resistance is an increasingly problematic issue, the efforts to develop modalities that would overcome this obstacle and avoid antibiotic side effects is an ongoing challenge.

http://ift.tt/2sFC4bB

Auditory, visual and auditory-visual memory and sequencing performance in typically developing children

The study evaluated whether there exists a difference/relation in the way four different memory skills (memory score, sequencing score, memory span, & sequencing span) are processed through the auditory modality, visual modality and combined modalities.

http://ift.tt/2rmRRs7

Exome sequencing identifies a novel missense mutation of WFS1 as the cause of non-syndromic low-frequency hearing loss in a Chinese family

Autosomal dominant non-syndromic low-frequency sensorineural hearing loss (LFSNHL) DFNA6/14/38 is an uncommon type of hearing loss that classically affects low frequencies of 2000 Hz and below, demonstrating an ascending configuration. The current study aimed to investigate the cause of LFSNHL in a five-generation Chinese family.

http://ift.tt/2sFzfHL

Functional endoscopic sinus surgery improves the quality of life in children suffering from chronic rhinosinusitis with nasal polyps

To evaluate the impact of FESS in children with chronic rhinosinusitis with nasal polyps, regarding their overall postoperative quality-of-life (QoL) and constituent QoL domains. Potential differences between cystic fibrosis (CF) sufferers and non-sufferers, or cases with recurrent sinonasal polyposis versus single-operations were also explored.

http://ift.tt/2rmQPfu

Absence of KCNQ4 mutation in Bengali families with ADNSHL originated from West Bengal, India

Autosomal Dominant Non-Syndromic Hearing Loss (ADNSHL) is extremely heterogeneous in nature. More than 60 loci with 30 different genes have been identified linked to ADNSHL. Mutation in KCNQ4 is considered as one of the most common causative factor responsible for ADNSHL. No study focused on the genetic alteration of KCNQ4 gene among hearing loss patients in India. The present study for the first time was carried out to determine the mutation spectrum of KCNQ4 gene in ADNSHL patients of West Bengal state, India.

http://ift.tt/2sFLLab

Bilateral congenital cholesteatoma: Surgical treatment and considerations

To describe a multicenter study regarding surgical management of bilateral congenital cholesteatoma (BCC) and underline the importance of endoscopes in the management of this condition. In BCC, hearing preservation is more crucial than in unilateral cases. The endoscopic approach allows complete removal of cholesteatoma via a minimally invasive technique offering low residual disease rates while preserving the normal physiology of the middle ear and possibly the ossicular chain.

http://ift.tt/2rmqRca

Study of the effects of hearing on static and dynamic postural function in children using cochlear implants

The present study aimed to evaluate the postural control perturbations by the center of pressure parameters in two main approaches, cochlear implant turned "on" and "off".

http://ift.tt/2sFWMrJ

Sialadenoma papilliferum in the buccal mucosa detected on 18F-fluorodeoxyglucose-positron emission tomography

An incidental discovery of an accumulation of 18F-fluorodeoxyglucose (FDG) in the oral cavity of patients with malignant tumours on FDG positron emission tomography (PET) can pose a problem regarding the differential diagnosis of metastatic lesions. Large accumulations can often be found even when tumours in the salivary or thyroid gland are benign, so FDG-PET is limited in its ability to differentiate between benign and malignant disease. This report describes a rare case of sialadenoma papilliferum in the buccal mucosa that was discovered incidentally on FDG-PET in a patient with multiple metastases to bone after an operation for rectal cancer.

http://ift.tt/2rCU0PC

Re: Segmental mandibulectomies made easier: a simple drill guide

We read with interest the paper by Gordon et al1 in which they proposed the use of a reconstruction plate to accurately position the remaining mandible after a segmental mandibulectomy. We agree that this method is easy, simple to do, and cost effective.

http://ift.tt/2s7z7iU

Diathermy of split-thickness skin graft donor site: a new technique

Split-thickness skin graft donor sites have always been problematic postoperatively because of scarring, bleeding that can continue for several days or even weeks, pain, and a reduction in mobility.1–3 Many attempts have been made to mitigate these complications, but most have concentrated on pain control with various dressings.4 We describe a method that reduces the size of the donor site, as well as bleeding and pain.

http://ift.tt/2s7KIid

Biomechanical comparison of a multidirectional locking plate and conventional plates for the osteosynthesis of mandibular angle fractures—a preliminary study

The objective of surgical fracture management is to reduce and fixate fractures accurately and rapidly. Two osteosynthesis plates are usually used in the treatment of mandibular angle fractures in order to enhance torsional stiffness. We conducted biomechanical tests under static and cyclic loading in order to assess whether a single locking plate is as efficacious as two conventional plates in the osteosynthesis of mandibular angle fractures.

http://ift.tt/2svzAfB

Reconstruction of the bony chin using sagittal split osteotomies of the remaining mandible─a new technique for a special indication: Case report

There are several indications for resecting the bony chin, such as squamous cell carcinoma, sarcoma, or benign tumors of the jaw such as ameloblastoma. Several techniques for reconstruction of the bony chin, such as the use of metal plates and also revascularized free bone grafts of the iliac crest, fibula, or scapula, are common. In the case of poor vascular supply, however, alternative techniques may be necessary. In this report, a new technique is described using pedicled bone flaps from both sagittally split mandibular stumps following chin resection.

http://ift.tt/2ttBnia

Long-term contextual memory in infant rats as evidenced by an ethanol conditioned tolerance procedure

Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Stefanía Castelló, Juan Carlos Molina, Carlos Arias
Conditioned tolerance can be conceptualized as a particular case of Pavlovian conditioning in which contextual cues play the role of the conditioned stimulus. Although the evidence is contradictory, it is frequently assumed that long-term contextual conditioning in pre-weanling rats is weak or even absent. This hypothesis comes from and is sustained mainly by behavioral studies that explored different contextual effects in 16–18day-old rats using a fear-conditioning paradigm, but their conclusions are stated in terms of an immature (hippocampal-dependent) declarative memory system. The main goal of the present manuscript was based on a recent antecedent from our laboratory, to analyze whether context-dependent tolerance induced by ethanol during the pre-weanling period persists over time. Results showed that the context was able to modulate ethanol-induced tolerance in 2- and 3-week-old rats. Interestingly, contextual conditioned tolerance was stronger (in terms of persistence) during the third than during the second postnatal week. When subjects were tested 8days after training, when the context presumably lost its influence over tolerance, the opposite effect emerged (sensitization). These results are important for the ethanol literature, adding new evidence of long-term retention of ethanol effects acquired during infancy, whilst also showing striking ontogenetic differences in the sensitivity to ethanol between the 2nd and 3rd postnatal weeks. Importantly, contextual information modulates the expression of these ethanol effects even eight days after training, a result that is particularly relevant to the discussion of the ontogeny of contextual memory.



http://ift.tt/2shdN9k

Restraint stress enhances alcohol intake in adolescent female rats but reduces alcohol intake in adolescent male and adult female rats

Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Aranza Wille-Bille, Ana Ferreyra, Martina Sciangula, Florencia Chiner, Michael E. Nizhnikov, Ricardo Marcos Pautassi
Adolescents may be more sensitive to stress-induced alcohol drinking than adults, which would explain the higher prevalence of alcohol abuse and dependence in late adolescence than in adulthood. The present study analyzed the impact of restraint stress on the initiation of alcohol intake across 2 weeks of intermittent, two-bottle choice intake in male and female adolescent rats and adult female rats. Restraint stress significantly increased alcohol intake and preference in female adolescent rats but decreased alcohol intake and preference in male adolescent and female adult rats. The effects of restraint stress on alcohol intake were mitigated in adolescent females following administration of the κ opioid receptor antagonist norbinaltorphimine. Adolescent but not adult female rats that were subjected to restraint stress spent more time on the open arms of the elevated plus maze. Female adolescents exposed to stress also exhibited greater risk-taking behaviors in a concentric square field test compared with non-stressed controls. These results indicate age- and sex-related differences in the sensitivity to alcohol-stress interactions that may facilitate the initiation of alcohol use in female adolescents. The facilitatory effect of stress on alcohol intake was related to greater exploratory and risk-taking behaviors in young females after stress exposure.



http://ift.tt/2rxsOX6

Role of static fluid MR urography in detecting post urinary diversion complications

Publication date: Available online 16 June 2017
Source:Alexandria Journal of Medicine
Author(s): Amr Farouk Ibrahim Moustafa, Tamer M. Abd el Rahman, Amr Abd Elfattah Hassan Gadalla, Karam Gaber Mohamed, Ahmed Morsi Moustafa Fahmy, Sameh Abd AlAziz Zaki Hanna
Aim of workThe aim of the study was to assess the diagnostic performance of static MR urography in detection of post cystectomy complications & the ability of static fluid MR urography in visualization of urinary tract segments.Material & methodsWe prospectively reviewed 21 MR urograms with urinary diversion. The most common surgical procedures included Ileal conduit & Ileocecal neobladder diversion.Magnetic resonance urography examinations were performed with 1.5-T MR scanners. T2 weighted (static fluid) MR urography techniques were done, in addition to conventional T1- and T2-weighted axial and coronal sequences. Urinary tract was divided in different parts: pelvicalyceal systems, upper, mid and lower ureteric segments & the reservoir or conduit Imaging features of the urinary collecting systems were evaluated for their visualization and complications detection.ResultsT2-weighted MR urography could demonstrate 95% of urinary tract segments & together with conventional MR sequences all urinary tract segments can be visualized. Urinary diversion related complications were encountered included in 15 patients (71.4%) & no urological complications were seen in 6 patients (28.6%).ConclusionComprehensive T2-weighted MR urography is an effective imaging method for the visualization of the urinary system and detection of early and late postoperative complications in patients with urinary diversion.



http://ift.tt/2rxsDew

Socio-demographic and clinical factors predicting time to presentation for children with pneumonia in Ilorin, Nigeria

Publication date: Available online 16 June 2017
Source:Alexandria Journal of Medicine
Author(s): Rasheedat M. Ibraheem, Mohammed B. Abdulkadir, Aishat A. Gobir, Wahab B.R. Johnson
BackgroundPneumonia is a major contributor to morbidity and mortality in children, and the time to presentation is a recognized contributor towards disease severity and outcome.ObjectivesThe current study aimed to explore the influence of some socio-demographic and clinical factors in children with pneumonia on the time to presentation at a health facility in Ilorin, North Central Nigeria.Materials and methodA prospective cross-sectional study of 167 children with pneumonia was done. The duration of the various symptoms and first presentation to a health facility was obtained. Time to presentation was categorized as 0–2days (early), 3–5days (intermediate) and greater than five days (late). Multinomial logistic regression analysis was used to identify significant predictors of either early or intermediate presentation compared with late presentation. A p-value of less than 0.05 was considered significant.ResultsFifty-one (30.5%) children with pneumonia had an early presentation, 73 (43.7%) had intermediate presentation and 43 (25.7%) were late in presentation. Predictors of early presentation were younger age (OR 0.96, 95%CI 0.93–0.99), higher respiratory rates (OR 1.03, 95%CI 1.01–1.06) and bronchopneumonia (OR 6.93, 95%CI 1.52–31.63). Predictors of intermediate presentation were families with few number of children (OR 0.73, 95%CI 0.57–0.92) and bronchopneumonia (OR 3.41, 95%C.I. 1.02–11.38).ConclusionInfancy and families with few children are socio-demographic features that are likely to determine early-to-intermediate presentation of children with pneumonia while high respiratory rates and bronchopneumonia are disease related factors that predict early presentation.



http://ift.tt/2sh7Edb

Kaempferol increases levels of coenzyme Q in kidney cells and serves as a biosynthetic ring precursor

Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Lucía Fernández-del-Río, Anish Nag, Elena Gutiérrez Casado, Julia Ariza, Agape M. Awad, Akil I. Joseph, Ohyun Kwon, Eric Verdin, Rafael de Cabo, Claus Schneider, Jorge Z. Torres, María I. Burón, Catherine F. Clarke, José M. Villalba
Coenzyme Q (Q) is a lipid-soluble antioxidant essential in cellular physiology. Patients with Q deficiencies, with few exceptions, seldom respond to treatment. Current therapies rely on dietary supplementation with Q10, but due to its highly lipophilic nature, Q10 is difficult to absorb by tissues and cells. Plant polyphenols, present in the human diet, are redox active and modulate numerous cellular pathways. In the present study, we tested whether treatment with polyphenols affected the content or biosynthesis of Q. Mouse kidney proximal tubule epithelial (Tkpts) cells and human embryonic kidney cells 293 (HEK 293) were treated with several types of polyphenols, and kaempferol produced the largest increase in Q levels. Experiments with stable isotope ¹³C-labeled kaempferol demonstrated a previously unrecognized role of kaempferol as an aromatic ring precursor in Q biosynthesis. Investigations of the structure-function relationship of related flavonols showed the importance of two hydroxyl groups, located at C3 of the C ring and C4′ of the B ring, both present in kaempferol, as important determinants of kaempferol as a Q biosynthetic precursor. Concurrently, through a mechanism not related to the enhancement of Q biosynthesis, kaempferol also augmented mitochondrial localization of Sirt3. The role of kaempferol as a precursor that increases Q levels, combined with its ability to upregulate Sirt3, identify kaempferol as a potential candidate in the design of interventions aimed on increasing endogenous Q biosynthesis, particularly in kidney.

Graphical abstract

http://ift.tt/2rmci8A

Academic Productivity, Knowledge, and Education in Plastic Surgery: The Benefit of the Clinical Research Fellow.

Summary: Academic research productivity is limited by strenuous resident and faculty schedules, yet is imperative to the growth and success of our discipline. We report institutional experience with our clinical research fellowship model, providing two positions per year. A critical analysis of research productivity was performed for all trainees, faculty, and research fellows from 2000-2015. All articles in-print were individually collected to identify academic appointment at time of publication for the authors. Academic productivity was determined by number of peer-reviewed publications, podium presentations, and h-index. Podium presentations at two national and one regional plastic surgery meetings were collected. Academic fate of previous research fellows was also noted. Overall, 18 faculty, 38 fellows, 41 residents, and 8 research fellows were included. During the 16-year time-frame, 484 articles were published in print. Notably, 92 articles were published from 2000-2007 and 392 articles were published from 2008-2015 (p=0.0066), demonstrating linear growth after instituting the research fellowship. Additionally, 33 articles were published from 2002-2004 pre-leadership change, 47 from 2005-2007 post- leadership change but pre-fellowship, and 58 from 2008-2010 in the first few years of the fellowship (p=0.0204). Overall, 39.9% of publications appeared in PRS, with a total of 77 different peer-reviewed journal inclusions. AAPS, ASPS, and NESPS podium presentations totaled 143 between 2005-2015. Of the 8 previous fellows who applied into integrated and independent programs, 100% have matched. Incorporation of a formalized research fellowship into a plastic surgery program can drastically increase clinical research contribution in a reproducible fashion. (C)2017American Society of Plastic Surgeons

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3D Cone Beam Computed Tomography Volumetric Outcomes of rhBMP-2/demineralized bone matrix vs Iliac Crest Bone Graft for Alveolar Cleft Reconstruction*.

Background: Recent studies indicate that recombinant human bone morphogenetic protein (rhBMP-2) in a demineralized bone matrix scaffold (MS) is a comparable alternative to iliac bone autograft in the setting of secondary alveolar cleft repair. Post-reconstruction occlusal radiographs demonstrate improved bone stock when rhBMP-2/MS is used, but lack the capacity to evaluate bone growth in three dimensions. This study uses cone beam computed tomography (CBCT) to provide the first clinical evaluation of volumetric and density comparisons between these two treatment modalities. Methods: A prospective study was conducted with 31 patients and 35 repairs of the alveolar cleft over a two-year period. Twenty-one repairs utilized rhBMP-2/MS while 14 repairs utilized iliac bone grafting. Postoperatively, occlusal radiographs were obtained at 3 months to evaluate bone fill; CBCT images were obtained at 6-9 months to compare volumetric and density data. Results: At 3 months, postoperative occlusal radiographs demonstrate that 67% of patients receiving rhBMP-2/MS had complete bone fill of the alveolus, vs 56% of patients in the autologous group. In contrast, CBCT data shows 31.6% (95% CI: 24.2- 38.5%) fill in the rhBMP-2/MS group compared with 32.5% (95% CI: 22.1-42.9%) in the autologous population. Density analysis demonstrated identical average values between the rhBMP-2/MS and iliac bone crest group (1.38g/cc). Conclusions: These data demonstrate comparable bone regrowth and density values following secondary alveolar cleft repair using rhBMP-2/MS vs. autologous iliac bone graft. CBCT provides a more nuanced understanding of true bone regeneration within the alveolar cleft that may contribute to the information provided by occlusal radiographs alone. (C)2017American Society of Plastic Surgeons

http://ift.tt/2rCtK7T

The Whitaker Classification of Craniosynostosis Outcomes: An Assessment of Inter-Rater Reliability.

Purpose: The Whitaker classification (WC) is a simple and widely used system for describing aesthetic outcomes after craniosynostosis surgery. The purpose of this study is to evaluate its inter-rater reliability for patients who have undergone frontal-orbital surgery. Methods: A retrospective review of patients with craniosynostosis who underwent surgical intervention at a tertiary referral center was conducted. Inclusion criteria were: single-suture craniosynostosis, surgical intervention before age two years, and photographs taken prior to revisions between 5 and 20 years of age. Thirteen craniofacial surgeons independently reviewed the subject's photographs and assigned WC. Inter-rater reliability was assessed with Cohen's kappa. Results: Twenty-nine subjects were included. Average ages at surgery and the time of post-operative photographs were 0.8 years, and 12.8 years, respectively. The [kappa] value for all 13 raters was 0.1567 (p

http://ift.tt/2s7o1KG

Soft Tissue Reconstruction of Large Spinal Defects: A 12-year Institutional Experience.

Background: Radical spinal resections can lead to considerable defects requiring soft tissue reconstruction. The purpose of this study was to review our institutional experience of over a decade with reconstruction of spinal defects and identify risk factors predictive of wound complications, particularly focusing on timing of reconstruction with ablative surgery. Methods: We retrospectively reviewed patients who underwent spinal resection and required soft tissue reconstruction from 2002-2014. Patient characteristics, operative details, and complication rates were collected. Logistic regression was performed to identify risk factors for wound complications. Results: Of 289 reconstructions performed in 259 patients, 64 cases (22.1%) had major wound complications requiring reoperation. Lumbosacral defects were the most common location (43.6%) and paraspinous muscle flaps were the preferred reconstructive method used for all defect regions. A total of 224 reconstructions (77.5%) were performed immediately at time of spinal surgery, and 65 (22.5%) were performed in delayed fashion as result of wound complications from previous spinal surgery. Patients with immediate reconstructions required significantly fewer instrumentation removal rates (0.9% v. 4.6%, p=0.043), unplanned reoperations (0.5 v. 1.3, p

http://ift.tt/2rCeTKB

Discussion: Gynecomastia Classification for Surgical Management: A Systematic Review and Novel Classification System.

No abstract available

http://ift.tt/2rCgzUq

Facial Contouring by Targeted Restoration of Facial Fat Compartment Volume: The Midface.

No abstract available

http://ift.tt/2s7DfzG

Discussion: Gynecomastia classification for surgical management: A systematic review and novel classification system.

No abstract available

http://ift.tt/2rCICmQ

Symmetry restoration at rest after masseter-to-facial nerve transfer: Is it as efficient as smile reanimation?.

Background: Masseter-to-facial nerve transfer is a highly efficient technique for reanimating paralyzed muscle and has been reported to restore facial symmetry at rest. However, no systematic studies have been performed, and the effects of preoperative droop oral commissure on postoperative symmetry at rest have rarely been reported. Methods: The authors retrospectively analyzed 35 patients with masseteric-facial nerve anastomosis and assessed the quality and quantity of the dynamic recovery and the oral commissure symmetry at rest. The dynamic and static effects were then compared. Results: All of the patients' Terzis scores were increased post-operatively, and over half of the patients presented restored symmetrical smiles (Terzis scores of 4 or 5). The postoperative symmetry scale of oral commissure at rest improved in 18 of 35 patients. Both the mean postoperative AD-OCE (altitude difference of oral commissure excursion) and the postoperative AD-OCP (altitude difference of bilateral oral commissure position) were decreased compared to preoperative values. The preoperative symmetry had a significant effect on the postoperative AD-OCP. The effects of the dynamic and static symmetry improvements were transformed to a comparable factor '[alpha]'. The dynamic [alpha] was significantly greater than static [alpha]. Conclusions: Masseter-to-facial nerve transfer is a reliable technique for smile reanimation. However, it has only a limited effect on the improvement of symmetry at rest. Assessing the preoperative symmetry of oral commissure at rest can be used to predict postoperative outcomes, and patients with severely droop oral commissure (symmetry scale III or IV) should receive static suspension. (C)2017American Society of Plastic Surgeons

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Sequential matched analysis of racial disparities in breast cancer hospitalization outcomes among African American and White patients

Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Kemi Ogunsina, Gurudatta Naik, Neomi Vin-Raviv, Tomi F. Akinyemiju
BackgroundThe purpose of this study is to determine if racial disparities in inpatient outcomes persist among hospitalized patients comparing African American and White breast cancer patients matched on demographics, presentation and treatment.MethodsA total of 136,211 African American and White breast cancer patients from the Healthcare Cost and Utilization Project − Nationwide Inpatient Sample (HCUP-NIS) database, matched on demographics alone, demographics and presentation or demographics, presentation and treatment were studied. Conditional logistic regression was conducted to evaluate post-surgical complications, length of stay and in-hospital mortality outcomes. Analysis was further stratified by age (≤65 years and >65years) to evaluate whether disparities were larger in younger or older patients. All analysis was conducted using SAS 9.3.ResultsWhite women had significantly shorter hospital length of stay when matched on demographics (β=−0.87, p-value=<0.0001), demographics and presentation (β=−0.63, p-value=<0.0001), and demographics, presentation and treatment (β=−0.51, p-value=<0.0001) compared with African Americans. White women also had lower odds of mortality compared with African American women when matched on demographics (OR: 0.72, 95% CI: 0.65-0.79), demographics and presentation (OR: 0.77, 95% CI: 0.71-0.85), or matched on demographics, presentation and treatment (OR: 0.80, 95% CI: 0.73-0.88). The racial difference observed in length of stay and mortality was larger in the age group ≤65 years compared with >65yearsConclusionAfrican American women experienced higher odds of inpatient mortality and longer length of stay compared with White women even after accounting for differences in demographics, presentation and treatment characteristics.



http://ift.tt/2rCn1Ld

A Randomized, Placebo-controlled, Double-blinded, Crossover Trial of Pioglitazone for Severe Asthma

The PPAR-γ agonist, pioglitazone, was associated with significant side effects and did not improve the primary outcome measure of the Juniper Asthma Quality of Life Questionnaire (AQLQ) score in severe asthmatics. We conclude that no further studies should be performed with pioglitazone for severe asthma.

http://ift.tt/2rmxzyN

Responsiveness and Minimal Important Difference of the Urticaria Control Test (UCT)

This study demonstrates the responsiveness of the Urticaria Control Test (UCT). Changes of its score by 3 points or more reflect a clinically relevant change of disease control (minimal important difference).

http://ift.tt/2sFMecl

Evidence for altered levels of Immunoglobulin D in the nasal airway mucosa of patients with chronic rhinosinusitis

Soluble IgD levels and IgD+CD19+CD38bright plasmablasts were significantly increased in nasal airway mucosa from patients with CRSsNP. Local factors including IL-2 levels and presence of pathogenic bacteria may enhance IgD production in nasal airway mucosa.

http://ift.tt/2rmGWP9

Relationship between EASI and SCORAD severity assessments for atopic dermatitis

The present study shows a complex relationship between EASI and SCORAD. The results provide support for inclusion of objective-SCORAD and/or SCORAD in addition to EASI in clinical trials.

http://ift.tt/2sFOkch

Microsurgical Hepatic Artery Reconstruction Using Ikuta A-II Double Clamp

Summary: We performed hepatic artery (HA) reconstruction on 24 patients between January 2010 and October 2016. Six of 24 patients used an Ikuta type A-II vascular clamp (A-II group). The mean age was 38.0 years (range, 1–61 years). There was no blood leakage at the anastomosed site in any of the patients. No patients required an additional vascular clamp, and none developed HA thrombosis. Eighteen of 24 patients used a conventional vascular clamp. The mean age was 36.1 years (range, 1–65 years; conventional group). Sixteen of 18 patients required an additional vascular clamp due to blood leakage from the HA. There was no significant difference between the 2 groups in mean age or diameter of the recipient HA. However, there was a significant difference in the proportion of patients who required an additional vascular clamp (n

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Adjuvants for Animal Vaccines

Viral Immunology , Vol. 0, No. 0.


http://ift.tt/2sgRHU7

Update on the supraclavicular flap.

Purpose of review: The purpose of this study is to describe the supraclavicular flap and its utility in head and neck reconstruction in the context of recent studies. Recent findings: Current literature regarding the supraclavicular flap has described its expanded uses in a variety of head and neck reconstructive settings. Its reliability and limited morbidity have been well demonstrated, and it has been cited as a reasonable alternative to other reconstructive options including, in some situations, free tissue transfer. Summary: The supraclavicular flap has shown dependability in reconstruction of defects in the head and neck, and it warrants consideration among reconstructive surgeons, especially for circumstances in which free tissue or other pedicled flaps are less than ideal. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2sFiix7

In Response.

No abstract available

http://ift.tt/2rC7POa

Wind of Change or Siren Song?.

No abstract available

http://ift.tt/2s7qdSL

In Response.

No abstract available

http://ift.tt/2rCcwHF

In Response.

No abstract available

http://ift.tt/2s7sgpy

Intraperitoneal Instillation of Local Anesthetics: Is This a Suitable Alternative for Postcesarean Pain Relief Without Toxicity Profiling?.

No abstract available

http://ift.tt/2rCeh7R

Evaluation of the Temple Touch Pro, a Novel Noninvasive Core-Temperature Monitoring System.

BACKGROUND: The Temple Touch Pro (TTP) is a novel system that estimates core temperature from skin over the temporal artery. We tested the hypothesis that this noninvasive system estimates core temperature to an accuracy within 0.5[masculine ordinal indicator]C. METHODS: Core temperature was continuously monitored in 50 adult and pediatric surgical patients by positioning the sensor patch of a TTP over one temporal artery. The sensor consists of a thermistor array near the skin surface, another set of thermistors above an insulator, and a second insulator between the upper unit and the environment. The sensor measures skin temperature and heat flux, from which the monitor unit estimates core temperature from a proprietary algorithm. Reference core temperature was measured from the esophagus or nasopharynx. We conducted agreement analysis between the TTP and the reference core temperature measurements using the 95% Bland-Altman limits of agreement for repeated measurement data. The proportion of all differences that were within 0.5[masculine ordinal indicator]C and repeat measures concordance correlation coefficient (CCC) were estimated as well. RESULTS: TTP and the reference core temperature measurements agreed well in both adults and pediatric patients. Bland-Altman plots showed no evidence of systematic bias or variability over the temperature from 35.2[masculine ordinal indicator]C to 37.8[masculine ordinal indicator]C. The estimated 95% lower and upper limits of agreement were -0.57[masculine ordinal indicator]C (95% confidence interval [CI], -0.76 to -0.41) and 0.57[masculine ordinal indicator]C (95% CI, 0.44 to 0.71), indicating good agreement between the 2 methods. Ninety-four percentage (95% CI, 87% to 99%) of the TTP temperatures were within 0.5[masculine ordinal indicator]C of the reference temperature. Good agreement was also supported by an estimated repeated measures CCC of 0.82 (95% CI, 0.66 to 0.91). The TTP core temperature measurements also agreed well with nasopharyngeal reference temperatures. CONCLUSIONS: The noninvasive TTP system is sufficiently accurate and reliable for routine intraoperative core temperature monitoring. (C) 2017 International Anesthesia Research Society

http://ift.tt/2s7dOOl

Update on the supraclavicular flap.

Purpose of review: The purpose of this study is to describe the supraclavicular flap and its utility in head and neck reconstruction in the context of recent studies. Recent findings: Current literature regarding the supraclavicular flap has described its expanded uses in a variety of head and neck reconstructive settings. Its reliability and limited morbidity have been well demonstrated, and it has been cited as a reasonable alternative to other reconstructive options including, in some situations, free tissue transfer. Summary: The supraclavicular flap has shown dependability in reconstruction of defects in the head and neck, and it warrants consideration among reconstructive surgeons, especially for circumstances in which free tissue or other pedicled flaps are less than ideal. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2sFiix7

New paradigms for the Hedgehog signaling network in mammary gland development and breast Cancer

Publication date: Available online 15 June 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Teresa Monkkonen, Michael T. Lewis
The Hedgehog signaling network regulates organogenesis, cell fate, proliferation, survival, and stem cell self-renewal in many mammalian tissues. Aberrant activation of the Hedgehog signaling network is present in ~25% of all cancers, including breast. Altered expression of Hedgehog network genes in the mammary gland can elicit phenotypes at many stages of development. However, synthesizing a cohesive mechanistic model of signaling at different stages of development has been difficult. Emerging data suggest that this difficulty is due, in part, to non-canonical and tissue compartment-specific (i.e., epithelial, versus stromal, versus systemic) functions of Hedgehog network components. With respect to systemic functions, Hedgehog network genes regulate development of endocrine organs that impinge on mammary gland development extrinsically. These new observations offer insight into previously conflicting data, and have bearing on the potential for anti-Hedgehog therapeutics in the treatment of breast cancer.



http://ift.tt/2syjaDT

Update on the supraclavicular flap.

Purpose of review: The purpose of this study is to describe the supraclavicular flap and its utility in head and neck reconstruction in the context of recent studies. Recent findings: Current literature regarding the supraclavicular flap has described its expanded uses in a variety of head and neck reconstructive settings. Its reliability and limited morbidity have been well demonstrated, and it has been cited as a reasonable alternative to other reconstructive options including, in some situations, free tissue transfer. Summary: The supraclavicular flap has shown dependability in reconstruction of defects in the head and neck, and it warrants consideration among reconstructive surgeons, especially for circumstances in which free tissue or other pedicled flaps are less than ideal. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2sFiix7

SPEF2 functions in microtubule-mediated transport in elongating spermatids [RESEARCH ARTICLE]

Mari S. Lehti, Fu-Ping Zhang, Noora Kotaja, and Anu Sironen

Sperm differentiation requires specific protein transport for correct sperm tail formation and head shaping. A transient microtubular structure, the manchette, appears around the differentiating spermatid head and serves as a platform for protein transport to the growing tail. Sperm flagellar protein 2 (SPEF2) is known to be essential for sperm tail development. In this study we investigated the function of SPEF2 during spermatogenesis using a male germ cell-specific Spef2 knockout mouse model. In addition to defects in sperm tail development, we observed a duplication of the basal body and failure in the manchette migration resulting in an abnormal head shape. We identified cytoplasmic Dynein 1 and GOLGA3 as novel interaction partners for SPEF2. SPEF2 and Dynein 1 colocalize in the manchette and the inhibition of Dynein 1 disrupts the manchette localization of SPEF2. Furthermore, the transport of a known SPEF2-binding protein IFT20 from the Golgi complex to the manchette was delayed in the absence of SPEF2. This data underline a possible novel role of SPEF2 as a linker protein for Dynein 1-mediated cargo transport along microtubules.

http://ift.tt/2ttj7FS

A toolkit for GFP-mediated tissue-specific protein degradation in C. elegans [TECHNIQUES AND RESOURCES REPORT]

Shaohe Wang, Ngang Heok Tang, Pablo Lara-Gonzalez, Zhiling Zhao, Dhanya K. Cheerambathur, Bram Prevo, Andrew D. Chisholm, Arshad Desai, and Karen Oegema

Proteins essential for embryo production, cell division, and early embryonic events are frequently re-utilized later in embryogenesis, during organismal development, or in the adult. Examining protein function across these different biological contexts requires tissue-specific perturbation. Here, we describe a method that utilizes expression of a fusion between a GFP-targeting nanobody and a SOCS-box containing ubiquitin ligase adaptor to target GFP tagged proteins for degradation. When combined with endogenous locus GFP tagging by CRISPR-Cas9 or rescue of a null mutant with a GFP fusion, this approach enables routine and efficient tissue-specific protein ablation. We show that this approach works in multiple tissues—the epidermis, intestine, body wall muscle, ciliated sensory neurons, and touch receptor neurons—where it recapitulates expected loss-of-function mutant phenotypes. The transgene toolkit and the strain set described here will complement existing approaches to enable routine analysis of the tissue-specific roles of C. elegans proteins.

http://ift.tt/2svi23c

Sin3a regulates epithelial progenitor cell fate during lung development [RESEARCH ARTICLE]

Changfu Yao, Gianni Carraro, Bindu Konda, Xiangrong Guan, Takako Mizuno, Norika Chiba, Matthew Kostelny, Adrianne Kurkciyan, Gregory David, Jonathan L. McQualter, and Barry R. Stripp

Mechanisms that regulate tissue-specific progenitors for maintenance and differentiation during development are poorly understood. Here, we demonstrate that the co-repressor protein Sin3a is critical for lung endoderm development. Loss of Sin3a in early foregut endoderm leads to a specific and profound defect in lung development with lung buds failing to undergo branching morphogenesis and progressive atrophy of the proximal lung endoderm with complete epithelial loss at later stages of development. Consequently, neonatal pups died at birth due to respiratory insufficiency. Further analysis revealed that loss of Sin3a resulted in embryonic lung epithelial progenitor cells adopting a senescence-like state with permanent cell cycle arrest in G1 phase. This was mediated at least partially through the upregulation of cell cycle inhibitors p21/Cdkn1a and p18/Cdkn2c. At the same time, loss of endodermal Sin3a also disrupted cell differentiation of the mesoderm, suggesting aberrant epithelial-mesenchymal signaling. Together, these findings reveal that Sin3a is an essential regulator for early lung endoderm specification and differentiation.

http://ift.tt/2svobMv

Architectural protein Pita cooperates with dCTCF in organization of functional boundaries in Bithorax Complex [RESEARCH ARTICLE]

Olga Kyrchanova, Nikolay Zolotarev, Vladic Mogila, Oksana Maksimenko, Paul Schedl, and Pavel Georgiev

Boundaries in the Bithorax Complex (BX-C) of Drosophila delimit autonomous regulatory domains that drive parasegment-specific expression of homeotic genes. BX-C boundaries have two critical functions: they must block crosstalk between adjacent regulatory domains, and at the same time facilitate boundary bypass. The C2H2 zinc finger Pita protein binds to several BX-C boundaries including Fab-7 and Mcp. To study Pita functions, we have used a boundary replacement strategy by substituting modified DNAs for the Fab-7 boundary, which is located between the iab-6 and iab-7 regulatory domains. Multimerized Pita sites block iab-6ßàiab-7 crosstalk but fail to support iab-6 regulation of Abd-B (bypass). In the case of Fab-7 we used a novel sensitized background to show that the two Pita sites contribute its boundary function. Although Mcp is from BX-C, it does not function appropriately when substituted for Fab-7; it blocks crosstalk but does not support bypass. Mutation of the Mcp Pita site disrupts blocking activity and also eliminates dCTCF binding. In contrast, mutation of the Mcp dCTCF site does not affect Pita binding, and this mutant boundary retains partial function.

http://ift.tt/2tsWJfS

The histone 3 lysine 4 methyltransferase Setd1b is a maternal effect gene required for the oogenic gene expression program [RESEARCH ARTICLE]

David Brici, Qinyu Zhang, Susanne Reinhardt, Andreas Dahl, Hella Hartmann, Kerstin Schmidt, Neha Goveas, Jiahao Huang, Lenka Gahurova, Gavin Kelsey, Konstantinos Anastassiadis, A. Francis Stewart, and Andrea Kranz

Germ cell development involves major reprogramming of the epigenome to prime the zygote for totipotency. Histone 3 lysine 4 (H3K4) methylations are universal epigenetic marks mediated in mammals by six H3K4 methyltransferases related to fly Trithorax, including two yeast Set1 orthologs: Setd1a and Setd1b. Whereas Setd1a plays no role in oogenesis, we report that Setd1b deficiency causes female sterility. Oocyte specific Gdf9iCre conditional knockout (Setd1b^Gdf9cKO) ovaries develop through all stages however follicular loss accumulated with age and unfertilized metaphase II (MII) oocytes exhibited irregularities of the zona pellucida and meiotic spindle. Most Setd1b^Gdf9cKO zygotes remained in the pronuclear stage and displayed polyspermy in the perivitelline space. Expression profiling of Setd1b^Gdf9cKO MII oocytes revealed (i) that Setd1b promotes the expression of the major oocyte transcription factors including Obox1, 2, 5, 7, Meis2 and Sall4; and (ii) two-times more up- than downregulated mRNAs suggesting that Setd1b also promotes the expression of negative regulators of oocyte development with multiple Zfp-KRAB factors implicated. Together, these findings indicate that Setd1b serves as maternal effect gene through regulation of the oocyte gene expression program.

http://ift.tt/2sviWfZ

COP9 signalosome subunits protect Capicua from MAP kinase-dependent and independent mechanisms of degradation [RESEARCH ARTICLE]

Annabelle Suisse, DanQing He, Kevin Legent, and Jessica E. Treisman

The COP9 signalosome removes Nedd8 modifications from the Cullin subunits of ubiquitin ligase complexes, reducing their activity. Here we show that mutations in the Drosophila COP9 signalosome subunit 1b (CSN1b) gene increase the activity of ubiquitin ligases that contain Cullin 1. Analysis of CSN1b mutant phenotypes revealed a requirement for the COP9 signalosome to prevent ectopic expression of Epidermal growth factor receptor (EGFR) target genes. It does so by protecting Capicua, a transcriptional repressor of EGFR target genes, from EGFR pathway-dependent ubiquitination by a Cullin 1/SKP1-related A/Archipelago E3 ligase and subsequent proteasomal degradation. The CSN1b subunit also maintains basal Capicua levels by protecting it from a separate mechanism of degradation that is independent of EGFR signaling. As a suppressor of tumor growth and metastasis, Capicua may be an important target of the COP9 signalosome in cancer.

http://ift.tt/2tsYbP9

SoxF factors induce Notch1 expression via direct transcriptional regulation during early arterial development [RESEARCH ARTICLE]

Ivy Kim-Ni Chiang, Martin Fritzsche, Cathy Pichol-Thievend, Alice Neal, Kelly Holmes, Anne Lagendijk, Jeroen Overman, Donatella D'Angelo, Alice Omini, Dorien Hermkens, Emmanuelle Lesieur, Ke Liu, Indrika Ratnayaka, Monica Corada, George Bou-Gharios, Jason Carroll, Elisabetta Dejana, Stefan Schulte-Merker, Benjamin Hogan, Monica Beltrame, Sarah De Val, and Mathias Francois

Arterial specification and differentiation are influenced by a number of regulatory pathways. While it is known that the Vegfa-Notch cascade plays a central role in this biological process, the transcriptional hierarchy controlling arterial specification has not been fully delineated. To elucidate the direct transcriptional regulators of Notch receptor expression in arterial endothelial cells, we used histone signatures, DNaseI hypersensitivity and ChIP-seq data to identify enhancers for the human NOTCH1 and zebrafish notch1b genes. These enhancers were able to direct arterial endothelial cell-restricted expression in transgenic models. Genetic disruption of SOXF binding sites clearly established a requirement for members of the SOXF group of transcription factors (SOX7,-17 and-18) to drive these enhancers activity in vivo. Further, endogenous deletion of the notch1b enhancer led to a significant augmentation of arterio-venous defects in notch-pathway deficient zebrafish. Loss of SoxF function revealed that these factors are necessary for the activity of NOTCH1 and notch1b enhancers, and for correct endogenous Notch1 gene transcription. These findings therefore position SOXF transcription factors directly upstream of Notch receptor expression during the acquisition of arterial identity in vertebrates.

http://ift.tt/2svb3XU

Convergence of signaling pathways underlying habenular formation and axonal outgrowth [RESEARCH ARTICLE]

Sara Roberson and Marnie E. Halpern

The habenular nuclei are a conserved integrating center in the vertebrate epithalamus where they modulate diverse behaviors. Despite their importance, our understanding of habenular development is incomplete. Time-lapse imaging and fate mapping demonstrate that the dorsal habenulae (dHb) of zebrafish are derived from dbx1b-expressing (dbx1b⁺) progenitors, which transition into cxcr4b-expressing neuronal precursors. The precursors give rise to differentiated neurons whose axons innervate the midbrain interpeduncular nucleus (IPN). Formation of the dbx1b⁺ progenitor population relies on the activity of the Shh, Wnt and Fgf signaling pathways. Wnt and Fgf function additively to generate dHb progenitors. Surprisingly, Wnt signaling also negatively regulates fgf8a, confining expression to a discrete dorsal diencephalic domain. Moreover, the Wnt and Fgf pathways have opposing roles in transcriptional regulation of components of the Cxcr4-chemokine signaling pathway. The chemokine pathway, in turn, directs the posterior outgrowth of dHb efferents towards the IPN and, when disrupted, results in ectopic, anteriorly directed axonal projections. The results define a signaling network underlying the generation of dHb neurons and connectivity with their midbrain target.

http://ift.tt/2tt15DC

canoe and scribble loss synergizes causing tumor-like overgrowth via Ras activation in neural stem cells and epithelia [RESEARCH ARTICLE]

Noemi Rives-Quinto, Maribel Franco, Ana de Torres-Jurado, and Ana Carmena

Over the past decade an intriguing connection between asymmetric cell division, stem cells and tumorigenesis has emerged. Neuroblasts, the neural stem cells of the Drosophila central nervous system, divide asymmetrically and constitute an excellent paradigm for further investigating that connection. Here we show that the simultaneous loss of the asymmetric cell division regulators Canoe (Afadin in mammals) and Scribble in neuroblast clones leads to tumor-like overgrowth through both a severe disruption of the asymmetric cell division process and a canoe loss-mediated Ras-PI3K-Akt activation. Moreover, canoe loss also interacts synergistically with scribble to promote overgrowth in epithelial tissues, here just by activating the Ras-Raf-MAPK pathway. Finally we find that the scribble functionally related genes discs large and lethal (2) giant larvae contribute to repress the Ras-MAPK signaling cascade in epithelia. Hence, our work uncovers novel cooperative interactions between all these well-conserved tumor suppressors to ensure a tight regulation of the Ras signaling pathway.

http://ift.tt/2svo97l

Yorkie and Hedgehog independently restrict BMP production in Escort cells to permit germline differentiation in the Drosophila ovary [RESEARCH ARTICLE]

Jianhua Huang, Amy Reilein, and Daniel Kalderon

Multiple signaling pathways guide the behavior and differentiation of both germline stem cells (GSCs) and somatic stem cells (FSCs) in the Drosophila germarium, necessitating careful control of signal generation, range and responses. Signal integration involves Escort Cells (ECs), which promote differentiation of the GSC derivatives they envelop, provide niche signals for FSCs and derive directly from FSCs in adults. Hedgehog (Hh) signaling induces the Hippo pathway effector Yorkie (Yki) to promote proliferation and maintenance of FSCs but Hh also signals to ECs, which are quiescent. Here we show that in ECs both Hh and Yki limit production of BMP ligands to allow germline differentiation. Loss of Yki produced a more severe germarial phenotype than loss of Hh signaling and principally induced a different BMP ligand. Moreover, Yki activity reporters and epistasis tests showed that Yki does not mediate the key actions of Hh signaling in ECs. Thus, both the coupling and output of Hh and Yki signaling pathways differ between FSCs and ECs despite their proximity and the fact that FSCs give rise directly to ECs.

http://ift.tt/2ttbAqF

Antagonistic regulation of the second mitotic wave by Eyes absent-Sine oculis and Combgap coordinates proliferation and specification in the Drosophila retina [RESEARCH ARTICLE]

Trevor L. Davis and Ilaria Rebay

The transition from proliferation to specification is fundamental to the development of appropriately patterned tissues. In the developing Drosophila eye, Eyes absent (Eya) and Sine oculis (So) orchestrate the progression of progenitor cells from asynchronous cell division to G₁ arrest and neuronal specification at the morphogenetic furrow. Here, we uncover a novel role for Eya and So in promoting cell cycle exit in the Second Mitotic Wave (SMW), a synchronized, terminal cell division that occurs several hours after passage of the furrow. We show that Combgap (Cg), a zinc-finger transcription factor, antagonizes Eya-So function in the SMW. Based on Cg's ability to attenuate Eya-So transcriptional output in vivo and in cultured cells and on meta-analysis of their chromatin occupancy profiles, we speculate that Cg limits Eya-So activation of select target genes posterior to the furrow to ensure properly timed mitotic exit. Our work supports a model in which context-specific modulation of transcriptional activity enables Eya and So to promote both entry into and exit from the cell cycle in a distinct spatiotemporal sequence.

http://ift.tt/2svGrFD

Pre-adolescent and adolescent mice are less sensitive to the effects of acute nicotine on extinction and spontaneous recovery

Publication date: Available online 15 June 2017
Source:Brain Research Bulletin
Author(s): Munir Gunes Kutlu, Dana Zeid, Jessica M. Tumolo, Thomas J. Gould
Adolescence is a period of high risk for the initiation of nicotine product usage and exposure to traumatic events. In parallel, nicotine exposure has been found to age-dependently modulate acquisition of contextual fear memories; however, it is unknown if adolescent nicotine exposure alters extinction of fear related memories. Age-related differences in sensitivity to the effects of nicotine on fear extinction could increase or decrease susceptibility to anxiety disorders. In this study, we examined the effects of acute nicotine administration on extinction and spontaneous recovery of contextual fear memories in pre-adolescent (PND 23), late adolescent (PND 38), and adult (PND 53) C57B6/J mice. Mice were first trained in a background contextual fear conditioning paradigm and given an intraperitoneal injection of one of four doses of nicotine (0.045, 0.09, 0.18, or 0.36mg/kg, freebase) prior to subsequent extinction or spontaneous recovery sessions. Results indicated that all acute nicotine doses impaired extinction of contextual fear in adult mice. Late adolescent mice exhibited impaired extinction of contextual fear only following higher doses of acute nicotine, and extinction of contextual fear was unaffected by acute nicotine exposure in pre-adolescent mice. Finally, acute nicotine exposure enhanced spontaneous recovery of fear memory, but only in adult mice. Overall, our results suggest that younger mice were less sensitive to nicotine's impairing effects on extinction of contextual fear and to nicotine's enhancing effects on spontaneous recovery of contextual fear memory.



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Heightened Sympathetic Arousal is demonstrated by Skin Conductance Responsivity to Auditory Stimuli in a Small Cohort of Neonates with Opiate Withdrawal

Publication date: Available online 15 June 2017
Source:Brain Research Bulletin
Author(s): Christiana N Oji-Mmuo, Fumiyuki Chin Gardner, Kim K Doheny
To determine the effects of auditory stimulus on skin conductance (SC) in infants with severe neonatal abstinence syndrome (NAS) that required morphine treatment (MT) compared with NAS infants that did not require morphine treatment (non-MT). We prospectively enrolled opiate-exposed term infants without polysubstance exposure. Skin conductance responses to an auditory stimulus (ringing a bell for 3seconds) near the time of discharge were obtained. Skin conductance was measured before, during, and after the stimulus. Non-parametric tests were used to determine between group and within phase differences. Infants were off MT at the time of SC measurement in response to an auditory stimulus. In a 2-group comparison of MT vs. non-MT infants, there was significantly higher SC responsivity to an auditory stimulus (p <0.05) in the MT group as compared with the non-MT group near discharge. The mean +SE peak morphine dose was 0.85+0.20mg/kg/day in the MT group. The mean Length of Stay (LOS) was 32 vs. 7 (p <0.05) days respectively, for the MT vs. the non-MT group. Our preliminary data suggest that in infants with severe NAS symptoms, higher sympathetic arousal in response to an auditory stimulus persists at discharge, underscoring the need for ongoing evaluation and specialized care at home.



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Corrigendum to “Involvement of autophagy in connexin 40 reduction in the late phase of traumatic brain injury in rats” [Brain Res. Bull. 131 (2017) 100–106]

Publication date: Available online 15 June 2017
Source:Brain Research Bulletin
Author(s): Wei Chen, Yijun Guo, Wenjin Yang, Ping Zheng, Jinsong Zeng, Wusong Tong




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Cerebral ischemia/repefusion injury: from bench space to bedside

Publication date: Available online 15 June 2017
Source:Brain Research Bulletin
Author(s): Z. Nagy, S. Nardai
While stroke research represents the primary interface between circulation and brain research, the hemostasis system also carries a pivotal role in the mechanism of vascular brain injury. The complex interrelated events triggered by the energy crisis have a specific spatial and temporal pattern arching from the initial damage to the final events of brain repair. The complexity of the pathophysiology make it difficult to model this disease, therefore it is challenging to find appropriate therapeutic targets. The ever-persistent antagonism between the positive results of drug candidates in the experimental stroke models and the failures of the clinical trials prompts changes in the research strategy, especially in the field of potential neuroprotective therapies. System biology approach could initiate new directions in the future for both preclinical and clinical research.Incentive methods aimed at anti-apoptosis mechanisms and the augmentation of post-ischemic brain repair could benefit the facts, that these processes can be targeted much longer following the cell-necrosis in the hyper-acute phase. Sequential monitoring of candidate genes and proteins responsible for stroke progression and post-stroke repair seems to be useful both in therapeutic target-identification, and in clinical testing. Understanding the mechanism behind the effect of selegiline and other drugs capable of activating the anti-apoptotic gene expression could help to find new approaches to enhance the regenerative potential in the remodeling of neuronal and microvascular networks.



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Drug induces depression-like phenotypes and alters gene expression profiles in Drosophila

Publication date: Available online 15 June 2017
Source:Brain Research Bulletin
Author(s): Ming-Di Jiang, Ya Zheng, Jia-Lin Wang, Yu-Feng Wang
BackgroundMajor depressive disorder (MDD) is a severe mental illness that affects more than 350 million people worldwide. However, the molecular mechanisms of depression are currently unclear. Studies suggest that Drosophila and humans have similar depression-like symptoms under pressure. In this research, we choose Drosophila melanogaster as the animal model to explore the molecular mechanisms that trigger depression.ResultsWe found that feeding D. melanogaster with the medium containing Levodopa or Chlorpromazine could induce depression-like phenotypes in both behavioral and biochemical biomarkers, including significantly decreased food intake, mating frequency, serotonin (5-HT) concentration, and increased malondialdehyde (MDA) concentration as well as reduced activity of superoxide dismutase (SOD). Moreover, the progeny of Chlorpromazine-treated flies also showed these depression-like features. By RNA-seq technology, we identified 467 gens that were differentially expressed between Chlorpromazine treated (CPZ) and control male flies [fold-change of ≥2 (q-value <5%)]. When comparing CPZ with control flies, 312 genes were upregulated and 155 genes downregulated. Differential expression of genes related to metabolic pathway, Parkinson's disease, Huntington's disease, Alzheimer's disease and lysozyme pathways were observed. Quantitative reverse transcriptase PCR (qRT-PCR) confirmed that 19 genes are differentially expressed in CPZ and control male flies.ConclusionsLevodopa, or Chlorpromazine can induce depression-like phenotypes in D. melanogaster regarding changes of appetite and sexual activity, and some key biochemical markers. A total of 467 genes were identified by RNA-seq analysis to have at least a 2-fold-change in expression between CPZ and control flies, including genes involved in metabolism, neurological diseases and lysozyme pathways. Our data provide additional insight into molecular mechanisms underlying depressive disorders in humans and may also contribute to clinical treatment.



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Scoparone attenuates hepatic stellate cell activation through inhibiting TGF-β/Smad signaling pathway

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Xing Liu, Xiuxia Zhao
Activation of hepatic stellate cells (HSCs) plays a critical role in liver fibrosis. Scoparone, a major constituent isolated from Artemisia capillaris, was reported to possess hepatoprotective effect. However, the role of scoparone in liver fibrosis remains unknown. In the present study, we investigated the effects of scoparone on liver fibrosis in HSCs. Our results demonstrated that scoparoene inhibited the proliferation of HSCs exposed to transforming growth factor (TGF)-β1. In addition, scoparoene significantly suppressed TGF-β1-induced the expression of α-smooth muscle actin (α-SMA) and collagen I in HSC-T6 cells, as well as attenuated the expression of NADPH oxidase (NOX) isoforms expression and ROS production in TGF-β1-stimialted HSC-T6 cells. Mechanistically, scoparoene suppressed the phosphorylation level of Smad3 in TGF-β1-stimialted HSC-T6 cells. In conclusion, these findings showed that scoparone significantly inhibited the proliferation and activation of HSCs through the inactivation of TGF-β/Smad signaling pathway. These data provide that scoparone may have potential to treat liver fibrosis.



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Antihypertensive and vasodilator effects of methanolic extract of Inula viscosa: Biological evaluation and POM analysis of cynarin, chlorogenic acid as potential hypertensive

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Zineb Hakkou, Alexandre Maciuk, Veronique Leblais, Nour Elhouda Bouanani, Hassane Mekhfi, Mohammed Bnouham, Mohammed Aziz, Abderrahime Ziyyat, Abdur Rauf, Taibi Ben Hadda, Usama Shaheen, Seema Patel, Rodolphe Fischmeister, Abdelkhaleq Legssyer
Background: Inula viscosa L. (Asteraceae) is a medicinal plant widely used as a folk medicine in oriental Morocco, to treat hypertension. The antihypertensive effect of the methanolic extract obtained from I. viscosa leaves was evaluated in hypertensive L-NAME rats. Systolic blood pressure (SBP) was measured using a non-invasive indirect tail-cuff plethysmographic method. Four groups of rats were used: a control group; a hypertensive group treated with L-NAME (32mg/kg/day); a positive control group treated with L-NAME plus enalapril (15mg/kg/day) as a reference antihypertensive agent; and a group treated with L-NAME plus MeOH-extract (40mg/kg/day).Methods: Treatment with L-NAME alone caused a progressive increase in SBP. After 4 weeks, the value of SBP reached 160±2mmHg which shows the installation of hypertension. Enalapril prevented the increase in SBP, which remained normal at 123±1mmHg after 4 weeks of treatment. The administration of MeOH-extract along with L-NAME prevented the increase in SBP as well, which remained constant at 115±1mmHg after 4 weeks of treatment.In ex-vivo models, MeOH-extract produced a relaxation of pre-contracted ring aorta (54 ± 2% of relaxation at 3g/L). But, when the rings were denuded, MeOH-extract failed to relax pre-contracted rings of aorta. Phytochemical study of I. viscosa MeOH-extract revealed the presence of phenolic compounds, such as cynarin and chlorogenic acid.Results: The present results suggest that I. viscosa MeOH-extract has an antihypertensive, predominantly mediated by an endothelium-dependent vasodilatory effect. Cynarin and chlorogenic acid, which have a strong vasorelaxant effect may be involved in the antihypertensive effect of the plant extract. The bioinformatic POM analysis confirms the therapeutic potential of cynarin and chlorogenic acids as inhibitors of various biotargets. Based on the results, the coordination of these phytochemicals with calcium and transition metals should be studied, for better scope at antihypertensive drug development.

Graphical abstract

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Saponins extracted from Dioscorea collettii rhizomes regulate the expression of urate transporters in chronic hyperuricemia rats

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Liran Zhu, Yifan Dong, Sha Na, Ru Han, Chengyin Wei, Guangliang Chen
ObjectiveThe current study aimed to investigate whether the saponins, bioactive component of effects of D. collettii, could reduce the serum uric acid level in a hyperuricemic mouse via regulation of urate transporters.MethodsChronic hyperuricemia model was established by combine administration of adenine (100mg/kg) and ethambutol (250mg/kg). In the model group, the serum uric acid (SUA), urine uric acid (UUA) volume, and 24-h UUA values increased significantly, while the uric acid clearance rate (CUr) and creatinine clearance rate (CCr) values decreased. Further, the model groups showed significantly lower expression of organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) and significantly higher expression of renal tubular urate transporter 1 (URAT1), glucose transporter 9 (GLUT9) and URAT1 mRNA than the normal control group.ResultsSaponins administration was found to have a dose-dependent effect, as evidenced by the increase in the 24-h UUA, CUr and CCr values; the decrease in SUA; the decrease in the renal expression of URAT1 mRNA and URAT1 and GLUT9 proteins; and the increase in the renal expression of the OAT1 and OAT3 proteins.ConclusionThe saponins extracted from D. collettii rhizomes had an obvious anti-hyperuricemic effect through downregulation of the URAT1 mRNA and the URAT1 and GLUT9 proteins and upregulation of the OAT1 and OAT3 proteins.



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The Evolution of Clinical Trials in Oncology: Defining Who Benefits from New Drugs Using Innovative Study Designs

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MALDI (matrix assisted laser desorption ionization) Imaging Mass Spectrometry (IMS) of skin: Aspects of sample preparation

Publication date: 1 November 2017
Source:Talanta, Volume 174
Author(s): Cristiana Santos de Macedo, David M. Anderson, Kevin L. Schey
MALDI (matrix assisted laser desorption ionization) Imaging Mass Spectrometry (IMS) allows molecular analysis of biological materials making possible the identification and localization of molecules in tissues, and has been applied to address many questions on skin pathophysiology, as well as on studies about drug absorption and metabolism. Sample preparation for MALDI IMS is the most important part of the workflow, comprising specimen collection and preservation, tissue embedding, cryosectioning, washing, and matrix application. These steps must be carefully optimized for specific analytes of interest (lipids, proteins, drugs, etc.), representing a challenge for skin analysis. In this review, critical parameters for MALDI IMS sample preparation of skin samples will be described. In addition, specific applications of MALDI IMS of skin samples will be presented including wound healing, neoplasia, and infection.

Graphical abstract

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A novel calibration strategy based on background correction for quantitative circular dichroism spectroscopy

Publication date: 1 November 2017
Source:Talanta, Volume 174
Author(s): Qi Zuo, Shun Xiong, Zeng-Ping Chen, Yao Chen, Ru-Qin Yu
When using circular dichroism (CD) spectroscopy for quantitative analysis, the samples to be analyzed must be free of light-absorbing interferences. However, in real-world samples, the presence of background absorbers is practically unavoidable. The difference in the matrices between the real-world samples to be analyzed and the standard samples (on which either univariate or multivariate calibration model was built) would result in systematic errors in the quantification results of CD spectroscopy. In this contribution, a novel calibration strategy for quantitative CD spectroscopic analysis was proposed. The main idea of the proposed calibration strategy is to project the CD spectra of both the standard samples and the real-world sample to be analyzed onto a projection space orthogonal to the space spanned by the background CD spectrum of the real-world sample and then build a multivariate calibration model on the transformed CD spectra of the standard samples. The performance of the proposed calibration strategy was tested and compared with conventional univariate and multivariate calibration methods in the quantification of Pb²⁺ in cosmetic samples using CD spectroscopy in combination with a G-quadruplex DNAzyme (e.g. PS2.M). Experiments results revealed that the proposed calibration strategy could mitigate the influence of the difference in the matrices between the standard samples and cosmetic samples and realized quantitative analysis of Pb²⁺ in cosmetic samples, with precision and accuracy comparable to atomic absorption spectroscopy. The proposed calibration strategy has the features of simplicity and effectiveness, its combination with CD spectroscopic probes can realize accurate and precise quantification of analytes in complex samples using CD spectroscopy.

Graphical abstract

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2-aminopurine probe in combination with catalyzed hairpin assembly signal amplification for simple and sensitive detection of microRNA

Publication date: 1 November 2017
Source:Talanta, Volume 174
Author(s): Chan Liu, Sifang Lv, Hang Gong, Chunyan Chen, Xiaoming Chen, Changqun Cai
A quencher-free and enzyme-free fluorescent sensor was proposed to simply and sensitively detect miRNA via the target catalyzed hairpin assembly (CHA) signal amplification in combination with 2-aminopurine (2-AP) molecular beacon (MBs). This sensor contains two DNA hairpins termed as H1 and H2. H1 labeled by 2-AP needs no quenchers because 2-AP can be quenched through its stacking interaction with the adjacent bases. H2 is partially complementary to H1. In the presence of the target microRNA (miRNA), H1 is unfolded and produces the DNA/RNA complexes, enhancing the fluorescent signal. Then, the RNA of the DNA/RNA complexes can be displaced by H2 and the free miRNA can interact with another H1, resulting in the significant fluorescence enhancement of the system. This signal amplification process is enzyme-free, making the sensor more simple and cost effective. The detection limit of this sensor could be as low as 3.5pM. We further applied this assay to monitor the overexpressed miRNA-21 from human breast cancer cells to confirm its applicability. The proposed sensor could be used as a simple and sensitive platform for target miRNA detection, holding great potential for convenient monitoring of different miRNA biomarkers for early diagnosis of various cancers.

Graphical abstract

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Langerhans und Merkel: a nervous epidermal dispute

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Ceruminous adenoma: A rare tumor diagnosed on cytology with histological correlation

Rumpa Das, Gorakh Nath, Sangita Bohara, Shivanjali Raghuvanshi

Journal of Cytology 2017 34(3):168-170

Ceruminous adenoma (CA) is a rare, benign tumor of the ceruminous gland found in the cartilaginous part of the external auditory canal (EAC). The tumor is diagnosed on histopathology and shows a characteristic dual population of luminal epithelial cells and basal myoepithelial cells. However, CA can be diagnosed on fine-needle aspiration cytology (FNAC) prior to surgery and the cytopathologist should be well aware of its cytological findings to avoid any misdiagnosis. The tumor shows an excellent prognosis with possible recurrence and malignant transformation. The present case emphasizes the cytological features of CA, which have been scantily described in the literature and highlights the role of cytopathologists in preoperative diagnosis.

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Tuberculous mastitis diagnosed on cytology - case report of a rare entity

Riti Tushar Kanti Sinha, Aniruna Dey, Seema Agarwal

Journal of Cytology 2017 34(3):162-164

Tuberculous mastititis is a rare clinical entity and usually affects women from the Indian subcontinent. It often mimics breast carcinoma and pyogenic breast abscess. Fine needle aspiration cytology (FNAC) is a very essential diagnostic tool when other routine laboratory investigations are not helpful in reaching to the conclusion. Tuberculosis (TB) of the breast is an uncommon presentation of TB even in countries where the incidence of pulmonary and extrapulmonary TB is high. Radiological imaging is not diagnostic.

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Liquid-based and conventional cytology for bronchial washings/bronchoalveolar lavages in the diagnosis of malignancy - An institutional experience

Abha Thakur, Pooja Bakshi, Gagandeep Kaur, Kusum Verma

Journal of Cytology 2017 34(3):127-132

Background: Liquid-based cytology (LBC) has been developed as an alternative for conventional cytology (CC) in cervical smears. It is now increasingly being used all over the world for cervical cancer screening. However, its role and diagnostic accuracy in bronchial wash (BW)/bronchoalveolar lavage (BAL) specimens remains undetermined. Aims: To assess and compare the diagnostic performance and accuracy of LBC with CC for detecting malignancy in bronchial specimens. Settings and Design: This was a retrospective analytical hospital-based study. Materials and Methods: Bronchial specimens (BW/BAL) received over a period of 4.5 years were reviewed. The samples were processed by CC from June 2010 to September 2012 (2.25 years) and by LBC from October 2012 to December 2014 (2.25 years). Data were retrieved from the records of cytology laboratory and compared among both the groups. Detection rate for histologically or cytologically verified samples was calculated. Results: A total of 559 cases verified by histological and cytological follow-up were evaluated. These included 247 CC cases and 312 LBC cases. The positive diagnostic rate for malignancy in CC was 28.6% whereas that for LBC was 32.9%. The negative diagnostic rates were 66.5% and 66.3% for CC and LBC, respectively. However, unsatisfactory rates had shown a good reduction from 4.4% in CC to 0.6% after LBC introduction. The smears showed more homogeneous distribution of cells with elimination of obscuring factors such as blood, inflammation, and mucus. Conclusions: The diagnostic accuracy of LBC was slightly better than CC. The unsatisfactory rates showed reduction in LBC preparation. Thus, LBC is a viable alternative to CC and has the advantages of standardization of preparation with decrease in unsatisfactory rates.

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Role of cell block in cytopathologic evaluation of image-guided fine needle aspiration cytology

Elizabath P Mathew, Vijayalakshmi Nair

Journal of Cytology 2017 34(3):133-138

Context: Fine needle aspiration cytology (FNAC) of superficial or deep-seated lesion is an increasingly common practice, eliminating time consuming and costly diagnostic procedures and providing rapid and safe diagnosis. Aims: To assess utility of cell block preparation method in increasing sensitivity of cytodiagnosis in deep-seated image-guided FNACs. Settings and Design: This was a hospital-based observational study conducted in the Department of Pathology, over a period of one and a half years. Materials and Methods: A total of 46 cases of abdomino-pelvic and intrathoracic masses subjected to guided FNACs were included. Along with conventional smears, cell blocks were prepared by using AAF (95% Ethanol 34 ml + formalin 4 ml + Glacial acetic acid 2 ml) as fixative agent. Statistical Analysis Used: Done using MedCalc Version 12.7.5.0 to find out the sensitivity, specificity, and diagnostic accuracy of conventional smears and cell blocks. Results: The sensitivity, specificity, and diagnostic accuracy of cell blocks in our study was 71.11%, 100%, and 71.73%, respectively. The figures for FNA smears were 62.22%, 100%, and 63.04%, respectively. Conclusions: Cell block technique by AAF fixative is a simple, inexpensive procedure. Cell block method allows the recovery and processing of minute amounts of cellular material, facilitating better classification of tumor when reviewed along with cytological smears, the ability to obtain many sections for immunostains and other studies to be performed akin to paraffin sections produced in histopathology.

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Cytomorphological patterns of tubercular lymphadenitis and its comparison with Ziehl-Neelsen staining and culture in eastern up. (Gorakhpur region): Cytological study of 400 cases

Shaila K Mitra, Rajiv K Misra, Priyanka Rai

Journal of Cytology 2017 34(3):139-143

Background: Tuberculous lymphadenitis is most common cause of lymphadenopathy in developing countries. Although enormous literature is available on various aspects of the disease including cytological patterns and its incidence in others parts of India and in other countries, only limited literature is available regarding its incidence and morphological spectrum on cytology in eastern parts of Uttar Pradesh in Gorakhpur region. Aim: The present study was undertaken to estimate the incidence of tuberculous lymphadenitis in our settings along with its morphological spectrum on cytology as well as to determine the utility of culture of fine needle aspirates in addition to cytology and Ziehl–Neelsen (ZN) staining. Material and Methods: Four hundred cases of superficial lymphadenopathy were subjected to fine needle aspiration cytology (FNAC), and in case, smears were stained with Hematoxylin and eosin (H and E), Giemsa, and ZN stain and categorized into three cytomorphological patterns. All the aspirates were inoculated on two sterile Lowenstein Jensen (LJ) medium. Result: Out of 400 cases of consecutive lymph nodes aspirated, 180 cases (45%) showed features of tuberculous lymphadenitis. Smears revealed epithelioid granulomas with caseous necrosis in maximum cases (40%). On statistical analysis, difference between group I and group II was found to be significant (P < 0.05); while comparison between groups II and III as well as between groups I and III was found to be statistically insignificant. Overall, acid fast bacilli positivity was seen in 51.6% of the cases. Conclusion: FNAC has been proved very safe, highly sensitive, and first line investigation in diagnosing tubercular lymphadenitis. The sensitivity can be further be increased by complementary cytomorphology with acid fast staining. Diagnostic accuracy can further be increased by culture.

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Fine needle aspiration cytology diagnosis of metastatic malignant diffuse type tenosynovial giant cell tumor

Prashant Ramteke, Venkat K Iyer, Karan Madan, Shivanand Gamangatti, Asit R Mridha

Journal of Cytology 2017 34(3):174-176

Tenosynovial giant cell tumors (TGCTs) arise from the synovium of joint, bursa, and tendon sheath, and are classified into localized and diffuse types. Diffused type often affects the large joint, and has more recurrence, metastasis, and malignant transformation potential compared to the localized type. Malignant diffused TGCT (D-TGCT) usually occurs as a large tumor (>5 cm), in older patients, and its histopathologic features include necrosis, cellular anaplasia, prominent nucleoli, high nuclear cytoplasmic ratio, brisk mitosis, discohesion of tumor cells, paucity of giant cells, and a diffuse growth pattern. At least five of these criteria are required for the histopathologic diagnosis of malignant TGCT because the benign TGCT also shares many of these morphological features. We describe the cytomorphologic features of a malignant D-TGCT from an unusual case of pulmonary metastasis in an adult patient. Fine needle aspiration cytologic features of malignant D-TGCT have not been described earlier in the English literature.

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Malignancy rate in thyroid nodules categorized as atypia of undetermined significance or follicular lesion of undetermined significance - An institutional experience

Smita Chandra, Harish Chandra, Sampan S Bisht

Journal of Cytology 2017 34(3):144-148

Introduction: Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) of Bethesda system for reporting thyroid cytopathology has emerged as most controversial category due to its heterogeneity and inconsistent usage. Initially associated risk of malignancy was estimated to be about 5–15%, but eventually different results have been obtained across institutions due to variable follow-ups and interpretation. The present study was conducted to evaluate the rate of malignancy along with appropriate management in this category. Materials and Methods: The study included AUS/FLUS cases diagnosed over period of 4 years on thyroid fine needle aspiration cytology (FNAC). Detailed clinical history and radiological examination were recorded along with follow-ups and management of all cases. Histopathology was available for cases which underwent surgery due to high clinical suspicion, worrisome radiological features or two consecutive AUS/FLUS reports. Results: The incidence of AUS/FLUS was 6.4% with repeat FNAC done in 39.6%, immediate surgery in 49.2% and follow-up without intervention in 11.1% cases. The overall malignancy rate was 28.5% with most common malignancy being follicular variant of papillary carcinoma (FVPC). Malignancy rate was more in cases (24.1%) which morphologically showed atypical nuclear features in comparison to architectural atypia. Conclusion: AUS/FLUS is associated with higher risk of malignancy than previously anticipated. Surgical intervention may have greater implication than repeat FNAC in appropriate management of this category. Substratification of this category according to nuclear features and architecture may be more useful in predicting malignancy risk and reducing the variability in the group.

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Intestinal GIST masquerading as an ovarian mass: Diagnosed on FNAC

Surbhi Goyal, Vinod K Arora, Mohit K Joshi, Navjeevan Singh, Gita Radhakrishnan

Journal of Cytology 2017 34(3):159-161

The preoperative diagnosis of metastatic intestinal gastrointestinal stromal tumors (GIST) on cytology can be quite difficult at times. The present case characterizes the cytomorphological and immunocytochemical features of GIST, emphasizing the utility of fine-needle aspiration cytology (FNAC) in the evaluation of spindle cell tumors of gastrointestinal tract. An accurate and early diagnosis of GIST affects the treatment, primarily allowing the use of tyrosine kinase inhibitors in unresectable or metastatic cases. Presence of highly cellular fragments of spindle-to-oval cells with variable degree of pleomorphism, atypia, and necrosis supplemented by immunocytochemistry can render a cytological diagnosis of GIST in dilemmatic clinical situations. Our case highlights the diagnostic role of FNAC in the evaluation of a pelvic mass, which was clinicoradiologically misdiagnosed as ovarian carcinoma.

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Modified ultrafast Papanicolaou staining technique: A comparative study

Moni Thakur, Venkateswara Rao Guttikonda

Journal of Cytology 2017 34(3):149-153

Introduction: Ultrafast Papanicolaou stain (UFP) was introduced as a hybrid of Romanowsky and Papanicolaou (PAP) stain. It enhances the quality and reduces the time. In the present study, a modified staining technique was adapted where Gill's Hematoxylin was replaced by Harris Hematoxylin. Aims: The aim of the study was to assess the use of the modified ultrafast Papanicolaou (MUFP) stain for fine needle aspiration cytology (FNAC) of head and neck swellings in comparison with the routine PAP stain, hematoxylin and eosin (H and E), and Giemsa. Materials and Methods: Forty FNACs of head and neck swellings were collected. FNAC procedure was performed by standard method; two smears were fixed in 95% propanol and stained with PAP and H and E. Two smears were air dried, 1 was stained with Giemsa, and 1 was rehydrated with normal saline, fixed in alcoholic formalin, and stained with MUFP. Four parameters were considered and scored background, cell morphology, nuclear staining, and overall staining pattern). Results: The quality of MUFP smears were better when compared to routine PAP, H and E, and Giemsa, and was statistically significant by Wilcoxon matched pair test. Conclusions: MUFP stain in comparison to routine PAP, H and E, and Giemsa provides an excellent and suitable alterative in cytological staining for the study of various organs.

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Anaplastic large cell lymphoma: A great mimic on cytology

Mona A Agnihotri, Kanchan S Kothari, Leena P Naik, Sharada Patil

Journal of Cytology 2017 34(3):165-167

Anaplastic large cell lymphoma (ALCL) is a T-cell lymphoma, accounting for <5% of non-Hodgkin's lymphoma. Cutaneous involvement can be primary or secondary arising in systemic ALCL. The diagnostic feature in both is the presence of pleomorphic, CD30 positive hallmark cells. We present a case of ALCL in a 19-year-old male presenting as an ulcerated scalp swelling. Clinical impression was actinomycosis or scrofuloderma. Cytology smears showed large dispersed pleomorphic cells with hyperlobated nuclei and multinucleated giant cells. The differentials considered were ALCL, rhabdomyosarcoma, and poorly differentiated carcinoma. Immunocytochemistry (ICC) showed positivity for leukocyte common antigen (LCA) and CD30 while negativity for desmin, favoring ALCL. Computed tomography (CT) showed a lytic paravertebral lesion. Subsequently, both paraspinal and scalp lesions were biopsied and immunochemistry confirmed the diagnosis of ALCL. Thus, cutaneous involvement in ALCL can resemble inflammatory and other neoplastic lesions clinically and cytologically. Hence, a high index of suspicion and ICC can aid in the correct diagnosis on fine needle aspiration cytology (FNAC).

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