bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral Ketamine in Treatment-Resistant Depression
Authors: Al Shirawi Maryam I. , Kennedy Sidney H. , Ho Keith T. , Byrne Roisin , Downar Jonathan 
Published: May 2017

Abstract

Purpose
The aim of the study was to assess the effectiveness, tolerability, and safety of oral ketamine as an antidepressant treatment in adults with treatment-resistant depression.

Methods
We reviewed retrospective data on 22 patients with treatment-resistant depression, who failed at least 3 adequate antidepressant treatment trials and 1 adequate trial of repetitive transcranial magnetic stimulation; subsequently, they received open-label treatment with oral ketamine, commenced at a dose of 50 mg every 3 days, titrated up by 25 mg every 3 days, according to response and tolerability. The primary outcome measure was the Beck Depression Inventory II, which was used to rate subjective mood improvement at baseline and then at each follow-up visit. Data about adverse effects related to ketamine and a self-harm risk assessment were also obtained.

Findings
Over the course of treatment, 18% of the patients showed greater than 50% reduction in the Beck Depression Inventory II scores, 14% reported partial improvement in mood symptoms, while 45% had no response to ketamine and 23% showed a mild worsening in their depressive symptoms. The most frequent adverse effects were acute dissociation, dizziness, blurred vision, numbness and sedation. Neither serious adverse effects, nor any cases of abuse or dependence were observed.

Conclusions
Although this case series found oral ketamine to be safe and well tolerated, the findings also showed rather modest effectiveness of oral ketamine in treatment-resistant depression, with only approximately 30% reporting some benefit and approximately 70% reporting no change or worsening of mood. However, bearing in mind the limitations of this small, open-label case series, further exploration of the effectiveness of oral ketamine is warranted.
Role of tyrosine kinase inhibitors in the treatment of pituitary tumours: from bench to bedside
Authors: Ben-Shlomo Anat , Cooper Odelia 
Published: May 2017

Purpose of review
Treatment of aggressive pituitary tumours often yields suboptimal control of the tumour and confers significant morbidity. Lactotroph and corticotroph-derived tumours express ErbB receptors and ligands, and mutations in ubiquitin-specific protease 8 (USP8), which alters epidermal growth factor receptor (EGFR) degradation, have been implicated in Cushing disease pathogenesis. EGFR tyrosine kinase inhibitor (TKI) therapy has emerged as a potential new therapeutic approach for patients with aggressive prolactinomas and Cushing disease.

Recent findings
Using EGFR or human epidermal growth factor receptor 2-driven prolactin (PRL) promoters, transgenic mice develop large tumours that respond to TKI inhibition. In human corticotroph primary cultures, treatment with the pan-ErbB TKI canertinib as well as the EGFR TKI gefitinib suppresses proopiomelanocortin mRNA. USP8 mutations, detected in up to two-thirds of Cushing disease, may underlie the increase in EGFR signalling in these tumours. Human prolactinomas have differential ErbB receptor expression associated with aggressive behaviour and data from an ongoing clinical trial suggest that resistant prolactinomas may respond to the EGFR TKI lapatinib.

Summary
Preclinical and clinical models substantiate the role of the EGFR pathway in corticotroph and lactotroph adenomas. Although further study is needed, results to date suggest that targeting the ErbB pathway may be an effective therapeutic approach for patients with aggressive pituitary tumours.
Stem cell therapy and its potential role in pituitary disorders
Authors: Lara-Velazquez Montserrat , Akinduro Oluwaseun O. , Reimer Ronald , Woodmansee Whitney W. , Quinones-Hinojosa Alfredo 
Published: May 2017

Purpose of review
The pituitary gland is one of the key components of the endocrine system. Congenital or acquired alterations can mediate destruction of cells in the gland leading to hormonal dysfunction. Even though pharmacological treatment for pituitary disorders is available, exogenous hormone replacement is neither curative nor sustainable. Thus, alternative therapies to optimize management and improve quality of life are desired.

Recent findings
An alternative modality to re-establish pituitary function is to promote endocrine cell regeneration through stem cells that can be obtained from the pituitary parenchyma or pluripotent cells. Stem cell therapy has been successfully applied to a plethora of other disorders, and is a promising alternative to hormonal supplementation for resumption of normal hormone homeostasis.

Summary
In this review, we describe the common causes for pituitary deficiencies and the advances in cellular therapy to restore the physiological pituitary function.
Orthotopic liver transplantation changes the course of gastric antral vascular ectasia: a case series from a transplant center
Authors: Allamneni Chaitanya , Alkurdi Basem , Naseemuddin Rehan , McGuire Brendan M. , Shoreibah Mohamed G. , Eckhoff Devin E. , Peter Shajan 
Published: May 2017

Background and aim
Gastric antral vascular ectasia (GAVE) is an important cause of upper gastrointestinal bleeding and anemia in patients with cirrhosis. The aim of our study was to evaluate the effect of orthotopic liver transplantation (OLT) on GAVE and associated anemia.

Patients and methods
We performed a chart review and identified all cirrhotic patients with GAVE who underwent OLT at the University Of Alabama at Birmingham between 2005 and 2013. Population’s demographics, etiology of cirrhosis, comorbidities, presentation and treatment modalities of GAVE, endoscopic and histopathologic reports, hemoglobin values before and after transplant, and immunosuppressive regimens were collected.

Results
Twelve patients were identified, mean age 52.4±4.4 years; seven were men (58.3%); 11 (91.7%) were White; and 6 of 12 patients had biopsy-proven GAVE. The most common etiology of cirrhosis in the cohort was chronic hepatitis C and obesity was the most common chronic condition in 50 and 83.3%, respectively. Anemia resolution was observed in 9/12 (75%) patients who underwent OLT with an increase in hemoglobin from 8.1±2.4 (5.7–13.1) before transplant to 12.0±1.4 (10–15) after transplant (P<0.0001). Esophagogastroduodenoscopy after transplant was performed in all 12 (100%) patients. The mean time between transplant and post-OLT esophagogastroduodenoscopy was 13.8±18.28 (2–57) months; complete resolution of GAVE was observed in 10 (83.3%) patients, with resolving GAVE in one (8.3%) patient.

Conclusion
GAVE is an important cause of anemia and upper gastrointestinal bleeding in patients with liver cirrhosis. Our findings show that liver transplantation can resolve GAVE and related anemia.
Key performance indicators’ assessment to develop best practices in an Emergency Medical Communication Centre
Authors: Penverne Yann , Leclere Brice , Labady Julien , Berthier Frederic , Jenvrin Joel , Javaudin Francois , Batard Eric , Montassier Emmanuel 
Published: May 2017

Introduction
Emergency Medical Communication Centre (EMCC) represents a pivotal link in the chain of survival for those requiring rapid response for out-of-hospital medical emergencies. Assessing and grading the performance of EMCCs are warranted as it can affect the health and safety of the served population.

Objective
The aim of our work was to describe the activity on an EMCC and to explore the associations between different key performance indicators.

Methods
We carried out our prospective observational study in the EMCC of Nantes, France, from 6 June 2011 to 6 June 2015. The EMCC performance was assessed with the following key performance indicators: answered calls, Quality of Service 20 s (QS20), occupation rate and average call duration.

Results
A total of 35 073 h of dispatch activity were analysed. 1 488 998 emergency calls were answered. The emergency call incidence varied slightly from 274 to 284 calls/1000 citizens/year between 2011 and 2015. The median occupation rate was 35% (25–44). QS20 was correlated negatively with the occupation rate (Spearman’s ρ: −0.78). The structural equation model confirmed that the occupation rate was highly correlated with the QS20 (standardized coefficient: −0.89). For an occupation rate of 26%, the target value estimated by our polynomial model, the probability of achieving a QS20 superior or equal to 95% varied between 56 and 84%.

Conclusion
The occupation rate appeared to be the most important factor contributing towards the QS20. Our data will be useful to develop best practices and guidelines in the field of emergency medicine communication centres.
Eating disorders and bone metabolism in women
Authors: Robinson Lauren , Micali Nadia , Misra Madhusmita 
Published: May 2017

Purpose of review
Eating Disorders are psychiatric disorders associated with a high risk for low bone mineral density (BMD) and fractures. Low BMD is a consequence of undernutrition, changes in body composition, and hormonal alterations. This review summarizes recent findings regarding novel strategies for assessing bone outcomes in patients with eating disorders, factors contributing to altered bone metabolism, and possible therapeutic strategies.

Recent findings
Emerging research in this field suggests that not only anorexia nervosa, but also bulimia nervosa results in lower BMD compared to controls. To date studies of bone structure, and all randomized controlled trials examining the impact of various therapies on bone outcomes in anorexia nervosa, have focused on adolescent girls and women. We discuss the impact of anorexia nervosa on bone structure, and associations of resting energy expenditure, marrow adipose tissue (including the ratio of saturated to unsaturated fat), and cold activated brown adipose tissue with BMD and bone structure. Promising strategies for treatment include physiological estrogen replacement (rather than oral contraceptives) in adolescent girls with anorexia nervosa, and bisphosphonates, as well as teriparatide, in adult women with anorexia nervosa.

Summary
Recent data on (i) BMD and bone structure in adolescent girls and women with eating disorders, (ii) factors that contribute to altered bone metabolism, and (iii) randomized controlled trials reporting positive effects of physiologic estrogen replacement, bisphosphonates and teriparatide on bone health, provide us with a greater understanding of the impact of eating disorders on bone and novel management strategies.
Selective Y Centromere Inactivation Triggers Chromosome Shattering in Micronuclei and Repair by Non-homologous End Joining
Authors: Ly Peter , Teitz Levi S. , Kim Dong H. , Shoshani Ofer , Skaletsky Helen , Fachinetti Daniele , Page David C. , Cleveland Don W. 
Published: May 2017

(Abstracted from Nat Cell Biol 2017;19:68–75)
Evidence from plant models, human-cell models, and yeast genetics has suggested that complex and localized rearrangements termed chromothripsis can be triggered by chromosome missegregation into nuclear compartments called micronuclei. Chromothripsis is likely to arise through chromosome breakage and inaccurate reassembly.
Impact of Sexual Violence Across the Lifespan on HIV Risk Behaviors Among Transgender Women and Cisgender People Living With HIV
Authors: Smith Laramie R. , Yore Jennifer , Triplett Daniel P. , Urada Lianne , Nemoto Tooru ,   Kaiser Permanente Community-Based HIV Test and Treat Study Team, Raj Anita 
Published: May 2017

Background:
To examine sexual violence across the lifespan among transgender and cisgender people living with HIV and its associations with recent risk behaviors.

Setting:
Seven community-based sites serving priority populations disproportionately affected by HIV in the United States, including major metropolitan areas in the West and East Coast, as well as the suburban Mid-Atlantic and rural Southeastern regions.

Methods:
From 2013 to 2016, baseline survey data were collected from participants (N = 583) of a multisite community-based HIV linkage to/retention in care study conducted at 7 sites across the United States. Adjusted mixed-effects logistic regression models with random effect for site-assessed associations of sexual violence and gender identity with risk outcomes including condomless sex, sex trade involvement, and substance use–related harms.

Results:
One-third of participants reported a history of sexual violence; transgender [adjusted odds ratio (AOR) = 5.1, 95% confidence interval (CI): 2.6 to 10.1] and cisgender women (AOR = 3.8, 95% CI: 2.3 to 6.4) were more likely than cisgender men to experience sexual violence. Sexual violence was associated with experiencing drug-related harms (AOR = 2.6, 95% CI: 1.2 to 5.5). Transgender women were more likely than cisgender men to have sold sex (AOR = 9.3, 95% CI: 1.7 to 50.0).

Conclusions:
A history of sexual violence is common among transgender and cisgender women PLWH, and it increases risk for drug-related harms. Transgender women are also more likely to report selling sex.
Effectiveness of an Integrated Approach to HIV and Hypertension Care in Rural South Africa: Controlled Interrupted Time-Series Analysis
Authors: Ameh Soter , Klipstein-Grobusch Kerstin , Musenge Eustasius , Kahn Kathleen , Tollman Stephen , Gómez-Olivé Francesc Xavier 
Published: May 2017

Background:
South Africa faces a dual burden of HIV/AIDS and noncommunicable diseases. In 2011, a pilot integrated chronic disease management (ICDM) model was introduced by the National Health Department into selected primary health care (PHC) facilities. The objective of this study was to assess the effectiveness of the ICDM model in controlling patients' CD4 counts (>350 cells/mm3) and blood pressure [BP (<140/90 mm Hg)] in PHC facilities in the Bushbuckridge municipality, South Africa.

Methods:
A controlled interrupted time-series study was conducted using the data from patients' clinical records collected multiple times before and after the ICDM model was initiated in PHC facilities in Bushbuckridge. Patients ≥18 years were recruited by proportionate sampling from the pilot (n = 435) and comparing (n = 443) PHC facilities from 2011 to 2013. Health outcomes for patients were retrieved from facility records for 30 months. We performed controlled segmented regression to model the monthly averages of individuals' propensity scores using autoregressive moving average model at 5% significance level.

Results:
The pilot facilities had 6% greater likelihood of controlling patients' CD4 counts than the comparison facilities (coefficient = 0.057; 95% confidence interval: 0.056 to 0.058; P < 0.001). Compared with the comparison facilities, the pilot facilities had 1.0% greater likelihood of controlling patients' BP (coefficient = 0.010; 95% confidence interval: 0.003 to 0.016; P = 0.002).

Conclusions:
Application of the model had a small effect in controlling patients' CD4 counts and BP, but showed no overall clinical benefit for the patients; hence, the need to more extensively leverage the HIV program for hypertension treatment.
Balloon Dilatation of the Minor Duodenal Papilla Up to 4 mm is Safe in a Porcine Model
Authors: Müller Philip C. , Steinemann Daniel C. , Sauer Peter , Z’graggen Kaspar , Linke Georg R. , Müller-Stich Beat P. 
Published: May 2017

Objectives:
Balloon dilatation of the minor duodenal papilla is a treatment option for symptomatic pancreas divisum. The histologic effects of balloon dilatation have not yet been evaluated. The aim of this study is to investigate the tolerated extent of dilatation of the minor papilla.

Materials and Methods:
A dilatation of the minor papilla was performed in freshly explanted pancreas of pigs using biliary balloon dilatators. Three organs were not dilated (control group), in each 8 organs a dilatation of 4, 6, and 8 mm, respectively, was performed. Tissue damage was assessed by microscopic evaluation. Ductal wall disruption and perforation as well as a semiquantitative inflammation score was described and compared.

Results:
Ductal wall disruption was increased by dilatation of 6 (5/8; P=0.019) and 8 mm (6/8; P=0.006) compared with 4 mm (1/8). Median inflammation score was 0 (0 to 0), 1 (0 to 2), and 1 (0 to 2) for dilatation of 4, 6, and 8 mm, respectively (4 vs. 6 mm, P=0.007; 4 vs. 8 mm, P=0.026). No perforation occurred in the 4 (0/8) and 6 mm (0/8) group, 1 perforation occurred in the 8 mm group (1/8).

Conclusions:
A dilatation of up to 4 mm seems to be safe. However, dilatation of the minor papilla from 4 mm onwards is increasingly associated with tissue damage. These findings should be considered in endoscopic procedures dilating the minor duodenal papilla.
Disruption of Brain–Heart Coupling in Sepsis
Authors: Admiraal Marjolein M. , Gilmore Emily J. , Van Putten Michel J. A. M. , Zaveri Hitten P. , Hirsch Lawrence J. , Gaspard Nicolas 
Published: May 2017

Purpose:
To investigate heart rate and EEG variability and their coupling in patients with sepsis and determine their relationship to sepsis severity and severity of sepsis-associated brain dysfunction.

Methods:
Fifty-two patients with sepsis were prospectively identified, categorized as comatose (N = 30) and noncomatose (N = 22), and compared with 11 control subjects. In a 30-minute EEG and electrocardiogram recording, heart rate variability and EEG variability (measured by the variability of relative power in a modified alpha band = RAP) and their coupled oscillations were quantified using linear (least-square periodogram and magnitude square coherence) and nonlinear (Shannon entropy and mutual information) measures. These measures were compared between the three groups and correlated with outcome, adjusting for severity of sepsis.

Results:
Several measures of heart rate variability and EEG variability and of their coupled oscillations were significantly lower in patients with sepsis compared with controls and correlated with outcome. This correlation was not independent when adjusting for severity of sepsis.

Conclusions:
Sepsis is associated with lower variability of both heart rate and RAP on EEG and reduction of their coupled oscillations. This uncoupling is associated with the severity of encephalopathy. Combined EEG and electrocardiogram monitoring may be used to gain insight in underlying mechanisms of sepsis and quantify brainstem or thalamic dysfunction.
Insular Cortex Surgery for the Treatment of Refractory Epilepsy
Authors: von Lehe Marec , Parpaley Yaroslav 
Published: May 2017

Summary:
Focal epilepsy originating from the insular cortex is rare. One reason is the small amount of cortical tissue compared with other lobes of the brain. However, the incidence of insular epilepsy might be underestimated because of diagnostic difficulties. The semiology and the surface EEG are often not meaningful or even misleading, and elaborated imaging might be necessary. The close connections of the insular cortex with other potentially epileptogenic areas, such as the temporal lobe or frontal/central cortex, is increasingly recognized as possible reason for failure of epilepsy surgery for temporal or extratemporal seizures. Therefore, some centers consider invasive EEG recording of the insular cortex not only in case of insular epilepsy but also in other focal epilepsies with nonconclusive results from the presurgical work-up. The surgical approach to and resection of insular cortex is challenging because of its deep location and proximity to highly eloquent brain structures. Over the last decades, technical adjuncts like navigation tools, electrophysiological monitoring and intraoperative imaging have improved the outcome after surgery. Nevertheless, there is still a considerable rate of postoperative transient or permanent deficits, in some cases as unavoidable and calculated deficits. In most of the recent series, seizure outcome was favorable and comparable with extratemporal epilepsy surgery or even better. Up to now, the data volume concerning long-term follow-up is limited. This review focusses on the surgical challenges of resections to treat insular epilepsy, on prognostic factors concerning seizure outcome, on postoperative deficits and complications. Moreover, less invasive surgical techniques to treat epilepsy in this highly eloquent area are summarized.
Temporal dynamics of gene expression in heat-stressed Caenorhabditis elegans
Authors: Jovic Katharina , Sterken Mark G. , Grilli Jacopo , Bevers Roel P. J. , Rodriguez Miriam , Riksen Joost A. G. , Allesina Stefano , Kammenga Jan E. , Snoek L. Basten 
Published: May 2017

AbstractThere is considerable insight into pathways and genes associated with heat-stress conditions. Most genes involved in stress response have been identified using mutant screens or gene knockdowns. Yet, there is limited understanding of the temporal dynamics of global gene expression in stressful environments. Here, we studied global gene expression profiles during 12 hours of heat stress in the nematode C. elegans. Using a high-resolution time series of increasing stress exposures, we found a distinct shift in gene expression patterns between 3-4 hours into the stress response, separating an initially highly dynamic phase from a later relatively stagnant phase. This turning point in expression dynamics coincided with a phenotypic turning point, as shown by a strong decrease in movement, survival and, progeny count in the days following the stress. Both detectable at transcriptional and phenotypic level, this study pin-points a relatively small time frame during heat stress at which enough damage is accumulated, making it impossible to recover the next few days.
Mutations in the pantothenate kinase ofPlasmodium falciparumconfer diverse sensitivity profiles to antiplasmodial pantothenate analogues
Authors: Tjhin Erick T. , Spry Christina , Sewell Alan L. , Hoegl Annabelle , Barnard Leanne , Sexton Anna E. , Howieson Vanessa M. , Maier Alexander G. , Creek Darren J. , Strauss Erick , Marquez Rodolfo , Auclair Karine , Saliba Kevin J. 
Published: May 2017

AbstractThe malaria-causing blood stage ofPlasmodium falciparumrequires extracellular pantothenate for proliferation. The parasite converts pantothenate into coenzyme A (CoA) via five enzymes, the first being a pantothenate kinase (PfPanK). Multiple antiplasmodial pantothenate analogues, including pantothenol and CJ-15,801, kill the parasite by targeting CoA biosynthesis/utilisation. Their mechanism of action, however, remains unknown. Here, we show that parasites pressured with pantothenol or CJ-15,801 become resistant to these analogues. Whole-genome sequencing revealed mutations in one of two putative PanK genes (Pfpank1) in each resistant line. These mutations significantly alterPfPanK activity, with two conferring a fitness cost, consistent withPfpank1coding for a functional PanK that is essential for normal growth. The mutants exhibit a different sensitivity profile to recently-described, potent, antiplasmodial pantothenate analogues, with one line beinghypersensitive. We provide evidence consistent with different pantothenate analogue classes having different mechanisms of action: some inhibit CoA biosynthesis while others inhibit CoA-utilising enzymes.
Molecular mechanisms of human papillomavirus-related carcinogenesis in head and neck cancer
Authors: Faraji Farhoud , Zaidi Munfarid , Fakhry Carole , Gaykalova Daria A. 
Published: May 2017

ABSTRACTThis review examines the general cellular and molecular underpinnings of human papillomavirus (HPV)-related carcinogenesis in the context of head and neck squamous cell carcinoma (HNSCC) and focuses on HPV-positive oropharyngeal squamous cell carcinoma in areas for which specific data is available. It covers the major pathways dysregulated in HPV- positive HNSCC and the genome-wide changes associated with this disease.