Transcription Factor EB Controls Metabolic Flexibility during Exercise

Publication date: Available online 20 December 2016
Source:Cell Metabolism
Author(s): Gelsomina Mansueto, Andrea Armani, Carlo Viscomi, Luca D'Orsi, Rossella De Cegli, Elena V. Polishchuk, Costanza Lamperti, Ivano Di Meo, Vanina Romanello, Silvia Marchet, Pradip K. Saha, Haihong Zong, Bert Blaauw, Francesca Solagna, Caterina Tezze, Paolo Grumati, Paolo Bonaldo, Jeffrey E. Pessin, Massimo Zeviani, Marco Sandri, Andrea Ballabio
The transcription factor EB (TFEB) is an essential component of lysosomal biogenesis and autophagy for the adaptive response to food deprivation. To address the physiological function of TFEB in skeletal muscle, we have used muscle-specific gain- and loss-of-function approaches. Here, we show that TFEB controls metabolic flexibility in muscle during exercise and that this action is independent of peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α). Indeed, TFEB translocates into the myonuclei during physical activity and regulates glucose uptake and glycogen content by controlling expression of glucose transporters, glycolytic enzymes, and pathways related to glucose homeostasis. In addition, TFEB induces the expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, and oxidative phosphorylation. This coordinated action optimizes mitochondrial substrate utilization, thus enhancing ATP production and exercise capacity. These findings identify TFEB as a critical mediator of the beneficial effects of exercise on metabolism.

Graphical abstract

Teaser

Mansueto et al. show that TFEB acts as a central coordinator of skeletal muscle insulin sensitivity, glucose homeostasis, lipid oxidation, and mitochondrial function in the adaptive metabolic response to physical exercise in a PGC1α-independent manner.


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Letter Response to Dr. Putterman Regarding the Article "Pretarsal Augmented Lower Blepharoplasty".

No abstract available

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"Commentary To: Use of ADM in Breast Surgery: our experience and analysis of satisfaction using BREAST-Q".

No abstract available

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Re: Complications of Vertical Medial Thigh Lift in Massive Weight Loss Patients.

No abstract available

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Reply: Superomedial versus Inferior Pedicle Reduction Mammoplasty.

No abstract available

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Use of ADM in Breast Surgery: our experience and analysis of satisfaction using BREAST-Q.

No abstract available

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Inadequate enoxaparin dosing predicts 90-day venous thromboembolism risk among plastic surgery inpatients: an examination of enoxaparin pharmcodynamics.

Introduction: Evidence-based plastic surgery guidelines support the effectiveness of once daily enoxaparin prophylaxis. Despite prophylaxis, one in 25 highest risk patients has a VTE event. We examined the pharmacodynamics of standard enoxaparin doses in plastic surgery patients to examine whether patient-level factors predict enoxaparin metabolism, whether inadequate enoxaparin dose predicts downstream VTE events, and whether a pharmacist-driven dose adjustment protocol was effective. Methods: We recruited adult plastic surgery patients who received post-operative enoxaparin at 40mg daily. Steady state peak anti-Factor Xa (aFXa) levels, a marker of enoxaparin effectiveness and safety, were drawn. Patients with out of range aFXa levels had real-time dose adjustment based on a written protocol. Patients were followed for 90-day VTE events. Results: 94 patients were recruited, and 44% had in range peak aFXa levels in response to standard enoxaparin dosing. Patient-level factors including extent of surgical injury and gross weight were independent predictors of enoxaparin metabolism. Patients with low aFXa levels were significantly more likely to have 90-day VTE (10.2% vs. 0%, p=0.041). Real time dose adjustment allowed a significantly increased proportion of patients to have in range levels (67.1% vs. 44.3%, p=0.002). Conclusion: Based on pharmacodynamic data, the majority of plastic surgery patients receive inadequate enoxaparin prophylaxis using fixed dosing. Patient-level factors can predict how patients will metabolize enoxaparin, and patients who receive inadequate enoxaparin prophylaxis are significantly more likely to have downstream VTE events. Individualization of enoxaparin prophylaxis may minimize peri-operative VTE risk and further improve patient safety after plastic and reconstructive surgery procedures. (C)2016American Society of Plastic Surgeons

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Reply: Concomitant Liposuction Reduces Complications of Vertical Medial Thigh Lift in Massive Weight Loss Patients.

No abstract available

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Modified lipoabdominoplasty: updating concepts. Our post-bariatric experience.

No abstract available

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Cultural Differences in Pretarsal Fullness Acceptance.

No abstract available

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Microsurgical Reconstruction of Traumatic Lower Extremity Defects in the Pediatric Population.

Background: Very few reports focus exclusively on microsurgical reconstruction of traumatic lower extremity defects in children. As such, we felt it prudent to contribute to this area of clinical research. We hypothesized that reconstructive success would be comparable to success rates reported in adults and that young age or concerns regarding vessel size or behavior do not negatively impact surgical outcome. Methods: A retrospective review of microsurgical lower extremity reconstruction cases at two academic medical centers (University of Pennsylvania and Duke University) was performed. All pediatric patients who underwent microsurgical reconstruction of traumatic lower extremity defects between 1997 and 2012 were included for analysis. Results: Forty flaps were transferred in 40 patients with a mean age of 11.4 years (range, 1 to 17 years) were included for final analysis. Muscle flaps were predominantly used (N=23; 57.5%); however, with a recent increase in fasciocutaneous flaps (N=16; 40%). Postoperative complications were seen in 25% of patients with total flap loss rate of 5%. No donor-site complications were observed. The mean postoperative length of hospital stay was 12.9 days (range, 4 to 41 days) with patients returning to full weight bearing after a mean of 2.6 months (range, 1 to 8 months). Conclusions: Microsurgical reconstruction of traumatic lower extremity defects in the pediatric population is safe as evidenced by a flap survival rate of 95%. Concerns related to patient age, vessel size, or vessel behavior (i.e. vasospasm) should not detract from offering free flap reconstruction, as they do not negatively impact outcomes. (C)2016American Society of Plastic Surgeons

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A Comparison of Superomedial versus Inferior Pedicle Reduction Mammoplasty Using Three Dimensional Analysis.

No abstract available

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BREAST-Q following breast reconstruction: analysis of breast perception and sexuality.

No abstract available

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5-Fluorouracil 0.5%/Salicylic Acid 10%

http://orlnow.blogspot.gr/2016/12/5-fluorouracil-05salicylic-acid-10-in.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Management of Carotid Body Tumor in pediatric patients: A case report and review of the literature

Publication date: Available online 20 December 2016
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Apanisile Ifeoluwa, István Lázár, Éva Szövördi, Tamás Karosi
Carotid body tumors (CBTs) are rare types of extra-adrenal paragangliomas, which originate from the neuroendocrine cells of the adventitial layer of carotid bifurcation. An 8-year-old girl was admitted to our department with left-sided and pulsating neck swelling, which progressively grew over several months. The patient had no family history of CBTs. Computed tomography (CT) and CT angiography (CTA) scans revealed a contrast material enhancing, hypervascularized mass involving the left carotid bifurcation, internal carotid artery (ICA), and external carotid artery (ECA), respectively. Preoperative embolization and surgical resection were performed. Histopathological examination later confirmed a benign CBT. Current follow-up examination revealed no evidence of residual or recurrent tumor. A systemic review of the literature indicates that early diagnosis, and experienced multi-disciplinary management is required in case of unilateral, resectable forms of CBTs with no distant metastasis, in order to provide a long-time survival of patients. Surgical intervention of unilateral, solitary CBTs with preoperative embolization is a relatively safe procedure, allowing complete tumor removal with minimal morbidity and low recurrence rate.



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Topical corticosteroids (TCSs) or topical calcineurin inhibitors in the Treatment of Atopic Dermatitis in the Pediatric Population

http://orlnow.blogspot.gr/2016/12/topical-corticosteroids-tcss-or-topical.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Oral 30% glucose provides sufficient sedation in newborns during MRI

Abstract

Purpose

Newborns are often sedated during MRI but sedation itself creates adverse events and management is more challenging in this environment. Oral glucose/sucrose administration has been studied in newborns during painful procedures; however, its effectiveness in keeping newborns sleepy and motionlessness during painless procedures has not been demonstrated. The objective of this study was to describe effectiveness of oral 30% glucose administration by comparing with intravenous midazolam sedation for newborns during MRI.

Methods

One hundred twelve ASA II-III newborns who required care in the ICU and were scheduled for MRI with sedation were included. Group I received 30% glucose solution orally with 0.5–1 ml increments up to 2 ml/3 kg doses and group II received intravenous 0.1 mg/kg midazolam with 0.05 mg/kg repetition. The procedure was considered satisfactory when MRI images were not disturbed by patient movement after oral glucose or intravenous midazolam administration. The efficiency of the techniques, additional dose and rescue sedation requirements, blood glucose levels following oral 30% glucose suckling and presence of adverse events were recorded.

Results

Demographic data was similar between groups. The efficiency of the procedures were similar between groups (78.9%, in group I and 66.1%, in group II). The blood glucose levels were within normal range in group I whereas transient desaturation and apnea occurred in 8 neonates in group II (p = 0.006).

Conclusion

Oral 30% glucose administration for newborns during MRI is as effective as standard sedation protocol with midazolam. Thereby, we recommend and support the integration of this safe and reliable technique into routine practice for newborns during MRI.

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Hypothyroid-induced acute compartment syndrome in all extremities

Acute compartment syndrome (ACS) is an uncommon complication of uncontrolled hypothyroidism. If unrecognized, this can lead to ischemia, necrosis and potential limb loss. A 49-year-old female presented with the sudden onset of bilateral lower and upper extremity swelling and pain. The lower extremity anterior compartments were painful and tense. The extensor surface of the upper extremities exhibited swelling and pain. Motor function was intact, however, limited due to pain. Bilateral lower extremity fasciotomies were performed. Postoperative Day 1, upper extremity motor function decreased significantly and paresthesias occurred. She therefore underwent bilateral forearm fasciotomies. The pathogenesis of hypothyroidism-induced compartment syndrome is unclear. Thyroid-stimulating hormone-induced fibroblast activation results in increased glycosaminoglycan deposition. The primary glycosaminoglycan in hypothyroid myxedematous changes is hyaluronic acid, which binds water causing edema. This increases vascular permeability, extravasation of proteins and impaired lymphatic drainage. These contribute to increased intra-compartmental pressure and subsequent ACS.

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Splenic injury following elective colonoscopy: a rare complication

Splenic injury is an extremely rare, yet serious, complication related to colonoscopy. So far, less than 80 cases have been reported worldwide since 1970. With the increasing use of colonoscopy, endoscopists, surgeons and radiologists are more likely to encounter this unusual complication. Increased splenocolic adhesions, splenomegaly or underlying splenic disease might, inter alia, constitute a predisposing factor. However, it might also occur in patients without significant adhesions or underlying splenic pathology. Patients with abdominal pain, hypotension and a fall in hematocrit without rectal bleeding after colonoscopy, should be suspected of having splenic injury. Most patients present with symptoms within 24 hours after colonoscopy, nevertheless, delayed presentations have been described as well. We report such a case of splenic injury secondary to colonoscopy. The patient was presented with hemorrhagic shock and abdominal pain following a colonoscopy which had taken place before 36 hours, an urgent splenectomy was required with successful outcome.

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Rare small intestinal volvulus from entrapment in hepato-diaphragmatic adhesions in a 45-year-old lady

Small intestinal volvulus is rare in adults and rarely caused by string adhesions between the liver and the diaphragm. Similar adhesions were described in Fitz-Hugh-Curtis syndrome. We report a 45-year-old lady with small intestinal volvulus from entrapment of a loop in string adhesions between the liver and the diaphragm. Her plain radiographs showed a significant shadow of the trapped loop.

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Breast, prostate, and thyroid cancer screening tests and overdiagnosis

Publication date: Available online 20 December 2016
Source:Current Problems in Cancer
Author(s): Minsoo Jung
The purpose of this study was to examine overdiagnosis and overtreatment related to cancer screening and reviewed relevant reports and studies. A comprehensive search of peer reviewed and grey literature was conducted for relevant studies published between January 2000 and December 2015 reporting breast, prostate, and thyroid cancer screening tests and overdiagnosis. This study revealed no dichotomy on where screening would lower risk or cause overdiagnosis and overtreatment. Many screening tests did both, i.e., at population level, there were both benefit (decreased disease specific mortality) and harm (overdiagnosis and overtreatment). Therefore, we need to consider a balanced argument with citations for the potential benefits of screening along with the harms associated with screening. Although the benefits and harms can only be tested through randomized trials, important data from cohort studies, diagnostic accuracy studies, and modelling work can help define the extent of benefits and harms in the population. The healthcare cycle that prompt patients to undergo periodic screening tests is self-reinforcing. In most developed countries, screening test recommendations encourage periodic testing. Therefore, patients are continuing their screening. It is necessary for patients to become wise consumers of screening tests and make decisions with their physicians regarding further testing and treatments.



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Age-Related Reduction of Contractile Responses to Urotensin II Is Seen in Aortas from Wistar Rats but Not from Type 2 Diabetic Goto-Kakizaki Rats

Rejuvenation Research , Vol. 0, No. 0.


http://ift.tt/2hYqCQ7

Single Point Mutations in Pediatric Differentiated Thyroid Cancer

Thyroid , Vol. 0, No. 0.


http://ift.tt/2hpAMZi

Vascular structures in dermal nevi: a reappraisal

http://ift.tt/2hpp4OB

Zika virus infection, issue on dermatological problem

http://ift.tt/2haTLLp

Single Point Mutations in Pediatric Differentiated Thyroid Cancer

Thyroid , Vol. 0, No. 0.


http://ift.tt/2hpAMZi

Editorial Board/Reviewing Committee

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Early severe acute respiratory distress syndrome: What’s going on? Part II: controlled vs. spontaneous ventilation?

 

The second part of this overview on early severe ARDS delineates the pros and cons of the following: a) controlled mechanical ventilation (CMV: lowered oxygen consumption and perfect patient-to-ventilator synchrony), to be used during acute cardio-ventilatory distress in order to "buy time" and correct circulatory insufficiency and metabolic defects (acidosis, etc.); b) spontaneous ventilation (SV: improved venous return, lowered intrathoracic pressure, absence of muscle atrophy). Given a stabilized early severe ARDS, as soon as the overall clinical situation improves, spontaneous ventilation will be used with the following stringent conditionalities: upfront circulatory optimization, upright positioning, lowered VO2, lowered acidotic and hypercapnic drives, sedation without ventilatory depression and without lowered muscular tone, as well as high PEEP (titrated on transpulmonary pressure, or as a second best: "trial"-PEEP) with spontaneous ventilation + pressure support (or newer modes of ventilation). As these propositions require evidence-based demonstration, the reader is reminded that the accepted practice remains, in 2016, controlled mechanical ventilation, muscle relaxation and prone position.

 

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Early severe acute respiratory distress syndrome: What’s going on? Part I: pathophysiology

Severe acute respiratory distress syndrome (ARDS, PaO₂/FiO₂ < 100 on PEEP ≥ 5 cm H₂O) is treated using controlled mechanical ventilation (CMV), recently combined with muscle relaxation for 48 h and prone positioning. While the amplitude of tidal volume appears set < 6 mL kg^-1, the level of positive end-expiratory pressure (PEEP) remains controversial. This overview summarizes several salient points, namely: a) ARDS is an oxygenation defect: consolidation/ difuse alveolar damage is reversed by PEEP and/or prone positioning, at least during the early phase of ARDS b) ARDS is a dynamic disease and partially iatrogenic. This implies that the management of the ventilator may be a life-saver by reducing the duration of mechanical ventilation, or detrimental by extending this duration, leading into critical care-acquired diseases. Indeed, a high PEEP (10−24 cm H₂O) appears to be a life-saver in the context of early severe diffuse ARDS; c) tidal volume and plateau pressure cannot be identical for all patients; d) the only remaining rationale for CMV and muscle relaxation is to suppress patient-ventilator asynchrony and to lower VO2, during the acute cardio-ventilatory distress. Therefore, in early severe diffuse ARDS, this review argues for a combination of a high PEEP (preferably titrated on transpulmonary pressure) with spontaneous ventilation + pressure support (or newer modes of ventilation). However, conditionalities are stringent: upfront circulatory optimization, upright positioning, lowered VO₂, lowered acidotic and hypercapnic drives, sedation without ventilatory depression and without lowered muscular tone. As these propositions require evidence-based demonstration, the accepted practice remains, in 2016, controlled mechanical ventilation, muscle relaxation, and prone position.

 

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Comparison of continuous epidural block and continuous paravertebral block in postoperative analgaesia after video-assisted thoracoscopic surgery lobectomy: a randomised, non-inferiority trial

BACKGROUND: Video-assisted (VATS) lung lobectomy can be associated with stronger postoperative pain than is commonly believed. It is generally accepted to introduce multimodal analgaesic strategies based on regional blockade, opioids and non-steroidal anti-inflammatory drugs. However, there is still no consensus regarding the optimal regional technique. The aim of this study was to compare the analgaesic efficacy of continuous thoracic epidural block (TEA) and percutaneous continuous paravertebral block (PVB) in patients undergoing video-assisted lung lobectomy.

METHODS: Fifty-one patients undergoing VATS lobectomy were enrolled in the present prospective, randomised clinical trial. The same analgaesic regimen in both groups included continuous infusion of 0.25% bupivacaine with epinephrine, intravenous ketoprofen and paracetamol. The doses of local anaesthetics were determined to achieve the spread of at least 4 segments in both groups. Postoperative static and dynamic visual analogue pain scores, as well as patient-controlled morphine usage, were used to compare the efficacy of analgaesia. Side effects and failure rates of both blocks were analysed.

RESULTS: Static and dynamic pain scores at 24 postoperative hours were significantly lower in the paravertebral group, as were the static pain score at 36 and 48 postoperative hours (P < 0.05). No difference between the treatment groups was identified regarding postoperative morphine usage. The failure rate was higher in the epidural group than in the paravertebral group. No complications were noted in either group, but side effects (urinary retention, hypotension) were more frequent in the epidural group (P < 0.05).

CONCLUSIONS: Postoperative pain following VATS lung resection procedures is significant and requires the application of complex analgaesic techniques. Percutaneous paravertebral block is equally effective as thoracic epidural block in providing analgaesia in patients undergoing VATS lobectomy. Paravertebral block has a better safety profile than thoracic epidural block.

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Dexmedetomidine for attenuating haemodynamic response to intubation stimuli in morbidly obese patients anaesthetised using low-opioid technique: comparison with fentanyl-based general anaesthesia

 

BACKGROUND: Anaesthesiologists are facing the problem of an increasing population of morbidly obese patients. In order to minimize the risk of opioid-induced postoperative respiratory failure, the intraoperative administration of opioids should be reduced or replaced with other drugs. The purpose of this study was to compare haemodynamic response elicited by intubation in morbidly obese patients between two variants of anaesthesia induction: fentanylbased or low-opioid using dexmedetomidine.

METHODS: Forty-two morbidly obese patients scheduled for bariatric surgery were randomly assigned to two groups: low-opioid using dexmedetomidine (DEX) or fentanyl-based (FNT) anaesthesia. Patients were premedicated with 100 μg of fentanyl i.v. In the DEX group, a 10 minute infusion of a loading dose of 200 μg of dexmedetomidine was started. In the FNT group, 2 mg of intravenous midazolam was given. Thereafter, propofol was used in both groups. In the FNT group, patients received a dose of fentanyl up to 5 μg kg^-1 of ideal body weight. Following administration of rocuronium, laryngoscopy and tracheal intubation were performed. Haemodynamic parameters, including systolic (SBP), diastolic (DBP) and mean arterial (MAP) blood pressure, as well as heart rate (HR), were recorded before and after intubation. Patients who were not intubated at first attempt were excluded from the study.

RESULTS: Data from 33 patients were analysed. There were no statistically significant differences between the DEX and FNT groups regarding demographic data. Haemodynamic response to intubation was defined as mean change (d) in values of analysed parameters that occurred during intubation. The following differences were observed: dSBP FNT +11.6 mm Hg vs. DEX +0.4 mm Hg (P = 0.15); dDBP FNT +3.7 mm Hg vs. DEX +3.5 mm Hg (P = 0.98); dMAP FNT +8.6 mm Hg vs. DEX +1.4 mm Hg (P = 0.36); dHR FNT +2 beats min-1 vs. DEX −1 beat min^-1 (P = 0.30). None of these comparisons yielded significant differences.

CONCLUSIONS: The study revealed no advantage of fentanyl over low opioid dexmedetomidine-based induction of general anaesthesia in attenuating cardiovascular response to intubation in morbidly obese patients.

 

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Infraclavicular access to the axillary vein — new possibilities for the catheterization of the central veins in the intensive care unit

 

Central vein cannulation is one of the most commonly performed procedures in intensive care. Traditionally, the jugular and subclavian vein are recommended as the first choice option. Nevertheless, these attempts are not always obtainable for critically ill patients. For this reason, the axillary vein seems to be a rational alternative approach. In this narrative review, we evaluate the usefulness of the infraclavicular access to the axillary vein. The existing evidence suggests that infraclavicular approach to the axillary vein is a reliable method of central vein catheterization, especially when performed with ultrasound guidance.

 

http://ift.tt/2h8wlV3

Incidence of in-hospital cardiac arrest in Poland

 

BACKGROUND: In-hospital cardiac arrest with its poor prognosis is a challenging problem in hospitals. The aim of this study was to evaluate in Polish hospitals the frequency of in-hospital cardiac arrests with the subsequent mortality, with special emphasis on the type of unit at which the event occurred, and the patient's demographic data, such as age and sex.

METHODS: The study was a retrospective analysis of data for 2012 registered in the Polish General Hospital Morbidity Study. This research covered all Polish hospitals, excluding only government and psychiatric hospitals. The study inclusion criterion was the incidence of cardiac arrest in any hospital ward, recorded by the respective ICD-10 diagnosis code.

RESULTS: Of the 7,775,553 patients hospitalized, the diagnosis of cardiac arrest was reported in a total of 22,602 patients, which included 22,317 adults (98.7% of all patients) and 285 children (1.3%). Overall mortality after cardiac arrest among adults was 74.2%, and in children 46.7%. In both absolute numbers and as percentages of all documented cases, cardiac arrests occurred most often at the departments of intensive care, internal medicine, cardiology and emergency medicine. The accompanying mortality was lower than average at the departments of intensive care, cardiology, cardiology high dependency unit and emergency medicine. The median age of patients with cardiac arrest who died in the hospital was higher than the median age of those who survived (72 vs. 64; P < 0.05). Although cardiac arrests were reported more often among men than women (58.2% vs. 41.8%; P < 0.001), the hospital mortality was higher among women (79.2% vs. 71.6%; P < 0.001).

CONCLUSION: The frequency of in-hospital cardiac arrests in Polish hospitals and the subsequent mortality is not substantially different from that observed in other countries. However, our study, based on ICD-10 diagnosis codes, gives only limited information about the patients and circumstances of this event. An in-depth analysis of the causes, prognoses, and outcome of in-hospital cardiac arrests could be facilitated by the creation of a national registry.

 

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Clinical outcome of critically ill patients with thrombocytopenia and hypophosphatemia in the early stage of sepsis

 

BACKGROUND: Hypophosphatemia and thrombocytopenia may both be independent risk factors for the development of multiple organ failure and correlate well with the severity of sepsis. In the present study we wanted to analyze the potential clinical role and prognostic significance of both early hypophosphatemia and thrombocytopenia on clinical outcomes of critically ill ICU patients with severe sepsis Methods: We analyzed the clinical data, including the outcome of critically ill ICU patients with severe sepsis who presented during a 5 year period with early hypophosphatemia and thrombocytopenia.This study was retrospective and single centre. All clinical and laboratory data was collected from the patients' ICU and hospital electronic records. All laboratory measurements were done on admission and during the ICU stay.

RESULTS: The included patients were distributed into one of three study groups based on the presence of hypophosphatemia and/or thrombocytopenia during the first 24 hours of admission to the ICU: group 1 — early hypophosphatemia; group 2 — early hypophosphatemia and thrombocytopenia and group 3 — early thrombocytopenia. The ICU mortality rate was significantly higher in groups 2 and 3 (25.9% and 22% vs. 9.3%, respectively, P = 0.034). An APACHE II > 27, a TISS > 25 following the first 24 hours of ICU stay , an age higher than 70, male gender and total parenteral nutrition were independent predictors of ICU and hospital mortality in this study population.

CONCLUSION: It may be considered that hypophosphatemia and thrombocytopenia in the early stage of sepsis, even when severe and coexisting, reflect the degree of initial illness severity of sepsis. However, further investigations need to be done for a better understanding of the potential clinical role of these features in the septic critically ill population.

 

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Effect of preoperative intravenous oxycodone administration on sufentanil consumption after retroperitoneal laparoscopic nephrectomy

 

BACKGROUND: The aim of this study was to evaluate the efficacy of preoperative intravenous oxycodone administration on postoperative sufentanil consumption in patients undergoing retroperitoneal laparoscopic nephrectomy.

METHODS: Fifty patients scheduled for retroperitoneal laparoscopic nephrectomy were enrolled and randomly assigned to two groups — patients in Group O (n = 25) received intravenously 0.1 mg kg^-1 oxycodone; while the patients in Group C (n = 25) received 0.1 mL kg^-1 normal saline for 2 min, 10 min before the operation. All of the participants received intravenous sufentanil patient-controlled analgesia (PCA) after extubation, using a PCA device. The sufentanil consumption, rescue analgesia, Ramsay sedation scale (RSS) and visual analogue scale (VAS) scores at rest and during cough, the overall satisfaction and undesired events were all assessed.

RESULTS: Cumulative sufentanil consumption delivered by PCA was significantly lower in Group O at all time points. VAS scores at rest and during coughing at 1, 2, 4, 8 and 12 hours after extubation of the patient were significantly lower in Group O than in Group C. There were no significant differences between the two groups according to the number of patients administered tramadol, RSS and the incidence of side effects. The degree of patients' satisfaction was higher in Group O.

CONCLUSION: Preoperative intravenous oxycodone can reduce postoperative cumulative sufentanil consumption and postoperative pain intensity without an increase in side effects.

 

http://ift.tt/2idOLBo

Anaesthesia management for non-cardiac surgery in children with congenital heart disease

 

Congenital heart disease (CHD) is the most common form of congenital abnormality and occurs in over 1% of newborns. Approximately 30% of children with CHD have other extra-cardiac anomalies, which significantly increases mortality in CHD patients. It is expected that the number of CHD patients who consult non-specialized hospitals for non-cardiac surgery after palliative or corrective operations will increase because of the extraordinary progression of treatments, such as surgical procedures, interventional procedures, and intensive care medicine, as well as diagnosis. The aim of this article is to enable anaesthesiologists who are not usually engaged in the anaesthesia management of CHD patients to provide perioperative management for CHD patients safely and with confidence by having basic and advanced knowledge about CHD patients and their pathophysiological characteristics.

 

http://ift.tt/2h8sCa3

Coagulopathy in sepsis — a new look at an old problem

 

Sepsis is a life-threatening condition characterized by a systemic response to microbial infection. Despite considerable progress in intensive care medicine, the incidence of sepsis and the number of sepsis-related deaths are increasing world-wide. There is a complex relationship between the coagulation, immune and inflammatory systems in sepsis. Activation of the coagulation cascade in sepsis is a result of a pathogen invasion and is a part of a immuno-inflammatory host response. In sepsis, the close cooperation of the immune and coagulation systems through cross signalling results in immunothrombosis. According to a recently described new theory, immunothrombosis is a immune response in which the local activation of coagulation facilitates the recognition and destruction of pathogens. Small amounts of clot formation are beneficial for the host because of bacteria trapping and prevention of the systemic spread of infection. Sepsis is a dynamic syndrome and in all patients with sepsis coagulation changes may progress from a normal profile to hypercoagulability and hypofibrinolysis, hyperfibrinolysis, and ultimately hypocoagulability.

 

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Isolated lower limb gangrene: a caveat of terlipressin therapy

http://ift.tt/2h8tzPN

Successful retrieval of a knotted Swan-Ganz catheter using interventional approach in an adult: a case report

http://ift.tt/2idCOMa

Hormonal alterations in PCOS and its influence on bone metabolism

According to the World Health Organization (WHO) polycystic ovary syndrome (PCOS) occurs in 4–8% of women worldwide. The prevalence of PCOS in Indian adolescents is 12.2% according to the Indian Council of Medical Research (ICMR). The National Institute of Health has documented that it affects approximately 5 million women of reproductive age in the United States. Hormonal imbalance is the characteristic of many women with polycystic ovarian syndrome (PCOS). The influence of various endocrine changes in PCOS women and their relevance to bone remains to be documented. Hormones, which include gonadotrophin-releasing hormone (GnRH), insulin, the leutinizing/follicle-stimulating hormone (LH/FSH) ratio, androgens, estrogens, growth hormones (GH), cortisol, parathyroid hormone (PTH) and calcitonin are disturbed in PCOS women. These hormones influence bone metabolism in human subjects directly as well as indirectly. The imbalance in these hormones results in increased prevalence of osteoporosis in PCOS women. Limited evidence suggests that the drugs taken during the treatment of PCOS increase the risk of bone fracture in PCOS patients through endocrine disruption. This review is aimed at the identification of the relationship between bone mineral density and hormonal changes in PCOS subjects and identifies potential areas to study bone-related disorders in PCOS women.

http://ift.tt/2idILsF

Fournier’s gangrene during ACTH therapy

Publication date: Available online 20 December 2016
Source:Brain and Development
Author(s): Shingo Numoto, Hirokazu Kurahashi, Yoshiteru Azuma, Atsushi Numaguchi, Kozaburo Nakahara, Takahisa Tainaka, Michihiko Takasu, Kiyoshi Yamakawa, Nozomi Nago, Taichiro Muto, Yoshiro Kitagawa, Akihisa Okumura
Fournier's gangrene is an infectious necrotizing fasciitis of the perineal, genital, or perianal regions and is uncommon in children. Adrenocorticotropic hormone (ACTH) is effective for the treatment of infantile spasms; however, suppression of immune function is one of the major adverse effects of this approach. We encountered a 2-month-old boy with infantile spasms that had been treated with ACTH and had developed complicating Fournier's gangrene. Strangulation of a right inguinal hernia was observed after ACTH treatment. Although surgical repair was successful and no intestinal injuries were detected, swelling and discoloration of the right scrotum developed in association with pyrexia and a severe inflammatory response. A scrotal incision revealed pus with a putrid smell. The patient was subsequently diagnosed with Fournier's gangrene complicated by septic shock and disseminated intravascular coagulation. Extensive debridement and intensive care was performed. Enterobactor aerogenes, methicillin-resistant Staphylococcus aureus, and Enterococcus faecalis were isolated from the pus. Meropenem, teicoplanin, and clindamycin were administered to control the bacterial infection. The patient was discharged from the intensive care unit without any obvious neurological sequelae. Suppression of immune function associated with ACTH therapy may have been related to the development of Fournier's gangrene in this case.



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Central tegmentum tract hyperintensities in pediatric neurological patients: Incidence or coincidence

Publication date: Available online 20 December 2016
Source:Brain and Development
Author(s): Uğur Işık, Alp Dinçer
AimThe central tegmental tract hyperintensities (CTTH) have been found in many different pediatric neurological conditions. There is only scarce data about the value of this radiological phenomenon. In this study we aimed to show the neurological conditions associated with this radiological finding.Materials and methodsWe performed a retrospective analysis of all pediatric brain MRI's between 2013 and 2015. After finding those patients with CTTH, we evaluated them in the pediatric neurology clinic.ResultsThere were 41 out of 1464 brain MRI's with CTTH with 2.8% prevalence. Thirty four patients (23 male, age range 3months–98months) were available for evaluation. CTTH were present in mainly younger age group. There were many different neurological conditions associated with CTTH. These included brain tumors, epilepsy, developmental delay, metabolic disorders and genetic syndromes.ConclusionCTTH is found in many different pediatric neurological conditions. Further neuropathological and prospective MRI and clinical studies are needed to better understand this interesting radiological finding.



http://ift.tt/2hYi5gg

Anti-inflammatory effect of the six compounds isolated from Nauclea officinalis Pierrc ex Pitard, and molecular mechanism of strictosamide via suppressing the NF-κB and MAPK signaling pathway in LPS-induced RAW 264.7 macrophages

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): DongYu Li, JiaQuan Chen, JiQing Ye, XiaoTing Zhai, Jie Song, CuiHua Jiang, Jing Wang, Hao Zhang, XiaoBin Jia, FenXia Zhu
Ethnopharmacological relevanceNauclea officinalis Pierrc ex Pitard. is a Chinese medicinal herb that contains high level of alkaloids which is the most abundant and active constituent. Strictosamide isolated from Nauclea officinalis Pierrc ex Pitard. showed significant effects on inflammatory response, compared with pumiloside, 3-epi-pumiloside, vincosamide, 3α,5α-tetrahydrodeoxycordifoline lactam and naucleamide A-10-O-β-D-glucopyranoside of this plant.Aim of studywe investigated the biological activities of the six compounds mentioned-above, and the underlying molecular mechanism exerted by the most potent one, strictosamide.Materials and methodsThe effects of strictosamide and other five compounds on the inhibitory activity of nitric oxide (NO) were screened by Griess test. The contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in media were detected by using Enzyme-linked immunosorbent (ELISA) kits. The effects on the mRNA expression of nitric oxide synthase (iNOS), TNF-α and IL-1β of strictosamide were further investigated by RT-qPCR. Western blot assay was conducted to illustrate the effects of strictosamide on iNOS and phosphorylation of p65, inhibitor of NF-κB (IκB)-α, IκB-kinase (IKK)-α as well as p-extracellular signal-regulated kinase (ERK), p-c-jun N-terminal kinase (JNK) and p-p38 in the protein levels.ResultsStrictosamide potently suppressed the productions of NO, TNF-α and IL-1β in LPS-induced RAW 264.7 macrophages, and it dose-dependently alleviated the LPS-simulated protein level of iNOS as well as the mRNA expressions of iNOS, TNF-α and IL-1β. In addition, molecular data revealed that strictosamide markedly decreased the expressions of p-p65, p-IκBα and p-IKKα. Furthermore, strictosamide significantly attenuated LPS-induced the phosphorylation of p38, ERK and JNK.ConclusionsAt present study, the results indicated that the anti-inflammatory activity of strictosamide was associated with the restraint of NO, TNF-α and IL-1β via negative regulation of both NF-κB and mitogen-activated protein kinases (MAPKs) in LPS-induced RAW 264.7 cells.

Graphical abstract

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Reduced allergic lung inflammation by root extracts from two species of Peucedanum through inhibition of Th2 cell activation

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): A.-Reum Lee, Jin Mi Chun, A. Yeong Lee, Hyo Seon Kim, Gyo Jeong Gu, Bo-In Kwon
Ethnopharmacological evidencePeucedani Radix (PR), the root of Peucedanum praeruptorum Dunn (PPD) or Peucedanum decursivum (Miq.) Maxim. (PDM), has long been used in Korea to eliminate sputum, relieve cough, and reduce bronchus contraction. Furthermore, these therapeutic strategies are recognized as general and effective methods in western medicine as well as traditional Korean medicine.Aim of the studyTo determine and compare the anti-inflammatory effects of PPD extracts (PPDE) and PDM extracts (PDME) on allergic lung inflammation, using in vivo OVA-induced airway inflammation in mice and in vitro primary cell culture systems.Materials and methodsEight-week-old female C57BL/6 mice were placed into four groups (n=4 per group): saline control, OVA-induced allergic lung inflammation with vehicle, or PPDE (200mg/kg) or PDME (200mg/kg) treatment. PR extracts (PRE) were administered from 1 week before 1st OVA sensitization to the day before sacrifice. Mice were sacrificed 18h after last OVA intra-nasal challenge followed by histological and biochemical analyses.ResultsInflammatory phenotypes were alleviated with oral administration of PRE. PRE treatment decreased mucus production in airway epithelium, inflammatory cell number, eosinophilia, type 2 cytokines, and histamine in bronchoalveolar lavage fluid (BALF). Mice with PRE administration showed diminished activated CD4 T cell (CD4⁺CD25⁺ cell) and GATA-3 level in the lung. In addition, PRE treatment reduced Th2 cell activation in vitro, using Th2 polarization system.ConclusionOur findings indicate that the anti-inflammatory effects of PRE arise from reduced Th2 cell activation and validate the clinical use of PR in traditional Korean medicine.

Graphical abstract

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Immunogenicity Evaluation of Modified Adenovirus Vaccines Expressing Porcine Circovirus Type 2 Capsid Protein in Pigs

Viral Immunology , Vol. 0, No. 0.


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Three Reviews Highlight Different Aspects of the Host Response to Viral Infection

Viral Immunology , Vol. 0, No. 0.


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Fe-based soft magnetic composites coated with NiZn ferrite prepared by a co-precipitation method

Publication date: 15 April 2017
Source:Journal of Magnetism and Magnetic Materials, Volume 428
Author(s): Yuandong Peng, Yi Yi, Liya Li, Hengyu Ai, Xiaoxu Wang, Lulu Chen
Fe powder was coated with NiZn ferrite by a co-precipitation method using chlorate as the raw material. Soft magnetic composites were manufactured via compaction and heat treatment of the coated powder. The coated powder and heat treated powder were analysed using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and Raman spectroscopy. Their magnetic properties were determined using a Quantum Design-Vibrating Sample Magnetometer (QD-VSM). The composites were analysed with SEM and EDS. The permeability and magnetic loss of the composites were measured with a B-H curve analyzer. The results show that, using the co-precipitation method, the raw precipitate was successfully prepared and coated the pure Fe powder and turned into spinel NiZn ferrite treated at 600℃ for 1h. After heat treatment at 500℃ under air, the insulation coating layer of soft magnetic composite (SMC) was not destroyed and containing Fe, Ni, Zn and oxygen. The permeabilities of the SMC are stable at edge of the 2–200kHz frequency range and the total loss was lower.

Graphical abstract

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Editorial board

Publication date: December 2016
Source:Microbes and Infection, Volume 18, Issue 12





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Keyword index

Publication date: December 2016
Source:Microbes and Infection, Volume 18, Issue 12





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Author index

Publication date: December 2016
Source:Microbes and Infection, Volume 18, Issue 12





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Syndrome of inappropriate antidiuretic hormone secretion in a case of olfactory neuroblastoma without anti-diuretic hormone immunoreactivity: A case report and review of the literature

Publication date: Available online 20 December 2016
Source:Auris Nasus Larynx
Author(s): Takafumi Nakano, Junichi Motoshita, Fumi Sawada, Midori Okabe, Akihiro Tamae, Shinsuke Hiramatsu, Satoru Kodama, Hideki Shiratsuchi, Ryuji Yasumatsu, Torahiko Nakashima, Takashi Nakagawa
Olfactory neuroblastoma (ONB) is a relatively rare nasal or paranasal malignant tumor. This tumor is rarely accompanied by paraneoplastic syndromes such as syndrome of inappropriate antidiuretic hormone secretion (SIADH). Here, we report a 31-year-old female with histologically confirmed ONB who had been diagnosed with SIADH three years prior. She was treated with surgery followed by concurrent chemoradiotherapy. SIADH resolved immediately after surgical tumor resection. Immunohistochemically, both biopsy and resected specimens from the nasal cavity had been negative for ADH. Although extremely rare, ONB may be associated with SIADH, and the possibility of this cancer should be taken into account during the follow-up of idiopathic SIADH.



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Neck dissection with harmonic scalpel and electrocautery? A randomised study

Publication date: Available online 20 December 2016
Source:Auris Nasus Larynx
Author(s): Roshan K. Verma, Arulalan Mathiazhagan, Naresh K. Panda
ObjectiveIs the use of harmonic scalpel for neck dissection useful? Literature search did not show a single, prospective, randomised control trial. We intended to study the role of harmonic scalpel in neck dissection and compare it with conventional electrocautery technique for oral cavity carcinoma.Methods40 patients undergoing selective neck dissection for primary oral cavity malignancy were enrolled in this study. The harmonic scalpel (HS) group consisted of 20 patients, and the electrocautery technique (ET) group comprised of 20 patients. The following variables were examined: intraoperative blood loss, operative time, number of ligatures used, postoperative drain, and postoperative hospital stay.ResultsIntraoperative blood loss was found to be significantly reduced in harmonic scalpel group as compared to electrocautery group. However, we found no difference in other parameters like operative time, postop drain, postoperative hospital stay and number of ligatures used between both groups.ConclusionHarmonic scalpel for neck dissection is associated with significantly lesser intraoperative blood loss as compared to electrocautery. There is no effect on operative time and postoperative hospital stay in both groups.



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The temporalis muscle flap for reconstruction of soft palate and lateral oropharyngeal wall after transoral robotic surgery

Publication date: Available online 20 December 2016
Source:Auris Nasus Larynx
Author(s): Giuseppe Meccariello, Filippo Montevecchi, Alberto Deganello, Giovanni D'Agostino, Chiara Bellini, Ermelinda Zeccardo, Claudio Vicini
Trans Oral Robotic Surgery (TORS) is a prominent surgical approach for the resection of oropharyngeal tumors without division of the lip and mandible. Some defects following TORS are large and complex enough to benefit soft-tissue coverage. The pedicled temporalis muscle flap is a versatile and reliable flap and may be a valid option to reconstruct defects of the lateral pharyngeal wall and partial soft palate.



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A highly sensitive signal-amplified gold nanoparticle-based electrochemical immunosensor for dibutyl phthalate detection

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Ya-Ru Liang, Zong-Mian Zhang, Zhen-Jiang Liu, Kun Wang, Xiang-Yang Wu, Kun Zeng, Hui Meng, Zhen Zhang
A simple and signal-amplified, label-free electrochemical impedimetric immunosensor for dibutyl phthalate (DBP), a type of phthalate ester, was developed using gold nanoparticles (AuNPs) induced signal amplification. The approach was based on an indirectly competitive binding system of coating antigen that coated on antigen/chitosan/MWCNTs@GONRs/GCE (modified electrodes), target (DBP) and anti-DBP antibody. Signal amplification was performed via the enlargement of AuNPs through NADH-promoted catalytic precipitation, which caused a marked increase in the electron-transfer resistance and electrostatic repulsion after an AuNP-labeled second antibody conjugated to anti-DBP. Under the optimized conditions, this method displayed: (i) low detection limits (7ng/mL, 10 times lower than the traditional ELISA method using the same antibody); (ii) satisfactory accuracy (recoveries, 86.0–120.4%) and agreement with corresponding ELISA method; (iii) high tolerance to some environmental interferents; and (iv) low cost and low sample consumption (6µL). Our results demonstrate the great potential and high efficiency of this immunosensor in practical applications for the cost-effective and sensitive monitoring of DBP in aquatic environments.



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A disposable amperometric dual-sensor for the detection of hemoglobin and glycated hemoglobin in a finger prick blood sample

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Jong-Min Moon, Dong-Min Kim, Moo Hyun Kim, Jin-Yeong Han, Dong-Keun Jung, Yoon-Bo Shim
A disposable microfluidic amperometric dual-sensor was developed for the detection of glycated hemoglobin (HbA1C) and total hemoglobin (Hb), separately, in a finger prick blood sample. The accurate level of total Hb was determined through the measurements of the cathodic currents of total Hb catalyzed by a toluidine blue O (TBO)-modified working electrode. Subsequently, after washing unbound Hb in the fluidic channel of dual sensor with PBS, the cathodic current by only HbA1C captured on aptamer was monitored using another aptamer/TBO-modified working electrode in the channel. To modify the sensor probe, poly(2,2´:5´,5″-terthiophene-3´-p-benzoic acid) and a multi-wall carbon nanotube (MWCNT) composite layer (pTBA@MWCNT) was electropolymerized on a screen printed carbon electrode (SPCE), followed by immobilization of TBO for the total Hb probe and aptamer/TBO for the HbA1C probe, respectively. The characterization of each sensor surface was performed using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectroscopy (XPS), quartz crystal microbalance (QCM), field-emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM). The experimental conditions affecting the analytical signal were optimized in terms of the amount of TBO, pH, temperature, binding time, applied potential, and the content ratio of monomer and MWCNT. The dynamic ranges of Hb and HbA1C were from 0.1 to 10µM and from 0.006 to 0.74µM, with detection limits of 82(±4.2)nM and 3.7(±0.8)nM, respectively. The reliability of the proposed microfluidic dual-sensor for a finger prick blood sample (1µL) was evaluated in parallel with a conventional method (HPLC) for point-of-care analysis.



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The analysis of proteins and small molecules based on sterically tunable nucleic acid hyperbranched rolling circle amplification

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Hai Shi, Xiaoxia Mao, Xiaoxia Chen, Zihan Wang, Keming Wang, Xiaoli Zhu
In this work, we succeeded in establishing a new method for proteins and small molecules analysis based on the small molecule-linked DNA and nucleic acid hyperbranched rolling circle amplification (HRCA). Small molecule linked DNA by chemical modification was used as a flexible tool to study protein-small molecule interactions. The HRCA reaction which would produce signal amplification was regulated by the steric effect depending on whether the target proteins were present. In the implement of the proposed strategy, streptavidin (SA)-biotin and anti-digoxin antibody (anti-Dig)-digoxin were chosen as two model partners. Experimental results showed that the quantitative detection of SA and anti-Dig was realized both with nanomolar detection limits. The small molecules biotin and digoxin were also detected at nanomolar levels in a wide range of 1nM~100µM and 1nM~10µM, respectively. Meanwhile, the results indicated that the method had a favorable specificity in analyzing proteins or small molecules. Thus, it may be expected to quantitatively analyze some protein markers and small molecular drugs in complex biological samples.



http://ift.tt/2h0cWmc

An efficient ratiometric fluorescence sensor based on metal-organic frameworks and quantum dots for highly selective detection of 6-mercaptopurine

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Meng Jin, Zhao-Li Mou, Rui-Ling Zhang, Si-Si Liang, Zhi-Qi Zhang
The development of a simple and accurate quantitative method for the determination of 6-mercaptopurine (6-MP) is of great importance because of its serious side effects. Ratiometric fluorescence (RF) sensors are not subject to interference from environmental factors, and exhibit enhanced precision and accuracy. Therefore, a novel RF sensor for the selective detection of 6-MP was developed based on a dual-emission nanosensor. The nanosensor was fabricated by combining a blue-emission metal-organic framework (MOF) NH2-MIL-53(Al) (λem=425nm) with green-emission 3-mercaptopropionic acid-capped CdTe quantum dots (MPA-CdTe QDs) (λem=528nm) under a single excitation wavelength (335nm). Upon addition of 6-MP, the fluorescence of NH2-MIL-53(Al) in the nanohybrid was selectively quenched due to strong inner filter effects, while the fluorescence of the MPA-CdTe QDs was enhanced. The novel RF sensor exhibited higher selectivity towards 6-MP than CdTe QDs alone, and higher sensitivity than MOFs alone. 6-MP could be detected in the range of 0–50μM with a detection limit of 0.15μM (S/N=3). The developed sensor was applied for the determination of 6-MP in human urine samples and satisfactory results were obtained. Overall, a novel and efficient fluorescence-based method was developed for the detection of 6-MP in biosamples.

Graphical abstract

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Antibiotics mediated facile one-pot synthesis of gold nanoclusters as fluorescent sensor for ferric ions

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Mengqun Yu, Zheguo Zhu, Hong Wang, Linyao Li, Fei Fu, Yang Song, Erqun Song
In this paper, the cheap, easily obtained small antibiotic molecule of vancomycin was employed as reducer/stabilizer for facile one-pot synthesis of water exhibited a bluish fluorescence emission at 410nm within a short synthesis time about 50min. Based on the strong fluorescence quenching due to electron transfer mechanism by the introduction of ferric ions(Fe³⁺), the Van-AuNCs were interestingly designed for sensitive and selective detecting Fe³⁺ with a limit of 1.4μmol L⁻¹ in the linear range of 2–100μmol L⁻¹ within 20min. The Van-AuNCs based method was successfully applied to determine Fe³⁺ in tap water, lake water, river water and sea water samples with the quantitative spike recoveries from 97.50–111.14% with low relative standard deviations ranging from 0.49–1.87%, indicating the potential application of this Van-AuNCs based fluorescent sensor for environmental sample analysis.



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A graphene oxide-based strand displacement amplification platform for ricin detection using aptamer as recognition element

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Chun Hong Li, Xue Xiao, Jing Tao, Dong Mei Wang, Cheng Zhi Huang, Shu Jun Zhen
The toxic plant protein ricin is a potential agent for criminal or bioterrorist attacks due to the wide availability and relative ease of preparation. Herein, we developed a novel strategy for the detection of ricin B-chain (RTB) based on isothermal strand-displacement polymerase reaction (ISDPR) by using aptamer as a recognition element and graphene oxide (GO) as a low background platform. In this method, ricin-binding aptamer (RBA) hybridized with a short blocker firstly, and then was immobilized on the surface of streptavidin-coated magnetic beads (MBs). The addition of RTB could release the blocker, which could hybridize with the dye-modified hairpin probe and trigger the ISDPR, resulting in high fluorescence intensity. In the absence of RTB, however, the fluorescence of the dye could be quenched strongly by GO, resulting in the extremely low background signal. Thus, RTB could be sensitively detected by the significantly increased fluorescence signal. The linear range of the current analytical system was from 0.75μg/mL to 100μg/mL and the limit of detection (3σ) was 0.6μg/mL. This method has been successfully utilized for the detection of both the RTB and the entire ricin toxin in real samples, and it could be generalized to any kind of target detection based on an appropriate aptamer.



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A selective and sensitive optical sensor for dissolved ammonia detection via agglomeration of fluorescent Ag nanoclusters and temperature gradient headspace single drop microextraction

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Jiang Xue Dong, Zhong Feng Gao, Ying Zhang, Bang Lin Li, Nian Bing Li, Hong Qun Luo
In this paper, a simple sensor platform is presented for highly selective and sensitive detection of dissolved ammonia in aqueous solutions without pretreatment based on temperature gradient headspace single drop microextraction (HS-SDME) technique, and fluorescence and UV–vis spectrophotometry are utilized with the Ag nanoclusters (Ag NCs) functioned by citrate and glutathione as the probe. The sensing mechanism is based on the volatility of ammonia gas and the active response of Ag NCs to pH change caused by the introduction of ammonia. High pH can make the Ag NCs agglomerate and lead to the obvious decrease of fluorescence intensity and absorbance of Ag NCs solution. Moreover, the presented method exhibits a remarkably high selectivity toward dissolved ammonia over most of inorganic ions and amino acid, and shows a good linear range of 10–350μM (0.14–4.9mgNL⁻¹) with a low detection limit of 336nM (4.70μgNL⁻¹) at a signal-to-noise ratio of 3. In addition, the practical applications of the sensor have been successfully demonstrated by detecting dissolved ammonia in real samples.

Graphical abstract

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In vitro selection of DNA aptamers targeting β-lactoglobulin and their integration in graphene-based biosensor for the detection of milk allergen

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Shimaa Eissa, Mohammed Zourob
Food allergy has increased rapidly in recent years affecting millions of people worldwide. With the increased consumption of packed food nowadays, a sensitive, accurate and rapid screening method for potential food allergens has become an urgent need in order to protect the sensitive consumers from life-threatening reactions. The current detection methods for food allergens are mostly based on immunoassays which are costly and times-consuming. In this work, we developed an aptamer/graphene-based electrochemical biosensor for on-step, sensitive and low cost detection of β-lactoglobulin (β-LG) milk protein, one of the most common food allergens specially in infants. The selection of DNA aptamers against the two β-LG variants A and B was successfully realised using systemic evolution of ligands by exponential enrichment (SELEX) method. Among the selected aptamers, BLG14 aptamer sequence has shown high affinity and specificity to both β-LG A and B with dissociation constants (Kds) of 82 and 80nM, respectively as calculated using fluorescence binding assays. The aptamer was then integrated in a voltammetric biosensor utilizing graphene-modified screen printed carbon electrodes. The binding is monitored by following the change in the square wave voltammetry (SWV) reduction peak signal of ferrocyanide/ferricyanide redox couple due to the removal of the negatively charged aptamers from the surface upon protein binding. This one-step "signal on" biosensor takes 20min for the sensitive and selective detection of β-LG without using any labelling or sophisticated designs. The method was also tested in spiked food sample extract achieving good recovery percentage. The integration of the novel aptamer in the graphene biosensor allows a promising way for cost-effective, rapid and sensitive on-site detection of milk allergen in food stuff.



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Automated microraft platform to identify and collect non-adherent cells successfully gene-edited with CRISPR-Cas9

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Peter J. Attayek, Jennifer P. Waugh, Sally A. Hunsucker, Philip J. Grayeski, Christopher E. Sims, Paul M. Armistead, Nancy L. Allbritton
Microraft arrays have been used to screen and then isolate adherent and non-adherent cells with very high efficiency and excellent viability; however, manual screening and isolation limits the throughput and utility of the technology. In this work, novel hardware and software were developed to automate the microraft array platform. The developed analysis software identified microrafts on the array with greater than 99% sensitivity and cells on the microrafts with 100% sensitivity. The software enabled time-lapse imaging and the use of temporally varying characteristics as sort criteria. The automated hardware released microrafts with 98% efficiency and collected released microrafts with 100% efficiency. The automated system was used to examine the temporal variation in EGFP expression in cells transfected with CRISPR-Cas9 components for gene editing. Of 11,499 microrafts possessing a single cell, 220 microrafts were identified as possessing temporally varying EGFP-expression. Candidate cells (n=172) were released and collected from the microraft array and screened for the targeted gene mutation. Two cell colonies were successfully gene edited demonstrating the desired mutation.



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Ultrasensitive electrochemical DNA biosensor based on functionalized gold clusters/graphene nanohybrids coupling with exonuclease III-aided cascade target recycling

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Wei Wang, Ting Bao, Xi Zeng, Huayu Xiong, Wei Wen, Xiuhua Zhang, Shengfu Wang
In this work, a novel and ultrasensitive electrochemical biosensor was constructed for DNA detection based on functionalized gold clusters/graphene nanohybrids (AuNCs/GR nanobybrids) and exonuclease III (Exo III)-aided cascade target recycling. By utilizing the capacity of GR as universal template, different metal nanoclusters including AuNCs/GR nanobybrids and PtNCs/GR nanohybrids were synthesized through convenient ultrasonic method. Exo III-aided cascade recycling was initiated by target DNA, generating the final cleavage product (S2), which acted as a linkage between capture probe and the functionalized metal nanoclusters/GR conjugates in the construction of the biosensor. The AuNCs/GR-DNA-enzyme conjugates acted as interfaces of enzyme-catalyzed silver deposition reaction, achieving DNA detection ranging from 0.02 fM to 20 pM with a detection limit of 0.057 fM. In addition, PtNCs/GR-DNA conjugates presented peroxidase-like activity and the functionalized PtNCs/GR nanohybrids-based electrochemical biosensor also realized DNA detection by catalyzing the 3,3′,5,5′-tetramethylbenzidine-hydrogen peroxide (TMB-H2O2) system to produce electrochemical signal. This metal clusters/GR-based multiple-amplified electrochemical biosensor provided an universal method for DNA detection.

Graphical abstract

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Cyanine5-doped silica nanoparticles as ultra-bright immunospecific labels for model circulating tumour cells in flow cytometry and microscopy

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Claire L. O'Connell, Robert Nooney, Colette McDonagh
In this work, ultra-bright fluorescent silica nanoparticles (NPs) labels have been shown to selectively bind to a model circulating tumour cell (CTC) line, MCF-7, a metastatic breast cancer by targeting epithelial cellular adhesion molecule (EpCAM) present on the MCF-7 cell membrane. Silica NPs approximately 40nm in diameter were doped with different concentrations of Cyanine5 dye molecules, using the reverse microemulsion method. The NPs were two orders of magnitude brighter than Cyanine5 free dye and the measured fluorescence intensity matched a homo-Förster Resonance Energy Transfer model. NPs were conjugated with anti-EpCAM antibody to the NP surface for immunospecific targeting. In flow cytometry experiments the NPs were twice as bright as two commercial anti-EpCAM red fluorophore conjugates, APC and AlexaFluor®647. This increase is achieved while keeping non-specific binding low as established in control tests with a non-metastatic cancer cell line (HeLa). The NPs were also immunospecific in fluorescence microscopy experiments performed at room temperature on non-fixed cells. Confocal microscopy was used to confirm the NPs were located on the surface of the cells, matching with the location of the EpCAM marker. These NPs labels have excellent potential in biomedical diagnostics, particularly when high signal to noise and good photostability are needed, for example, in point-of-care testing.



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Differential White Matter Involvement Associated with Distinct Visuospatial Deficits after Right Hemisphere Stroke

Publication date: Available online 20 December 2016
Source:Cortex
Author(s): Alex R. Carter, Mark P. McAvoy, Joshua S. Siegel, Xin Hong, Serguei V. Astafiev, Jennifer Rengachary, Kristi Zinn, Nicholas V. Metcalf, Gordon L. Shulman, Maurizio Corbetta
Visuospatial attention depends on the integration of multiple processes, and people with right hemisphere lesions after a stroke may exhibit severe or no visuospatial deficits. The anatomy of core components of visuospatial attention is an area of intense interest. Here we examine the relationship between the disruption of core components of attention and lesion distribution in a heterogeneous group (N=70) of patients with right hemisphere strokes regardless of the presence of clinical neglect. Deficits of lateralized spatial orienting, measured as the difference in reaction times for responding to visual targets in the contralesional or ipsilesional visual field, and deficits in re-orienting attention, as measured by the difference in reaction times for invalidly vs. validly cued targets, were measured using a computerized spatial orienting task. Both measures were related through logistic regression and a novel ridge regression method to anatomical damage measured with magnetic resonance imaging. While many regions were common to both deficit maps, a deficit in lateralized spatial orienting was more associated with lesions in the white matter underlying the posterior parietal cortex, and middle and inferior frontal gyri. A deficit in re-orienting of attention toward unattended locations was associated with lesions in the white matter of the posterior parietal cortex, insular cortex and less so with white matter involvement of the anterior frontal lobe. An hodological analysis also supports this partial dissociation between the white matter tracts that are damaged in lateralized spatial biases versus impaired re-orienting. Our results underscore that the integrity of fronto-parietal white matter tracts is crucial for visuospatial attention and that different attention components are mediated by partially distinct neuronal substrates.



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Editorial Board

Publication date: January 2017
Source:Critical Reviews in Oncology/Hematology, Volume 109





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The 6-chromanol derivate SUL-109 enables prolonged hypothermic storage of adipose tissue-derived stem cells

Publication date: March 2017
Source:Biomaterials, Volume 119
Author(s): Ghazaleh Hajmousa, Pieter Vogelaar, Linda A. Brouwer, Adrianus C. van der Graaf, Robert H. Henning, Guido Krenning
Encouraging advances in cell therapy research with adipose derived stem cells (ASC) require an effective short-term preservation method that provides time for quality control and transport of cells from their manufacturing facility to their clinical destination. Hypothermic storage of cells in their specific growth media offers an alternative and simple preservation method to liquid nitrogen cryopreservation or commercial preservation fluids for short-term storage and transport. However, accumulation of cell damage during hypothermia may result in cell injury and death upon rewarming through the production of excess reactive oxygen species (ROS). Here, the ability of the cell culture medium additive SUL-109, a modified 6-chromanol, to protect ASC from hypothermia and rewarming damage is examined. SUL-109 conveys protective effects against cold-induced damage in ASC as is observed by preservation of cell viability, adhesion properties and growth potential. SUL-109 does not reduce the multilineage differentiation capacity of ASC. SUL-109 conveys its protection against hypothermic damage by the preservation of the mitochondrial membrane potential through the activation of mitochondrial membrane complexes I and IV, and increases maximal oxygen consumption in FCCP uncoupled mitochondria. Consequently, SUL-109 alleviates mitochondrial ROS production and preserves ATP production. In summary, here we describe the generation of a single molecule cell preservation agent that protects ASC from hypothermic damage associated with short-term cell preservation that does not affect the differentiation capacity of ASC.



http://ift.tt/2idwqVn

The Ethics of Human Enhancement: Understanding the Debate.

http://ift.tt/2hT4Obn

The Ballseye programme: a mixed-methods programme of research in traditional sexual health and alternative community settings to improve the sexual health of men in the UK.

The programme found that men find traditional health-care settings the most acceptable places to access screening for sexually transmitted infections. However, self-sampling kits in football clubs could widen access to screening offer a public health impact for men with limited local sexual health services. Accelerated Partner Therapy options appear to improve outcomes of partner notification in community settings but outcomes failed to reach national standards.

http://ift.tt/2hY2RYA

An observational study to assess if automated diabetic retinopathy image assessment software can replace one or more steps of manual imaging grading and to determine their cost-effectiveness.

Two automated retinal image analysis systems achieved acceptable sensitivity and false-positive rates for referable retinopathy and are cost-effective alternatives to a purely manual grading approach.

http://ift.tt/2hT4HfX

Too Much of a Good Thing? Chronic IFN Fuels Resistance to Cancer Immunotherapy

Publication date: 20 December 2016
Source:Immunity, Volume 45, Issue 6
Author(s): James L. Reading, Sergio A. Quezada
Immune checkpoint blockade (ICB) is revolutionizing cancer medicine, yet the molecular basis of resistance remains unclear. In a recent issue of Cell, Benci et al. (2016) demonstrate that sustained interferon signaling is central to the development of PD-L1-dependent and -independent resistance to ICB.

Teaser

Immune checkpoint blockade (ICB) is revolutionizing cancer medicine, yet the molecular basis of resistance remains unclear. In a recent issue of Cell, Benci et al. (2016) demonstrate that sustained interferon signaling is central to the development of PD-L1-dependent and -independent resistance to ICB.


http://ift.tt/2hFKUQE

Precision Targeting: Mast Cells Wipe Out Infected Bladder Epithelia

Publication date: 20 December 2016
Source:Immunity, Volume 45, Issue 6
Author(s): Hongnga T. Le, Booki Min
Exfoliating infected bladder epithelium is a powerful host defense mechanism that reduces bacterial burden. In this issue of Immunity, Choi et al. (2016) present a function of mast cells that orchestrates the infected epithelial cell exfoliation via cytolytic granules.

Teaser

Exfoliating infected bladder epithelium is a powerful host defense mechanism that reduces bacterial burden. In this issue of Immunity, Choi et al. (2016) present a function of mast cells that orchestrates the infected epithelial cell exfoliation via cytolytic granules.


http://ift.tt/2hREzzD

Sifting through CD8+ T Cell Memory

Publication date: 20 December 2016
Source:Immunity, Volume 45, Issue 6
Author(s): Matthew D. Martin, Vladimir P. Badovinac
In this issue of Immunity, Gerlach et al. (2016) describe three distinct memory CD8⁺ T cell subsets based upon expression of the fractalkine receptor CX3CR1. Their findings revise the paradigm of effector and central memory T cells by revealing a subset of CD8⁺ memory T cells defined by intermediate levels of expression of CX3CR1 that conducts tissue surveillance.

Teaser

In this issue of Immunity, Gerlach et al. (2016) describe three distinct memory CD8⁺ T cell subsets based upon expression of the fractalkine receptor CX3CR1. Their findings revise the paradigm of effector and central memory T cells by revealing a subset of CD8⁺ memory T cells defined by intermediate levels of expression of CX3CR1 that conducts tissue surveillance.


http://ift.tt/2hREAnb

Immune Cell Intolerance for Excess Cholesterol

Publication date: 20 December 2016
Source:Immunity, Volume 45, Issue 6
Author(s): Scott B. Widenmaier, Gökhan S. Hotamışlıgil
Chronic metabolic challenges have severe consequences on physiological systems. In this issue of Immunity, Ito et al. (2016) show that defects in cholesterol metabolism in CD11c⁺ immune cells result in impaired antigen presentation and ultimately in autoimmune disease.

Teaser

Chronic metabolic challenges have severe consequences on physiological systems. In this issue of Immunity, Ito et al. (2016) show that defects in cholesterol metabolism in CD11c⁺ immune cells result in impaired antigen presentation and ultimately in autoimmune disease.


http://ift.tt/2hFOVVa

Allergen Exposure: When Timing Is Everything

Publication date: 20 December 2016
Source:Immunity, Volume 45, Issue 6
Author(s): Tanel Mahlakõiv, David Artis
It is known that young children exposed to allergens are prone to develop asthma later in life. In this issue of Immunity, de Kleer et al. (2016) identify IL-33 as a key player in the developing lung for sensitization to environmental allergens and airway hyperreactivity.

Teaser

It is known that young children exposed to allergens are prone to develop asthma later in life. In this issue of Immunity, de Kleer et al. (2016) identify IL-33 as a key player in the developing lung for sensitization to environmental allergens and airway hyperreactivity.


http://ift.tt/2hRHecN

One Niche to Rule Both Maintenance and Loss of Stemness in HSCs

Publication date: 20 December 2016
Source:Immunity, Volume 45, Issue 6
Author(s): Motonari Kondo
Hemato-lymphopoiesis initiated by hematopoietic stem cells (HSCs) is tightly regulated by factors present in the bone marrow (BM) niche. Using genetically modified mice, Gomes et al. (2016) show that IL-7 is produced by HSC niche-forming cells and find that the same niche that controls HSC self-renewal can also support differentiation.

Teaser

Hemato-lymphopoiesis initiated by hematopoietic stem cells (HSCs) is tightly regulated by factors present in the bone marrow (BM) niche. Using genetically modified mice, Gomes et al. (2016) show that IL-7 is produced by HSC niche-forming cells and find that the same niche that controls HSC self-renewal can also support differentiation.


http://ift.tt/2hFPRZO

Expanding the Immunology Toolbox: Embracing Public-Data Reuse and Crowdsourcing

Publication date: 20 December 2016
Source:Immunity, Volume 45, Issue 6
Author(s): Rachel Sparks, William W. Lau, John S. Tsang
New technologies have been propelling dramatic increases in the volume and diversity of large-scale public data, which can potentially be reused to answer questions beyond those originally envisioned. However, this often requires computational and statistical skills beyond the reach of most bench scientists. The development of educational and accessible computational tools is thus critical, as are crowdsourcing efforts that utilize the community's expertise to curate public data for hypothesis generation and testing. Here we review the history of public-data reuse and argue for greater incorporation of computational and statistical sciences into the biomedical education curriculum and the development of biologist-friendly crowdsourcing tools. Finally, we provide a resource list for the reuse of public data and highlight an illustrative crowdsourcing exercise to explore public gene-expression data of human autoimmune diseases and corresponding mouse models. Through education, tool development, and community engagement, immunologists will be poised to transform public data into biological insights.

Teaser

New technologies have been propelling dramatic increases in the volume and diversity of large-scale public data, which can potentially be reused to answer questions beyond those originally envisioned. However, this often requires computational and statistical skills beyond the reach of most bench scientists. The development of educational and accessible computational tools is thus critical, as are crowdsourcing efforts that utilize the community's expertise to curate public data for hypothesis generation and testing. Here we review the history of public-data reuse and argue for greater incorporation of computational and statistical sciences into the biomedical education curriculum and the development of biologist-friendly crowdsourcing tools. Finally, we provide a resource list for the reuse of public data and highlight an illustrative crowdsourcing exercise to explore public gene-expression data of human autoimmune diseases and corresponding mouse models. Through education, tool development, and community engagement, immunologists will be poised to transform public data into biological insights.


http://ift.tt/2hRzF5V

The Heterogeneity of Ly6Chi Monocytes Controls Their Differentiation into iNOS+ Macrophages or Monocyte-Derived Dendritic Cells

Publication date: 20 December 2016
Source:Immunity, Volume 45, Issue 6
Author(s): Shinelle Menezes, Daisy Melandri, Giorgio Anselmi, Thibaut Perchet, Jakob Loschko, Juan Dubrot, Rajen Patel, Emmanuel L. Gautier, Stéphanie Hugues, M. Paula Longhi, Jake Y. Henry, Sergio A. Quezada, Grégoire Lauvau, Ana-Maria Lennon-Duménil, Enrique Gutiérrez-Martínez, Alain Bessis, Elisa Gomez-Perdiguero, Christian E. Jacome-Galarza, Hannah Garner, Frederic Geissmann, Rachel Golub, Michel C. Nussenzweig, Pierre Guermonprez
Inflammation triggers the differentiation of Ly6C^hi monocytes into microbicidal macrophages or monocyte-derived dendritic cells (moDCs). Yet, it is unclear whether environmental inflammatory cues control the polarization of monocytes toward each of these fates or whether specialized monocyte progenitor subsets exist before inflammation. Here, we have shown that naive monocytes are phenotypically heterogeneous and contain an NR4A1- and Flt3L-independent, CCR2-dependent, Flt3⁺CD11c⁻MHCII⁺PU.1^hi subset. This subset acted as a precursor for FcγRIII⁺PD-L2⁺CD209a⁺, GM-CSF-dependent moDCs but was distal from the DC lineage, as shown by fate-mapping experiments using Zbtb46. By contrast, Flt3⁻CD11c⁻MHCII⁻PU.1^lo monocytes differentiated into FcγRIII⁺PD-L2⁻CD209a⁻iNOS⁺ macrophages upon microbial stimulation. Importantly, Sfpi1 haploinsufficiency genetically distinguished the precursor activities of monocytes toward moDCs or microbicidal macrophages. Indeed, Sfpi1^+/− mice had reduced Flt3⁺CD11c⁻MHCII⁺ monocytes and GM-CSF-dependent FcγRIII⁺PD-L2⁺CD209a⁺ moDCs but generated iNOS⁺ macrophages more efficiently. Therefore, intercellular disparities of PU.1 expression within naive monocytes segregate progenitor activity for inflammatory iNOS⁺ macrophages or moDCs.

Graphical abstract

Teaser

Monocytes can differentiate into multiple progenies during inflammation. Here, Menezes et al. show that monocytes from naive mice are heterogeneous and contain distinct precursor subsets giving rise to iNOS⁺ inflammatory macrophages or GM-CSF-induced CD209a⁺ monocyte-derived dendritic cells.


http://ift.tt/2hFOWsc

Inhaled Fine Particles Induce Alveolar Macrophage Death and Interleukin-1α Release to Promote Inducible Bronchus-Associated Lymphoid Tissue Formation

Publication date: 20 December 2016
Source:Immunity, Volume 45, Issue 6
Author(s): Etsushi Kuroda, Koji Ozasa, Burcu Temizoz, Keiichi Ohata, Christine X. Koo, Tomohiro Kanuma, Takato Kusakabe, Shingo Kobari, Masanori Horie, Yasuo Morimoto, Saeko Nakajima, Kenji Kabashima, Steven F. Ziegler, Yoichiro Iwakura, Wataru Ise, Tomohiro Kurosaki, Takahiro Nagatake, Jun Kunisawa, Naoki Takemura, Satoshi Uematsu, Masayuki Hayashi, Taiki Aoshi, Kouji Kobiyama, Cevayir Coban, Ken J. Ishii
Particulate pollution is thought to function as an adjuvant that can induce allergic responses. However, the exact cell types and immunological factors that initiate the lung-specific immune responses are unclear. We found that upon intratracheal instillation, particulates such as aluminum salts and silica killed alveolar macrophages (AMs), which then released interleukin-1α (IL-1α) and caused inducible bronchus-associated lymphoid tissue (iBALT) formation in the lung. IL-1α release continued for up to 2 weeks after particulate exposure, and type-2 allergic immune responses were induced by the inhalation of antigen during IL-1α release and iBALT formation, even long after particulate instillation. Recombinant IL-1α was sufficient to induce iBALTs, which coincided with subsequent immunoglobulin E responses, and IL-1-receptor-deficient mice failed to induce iBALT formation. Therefore, the AM-IL-1α-iBALT axis might be a therapeutic target for particulate-induced allergic inflammation.

Graphical abstract

Teaser

Inhaled fine particulates are known to induce allergic responses, but the exact cell types and immunological factors that initiate the lung-specific immune responses remain unclear. Kuroda et al. (2016) show that particulates trigger tertiary lymphoid organ formation in the lung as a consequence of alveolar macrophage death and IL-1α release.


http://ift.tt/2hFFp4u

Cholesterol Accumulation in CD11c+ Immune Cells Is a Causal and Targetable Factor in Autoimmune Disease

Publication date: 20 December 2016
Source:Immunity, Volume 45, Issue 6
Author(s): Ayaka Ito, Cynthia Hong, Kazuhiro Oka, Jon V. Salazar, Cody Diehl, Joseph L. Witztum, Mercedes Diaz, Antonio Castrillo, Steven J. Bensinger, Lawrence Chan, Peter Tontonoz
Liver X receptors (LXRs) are regulators of cholesterol metabolism that also modulate immune responses. Inactivation of LXR α and β in mice leads to autoimmunity; however, how the regulation of cholesterol metabolism contributes to autoimmunity is unclear. Here we found that cholesterol loading of CD11c⁺ cells triggered the development of autoimmunity, whereas preventing excess lipid accumulation by promoting cholesterol efflux was therapeutic. LXRβ-deficient mice crossed to the hyperlipidemic ApoE-deficient background or challenged with a high-cholesterol diet developed autoantibodies. Cholesterol accumulation in lymphoid organs promoted T cell priming and stimulated the production of the B cell growth factors Baff and April. Conversely, B cell expansion and the development of autoantibodies in ApoE/LXR-β-deficient mice was reversed by ApoA-I expression. These findings implicate cholesterol imbalance as a contributor to immune dysfunction and suggest that stimulating HDL-dependent reverse cholesterol transport could be beneficial in the setting of autoimmune disease.

Graphical abstract

Teaser

Ito et al. show that dietary lipid excess and impairment of cholesterol efflux accelerate the development of autoimmunity. Accumulation of cholesterol in CD11c⁺ APCs promotes BAFF and April production and enhances antigen presentation, contributing to the development of autoimmune-related pathology. Conversely, promoting reverse cholesterol transport through ApoA-I expression ameliorates autoimmunity.


http://ift.tt/2hFNaaP

Impact of AIP and inhibitory G protein alpha 2 proteins on clinical features of sporadic GH-secreting pituitary adenomas

Introduction

In sporadic acromegaly, downregulation of AIP protein of the adenomas associates with invasive tumor features and reduced responsiveness to somatostatin analogues. AIP is a regulator of Ga_i signaling, but it is not known how the biological function of the Ga_i pathway is controlled.

Aim

To study GNAS and AIP mutation status, AIP and Ga_i-2 protein expressions, Ki-67 proliferation indices and clinical parameters in patients having primary surgery because of acromegaly at a single center between years 2000 and 2010.

Results

Sixty patients (F/M, 31/29), mean age 49 (median 50), mean follow-up 7.7 years (range 0.6–14.0) underwent primary surgery. Four adenoma specimens (6.8%) harbored an AIP and 21 (35.6%) an activating GNAS (Gsp+) mutation. Altogether 13/56 (23%) adenomas had low AIP protein levels, and 14/56 (25%) low Ga_i-2 staining. In regression modeling, AIP expression associated with Ga_i-2 (P = 2.33 x 10^–9) and lower Ki-67 (P = 0.04). In pairwise comparison, low AIP protein predicted high GH at last follow-up (mean 7.7 years after surgery, q = 0.045). Extent of treatments given for acromegaly associated with higher preoperative GH (P = 7.94 x 10^–4), KNOSP (P = 0.003) and preoperative hypopituitarism (P = 0.03) and remission at last follow-up with change in 3-month postoperative IGF1 (P = 2.07 x 10^–7).

Conclusions

We demonstrate, for the first time, that AIP protein expression associates with Ga_i-2 protein intensities in sporadic somatotropinomas, suggesting a joint regulation on somatostatin signaling. Low AIP level associates with higher proliferative activity and predicts high GH concentrations after long-term follow-up. The AIP mutation rate of 6.8% is fairly high, reflecting the genetic composition of the Finnish population.

http://ift.tt/2hY5GIV

Cell morphology and growth observation studies on novel, chemically unmodified and patterned polymer surfaces for advanced tissue culture applications

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): C.H. Trease, M.R. Longman, A.T. Augousti, P.J.S. Foot, B. Pierscionek
Creation of more physiologically relevant cell models in tissue culture is a requisite for advancing medical research. It can involve complex substrates, expensive manufacturing and largely inaccessible methods of increasing surface energy and patterning of materials that may be unnecessary in many circumstances. An array of various different adherent cell lines (human, mammalian, healthy and disease states) were grown on simple sterilised but otherwise untreated thin film surfaces as well as on electro-hydrodynamically patterned surfaces to produce topographically patterned culture surfaces. Room temperature cure epoxy resin and unmodified poly(methyl methacrylate) (PMMA) thin film surfaces were used for cell growth and morphological observations. Differing responses in growth, morphology and adherence were observed in a surface- and cell-specific manner. With no complex and expensive modifications required, we demonstrate the application of novel, suitable and easily patterned materials for use in more advanced tissue culture applications for a variety of clinically relevant cell lines showing unique responses and potentially new and wide-reaching applications.

Graphical abstract

http://ift.tt/2hXSq78

A new reactive polymethacrylate bearing pendant furfuryl groups: Synthesis, thermoreversible reactions, and self-healing

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Sungmin Jung, Jiang Tian Liu, Sung Hwa Hong, Dhamodaran Arunbabu, Seung Man Noh, Jung Kwon Oh
We report a new methacrylate copolymer having pendant furfuryl groups (PFu) reactive to maleimide-bearing compounds to form thermally-induced crosslinked networks exhibiting self-healability through thermoreversible Diels-Alder (DA)/Retro-DA reactions. The PFu is synthesized by a combination of a facile radical polymerization with post-modification methods through a base-catalyzed coupling reaction and a thermally-induced thiol-ene radical addition reaction. The resulting PFu is effective toward DA reaction with a maleimide-bearing crosslinker at moderate or elevated temperatures, yielding highly crosslinked films through DA linkages. Thermal analysis and spectroscopic studies along with NMR model study with small molecular weight precursors suggest the formation of DA-crosslinked networks at 50–100 °C and the occurrence of retro-DA reaction at >125 °C. The resulting DA-crosslinked network is dynamic, exhibiting self-healing through the occurrence of thermoreversible DA/retro-DA reactions, confirmed with sol-gel transition and optical microscopy.

Graphical abstract

http://ift.tt/2hY6dKY

Drug delivery systems for prolonged duration local anesthesia

Publication date: Available online 20 December 2016
Source:Materials Today
Author(s): Claudia M. Santamaria, Alan Woodruff, Rong Yang, Daniel S. Kohane
Numerous drug delivery systems have been applied to the problem of providing prolonged duration local anesthesia (PDLA). Here we review the rationale for PDLA, the desirable features for and important attributes of such systems, and specific examples that have been developed.



http://ift.tt/2harFQ4

Tongue Base Schwannoma

Abstract

Intraoral schwannomas account for 1% of head and neck schwannoma, with tongue base schwannoma being reported rarely. In an English literature search from 1988 to 2014, not more than 38 cases of tongue base schwannoma have been reported. Large tongue base schwannomas pose a significant risk to airway, thereby calling for an early intervention. We report a rare case of tongue base schwannoma in a 25 year old female managed surgically by lateral pharyngotomy approach.

http://ift.tt/2gXsxCV

Tongue Base Schwannoma

Abstract

Intraoral schwannomas account for 1% of head and neck schwannoma, with tongue base schwannoma being reported rarely. In an English literature search from 1988 to 2014, not more than 38 cases of tongue base schwannoma have been reported. Large tongue base schwannomas pose a significant risk to airway, thereby calling for an early intervention. We report a rare case of tongue base schwannoma in a 25 year old female managed surgically by lateral pharyngotomy approach.

http://ift.tt/2gXsxCV

Tongue Base Schwannoma

Abstract

Intraoral schwannomas account for 1% of head and neck schwannoma, with tongue base schwannoma being reported rarely. In an English literature search from 1988 to 2014, not more than 38 cases of tongue base schwannoma have been reported. Large tongue base schwannomas pose a significant risk to airway, thereby calling for an early intervention. We report a rare case of tongue base schwannoma in a 25 year old female managed surgically by lateral pharyngotomy approach.

http://ift.tt/2gXsxCV

A Decade of Experience of Management of Thyroglossal Duct Cyst in a Tertiary Care Hospital: Differentiation Between Children and Adults

Abstract

Variations in thyroglossal duct cysts (TGDCs) between children and adult are mentioned very little in literature. The lesion mostly found in children but adult population also possesses this anomaly. The aim of this study was to determine the differences in clinical presentations and surgical outcomes of TGDC between children and adults. A retrospective chart review of all patients with TGDCs managed in our hospital from July 2004 to June 2014. All records were reviewed for age, sex, location of cyst in neck and with relation to hyoid bone, size, postoperative complication and recurrence rates. Differences between children and adults were assessed. A total of 39 patients (21 children and 18 adults) were treated for TGDC. Of the pediatric group, 71.4% were male and 28.5% were female, whereas 72.2% of the adults were male and 27.7% were female. Adults were more likely to develop other complaints like neck pain, dysphagia and dyspnea. Position was almost similar in both age groups with midline and infrahyoid location while laterality was seen in adult only. Size of Cyst was found to be larger in adults. The recurrence and post operative complication rates between children and adults were not significantly different. TGDC has male predominance. Clinical presentations were almost similar in both age groups. Although lateral deviation, increase size of cyst and recurrences were seen in adults only, Sistrunk procedure is recommended as a safe and standard surgical treatment in both age groups.

http://ift.tt/2hTAsCJ

Tongue Base Schwannoma

Abstract

Intraoral schwannomas account for 1% of head and neck schwannoma, with tongue base schwannoma being reported rarely. In an English literature search from 1988 to 2014, not more than 38 cases of tongue base schwannoma have been reported. Large tongue base schwannomas pose a significant risk to airway, thereby calling for an early intervention. We report a rare case of tongue base schwannoma in a 25 year old female managed surgically by lateral pharyngotomy approach.

http://ift.tt/2gXsxCV

Optimizing acitretin use in patients with plaque psoriasis

Abstract

Acitretin is one of the systemic agents used for the treatment of psoriasis. Because different acitretin dosages resulted therapeutically successful, there is no general agreement on the optimal dose regimen. To report acitretin efficacy and safety in a real-life setting, wherein patient-tailored dose regimen is usually prescribed, a retrospective analysis evaluating charts of all plaque-type psoriasis patients treated with acitretin from the clinic database was performed. PASI score improvement, as well as PASI 50, 75, 90, and 100 responses were assessed throughout the observational period. Overall, 52% PASI score reduction and a satisfactory safety profile were detected. PASI 50, 75, 90, and 100 response was achieved by 53%, 48%, 28%, and 14%, respectively. Treatment consisted on a mean daily acitretin dose of 25.01 mg. The initial dose was increased (51.2% of cases) or decreased (48.8%) prescribing a mean daily dose of 29.8 mg and 20.02 mg, respectively. This study proposed a dose regimen customized on clinical response and patient's needs, to optimized acitretin benefit.

http://ift.tt/2gZRZHV

Effect of different types of therapeutic trauma on vitiligo lesions

Abstract

New treatment modalities for vitiligo acting by changing certain cytokines and metalloproteinases are newly emerging. The aim of this work is to To assess the efficacy of trichloroacetic acid (TCA) chemical peel, dermapen, and fractional CO₂ laser in treatment of stable non-segmental vitiligo and to detect their effects on IL-17 and MMP-9 levels. Thirty patients with stable vitiligo were recruited in a randomized controlled study. They were randomly categorized into three equal groups. Group 1: TCA peel, Group 2: dermapen machine, and Group 3: Fractional CO₂ laser. Skin biopsies were taken from treated areas and from control areas for which MMP-9 and IL-17 tissue levels were measured using ELISA. The 30 vitiligo patients had low basal tissue MMP-9 levels and high baseline IL-17 tissue levels. As regards the three different used modalities, all of them caused rise in MMP-9 as well as IL-17 levels and almost their levels were much more elevated with repetition of the previously mentioned traumatic procedures. TCA 25% peel proved to be the most effective modality both clinically and laboratory and it can be used prior or with other conventional therapies in the treatment of vitiligo.

http://ift.tt/2idkVx9

The V-shaped mini flap method for microform cleft lip repair

Abstract

Background

We have devised a new operative technique for microform cleft lip repair via the use of a V-shaped flap method. From 2006 to 2015, nine patients with unilateral cleft lip diagnosed as mini-microform cleft lip or microform cleft lip by the classification of Yuzuriha and Mulliken, were recorded.

Methods

With our procedure, a V-shaped mini flap with the vermillion border serving as the vertex is inserted into the incised area along the vermillion border on the affected side, thereby allowing reliable correction of the vermillion border notch. When this procedure is applied to cases of microform cleft lip, the white lip's linear mark is resected totally, followed by overlap suturing of the orbicularis oris muscle from the incised area to correct philtrum ridge deviation and nasal alar base lateral deviation. In cases of mini-microform cleft lip, the extent of resection of the skin and mucosa is reduced to the minimum necessary level to reduce the scar size as far as possible.

Results

This procedure was used for the treatment of microform cleft lip in six cases and mini-microform cleft lip in three cases. The mean age at operation was 13.3 months (range 6–45 months). There were no postoperative complications; moreover, no patient required additional surgery.

Conclusions

Regarding postoperative clinical findings, the scar was not evident because it was identical to the philtrum ridge. Furthermore, the cupid's bow was symmetrical, and constriction at the vermillion's free margin had been corrected. Level of Evidence: Level IV, therapeutic study.

http://ift.tt/2hSipj8

Optimizing acitretin use in patients with plaque psoriasis

Abstract

Acitretin is one of the systemic agents used for the treatment of psoriasis. Because different acitretin dosages resulted therapeutically successful, there is no general agreement on the optimal dose regimen. To report acitretin efficacy and safety in a real-life setting, wherein patient-tailored dose regimen is usually prescribed, a retrospective analysis evaluating charts of all plaque-type psoriasis patients treated with acitretin from the clinic database was performed. PASI score improvement, as well as PASI 50, 75, 90, and 100 responses were assessed throughout the observational period. Overall, 52% PASI score reduction and a satisfactory safety profile were detected. PASI 50, 75, 90, and 100 response was achieved by 53%, 48%, 28%, and 14%, respectively. Treatment consisted on a mean daily acitretin dose of 25.01 mg. The initial dose was increased (51.2% of cases) or decreased (48.8%) prescribing a mean daily dose of 29.8 mg and 20.02 mg, respectively. This study proposed a dose regimen customized on clinical response and patient's needs, to optimized acitretin benefit.

http://ift.tt/2gZRZHV

Effect of different types of therapeutic trauma on vitiligo lesions

Abstract

New treatment modalities for vitiligo acting by changing certain cytokines and metalloproteinases are newly emerging. The aim of this work is to To assess the efficacy of trichloroacetic acid (TCA) chemical peel, dermapen, and fractional CO₂ laser in treatment of stable non-segmental vitiligo and to detect their effects on IL-17 and MMP-9 levels. Thirty patients with stable vitiligo were recruited in a randomized controlled study. They were randomly categorized into three equal groups. Group 1: TCA peel, Group 2: dermapen machine, and Group 3: Fractional CO₂ laser. Skin biopsies were taken from treated areas and from control areas for which MMP-9 and IL-17 tissue levels were measured using ELISA. The 30 vitiligo patients had low basal tissue MMP-9 levels and high baseline IL-17 tissue levels. As regards the three different used modalities, all of them caused rise in MMP-9 as well as IL-17 levels and almost their levels were much more elevated with repetition of the previously mentioned traumatic procedures. TCA 25% peel proved to be the most effective modality both clinically and laboratory and it can be used prior or with other conventional therapies in the treatment of vitiligo.

http://ift.tt/2idkVx9