Head and Neck Diseases by Alexandros G.Sfakianakis: 08/21/17

Δευτέρα 21 Αυγούστου 2017

Moderate to severe hidradenitis suppurativa patients do not have an altered bacterial composition in peripheral blood compared to healthy controls

Abstract

Background

Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease defined by recurrent nodules, tunnels and scarring involving the intertriginous skin. HS patients often report an array of systemic symptoms such as fatigue and malaise. The etiology of these symptoms remains unclear. Previously, various bacteria have been associated with mature HS lesions and bacteremia has been reported in HS patients using traditional culturing methods. Thus, we hypothesized that a low-grade bacteremia contributes to the symptomatology in HS patients.

Objective

To explore the potential presence of bacteraemia in HS patients and healthy controls.

Method

A case control study. Compositions of bacteria in the blood of 27 moderate to severe HS patients and 26 healthy controls were investigated using Next Generation 16S ribosomal RNA gene Sequencing (NGS) and routine anaerobic and aerobic blood culturing.

None of the participants received any antibiotics (systemic or topical therapy) within one month prior to the study. HS patients with a recent flare were randomly selected by consecutive recruitment of eligible patients from the Department of Dermatology, Zealand University Hospital, Denmark. Healthy controls were recruited from the University of Copenhagen as well as from the health care staff.

Results

The different bacterial compositions were investigated using NGS and traditional anaerobic and aerobic blood culturing. Our NGS analysis provided a previously unreported characterization of the bacterial composition in peripheral blood from HS patients and healthy controls. Overall, our data demonstrated that HS patients do not have a different bacterial composition in their peripheral blood than healthy controls.

Conclusion

The study suggests the self-reported symptoms in HS such as malaise and fatigue may not be linked to bacteremia.

http://ift.tt/2v11ulP

Killing two birds with one stone: response to pembrolizumab in a patient with metastatic melanoma and B-cell chronic lymphocytic leukemia

Abstract

Pembrolizumab, a humanized immunoglobulin G4 monoclonal antibody against PD-1, has demonstrated antitumor activity and a manageable safety profile in patients with different solid tumors and hematologic malignancies in multiple clinical trials (1-4). Although these data highlight the effectiveness of PD-1 pathway inhibition, some patients, even those with highly immunogenic tumors, such as melanoma, do not achieve objective response (1).

An increased association of B-cell chronic lymphocytic leukemia (B-CLL) and melanoma, possibly related to an underlying immunologic defect, has been previously reported (5). We still have limited data on the management of advanced stages of cancer duplicities.

http://ift.tt/2vktVXm

Cutaneous disseminated sporotrichosis: Clinical experience of 24 cases

Abstract

Sporotrichosis is a subcutaneous mycosis, caused by complex Sporothrix schenckii, It is the most common implantation mycoses in worldwide. It is a polymorphic disease, cutaneous-lymphatic is the most frequent (75-90%).^1-3 We report our 25 years' experience (1990-2015) in cutaneous disseminated sporotrichosis (CDS). We conducted, an open, retrospective and observational study.

http://ift.tt/2vkjCT1

Melanoma and chronic exposure to contraceptives containing micro doses of ethinyl estradiol in young women: a retrospective study from the Research on Adverse Drug Events and Reports (RADAR) project comprising a large Midwestern U.S. patient population

Abstract

An association between the use of contraceptives containing exogenous estrogen compounds and subsequent diagnosis for malignant melanoma (MM) has been suspected for decades. This is, in part, due to the finding that estrogen stimulates melanogenesis¹ and the observation that the incidence of MM is greater in women vs. men before the age of 50, but lower than men after the age of 50², corresponding with the average age of menopause when estrogen levels dramatically decrease.

Prior studies assessing the relationship between the incidence of MM and exposure to exogenous estrogen provide conflicting results^3-6.

http://ift.tt/2v1hKDD

Trichothiodystrophy, complementation group A complicated with squamous cell carcinoma

Abstract

There are three related, clinically defined disorders of DNA repair: xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS).¹ Photosensitivity, neurological/developmental abnormalities, and skin cancer are important pathological features that can be used to distinguish between these three archetypes.^1,2 TTD is a rare, autosomal recessive disease characterized by brittle, sulfur-deficient hair and multisystem abnormalities.³

http://ift.tt/2vk7wJD

Unusually high prevalence of classical Kaposi's sarcoma in Druze Muslims of Northern Israel

Abstract

Kaposi's sarcoma (KS) is a systemic disease that can present with cutaneous lesions with or without internal involvement. It is the most common vascular neoplasm. It can involve any skin surface, including the genitalia. ^1,2 KS limited to the external genitalia is rare in HIV sero-negative individuals. Kaposi sarcoma became known because of the correlation with AIDS-defining illnesses in the 1980s.³

http://ift.tt/2v0T66a

The effect of botulinum neurotoxin A in patients with plaque psoriasis – an exploratory trial

Abstract

A few case stories have described patients with psoriasis who suffered from nerve injury which resulted in clearance of psoriasis (1, 2). Recently three reports have addressed a positive effect of botulinum neurotoxin A (BoNT-A) injections in patients with psoriasis (3-5). BoNT-A inhibits neuropeptide releasement and inflammatory cytokines(6), thus the hypothesis was that blocking neuromodulator could lower neurogenic inflammation resulting in improvement of psoriasis.

http://ift.tt/2vkdDxS

The clinical impact of bedside fiberoptic laryngoscopic recording on a tertiary consult service

Objectives/Hypothesis

Fiberoptic laryngoscopy is dependent on accurate descriptions of examination findings. Traditional recording methods can be impractical for inpatient consults. Therefore, we aim to determine the utility of a smartphone-coupled portable recording system with flexible laryngoscopy for transmitting information between resident and attending physicians in a real-time setting.

Study Design

Pilot prospective study in a tertiary academic hospital.

Methods

This is a prospective study of inpatient consultations in a tertiary referral hospital over a 3-month period from April 2015 to June 2015. Flexible laryngoscopy was performed by a resident physician, and mobile recordings were relayed to an attending physician. Concordance of laryngoscopy interpretations between resident and attending physicians as well as changes in management were documented.

Results

Seventy-nine fiberoptic examinations were recorded and compared. Each consult was categorized as follows: airway evaluation (AE) (43%, 34/79), voice evaluation (VE) (3.7%, 3/79), dysphagia (D) (24%, 19/79), and aerodigestive tract mass/pathology (ADM) (29.1%, 23/79). Nine examinations showed discordance between resident and attending interpretations. Inter-rater agreement was good, with a kappa value of 0.747 (95% confidence interval: 0.643-0.851). The frequency of discordant exams within each group was as follows: AE (15%, 5/34), VE (33%, 1/3), D (11%, 2/19), and ADM (4.3%, 1/23). In five patients, changes in laryngoscopy interpretation changed clinical management. Seven nondiscordant exams had a change in management after attending review. Of the 79 exams, only one required repeat flexible laryngoscopy by the attending physician.

Conclusions

Portable recording of flexible laryngoscopy is an effective tool for timely management of inpatient consultations.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2x7Ekrr

Semicircular canal dehiscence among idiopathic intracranial hypertension patients

Objectives/Hypothesis

The cause of superior semicircular canal dehiscence (SSCD) is unknown. Because of a demonstrated association with tegmental defects and obesity, some have suggested idiopathic intracranial hypertension (IIH) could contribute by eroding the bone over the canal and resulting in SSCD. However, an association between IIH and SSCD has not previously been evaluated. Our objective was to evaluate an association between IIH and SSCD.

Study Design

Retrospective cohort.

Methods

A retrospective study was performed of opening pressures for consecutive patients presenting at a lumbar puncture clinic between August 2012 and October 2015. Imaging for patients who also had thin-sectioned computed tomography (CT) imaging was reviewed for the presence of radiographic SSCD. Association between IIH and SSCD was evaluated using the Student t test and multivariate logistic regression.

Results

One hundred twenty-one patients had both a lumbar puncture performed and thin-sectioned CT imaging available, of which 24 patients (19.8%) met the criteria for IIH with an opening pressure >25 cm H₂O. The remaining 97 patients (80.2%) did not have elevated opening pressures and served as the control cohort. None of the 24 patients with IIH had radiographic SSCD, whereas eight of the 97 patients (8.2%) without IIH had radiographic SSCD. The average opening pressure in patients without radiographic SSCD was 20.2 cm H₂O compared to 19.3 cm H₂O in patients with radiographic SSCD (P = .521). In multivariate logistic regression controlling for age, body mass index, gender, and comorbidities (hypertension, diabetes, hyperlipidemia), opening pressure was not a significant predictor of radiographic SSCD.

Conclusions

The results of this retrospective pilot study do not suggest an association between IIH and SSCD.

Level of Evidence

3b Laryngoscope, 2017

http://ift.tt/2vUc2lX

In response to “in reference to is esophagoscopy necessary during panendoscopy?”

http://ift.tt/2x7NT9O

Gastrostomy in the era of minimally invasive head and neck cancer surgery

Objective

Minimally invasive transoral robotic surgery (TORS) is less likely to necessitate gastrostomy tube (GT) following resection of head and neck lesions versus conventional open procedures. However, the incidence of and indications for GT after TORS have not been reported in detail. This study defines the incidence of intra- and postoperative gastrostomy following robotic resection of advanced head and neck disease. It seeks to clarify the relevance of GT after TORS.

Study Design

Adult patients undergoing TORS and neck dissection from 2008 to 2014 were identified in the New York Statewide Planning and Research Cooperative System all-payer administrative database.

Methods

Demographic data and timing of GT in relation to surgery were recorded. Emergency department (ED) visits and inpatient readmissions were compared with multivariable logistic analysis.

Results

Of the 441 included patients, immediate, delayed, and total GT incidence within the first postoperative year was 9.5%, 11.6%, and 21.1%, respectively. Gastrostomy tube complications resulted in 4.5% of 30-day ED visits, 3.3% of 30-day readmissions, and 3.5% of 90-day readmissions. Thirty-nine percent of 90-day readmissions were linked to poor postoperative oral intake. Delayed GT status was associated with an increase in 30-day ED visits, and 30- or 90-day readmissions attributable to poor oral intake (P = 0.10, P < 0.0001, 0.002, respectively).

Conclusion

Even in the era of minimally invasive TORS, impaired oral intake is a significant postoperative burden to head and neck cancer patients with advanced disease. Attention to patient risk factors combined with a complicated hospital course may identify patients benefiting from early GT.

Level of Evidence

2c. Laryngoscope, 2017

http://ift.tt/2vTXHpj

A case-control evaluation of fungiform papillae density in burning mouth syndrome

Hypothesis

It has been hypothesized that high fungiform papillae density may be a risk factor for developing the taste and pain alterations characteristic of burning mouth syndrome.

Objective

Evaluate whether fungiform papillae density, taste sensitivity, and mechanical pain sensitivity differ between burning mouth syndrome cases and controls.

Study Design

This case-control study compared cases diagnosed with primary burning mouth syndrome with pain-free controls.

Methods

Participants (17 female cases and 23 female controls) rated the intensity of sucrose, sodium chloride, citric acid, and quinine applied separately to each side of the anterior tongue and sampled whole mouth. Mechanical pain sensitivity was assessed separately for each side of the tongue using weighted pins. Digital photographs of participants' tongues were used to count fungiform papillae.

Results

Burning mouth syndrome cases had increased whole mouth taste intensity. Cases also had increased sensitivity to quinine on the anterior tongue, as well as increased mechanical pain sensitivity on the anterior tongue. Fungiform papillae density did not differ significantly between cases and controls. Fungiform papillae density on the left and right sides of the tongue were correlated in controls; however, there was no left/right side correlation in cases.

Conclusion

Cases had increased pain and taste perception on the anterior tongue. The lack of correlation between left and right fungiform papillae density in cases may be an indication of asymmetrical lingual innervation in these patients.

Level of Evidence

3b. Laryngoscope, 2017

http://ift.tt/2x7EkaV

Persistent respiratory effort after adenotonsillectomy in children with sleep-disordered breathing

Objectives

Adenotonsillectomy (AT) markedly improves but does not necessarily normalize polysomnographic findings in children with adenotonsillar hypertrophy and related sleep-disordered breathing (SDB). Adenotonsillectomy efficacy should be evaluated by follow-up polysomnography (PSG), but this method may underestimate persistent respiratory effort (RE). Mandibular movement (MMas) monitoring is an innovative measurement that readily identifies RE during upper airway obstruction. We hypothesized that MMas indices would decrease in parallel of PSG indices and that children with persistent RE more reliably could be identified with MMas.

Methods

Twenty-five children (3–12 years of age) with SDB were enrolled in this individual prospective-cohort study. Polysomnography was supplemented with a midsagittal movement magnetic sensor that measured MMas during each respiratory cycle before and > 3 months after AT.

Results

Adenotonsillectomy significantly improved PSG indices, except for RE-related arousals (RERA). Mandibular movement index changes after AT significantly were correlated with corresponding decreases in sleep apnea–hypopnea index (AHI) and O₂ desaturation index (ODI) (Spearman's rho = 0.978 and 0.922, respectively), whereas changes in MMas duration significantly were associated with both RERA duration (rho = 0.475, P = 0.017) and index (rho = 0.564, P = 0.003). Conditional multivariate analysis showed that both AHI and RERA significantly contributed to the variance of MMas index after AT (P = 0.0003 and 0.0005, respectively), whereas MMas duration consistently was related to the duration of RERA regardless of AT.

Conclusion

Adenotonsillectomy significantly reduced AHI. However, persistent RERA were apparent in a significant proportion of children, and this was reflected by the remaining abnormal MMas pattern. Follow-up of children after AT can be recommended and readily achieved by monitoring MMas to identify persistent RE.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2x7K5FD

What is the role of imaging in the evaluation of the patient presenting with unilateral facial paralysis?

http://ift.tt/2vTrtdQ

Is acupuncture an effective complementary tool within otolaryngological perioperative care?

http://ift.tt/2x7JILn

Effect of postoperative radiotherapy in pT1pN1cM0 and pT2p/cN0cM0 oropharyngeal squamous cell carcinoma

Objectives/Hypothesis

Consulting of patients with oropharyngeal carcinoma, classified as pT1pN1cM0 and pT2p/cN0cM0, about postoperative radiotherapy is a precarious task as data are lacking. The aim of this study was to evaluate the effects of postoperative radiotherapy for patients with intermediate-stage oropharyngeal carcinoma.

Study Design

Multicentric retrospective study.

Methods

This analysis was conducted at seven Austrian institutions and included data of patients treated between 2000 and 2012. A total of 81 patients with oropharyngeal squamous cell carcinoma were included, of whom 33 patients received postoperative radiotherapy. p16 status determined by immunohistochemistry was available in 68 patients.

Results

Median follow-up was 47.9 months. Postoperative radiotherapy showed no benefits in regard to overall survival (P = .701). In contrast, disease-free survival was significantly shortened in all patients without postoperative radiotherapy (P = .001). When dividing the cohort in dependence of p16, p16-positive patients did not benefit from postoperative radiotherapy regarding overall and disease-free survival (P = .934 and P = .102), whereas p16-negative patients showed improved disease-free survival after postoperative radiotherapy (P = .007). Multivariate analysis showed that outcome of postoperative radiotherapy is dependent on p16 status.

Conclusions

In terms of disease-free survival, patients with p16-negative tumors may benefit from postoperative radiotherapy, whereas survival of p16-positive patients is good regardless of additional treatment.

Level of Evidence

4 Laryngoscope, 2017

http://ift.tt/2x7WklA

Expiratory muscle strength training for radiation-associated aspiration after head and neck cancer: A case series

Objective/Hypothesis

Expiratory muscle strength training (EMST) is a simple, inexpensive, device-driven exercise therapy. Therapeutic potential of EMST was examined among head and neck cancer survivors with chronic radiation-associated aspiration.

Study Design

Retrospective case series.

Methods

Maximum expiratory pressures (MEPs) were examined among n = 64 radiation-associated aspirators (per penetration–aspiration scale score ≥ 6 on modified barium swallow). Pre–post EMST outcomes were examined in a nested subgroup of patients (n = 26) who enrolled in 8 weeks of EMST (25 repetitions, 5 days/week, 75% load). Nonparametric analyses examined effects of EMST on the primary endpoint MEPs. Secondary measures included swallowing safety (Dynamic Imaging Grade of Swallowing Toxicity [DIGEST]), perceived dysphagia (M.D. Anderson Dysphagia Inventory [MDADI]), and diet (performance status scale for head and neck cancer patients [PSSHN]).

Results

Compared to sex-matched published normative data, MEPs were reduced in 91% (58 of 64) of aspirators (mean ± standard deviation: 89 ± 37). Twenty-six patients enrolled in EMST and three patients withdrew. MEPs improved on average 57% (87 ± 29 to 137 ± 44 cm H₂O, P < 0.001) among 23 who completed EMST. Swallowing safety (per DIGEST) improved significantly (P = 0.03). Composite MDADI scores improved post-EMST (pre-EMST: 59.9 ± 17.1, post-EMST: 62.7 ± 13.9, P = 0.13). PSSHN diet scores did not significantly change.

Conclusion

MEPs were reduced in chronic radiation-associated aspirators relative to normative data, suggesting that expiratory strengthening could be a novel therapeutic target to improve airway protection in this population. Similar to findings in neurogenic populations, these data also suggest improved expiratory pressure-generating capabilities after EMST and translation to functional improvements in swallowing safety in chronic radiation-associated aspirators.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2vTsTVO

The clinical impact of bedside fiberoptic laryngoscopic recording on a tertiary consult service

Objectives/Hypothesis

Study Design

Pilot prospective study in a tertiary academic hospital.

Methods

Results

Conclusions

Portable recording of flexible laryngoscopy is an effective tool for timely management of inpatient consultations.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2x7Ekrr

In response to “in reference to is esophagoscopy necessary during panendoscopy?”

http://ift.tt/2x7NT9O

Sonographic differentiation between lymphatic and metastatic diseases in cervical lymphadenopathy

Objectives/Hypothesis

The spectrum of differential diagnosis in cervical lymphadenopathy is extremely broad. In lymphoma and inflammatory diseases, surgical approaches are restricted to diagnostic lymph extirpation, whereas metastatic outgrowth into regional lymph nodes usually requires neck dissection. Lymph node surgery has to manage the balancing act between sufficient radicality and preservation of functional structures. The current study, therefore, aimed to identify parameters to differentiate between lymph nodes of lymphatic and metastatic origin.

Study Design

Single-center, retrospective cohort study.

Methods

Clinical and sonographic parameters from all patients who underwent diagnostic cervical lymphadenectomy from 2010 to 2015 (N = 262) were included in this retrospective analysis. Parameters with significant differences between the two subgroups were utilized to create a clinical algorithm to distinguish between cervical lymphadenopathy of lymphatic and metastatic genesis.

Results

Statistically significant differences between the two subgroups could be shown for clinical (gender, age, nicotine/alcohol abuse, B symptoms, history of cutaneous melanoma, or lymphoma) and ultrasonographic parameters (string-of-beads confirmation, bilaterality, homogenous echostructure, localization in level I, long-to-short axis ratio, and hilar vascularity). The proposed algorithm yielded a sensitivity of 92.4% for metastatic disease.

Conclusions

The implemented algorithm based on ultrasonographic and clinical criteria contributes to one-step surgical approaches that guarantee a sufficient radicality with a minimum of functional loss.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2vTU3Md

Intraosseous mucoepidermoid carcinoma: Outcome review

Objective

Identify the effect of patient characteristics, disease traits, and treatment modality on patient outcomes in the rare disease process of intraosseous mucoepidermoid carcinoma.

Study Design

Retrospective review of institutional case records and literature.

Methods

This study includes one case report, a literature review of the MEDLINE database from 1950 through June 2017 using keywords "intraosseous" and "mucoepidermoid," and a query of the University of California, Los Angeles, Department of Pathology database for all documented cases of intraosseous mucoepidermoid carcinoma of the head and neck.

Results

Indicators of poorer prognosis were male gender (P = 0.0071) and higher histological grade (P = 0.0095). Lesion site, size, association with odontogenic cyst, and treatment type did not have a statistically significant correlation with patient outcomes. There also was no statistically significant correlation observed between treatment modality and recurrent or progressive disease when stratified by histological grade of the cancer.

Conclusion

This study identified male gender and high histological tumor grade as poor prognostic indicators; however, it did not reveal a statistically significant relationship between treatment modality and patient outcomes. Data regarding patient outcomes following treatment was limited due to loss to follow-up, suggesting that further investigation is required. Based on this review, decisions regarding treatment should be clinically guided and individually tailored to the patient's baseline health, disease severity, and the patient's treatment goals. A multi-disciplinary conference, as was utilized in the presented case report, may be the best approach to treatment planning for these patients at this time.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2x82Cl1

Gastrostomy in the era of minimally invasive head and neck cancer surgery

Objective

Study Design

Adult patients undergoing TORS and neck dissection from 2008 to 2014 were identified in the New York Statewide Planning and Research Cooperative System all-payer administrative database.

Methods

Demographic data and timing of GT in relation to surgery were recorded. Emergency department (ED) visits and inpatient readmissions were compared with multivariable logistic analysis.

Results

Conclusion

Level of Evidence

2c. Laryngoscope, 2017

http://ift.tt/2vTXHpj

The effect of inferior turbinate surgery on ear symptoms

Objective

The aim of this placebo-controlled study was to evaluate the effect of various inferior turbinate surgery techniques on Eustachian tube dysfunction-related symptoms.

Study Design

Outcomes were evaluated using the Eustachian Tube Dysfunction Questionnaire (ETDQ-7) and tympanometry results.

Methods

A total of 72 consecutively blinded and randomized adult patients with enlarged inferior turbinates due to persistent year-round rhinitis underwent either a radiofrequency ablation, diode laser, microdebrider-assisted inferior turbinoplasty, or sham surgery procedure. Assessments were conducted prior to surgery and 3 months subsequent to the surgery.

Results

In the evaluation of all patients, radiofrequency ablation, microdebrider-assisted inferior turbinoplasty, and sham surgery procedures decreased the ETDQ-7 total score significantly. In a three-way analysis of covariance, there were no significant differences in the results between sham surgery and any of the active treatment procedures. Allergic sensitization, sex, and age also had no effect on the results. There were no significant changes in the pre- and postoperative amounts of abnormal tympanometry curves or in the pre- and postoperative tympanometric peak pressure values in the actively treated patients or in the sham surgery group.

Conclusion

The improvement of Eustachian tube dysfunction-related symptoms due to surgery of the anterior half of the inferior turbinate was found to be equal to placebo. The findings of this study do not support the use of reduction of the anterior half of the inferior turbinate as a sole procedure intended to treat the ear symptoms assessed by the ETDQ-7 questionnaire.

Level of Evidence

1b. Laryngoscope, 2017

http://ift.tt/2vU7Bav

Persistent respiratory effort after adenotonsillectomy in children with sleep-disordered breathing

Objectives

Methods

Results

Conclusion

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2x7K5FD

What is the role of imaging in the evaluation of the patient presenting with unilateral facial paralysis?

http://ift.tt/2vTrtdQ

Effect of postoperative radiotherapy in pT1pN1cM0 and pT2p/cN0cM0 oropharyngeal squamous cell carcinoma

Objectives/Hypothesis

Study Design

Multicentric retrospective study.

Methods

Results

Conclusions

In terms of disease-free survival, patients with p16-negative tumors may benefit from postoperative radiotherapy, whereas survival of p16-positive patients is good regardless of additional treatment.

Level of Evidence

4 Laryngoscope, 2017

http://ift.tt/2x7WklA

Expiratory muscle strength training for radiation-associated aspiration after head and neck cancer: A case series

Objective/Hypothesis

Study Design

Retrospective case series.

Methods

Results

Conclusion

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2vTsTVO

Volumetric analysis of olfactory neuroblastoma skull base laterality and implications on neck disease

Objective

To determine if the laterality of primary tumors in patients with olfactory neuroblastoma (ONB) influenced the pattern and development of neck disease.

Methods

Using a retrospective cohort study design from 1994 to 2015, the primary tumors of patients who either presented with or developed neck disease were volumetrically analyzed using iPlan software (version 3.0.0, BrainLAB, Feldkirchen, Germany) by two independent observers. Agreement of volume-derived sidedness was assessed with a kappa statistic, whereas agreement in volume-derived degree of tumor laterality was evaluated with an intraclass correlation coefficient. A one-sample t test was used to assess the difference in dominant percentage between the two observers.

Results

Sixty-one patients with histological diagnosis and treatment of ONB at our institution were identified. Twenty-four patients exhibited neck involvement, 13 of whom could be volumetrically analyzed. Tumors that were greater than 75% eccentric to one side all exhibited contralateral disease, whereas the majority of unilateral neck disease was associated with relatively midline masses. Within the entire cohort, ipsilateral level 2 lymph nodes displayed the highest involvement (83%, 20 of 24), followed by ipsilateral level 1 (54%, 13 of 24), contralateral level 2 (46%, 11 of 24), contralateral level 1 (21%, 5 of 24), and ipsilateral level 3 (21%, 5 of 24).

Conclusion

Ipsilateral neck involvement frequently was observed; however, the degree of ONB primary site laterality did not appear to have implications on the development of contralateral neck disease. Therefore, when considering elective therapy to the neck, ONB laterality should not be used to justify unilateral neck treatment.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2x85nTo

In response to letter to the editor to Does mutational analysis influence the management of differentiated thyroid cancers? - Molecular markers for thyroid nodules

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A typical presentation of a hepatocellular carcinoma in a middle-aged patient

Description

A 54-year-old man was admitted to our hospital due to experiencing a sudden, severe pain in the right shoulder after mild exercise. He had been losing weight over the previous month and had noticed a lump near his right shoulder. A chest X-ray showed a lytic lesion in the lateral half of his right collarbone (figure 1A) with a cortical break and the presence of a soft-tissue component. A chest CT scan showed the destruction of the bone and a 10x8x7 cm mass associated with the pathological fracture of the collarbone (figure 1B). The diagnostic workup was completed with an abdominal CT scan, which showed a large hepatic tumour, an alpha-fetoprotein blood test level of 1468 ng/mL (normal range <10 ng/mL) and a fine-needle aspiration cytology, which yielded the final diagnosis of disseminated disease of a hepatocellular carcinoma. Cells showed both TTF-1 and hepatocyte antigen positivity, whereas CK7,...

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Inflammation, Stem Cells, and the Aging Hypothalamus

Rejuvenation Research Aug 2017, Vol. 20, No. 4: 346-349.

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Deficient Data Dissemination Does Damage

Rejuvenation Research Aug 2017, Vol. 20, No. 4: 261-262.

http://ift.tt/2vjRkYZ

Exploring Furnas-McGregor paradox: describing normal distribution in central limb stereometric gain in 60° Z-plasty

http://ift.tt/2g0X9Zy

Clinical description of skin lesions in pathology requisition forms completed by plastic surgeons is lacking: a retrospective study of 499 lesions

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Anatomy of superficial inferior epigastric vessels: revival of superficial inferior epigastric (SIEA) flap

Abstract

Background

Development of perforator flaps evolves the perspective of reconstructive surgery to another level due to many of their advantages over the pedicled flaps, particularly lower donor-site morbidity and versatility in flap design. Superficial inferior epigastric artery (SIEA) flap offers this significant advantage over other lower abdominal flaps, as dissection of the rectus abdominis muscle is not required. However, both vascular agenesis and inappropriate vessel size for anastomosis are the major limitations. This study was therefore aimed to investigate these aspects of this flap.

Methods

Twenty cadavers were dissected bilaterally to demonstrate vascular anatomy of these vessels. The SIEA of each cadaver was dissected and traced from the origin (femoral arteries) to their presence in the subcutaneous layer. Originating patterns of these vessels, whether sharing a common trunk with other vessels such as superficial circumflex iliac (SCI) or superficial external pudendal (SEP) arteries, was determined and their diameters measured.

Results

SIEA agenesis rate was found to be 7.5% (3/40). The diameters greater than 1 and 1.5 mm were found in 86% (32/37) and 30% (11/37), respectively. The distance between its origin and point of entering Scarpa's fascia varies from 10.29 to 62.62 mm (mean 37.48 mm). As opposed to the artery, the superficial inferior epigastric vein was found to be present in all dissections with a diameter ranging from 2.12 to 5 mm (mean 3.09 mm) and the distance, as measured in SIEA, ranging from 20.1 to 74.28 mm (mean 41.24 mm). SIEA usually crosses the inguinal ligament within area between mid-inguinal point and 3 cm medially. Correlations were found (1) between SIEA diameter and pedicle length and (2) between bilateral pedicle lengths of both artery and vein.

Conclusions

The high prevalence of both SIEA presence and appropriate diameter for anastomosis, and thus flap success, makes the SIEA perforator flap an appropriate option for reconstructive treatment.

Level of Evidence: not ratable.

http://ift.tt/2ilQcD3

Swiss S1 guideline for the treatment of rosacea

Abstract

Rosacea (in German sometimes called 'Kupferfinne', in French 'Couperose' and in Italian 'Copparosa') is a chronic and frequently relapsing inflammatory skin disease primarily affecting the central areas of the face. Its geographic prevalence varies from 1% to 22%. The differential diagnosis is wide, and the treatment is sometimes difficult and varies by stage of rosacea. For erythematous lesions and telangiectasia, intense pulsed light (IPL) therapy and lasers are popular treatment option. In addition, a vasoconstrictor agent, brimonidine, has recently been developed. For papulopustular rosacea, topical antibiotics, topical and systemic retinoids, as well as systemic antibiotics are used. A topical acaricidal agent, ivermectin, has undergone clinical development and is now on the market. In the later stages, hyperplasia of the sebaceous glands develops, resulting in phymatous growths such as the frequently observed bulbous nose or rhinophyma. Ablative laser treatments have largely replaced classical abrasive tools. Here, we reviewed the current evidence on the treatment of rosacea, provide a guideline (S1 level) and discuss the differential diagnosis of rosacea.

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Potential Implications of NORSTENT (Norwegian Coronary Stent Trial) in Contemporary Practice.

Author: Wiseth, Rune MD, PhD; Bonaa, Kaare Harald MD, PhD

Page: 701-703

http://ift.tt/2wsob2P

Effect of Obesity and Underweight Status on Perioperative Outcomes of Congenital Heart Operations in Children, Adolescents, and Young Adults: An Analysis of Data From the Society of Thoracic Surgeons Database.

Author: O'Byrne, Michael L. MD, MSCE; Kim, Sunghee PhD; Hornik, Christoph P. MD, MPH; Yerokun, Babatunde A. MD; Matsouaka, Roland A. PhD; Jacobs, Jeffrey P. MD; Jacobs, Marshall L. MD; Jonas, Richard A. MD

Page: 704-718

http://ift.tt/2xmRLDe

Cerebral Perfusion and the Risk of Dementia: A Population-Based Study.

Author: Wolters, Frank J. MD; Zonneveld, Hazel I. MD; Hofman, Albert PhD; van der Lugt, Aad PhD; Koudstaal, Peter J. PhD; Vernooij, Meike W. PhD; Ikram, M. Arfan PhD; On Behalf of the Heart-Brain Connection Collaborative Research Group

Page: 719-728

http://ift.tt/2wsDPLC

Inhibition of MicroRNA-146a and Overexpression of Its Target Dihydrolipoyl Succinyltransferase Protect Against Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction.

Author: Heggermont, Ward A. MD, PhD *; Papageorgiou, Anna-Pia MSc, PhD *; Quaegebeur, Annelies MD, PhD; Deckx, Sophie MSc, PhD; Carai, Paolo MSc; Verhesen, Wouter BSc; Eelen, Guy MSc, PhD; Schoors, Sandra MSc, PhD; van Leeuwen, Rick BSc; Alekseev, Sergey MSc, PhD; Elzenaar, Ies MSc, PhD; Vinckier, Stefan MSc, PhD; Pokreisz, Peter MSc, PhD; Walravens, Ann-Sophie MSc; Gijsbers, Rik MSc, PhD; Van Den Haute, Chris MSc, PhD; Nickel, Alexander MSc, PhD; Schroen, Blanche MSc, PhD; van Bilsen, Marc MSc, PhD; Janssens, Stefan MD, PhD; Maack, Christoph MD, PhD; Pinto, Yigal MD, PhD; Carmeliet, Peter MD, PhD; Heymans, Stephane MD, PhD

Page: 747-761

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MicroRNA-146a as a Regulator of Cardiac Energy Metabolism.

Author: Demkes, Charlotte J. MSc; van Rooij, Eva PhD

Page: 762-764

http://ift.tt/2wsWCX3

Leveraging Behavioral Economics to Improve Heart Failure Care and Outcomes.

Author: Chang, Leslie L. BS; DeVore, Adam D. MD, MHS; Granger, Bradi B. PhD, MSN, RN; Eapen, Zubin J. MD, MHS; Ariely, Dan PhD; Hernandez, Adrian F. MD, MHS

Page: 765-772

http://ift.tt/2xmpcWC

An Irregular Wide Complex Tachycardia.

Author: Watts, Thomas E. MD; McElderry, H. Thomas MD; Kay, G. Neal MD

Page: 773-775

http://ift.tt/2wstO0V

Long Noncoding RNA Facilitated Gene Therapy Reduces Atherosclerosis in a Murine Model of Familial Hypercholesterolemia.

Author: Tontonoz, Peter MD, PhD; Wu, Xiaohui BS; Jones, Marius PhD; Zhang, Zhengyi PhD; Salisbury, David MS; Sallam, Tamer MD, PhD

Page: 776-778

http://ift.tt/2xn2DRz

Letter by the Society of NeuroInterventional Surgery, the Cerebrovascular Section of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons, and the Society of Vascular and Interventional Neurology Regarding Article, "Public Health Urgency Created by the Success of Mechanical Thrombectomy Studies in Stroke".

Author: Society of NeuroInterventional Surgery; American Association of Neurological Surgeons; Congress of Neurological Surgeons; Society of Vascular and Interventional Neurology

Page: 779-780

http://ift.tt/2wstLSN

Response by Hopkins and Holmes to Letter Regarding Article, "Public Health Urgency Created by the Success of Mechanical Thrombectomy Studies in Stroke".

Author: Hopkins, L. Nelson MD; Holmes, David R. Jr MD

Page: 781-782

http://ift.tt/2xn2AoR

Letter by Jiang and Qiao Regarding Article, "Chest Pain and T-Wave Inversions in a 56-Year-Old Man".

Author: Jiang, Xiao-Wei MD; Qiao, Shu-Bin MD, PhD

Page: 783

http://ift.tt/2wsoudS

Response by Verma and Knight to Letter Regarding Article, "Chest Pain and T-Wave Inversions in a 56-Year-Old Man".

Author: Verma, Nishant MD, MPH; Knight, Bradley P. MD

Page: 784

http://ift.tt/2xn2HAN

Therapeutic Strategies of Clustered Regularly Interspaced Palindromic Repeats-Cas Systems for Different Viral Infections

Viral Immunology , Vol. 0, No. 0.

http://ift.tt/2ilhRnB

HOXA5 plays tissue-specific roles in the developing respiratory system [RESEARCH ARTICLE]

Kim Landry-Truchon, Nicolas Houde, Olivier Boucherat, France-Helene Joncas, Jeremy S. Dasen, Polyxeni Philippidou, Jennifer H. Mansfield, and Lucie Jeannotte

Hoxa5 is essential for development of several organs and tissues. In the respiratory system, loss of Hoxa5 function causes neonatal death due to respiratory distress. Expression of HOXA5 protein in mesenchyme of the respiratory tract and in phrenic motor neurons of the central nervous system led us to address the individual contribution of these Hoxa5 expression domains with a conditional gene targeting approach. Hoxa5 does not play a cell-autonomous role in lung epithelium, consistent with lack of HOXA5 expression in this cell layer. In contrast, ablation of Hoxa5 in mesenchyme perturbed trachea development, lung epithelial cell differentiation and lung growth. Further, deletion of Hoxa5 in motor neurons resulted in abnormal diaphragm innervation and musculature, and lung hypoplasia. It also reproduced the neonatal lethality observed in null mutants, indicating that the defective diaphragm is the main cause of impaired survival at birth. Thus, Hoxa5 possesses tissue-specific functions that differentially contribute to the morphogenesis of the respiratory tract.

http://ift.tt/2vYCVn5

Cytoskeletal variations in an asymmetric cell division support diversity in nematode sperm size and sex ratios [RESEARCH ARTICLE]

Ethan S. Winter, Anna Schwarz, Gunar Fabig, Jessica L. Feldman, Andre Pires-daSilva, Thomas Müller-Reichert, Penny L. Sadler, and Diane C. Shakes

Asymmetric partitioning is an essential component of many developmental processes. As spermatogenesis concludes, sperm are streamlined by discarding unnecessary cellular into cellular wastebags called residual bodies (RBs). During nematode spermatogenesis, this asymmetric partitioning event occurs shortly after anaphase II, and both microtubules and actin partition into a central RB. Here we use fluorescence and transmission electron microscopy to elucidate and compare the intermediate steps of RB formation in C. elegans, Rhabditis sp. SB347 (recently named Auanema rhodensis) and related nematodes. In all cases, intact microtubules reorganize and move from centrosomal to non-centrosomal sites at the RB-sperm boundary while actin reorganizes through cortical ring expansion and clearance from the poles. However, in species with tiny spermatocytes, these cytoskeletal changes are restricted to one pole. Consequently, partitioning yields one functional sperm with the X-bearing chromosome complement and an RB with the other chromosome set. Unipolar partitioning may not require an unpaired X, since it also occurs in XX spermatocytes. Instead, constraints related to spermatocyte downsizing may have contributed to the evolution of a sperm cell equivalent to female polar bodies.

http://ift.tt/2wiV955

Maternal expression of the JMJD2A/KDM4A histone demethylase is critical for pre-implantation development [RESEARCH ARTICLE]

Aditya Sankar, Susanne Marije Kooistra, Javier Martin Gonzalez, Claes Ohlsson, Matti Poutanen, and Kristian Helin

Regulation of chromatin composition through post-translational modifications of histones contributes to transcriptional regulation and is essential for many cellular processes, including differentiation and development. JMJD2A/KDM4A is a lysine demethylase with specificity towards di- and tri-methylated lysine 9 and lysine 36 of histone H3 (H3K9me2/me3 and H3K36me2/me3). Here, we report that Kdm4a as a maternal factor plays a key role in embryo survival and is vital for female fertility. Kdm4a^–/- female mice ovulate normally with comparable fertilization but poor implantation rates, and cannot support healthy transplanted embryos to term. This is due to a role for Kdm4a in uterine function, where its loss causes reduced expression of key genes involved in ion transport, nutrient supply and cytokine signalling, that impact embryo survival. In addition, a significant proportion of Kdm4a deficient oocytes displays a poor intrinsic ability to develop into blastocysts. These embryos cannot compete with healthy embryos for implantation in vivo, highlighting Kdm4a as a maternal effect gene. Thus, our study dissects an important dual role for maternal Kdm4a in determining faithful early embryonic development and the implantation process.

http://ift.tt/2vYP8I8

A fixation method to preserve cultured cell cytonemes facilitates mechanistic interrogation of morphogen transport [TECHNIQUES AND RESOURCES ARTICLE]

William J. Bodeen, Suresh Marada, Ashley Truong, and Stacey K. Ogden

During development, extracellular cues guiding cell fate determination are provided by morphogens. One mechanism by which morphogens are proposed to traverse extracellular space is by traveling along specialized filopodia called cytonemes. These cellular highways extend between signal producing and receiving cells to enable direct morphogen delivery. Although genetic studies support cytoneme involvement in morphogen transport, mechanistic insight into how they are regulated is limited due to technical challenges associated with performing cell biological analysis of the delicate filopodial structures. Herein, we introduce a fixation method whereby cultured cell cytonemes can be preserved for imaging studies, allowing for interrogation of cytoneme regulation using standard cell biological techniques. Using this method, we examined Hedgehog-containing cytonemes and identified a role for the Hedgehog deployment protein Dispatched in cytoneme stabilization. We demonstrate Hedgehog and Dispatched colocalize in cytonemes, and cholesterol-modified Hedgehog acts through Dispatched to increase cytoneme occurrence. Live imaging suggests this occurs through Dispatched-mediated slowing of cytoneme retraction rates. Dispatched-induced cytoneme modulation was recapitulated in wing imaginal discs of transgenic Drosophila, supporting that cultured cell cytoneme analysis is predictive of in vivo functionality.

http://ift.tt/2whMCja

Spermatogonial kinetics in the human [TECHNIQUES AND RESOURCES REPORT]

Sara Di Persio, Rossana Saracino, Stefania Fera, Barbara Muciaccia, Valentina Esposito, Carla Boitani, Bartolomeo P. Berloco, Francesco Nudo, Gustavo Spadetta, Mario Stefanini, Dirk G. de Rooij, and Elena Vicini

The human spermatogonial compartment is essential for daily production of millions of sperm. Despite this crucial role, the molecular signature, kinetic behavior and regulation of human spermatogonia are poorly understood. Using human testis biopsies with normal spermatogenesis and studying marker protein expression, for the first time we identified different subpopulations of spermatogonia. MAGE-A4 marks all spermatogonia, KIT marks all B spermatogonia and UCLH1 all Apale-dark (Ap-d) spermatogonia. We suggest that at the start of the spermatogenic lineage there are Ap-d spermatogonia that are GFRA1^High likely including the spermatogonial stem cells. Then UTF1 becomes expressed, cells become quiescent and GFRA1 expression decreases. Finally, GFRA1 expression is lost and subsequently cells differentiate into B spermatogonia, losing UTF1 and acquiring KIT expression. Strikingly, most of human Ap-d spermatogonia are out of cell cycle and even differentiating type B spermatogonial proliferation is restricted. A novel scheme for human spermatogonial development is proposed that will facilitate further research in this field, the understanding of cases of infertility and the development of methods to increase sperm output.

http://ift.tt/2vYDhdd

Immune mechanisms of respiratory viral infections in asthma

Hugo A Farne | Sebastian L Johnston

http://ift.tt/2xmRmAS

The nonspecific face of adaptive immunity

Eric Muraille | Stanislas Goriely

http://ift.tt/2wsn9DR

Protective immunity against tuberculosis: what does it look like and how do we find it?

Lu Huang | David G Russell

http://ift.tt/2xmQgEW

Different engagement of TLR2 and TLR4 in Porphyromonas gingivalis vs. ligature-induced periodontal bone loss

Abstract This study was conducted to investigate the roles of different Toll-like receptor (TLR) signaling in Porphyromonas gingivalis (P. gingivalis)-induced and ligature-induced experimental periodontal bone resorption in mice. Wild-type (WT), TLR2 knockout (KO), TLR4KO, and TLR2&4 KO mice with C57/BL6 background were divided into three groups: control, P. gingivalis infection, and ligation. Live P. gingivalis or silk ligatures were placed in the sulcus around maxillary second molars over a 2-week period. Images were captured by digital stereomicroscopy, and the bone resorption area was measured with ImageJ software. The protein expression level of gingival RANKL was measured by ELISA. The gingival mRNA levels of RANKL, IL-1β, TNF-α, and IL-10 were detected by RT-qPCR. The results showed that P. gingivalis induced significant periodontal bone resorption in WT mice and TLR2 KO mice but not in TLR4 KO mice or TLR2&4 KO mice. For all four types of mice, ligation induced significant bone loss compared with that in control groups, and this bone loss was significantly higher than that in the P. gingivalis infection group. RANKL protein expression was significantly increased in the ligation group compared with that in the control group for all four types of mice, and in the P. gingivalis infection group of WT, TLR2 KO, and TLR4 KO mice. Expression patterns of RANKL, IL-1β, TNF-α, and IL-10 mRNA were different in the P. gingivalis infection group and the ligation group in different types of mice. In summary, P. gingivalis-induced periodontal bone resorption is TLR4-dependent, whereas ligation-induced periodontal bone resorption is neither TLR2- nor TLR4-dependent.

http://ift.tt/2v8Mizc

Ki-67 protein predicts survival in oral squamous carcinoma cells: an immunohistochemical study

Abstract The aim of this study was to identify the expression of Ki-67 and MCM3 in oral squamous cell carcinoma (OSCC) as well as to address the correlation with patient survival and clinical features. Samples were collected from 51 patients with OSCC who presented for follow-up. Immunohistochemical expression of Ki-67 and MCM3 in all groups was performed. The scoring system was previous published by Tsurutani in 2005. We used Kappa index to evaluate observers agreement degree. The associations between protein expression and clinical variables were examined for statistical significance using the chi-squared test. The overall survival rates were estimated by the Kaplan-Meier method and the relationship between protein expression and survival was compared using the log-rank test (p < 0.05). The overall survival time for a patient with positive immunostaining for Ki-67 is shorter than for a patient with negative immunostaining, (log-rank test, p = 0.00882). Patients with tumor size T3 and T4 showed a statistically significant relationship with Ki-67 immunoexpression (log-rank test, p = 0.0174). The relationship between Ki-67 expression and the relation between age, gender, smoking, tumor site, lymph node metastasis and disease stage was not significant. The examiners agreement degree by Kappa presented p value < 0.05. There was not a significant correlation when we evaluated MCM3 expression regarding clinical characteristics and survival rate. From these results, the present study suggests that positive Ki-67 expression found in OSCC patients may contribute to predict the survival in OSCC samples, as well as the relation between the protein and the tumor size.

http://ift.tt/2v8Qhfm

Risk factors for implant failure: a retrospective study in an educational institution using GEE analyses

Abstract This study aimed to evaluate dental implant outcomes and to identify risk factors associated with implant failure over 12 years via dental records of patients attending an educational institution. Dental records of 202 patients receiving 774 dental implants from 2002 to 2014 were analyzed by adopting a more reliable statistical method to evaluate risk factors with patients as the unit [generalized estimating equation (GEE)]. Information regarding patient age at implantation, sex, use of tobacco, and history of systemic diseases was collected. Information about implant location in the arch region and implant length, diameter, and placement in a grafted area was evaluated after 2 years under load. Systemic and local risk factors for early and late implant failure were studied. A total of 18 patients experienced 25 implant failures, resulting in an overall survival rate of 96.8% (2.84% and 0.38% early and late implant failures, respectively). The patient-based survival rate was 91.8%. GEE univariate and multivariate analyses revealed that a significant risk factor for implant failure was the maxillary implant (p = 0.006 and p = 0.014, respectively). Bone grafting appeared to be a risk factor for implant failure (p = 0.054). According to GEE analyses, maxillary implants had significantly worse outcomes in this population and were considered to be a risk factor for implant failure. Our results suggested that implants placed in a bone augmentation area had a tendency to fail.

http://ift.tt/2wyY8WQ

Large Subcapsular Splenic Hematoma with a Large Pancreatic Pseudocyst Was Successfully Treated with Splenic Arterial Embolization and Ultrasound-Guided Percutaneous Drainage of Pancreatic Pseudocyst

Subcapsular splenic hematoma is a rare complication of pancreatitis. The management for subcapsular splenic hematoma remains controversial. We herein report a case of a large subcapsular splenic hematoma with a large pancreatic pseudocyst, which was successfully treated with splenic arterial embolization and ultrasound- (US-) guided percutaneous drainage of pancreatic pseudocyst, for the first time. A 44-year-old male suffered from recurrent abdominal pain for more than two years. He had previous 3 episodes of pancreatitis. A subcapsular splenic hematoma (16.0 × 16.0 × 7.6 cm) with pancreatic pseudocyst (13.5 × 10.0 × 8.0 cm) was shown on abdominal computed tomography (CT). He underwent splenic arterial embolization to decrease the blood supply of the spleen and then ultrasound-guided percutaneous drainage of the large pancreatic pseudocyst. After 2 weeks, the repeated CT-Abdomen showed the disappearance of pancreatic pseudocyst and multiple areas of infarction on the spleen, while the splenic subcapsular hematoma had also significantly reduced. The patient was discharged after almost a month of his hospital admission with the drainage tube attached, and about 2 weeks later the drainage tube was removed upon CT scan confirmation of decrease in the volume of the subcapsular hematoma. Patient had no abdominal symptoms at the 1.5-year follow-up.

http://ift.tt/2x7bwzv

A newer toolkit to respond to sexual violence on a global scale: World Health Organization

Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(3):495-496

http://ift.tt/2v6Qqjq

Relationship of strategies for emotion cognitive adjustment with psychological well-being and anxiety in mothers with cancer children

Abed Mahdavi, Mahjubeh Pahlevani, Maryam Aghaei, Vian Aminnasab, Hurieh Haji, Simin Gholamrezaei

Annals of Tropical Medicine and Public Health 2017 10(3):702-706

Background and Purpose: The present study was aimed to examine the relationship between strategies of emotion cognitive adjustment and psychological well-being with anxiety in mothers with cancer children. Materials and Methods: The statistical population of the study consisted of 86 individuals, who were selected using convenience sampling method; they responded to psychological well-being and anxiety questionnaires. Results: The research method was descriptive of a correlational type. Data obtained from questionnaires were analyzed through multivariate regression in SPSS software, after being marked. Findings showed that there is a significant relationship between emotion cognitive adjustment strategies and anxiety and psychological well-being in mothers with cancer children. Conclusion: Results showed that emotion cognitive adjustment predicts about 27.1% of anxiety changes and about 26.8% of psychological well-being changes in mothers with cancer children.

http://ift.tt/2v6OneX

Addressing the challenges of diagnostic delay and longer treatment duration for multidrug resistant tuberculosis: World Health Organization

Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(3):497-498

http://ift.tt/2wwzO85

Zika virus disease: Potential risk for the athletes and the international visitors in the Rio Olympic Games, 2016

Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(3):762-764

http://ift.tt/2v6M9fE

Strengthening research and development activities to effectively contain the epidemics of infectious diseases: World health organization

Saurabh R Shrivastava, Prateek S Shrivastava, Ramasamy Jegadeesh

Annals of Tropical Medicine and Public Health 2017 10(3):499-500

http://ift.tt/2wwxT3z

Network creation to support the international collaboration: A short note on Surindra – Niigata University relationship

Atchara Phanurat, Wasana Kaewla, Viroj Wiwanitkit

Annals of Tropical Medicine and Public Health 2017 10(3):738-739

http://ift.tt/2v6DkT5

Safe space: An effective option to ensure normalcy in the lives of refugee women and girls in conflict-affected Syria

Saurabh RamBihariLal Shrivastava, Prateek Saurabh Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(3):501-502

http://ift.tt/2wwN8JA

Involving fathers in achieving gender equality through a television reality show

Saurabh RamBihariLal Shrivastava, Prateek Saurabh Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(3):503-504

http://ift.tt/2xmLgk2

Self-care and self-medication: A commentary

Tanmay Mahapatra

Annals of Tropical Medicine and Public Health 2017 10(3):505-506

http://ift.tt/2wsgLMQ

The challenges of antenna modification in medical practice: The MRI machine

ME Emetere, ES Sanni

Annals of Tropical Medicine and Public Health 2017 10(3):726-730

The challenges of modifying the antenna of imaging systems, e.g., MRI, are enormous. The electromagnetic principles for the non-ionizing radiation technique to view internal structures in the human body depend on many factors such as the ratings of the magnetic field, computer, digitizer, RF source, and electrical field. An incorporation of the Bloch NMR flow equation alongside the electromagnetic principles is quite complex. However, the modality was successfully developed to predict the radiofrequency appropriate for the successful imaging session. It was observed that the patient is currently under severe danger of excess exposure to electromagnetic fields.

http://ift.tt/2xmuCkg

INSPIRE: A comprehensive package to reduce violence against children and provide a safe and nurturing environment

Saurabh RamBihariLal Shrivastava, Prateek Saurabh Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(3):507-508

http://ift.tt/2wssHym

Taking major strides in dengue vaccine research: World health organization

Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(3):743-744

http://ift.tt/2xmyamQ

Challenges in HIV care: Accelerating the pace of HIV-related services to accomplish the set global targets

Saurabh RamBihariLal Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(3):509-510

http://ift.tt/2ws9Mns

Liver problem in zika virus infection: Possibility?

Beuy Joob, Viroj Wiwanitkit

Annals of Tropical Medicine and Public Health 2017 10(3):751-752

http://ift.tt/2xmMhsl

Census: A systematic and comprehensive tool to address the needs of the disadvantaged population groups

Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(3):511-512

http://ift.tt/2ws84lM

What can we learn from Google Map base GIS system on opisthorchiasis in northeastern Thailand?

Sora Yasri, Viroj Wiwanitkit

Annals of Tropical Medicine and Public Health 2017 10(3):758-759

http://ift.tt/2xmpRHw

Legal protection for women in Yemen: A sorry state

Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(3):513-514

http://ift.tt/2wsm5Qj

Concentration, sources and risk assessment of PAHs in bottom sediments

Abstract

The aims of the study were to investigate the concentration, sources and ecological risk of PAHs (polycyclic aromatic hydrocarbons) in bottom sediments collected from nine reservoirs located in south-eastern Poland. The concentration of ∑PAHs in sediments ranged from 150 to 33,900 μg kg⁻¹. The total PAH concentration in the bottom sediments was arranged in the following order: Rybnik > Rzeszów > Brzóza Królewska > Brzóza Stadnicka > Besko > Chechło > Ożanna > Głuchów > Narożniki. BAP was the major compound in sediments from the Besko, Brzóza Stadnicka and Rzeszów reservoirs; FLT in the sediments from the Rybnik, Narożniki, Ożanna and Brzóza Królewska reservoirs; and FLN from the Głuchów and Chechło reservoirs. The major inputs of PAHs were of pyrolytic origin. However, petrogenic sources of PAHs occurred especially in the Chechło and Głuchów reservoirs. The ecological risk assessment indicated that non-adverse effects on the benthic fauna may occur for sediments from the Głuchów, Narozniki and Ożanna reservoirs, while slightly adverse effects were found for sediments from the Brzóza Królewska, Besko, Brzóza Stadnicka and Chechło reservoirs. The other sediments showed moderate (Rzeszów reservoirs) and strong effect (Rybnik reservoir) on biological communities. Individual PAHs such as NAP, PHE, FLT, PYR, BAA, CHR and BAP in sediments from the Rybnik reservoir and BAP in sediments from the Rzeszów reservoirs indicated a higher possibility of occurrence of an adverse ecological effect. PCA analysis found slight difference between the reservoirs in the profile of variable PAHs. Only the sediments from the Rybnik and Chechło reservoirs differ considerably from this grouping.

http://ift.tt/2vY3GYI

Recommended standards for conducting and reporting ethnopharmacological field studies

Publication date: Available online 20 August 2017
Source:Journal of Ethnopharmacology
Author(s): Caroline S. Weckerle, Hugo J. de Boer, Rajindra K. Puri, Tinde van Andel, Rainer W. Bussmann, Marco Leonti
Ethnopharmacological relevanceWhat are the minimum methodological and conceptual requirements for an ethnopharmacological field study? How can the results of ethnopharmacological field studies be reported so that researchers with different backgrounds can draw on the results and develop new research questions and projects? And how should these field data be presented to get accepted in a scientific journal such as the Journal of Ethnopharmacology? The objective of this commentary is to create a reference that covers the basic standards necessary during planning, conducting and reporting of field research.Materials and methodsWe focus on conducting and reporting ethnopharmacological field studies on medicinal plants or materia medica and associated knowledge of a specific people or region.The article highlights the most frequent problems and pitfalls, and draws on published literature, fieldwork experience, and extensive insights from peer-review of field studies.ResultsResearch needs to be ethical and legal, and follow local and national regulations. Primary ethnopharmacological field data need to be collected and presented in a transparent and comprehensible way. In short this includes: 1) Relevant and concise research questions, 2) Thorough literature study encompassing all available information on the study site from different disciplines, 3) Appropriate methods to answer the research questions, 4) Proper plant use documentation, unambiguously linked to voucher specimens, and 5) Qualitative and quantitative analyses of the collected data, the latter relying on use-reports as basic units.ConclusionAlthough not exhaustive, we provide an overview of the necessary main issues to consider for field research and data reporting including a list of minimal standards and recommendations for best practices. For methodological details and how to correctly apply specific methods, we refer to further reading of suggested textbooks and methods manuals.

Graphical abstract

http://ift.tt/2ws7Paf

Pomegranate peel extract attenuates D-galactose–induced oxidative stress and hearing loss by regulating PNUTS/PP1 activity in the mouse cochlea

Publication date: November 2017
Source:Neurobiology of Aging, Volume 59
Author(s): Shuangyue Liu, Tao Xu, Xidi Wu, Yuhan Lin, Dongyan Bao, Yang Di, Tingting Ma, Yan Dang, Peili Jia, Jianqiao Xian, Aimei Wang, Yongxin Liu
Oxidative stress is considered to be a major contributor to age-related hearing loss (ARHL). Here, we investigated whether pomegranate peel extract (PPE) protected against hearing loss by decreased oxidative stress in the cochlea of D-galactose–induced accelerated aging mice. The aging mice exhibited an increase in hearing threshold shifts and hair cells loss, which were improved in the PPE-treated aging mice. The aging mice also exhibited an increase in 4-hydroxynonenal, the expression of protein phosphatase 1 nuclear targeting subunit (PNUTS), p53 and caspase-3, and a decrease in protein phosphatase 1 (PP1) and MDM2 in the cochlea. PPE treatment reversed the changes in aforementioned molecules. Our results suggested that PPE can protect against ARHL, the underlying mechanisms may involve in the inhibition of oxidative damage of cochlea, possibly by regulating PNUTS/PP1 pathway. The results from the present study provide a new therapeutic strategy to use PPE for prevention of ARHL.

Graphical abstract

http://ift.tt/2whWTf0

Brachytherapy attains abscopal effects when combined with immunostimulatory monoclonal antibodies

Publication date: Available online 21 August 2017
Source:Brachytherapy
Author(s): María E. Rodriguez-Ruiz, Inmaculada Rodriguez, Benigno Barbes, Lina Mayorga, Alfonso Rodriguez Sanchez-Paulete, Mariano Ponz-Sarvise, José Luis Pérez-Gracia, Ignacio Melero
Purpose/ObjectivesPreclinical and clinical evidence indicate that the proimmune effects of radiotherapy can be synergistically augmented with immunostimulatory monoclonal antibodies (mAb) to act both on irradiated tumor lesions and on tumors at distant, nonirradiated sites. We have recently reported that external beam radiotherapy achieves abscopal effects when combined with antagonist anti-PD1 mAbs and agonist anti-CD137 (4-1BB) mAbs. The goal of this work is to study the abscopal effects of radiotherapy instigated by brachytherapy techniques.Methods and MaterialsMice bearing a subcutaneous colorectal carcinoma, MC38 (colorectal cancer), in both flanks were randomly assigned to receive brachytherapy or not (8 Gy × three fractions) to only one of the two grafted tumors, in combination with intraperitoneal immunostimulatory monoclonal antibodies (anti-PD1, anti-CD137, and/or their respective isotype controls). To study the abscopal effects of brachytherapy, we established an experimental set up that permits irradiation of mouse tumors sparing a distant site resembling metastasis. Such second nonirradiated tumor was used as indicator of abscopal effect. Tumor size was monitored every 2 days.ResultsAbscopal effects on distant nonirradiated subcutaneous tumor lesions of transplanted MC38-derived tumors only took place when brachytherapy was combined with immunostimulatory anti-PD1 and/or anti-CD137 mAbs.ConclusionsOur results demonstrate that immunotherapy-potentiated abscopal effects can be attained by brachytherapy. Accordingly, immunotherapy plus brachytherapy combinations are suitable for clinical translation.

http://ift.tt/2xm3Mc9

Salvage brachytherapy for recurrent prostate cancer after definitive radiation therapy: A comparison of low-dose-rate and high-dose-rate brachytherapy and the importance of prostate-specific antigen doubling time

Publication date: Available online 21 August 2017
Source:Brachytherapy
Author(s): Marisa A. Kollmeier, Sean McBride, Amandeep Taggar, Erik Anderson, Mary Lin, Xin Pei, Shi Weiji, Laszlo Voros, Gilad Cohen, Yoshiya Yamada, Michael J. Zelefsky
BackgroundSalvage brachytherapy is a treatment option for patients with locally recurrent prostate cancer after primary radiation therapy. We reviewed our experience using low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy to compare the outcome and toxicity profiles of each approach in the salvage brachytherapy setting.Methods and MaterialsNinety-eight patients with biopsy-proven locally recurrent prostate cancer who underwent salvage brachytherapy (LDR = 37; HDR = 61) following an initial course of definitive radiotherapy between 4/2003 and 4/2015 were retrospectively reviewed. All patients underwent salvage brachytherapy using LDR or HDR. Androgen deprivation therapy was used in 45% of the patients. Prostate-specific antigen (PSA) failure was determined using the Phoenix (nadir+2) definition. Toxicity was graded using Common Terminology Criteria for Adverse Events version 4 and patient-reported questionnaires.ResultsMedian followup was 31 months. The 3-year PSA relapse-free survival (RFS) was 60.1% (95% CI, 49.6–72.5%). There was no difference between LDR and HDR brachytherapy in terms of PSA RFS (p = 0.84 by log-rank test). On multivariate analysis, only prostate-specific antigen doubling time (PSADT) <12 months was significantly associated with PSA relapse. The 3-year PSA RFS for patients with a PSADT <12 months was 39% compared with 73% for PSADT ≥12 months (p = 0.002 by long-rank test). There were no statistically significant differences in toxicity between LDR and HDR brachytherapy. There was a higher peak in urinary symptoms in LDR patients; however by 24–36 months, most patients in both groups returned to baseline.ConclusionsBoth LDR and HDR salvage brachytherapy are an excellent treatment options for appropriately selected patients with comparable outcome and toxicity. Patients with a PSADT < 12 months seem to have worse outcomes.

http://ift.tt/2ws84SZ

Calcification Volume Reduces Stretch Capability and Predisposes Plaque to Rupture in an in vitro Model of Carotid Artery Stenting

Publication date: Available online 21 August 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): H.E. Barrett, E.M. Cunnane, H. Hidayat, J.M. O Brien, E.G. Kavanagh, M.T. Walsh
Objective/BackgroundCarotid artery stenting (CAS) in calcified arteries carries a higher peri-operative risk. This study investigates the relationship between the stretching limits of carotid plaque samples and calcification in order to determine a stretch tolerance criterion for endovascular intervention.MethodsSeventeen carotid plaque samples were acquired from standard endarterectomy procedures. The maximum stretch capability of the global plaque was determined by circumferentially extending the tissue to complete failure. Quantitative assessment of calcification was performed using high resolution computed tomography, including measures of percent calcification volume fraction (%CVF) and calcification configuration. Maximum stretch properties were then related to calcification measures in order to evaluate the predictive power of calcification for determining plaque stretching limits.ResultsA strong negative correlation was found between %CVF and stretch ratio with respect to specific calcification configuration types. All plaques with < 70% stenosis superseded the minimum required stretch threshold. Severe stenosis (> 70%) warrants a stretch of at least 2.33 during revascularisation and only plaques containing concentric calcifications with < 20% CVF successfully reached this minimum required stretch threshold.ConclusionThe addition of calcification measures to the stenosis classification may help in guiding endovascular intervention techniques to achieve a balance between an acceptable residual patency level while avoiding plaque rupture in calcified carotid plaques.

Graphical abstract

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Hyperaccumulating potential of Bidens pilosa L. for Cd and elucidation of its translocation behavior based on cell membrane permeability

Abstract

Phytoremediation with the use of hyperaccumulating plant species to remove excess trace metals from contaminated soil and water is considered a cost-effective non-invasive technique. Over 400 plant taxa worldwide have been identified as natural hyperaccumulators, but only very few are reported to hyperaccumulate Cd. Bidens pilosa L. is a newly found, promising Cd hyperaccumulator, although its potential to accumulate Cd and mechanism of this process are not yet well known. This paper was aimed at exploring hyperaccumulation capacity of B. pilosa for Cd, and its translocation behavior related to cell membrane permeability. The highest Cd concentration in shoots of B. pilosa grown in soil was 405.91 mg kg⁻¹ and of that cultured in nutrient solution 1651.68 mg kg⁻¹, indicating very high accumulation potential. Cd concentrations in the root, stem, leaf, and shoot of B. pilosa cultured in nutrient solution were all much higher than those in soil, while biomass development was considerably lower. This resulted in lesser differences between Cd maximum accumulation loads in the shoot (462 and 365 μg pot⁻¹) and in the root (100 and 96 μg pot⁻¹) of B. pilosa grown in solution and in soil, respectively. Relative electric conductivity (REC), K⁺ relative permeability ratio, and MDA (malondialdehyde) contents, which are major indices expressing cell membrane permeability, appeared to be closely related to Cd translocation and accumulation. The relative molecular mechanism of Cd accumulation/translocation in B. pilosa was found of importance and needs to be elucidated.

http://ift.tt/2v8uzIh

Regeneration and reuse waste from an edible oil refinery

Abstract

A spent bleaching earth (SBE) from an edible oil refinery has been regenerated by thermal processing in oven, followed by washing with a cold solution of hydrochloric acid (1M). Optimal regeneration conditions have been controlled by decolorization tests of degummed and neutralized soybean oil. Optimal values of treatment (temperature 350°C, carbonization time 01 h, and HCl concentration 1M) gave a very efficient material. After bleaching oil by regenerated spent bleaching earth (RSBE), the chlorophyll-a and β-carotenes contained in crude edible oil and observed respectively at 430, 454, and 483 nm, value of λ _max, are very much decreased. The results obtained after decolorization of edible oil by RSBE material indicate, that, during the process, the bleaching oil did not undergo any changes in the free fatty acid content. The peroxide value (PV) was reduced from 4.2 to 1.8 meq O₂/kg, and the color has been improved (Lovibond color yellow/red: from 50/0.5 to 2.7/0.3, respectively). The RSBE material obtained was characterized by several techniques (FTIR, SEM). The results show that the heat treatment did not affect the mineral structure of RSBE, and the regenerated material recovered its porous structure.

http://ift.tt/2wxGcvS

Epithelial TNF Receptor Signaling Promotes Mucosal Repair in Inflammatory Bowel Disease [MUCOSAL IMMUNOLOGY]

TNF plays an integral role in inflammatory bowel disease (IBD), as evidenced by the dramatic therapeutic responses in Crohn's disease (CD) patients induced by chimeric anti-TNF mAbs. However, treatment of CD patients with etanercept, a decoy receptor that binds soluble TNF, fails to improve disease. To explore this discrepancy, we investigated the role of TNF signaling in Wnt/β-catenin–mediated intestinal stem cell and progenitor cell expansion in CD patients, human cells, and preclinical mouse models. We hypothesized that TNF exerts beneficial effects on intestinal epithelial cell (IEC) responses to injury. In CD patients, intestinal stem cell and progenitor cell Wnt/β-catenin signaling correlates with inflammation status. TNF-deficient (Tnf^–/–) mice exhibited increased apoptosis, less IEC proliferation, and less Wnt signaling when stimulated with anti-CD3 mAb. Bone marrow (BM) chimera mice revealed that mucosal repair depended on TNF production by BM–derived cells and TNFR expression by radioresistant IECs. Wild-type->Tnfr1/2^–/– BM chimera mice with chronic dextran sodium sulfate colitis exhibited delayed ulcer healing, more mucosal inflammation, and impaired Wnt/β-catenin signaling, consistent with the hypothesis that epithelial TNFR signaling participates in mucosal healing. The direct effect of TNF on stem cells was demonstrated by studies of TNF-induced Wnt/β-catenin target gene expression in murine enteroids and colonoid cultures and TNF-induced β-catenin activation in nontransformed human NCM460 cells (TOPFlash) and mice (TOP-GAL). Together, these data support the hypothesis that TNF plays a beneficial role in enhancing Wnt/β-catenin signaling during ulcer healing in IBD. These novel findings will inform clinicians and therapeutic chemists alike as they strive to develop novel therapies for IBD patients.

http://ift.tt/2fZM0Ik

Immune Protection by a Cytomegalovirus Vaccine Vector Expressing a Single Low-Avidity Epitope [IMMUNOTHERAPY AND VACCINES]

Experimental CMV-based vaccine vectors expressing a single MHC class I–restricted high-avidity epitope provided strong, T cell–dependent protection against viruses or tumors. In this study we tested the low-avidity epitope KCSRNRQYL, and show that a mouse CMV (MCMV) vector provides complete immune control of recombinant vaccinia virus expressing the same epitope if KCSRNRQYL is expressed within the immediate-early MCMV gene ie2. The same epitope expressed within the early M45 gene provided no protection, although MCMV vectors expressing the high-avidity epitope SSIEFARL induced protective immunity irrespective of gene expression context. Immune protection was matched by Ag-induced, long-term expansion of effector memory CD8 T cells, regardless of epitope avidity. We explained this pattern by observing regularities in Ag competition, where responses to high-avidity epitopes outcompeted weaker ones expressed later in the replicative cycle of the virus. Conversely, robust and early expression of a low-avidity epitope compensated its weak intrinsic antigenicity, resulting in strong and sustained immunity and immune protection.

http://ift.tt/2fZ4etk

Lactation-Based Maternal Educational Immunity Crosses MHC Class I Barriers and Can Impart Th1 Immunity to Th2-Biased Recipients [IMMUNE SYSTEM DEVELOPMENT]

We have previously demonstrated lactational transfer of T cell–based immunity from dam to foster pup. In the short term, a significant part of transferred immunity is passive cellular immunity. However, as time progresses, this is replaced by what we have described as maternal educational immunity such that by young adulthood, all immune cells responding to a foster dam immunogen are the product of the foster pup's thymus. To reduce confounding factors, this original demonstration used congenic/syngeneic dam and foster pup pairs. In this study, we investigated lactational transfer of immunity to Mycobacterium tuberculosis in MHC class I–mismatched animals, as well as from Th1-biased dams to Th2-biased foster pups. Using immunized C57BL/6J dams, lactational transfer to nonimmunized BALB/cJ foster pups resulted in much greater immunity than direct immunization in 5-wk-old pups (ex vivo assay of pup splenocytes). At this age, 82% of immunogen-responding cells in the pup spleen were produced through maternal educational immunity. FVB/NJ nonimmunized foster recipients had a greater number of maternal cells in the spleen and thymus but a much larger percentage was Foxp3⁺, resulting in equivalent immunity to direct immunization. Depletion of maternal Foxp3⁺ cells from pup splenocytes illustrated a substantial role for lactationally transferred dam regulatory T cells in suppression of the ex vivo response in FVB/NJ, but not BALB/cJ, recipients. We conclude that lactational transfer of immunity can cross MHC class I barriers and that Th1 immunity can be imparted to Th2-biased offspring; in some instances, it can be greater than that achieved by direct immunization.

http://ift.tt/2imqMVZ

Correction: Macrophage Mitochondrial and Stress Response to Ingestion of Cryptococcus neoformans [CORRECTIONS]

http://ift.tt/2ilTNAY

Correction: A CD80-Biased CTLA4-Ig Fusion Protein with Superior In Vivo Efficacy by Simultaneous Engineering of Affinity, Selectivity, Stability, and FcRn Binding [CORRECTIONS]

http://ift.tt/2fZWBmB

Retraction: Hypoxia-Inducible Factor-1{alpha}-Dependent Protection from Intestinal Ischemia/Reperfusion Injury Involves Ecto-5'-Nucleotidase (CD73) and the A2B Adenosine Receptor [LETTERS OF RETRACTION]

http://ift.tt/2in5wzo

Versican-Derived Matrikines Regulate Batf3-Dendritic Cell Differentiation and Promote T Cell Infiltration in Colorectal Cancer [TUMOR IMMUNOLOGY]

Colorectal cancer originates within immunologically complex microenvironments. To date, the benefits of immunotherapy have been modest, except in neoantigen-laden mismatch repair–deficient tumors. Approaches to enhance tumor-infiltrating lymphocytes in the tumor bed may substantially augment clinical immunotherapy responses. In this article, we report that proteolysis of the tolerogenic matrix proteoglycan versican (VCAN) strongly correlated with CD8⁺ T cell infiltration in colorectal cancer, regardless of mismatch repair status. Tumors displaying active VCAN proteolysis and low total VCAN were associated with robust (10-fold) CD8⁺ T cell infiltration. Tumor-intrinsic WNT pathway activation was associated with CD8⁺ T cell exclusion and VCAN accumulation. In addition to regulating VCAN levels at the tumor site, VCAN proteolysis results in the generation of bioactive fragments with novel functions (VCAN-derived matrikines). Versikine, a VCAN-derived matrikine, enhanced the generation of CD103⁺CD11c^hiMHCII^hi conventional dendritic cells (cDCs) from Flt3L-mobilized primary bone marrow–derived progenitors, suggesting that VCAN proteolysis may promote differentiation of tumor-seeding DC precursors toward IRF8- and BATF3-expressing cDCs. Intratumoral BATF3-dependent DCs are critical determinants for T cell antitumor immunity, effector T cell trafficking to the tumor site, and response to immunotherapies. Our findings provide a rationale for testing VCAN proteolysis as a predictive and/or prognostic immune biomarker and VCAN-derived matrikines as novel immunotherapy agents.

http://ift.tt/2fZLXME

Modified Vaccinia Virus Ankara Vector Induces Specific Cellular and Humoral Responses in the Female Reproductive Tract, the Main HIV Portal of Entry [MUCOSAL IMMUNOLOGY]

The female reproductive tract (FRT) is one of the major mucosal invasion sites for HIV-1. This site has been neglected in previous HIV-1 vaccine studies. Immune responses in the FRT after systemic vaccination remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized specific immune responses in all compartments of the FRT of nonhuman primates after systemic vaccination. Memory T cells were preferentially found in the lower tract (vagina and cervix), whereas APCs and innate lymphoid cells were mainly located in the upper tract (uterus and fallopian tubes). This compartmentalization of immune cells in the FRT was supported by transcriptomic analyses and a correlation network. Polyfunctional MVA-specific CD8⁺ T cells were detected in the blood, lymph nodes, vagina, cervix, uterus, and fallopian tubes. Anti-MVA IgG and IgA were detected in cervicovaginal fluid after a second vaccine dose. Thus, systemic vaccination with an MVA vector elicits cellular and Ab responses in the FRT.

http://ift.tt/2ilsxTi

The Development of Steady-State Activation Hubs between Adult LTi ILC3s and Primed Macrophages in Small Intestine [MUCOSAL IMMUNOLOGY]

Group 3 innate lymphoid cells (ILC3s) are important for intestinal health, particularly in controlling inflammation in response to epithelial dysregulation, but their role during homeostasis remains less well understood. We generated IL-22 reporter mice to assess production of this key cytokine by ILC3s in the small intestine during development and under basal conditions. Although IL-22 is produced by a variety of lymphocyte populations, constitutively high IL-22 expression was limited to lymphoid-tissue inducer (LTi) cells residing in lymph node–like structures in the gut called solitary intestinal lymphoid tissues (SILT). Constitutive IL-22 expression was dependent on the microbiota and MyD88 signaling, appeared upon weaning, and was present across the spectrum of SILT, including in cryptopatches. Activated SILT LTi cells colocalized with a rare subpopulation of activated macrophages constitutively positive for IL-12/23 p40 and capable of activating neonatal LTi cells in response to TLR stimulus. Thus, weaning leads to the organization of innate immune activation hubs at SILT that mature and are continuously sustained by signals from the microbiota. This functional and anatomic organization constitutes a significant portion of the steady-state IL-23/IL-22 axis.

http://ift.tt/2fZLZEg

Impaired Transmigration of Myeloid-Derived Suppressor Cells across Human Sinusoidal Endothelium Is Associated with Decreased Expression of CD13 [IMMUNE REGULATION]

Human monocytic myeloid-derived suppressor cells (MO-MDSCs) within the hepatic compartment suppress inflammation and impair immune surveillance in liver cancer. It is currently not known whether recruitment of MO-MDSCs from blood via hepatic sinusoidal endothelium (HSEC) contributes to their enrichment within the hepatic compartment. We compared the transmigratory potential of MO-MDSCs and monocytes after adhesion to hepatic endothelial monolayers in flow-based assays that mimic in vivo shear stress in the sinusoids. Despite comparable binding to HSEC monolayers, proportionally fewer MO-MDSCs underwent transendothelial migration, indicating that the final steps of extravasation, where actin polymerization plays an important role, are impaired in MO-MDSCs. In this article, we found reduced levels of CD13 on MO-MDSCs, which has recently been reported to control cell motility in monocytes, alongside reduced VLA-4 expression, an integrin predominantly involved in adherence to the apical side of the endothelium. CD13 and VLA-4 blocking and activating Abs were used in flow-based adhesion assays, live-cell imaging of motility, and actin polymerization studies to confirm a role for CD13 in impaired MO-MDSC transmigration. These findings indicate that CD13 significantly contributes to tissue infiltration by MO-MDSCs and monocytes, thereby contributing to the pathogenesis of hepatic inflammation.

http://ift.tt/2imrfaH

IL-7 Restores T Lymphocyte Immunometabolic Failure in Septic Shock Patients through mTOR Activation [CLINICAL AND HUMAN IMMUNOLOGY]

T lymphocyte alterations are central to sepsis pathophysiology, whereas related mechanisms remain poorly understood. We hypothesized that metabolic alterations could play a role in sepsis-induced T lymphocyte dysfunction. Samples from septic shock patients were obtained at day 3 and compared with those from healthy donors. T cell metabolic status was evaluated in the basal condition and after T cell stimulation. We observed that basal metabolic content measured in lymphocytes by nuclear magnetic resonance spectroscopy was altered in septic patients. Basal ATP concentration, oxidative phosphorylation (OXPHOS), and glycolysis pathways in T cells were decreased as well. After stimulation, T lymphocytes from patients failed to induce glycolysis, OXPHOS, ATP production, GLUT1 expression, glucose entry, and proliferation to similar levels as controls. This was associated with significantly altered mTOR, but not Akt or HIF-1α, activation and only minor AMPKα phosphorylation dysfunction. IL-7 treatment improved mTOR activation, GLUT1 expression, and glucose entry in septic patients' T lymphocytes, leading to their enhanced proliferation. mTOR activation was central to this process, because rapamycin systematically inhibited the beneficial effect of recombinant human IL-7. We demonstrate the central role of immunometabolism and, in particular, mTOR alterations in the pathophysiology of sepsis-induced T cell alterations. Our results support the rationale for targeting metabolism in sepsis with recombinant human IL-7 as a treatment option.

http://ift.tt/2fZ30yt

Control of Regulatory T Cell Differentiation by the Transcription Factors Thpok and LRF [IMMUNE SYSTEM DEVELOPMENT]

The CD4⁺ lineage–specific transcription factor Thpok is required for intrathymic CD4⁺ T cell differentiation and, together with its homolog LRF, supports CD4⁺ T cell helper effector responses. However, it is not known whether these factors are needed for the regulatory T cell (Treg) arm of MHC class II responses. In this study, by inactivating in mice the genes encoding both factors in differentiated Tregs, we show that Thpok and LRF are redundantly required to maintain the size and functions of the postthymic Treg pool. They support IL-2–mediated gene expression and the functions of the Treg-specific factor Foxp3. Accordingly, Treg-specific disruption of Thpok and Lrf causes a lethal inflammatory syndrome similar to that resulting from Treg deficiency. Unlike in conventional T cells, Thpok and LRF functions in Tregs are not mediated by their repression of the transcription factor Runx3. Additionally, we found that Thpok is needed for the differentiation of thymic Treg precursors, an observation in line with the fact that Foxp3⁺ Tregs are CD4⁺ cells. Thus, a common Thpok-LRF node supports both helper and regulatory arms of MHC class II responses.

http://ift.tt/2g0ho9u

Induction of Regulatory T Cells and Its Regulation with Insulin-like Growth Factor/Insulin-like Growth Factor Binding Protein-4 by Human Mesenchymal Stem Cells [CLINICAL AND HUMAN IMMUNOLOGY]

Human mesenchymal stem cells (MSCs) are multipotent and exert anti-inflammatory effects, but the underlying mechanism remains to be elucidated. In the current study, we investigated the regulatory mechanism of regulatory T cell (Treg) induction through the growth factors released by human MSCs. Human naive CD4⁺ T cells were stimulated with anti-CD3/28 Abs and cocultured with human MSC culture supernatant for 48 h. The proliferation and cytokine production of CD4⁺ T cells and surface molecule expression on CD4⁺ T cells were evaluated. The proliferation of anti-CD3/28 Abs–stimulated CD4⁺ T cells was suppressed by the addition of human MSC culture supernatant; in addition, the production of IL-10 and IL-4 increased. The human MSC culture supernatant induced CD4⁺FOXP3⁺ Tregs that expressed CD25, CTLA-4, glucocorticoid-induced TNFR-related protein, insulin-like growth factor (IGF)-1R, and IGF-2R, showing antiproliferative activity against CD4⁺ T cells. In addition, the induction of Tregs by human MSC culture supernatant was enhanced by the addition of IGF and suppressed by the inhibition of IGF-1R. In contrast, a significant amount of IGF binding protein (IGFBP)-4, an inhibitor of IGF action, was detected in the human MSC culture supernatant. After neutralization of IGFBP-4 in the human MSC culture supernatant by anti–IGFBP-4 Ab, Treg numbers increased significantly. Thus, our results raise the possibility that human MSC actions also involve a negative-regulatory mechanism that suppresses Treg proliferation by releasing IGFBP-4. The results of this study suggest that regulation of IGF may be important for treatments using human MSCs.

http://ift.tt/2fZ2Yql

Adaptive from Innate: Human IFN-{gamma}+CD4+ T Cells Can Arise Directly from CXCL8-Producing Recent Thymic Emigrants in Babies and Adults [IMMUNE SYSTEM DEVELOPMENT]

We recently demonstrated that the major effector function of neonatal CD4⁺ T cells is to produce CXCL8, a prototypic cytokine of innate immune cells. In this article, we show that CXCL8 expression, prior to proliferation, is common in newly arising T cells (so-called "recent thymic emigrants") in adults, as well as in babies. This effector potential is acquired in the human thymus, prior to TCR signaling, but rather than describing end-stage differentiation, such cells, whether isolated from neonates or adults, can further differentiate into IFN-–producing CD4⁺ T cells. Thus, the temporal transition of host defense from innate to adaptive immunity is unexpectedly mirrored at the cellular level by the capacity of human innate-like CXCL8-producing CD4⁺ T cells to transition directly into Th1 cells.

http://ift.tt/2imren9

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Δευτέρα 21 Αυγούστου 2017

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