bluuebunny/crossref_metadata_2025 huggingface dataset:
Clozapine and Norclozapine Plasma Levels in Patients Switched Between Different Liquid Formulations
Authors: Oloyede Ebenezer , Dzahini Olubanke , Whiskey Eromona , Taylor David
Published: October 2019

Background and Objective:

Clozapine is the drug of choice for treatment-resistant schizophrenia. The primary objective of this study was to compare plasma clozapine and N-desmethylclozapine levels in patients switched between 2 liquid formulations [Denzapine suspension and clozapine oral solution (St George's ZTAS)]. Secondary objectives included comparison of safety, tolerability, and patient acceptability.

Methods:

This was a noninterventional, observational, prospective follow-up of patients consecutively switched between formulations of clozapine liquid in a large inner-city NHS mental health trust. The authors also performed retrospective analysis of outcomes from patient case notes.

Results:

The authors identified 43 patients receiving Denzapine suspension in the trust. Data were available for 43 patients switched from Denzapine to clozapine oral solution (St George's ZTAS), among whom, 15 (32%) were excluded from the analysis. Of the 28 patients for whom data were available, the 90% confidence interval for the ratio of mean values for corrected Cmin 91.5 (85.2%–98.4%) and uncorrected Cmin 91.2 (84.4%–98.6%) were within the guideline range of bioequivalence (80%–125%). Safety and tolerability profiles were comparable between the 2 formulations (P = 0.10). Patient acceptability was also similar between the brands in most domains. However, there was a taste preference for Denzapine suspension.

Conclusions:

No significant difference in clozapine plasma levels was observed after switching from Denzapine suspension to a recently introduced clozapine solution. This study also highlights the significance of medicinal characteristics such as taste for patient acceptability and compliance.
Low Bone Mineral Density and High Bone Turnover in Patients With Non-Hodgkin's Lymphoma (NHL) Who Receive Frontline Therapy: Results of a Multicenter Prospective Study
Authors: Anargyrou Konstantinos , Fotiou Despina , Vassilakopoulos Theodoros P. , Christoulas Dimitrios , Makras Polyzois , Dimou Maria , Ntanasis-Stathopoulos Ioannis , Masouridou Stavroula , Angelopoulou Maria K. , Papatheodorou Athanasios , Tsionos Konstantinos , Panayiotidis Panayiotis , Dimopoulos Meletios A. , Terpos Evangelos
Published: October 2019

Chemotherapy associated osteoporosis is a severe problem in patients with malignant diseases as it increases the risk for fractures and deteriorates quality of life. There are very limited data in the literature for the effect of chemotherapy on bone metabolism of adult patients with Non-Hodgkin Lymphoma (NHL). We prospectively evaluated bone remodeling pre- and post-chemotherapy in 61 patients with newly diagnosed NHL. First-line chemotherapy resulted in high bone turnover, which led to increased bone loss and reduced bone mineral density (BMD) of lumbar spine (L1-L4) and femur neck (FN). The reduction of L1-L4 and FN BMD post-chemo was more profound in males and in older patients (>55 years). Patients who received 8 cycles of chemotherapy had a greater reduction of L1-L4 and FN BMD as compared to 6 cycles. The administration of chemotherapy also resulted in a dramatic increase of bone resorption markers (CTX and TRACP-5b), bone formation markers, (bALP and Osteocalcin) and of osteoblast regulator Dickkopf-1. During study period, one patient had a pathological fracture in his right FN.
Abdominal Surgery in Patients with Ventricular Assist Devices: a Single-Center Report
Authors: Beetz Oliver , Bajunaid Anwar , Meißler Luise , Vondran Florian W. R. , Kleine Moritz , Cammann Sebastian , Hanke Jasmin S. , Schmitto Jan D. , Haverich Axel , Klempnauer Jürgen , Ringe Kristina I. , Oldhafer Felix , Timrott Kai
Published: October 2019

This study was performed to evaluate the incidence and outcome of patients with ventricular assist devices (VADs) undergoing abdominal surgery at our institution. A total of 604 adult patients who underwent VAD implantation between February 2004 and February 2018 were analyzed retrospectively with a median follow-up time of 66 (6–174) months. Thirty-nine patients (6.5%) underwent abdominal surgery. Elective surgical procedures were performed in 22 patients (56.4%), mainly for abdominal wall hernia repairs, partial colectomies, and cholecystectomies. Early after elective abdominal surgery no patient died, resulting in a median survival of 23 (1–78) months. Emergency surgery was performed in 17 patients (43.6%). The most common emergency indications were intestinal ischemia and/or perforation. Eight patients undergoing emergent surgery (44.4%) died within the first 30 days after primary abdominal operation, mainly due to sepsis and consecutive multiple organ failure, resulting in a dismal median survival of one month (0–52). Patients undergoing abdominal surgery had significantly lower rates of realized heart-transplantation (p = 0.031) and a significantly higher rate of VAD exchange, before or after abdominal surgery, due to thromboses or infections (p = 0.037). Nonetheless, overall survival after primary VAD implantation in these patients (median 38 months; 0–107) was not significantly impaired when compared to all other patients undergoing VAD implantation (median 30 months; 0–171). In summary, elective abdominal surgery can be performed safely when well planned by an experienced multidisciplinary team. Abdominal complications in VAD patients requiring emergent surgery, however, lead to a significant increase in short-term morbidity and a high 30-day mortality rate.
Increased Posttransplant Mortality for Autoimmune Hepatitis Compared With Other Autoimmune Liver Diseases
Authors: Lee Jennifer Y. , Danford Christopher J. , Patwardhan Vilas R. , Bonder Alan
Published: October 2019

Goals:

We sought to compare posttransplant outcomes between autoimmune liver disease.

Background:

Autoimmune liver diseases, namely primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) generally have favorable posttransplant outcomes. PSC is known to require more retransplantation compared with PBC, however, comparisons to AIH are lacking. We sought to compare graft survival and the need for retransplant in AIH compared with other autoimmune liver disease.

Study:

We compared posttransplant graft survival among the 3 entities using Cox regression and competing for risk analyses using the United Network for Organ Sharing (UNOS) database.

Results:

We found AIH is associated with significantly decreased graft survival compared with PBC [hazard ratio: 0.86; 95% confidence interval (CI): 0.77-0.96] and PSC (hazard ratio: 0.89; 95% CI: 0.8-0.99) after controlling for potential confounders. This is mainly driven by posttransplant death. On competing for risk analysis, AIH was associated with higher risk of death compared with PBC [subdistribution hazard ratio (SHR): 0.79; 95% CI: 0.7-0.89] and PSC (SHR: 0.72; 95% CI: 0.64-0.82) and lower risk of retransplant compared with PSC (SHR: 1.48; 95% CI: 1.19-1.8).

Conclusion:

As prior studies have shown the similar risk of disease recurrence in AIH and PSC, our study indicates at least part of the increased posttransplant mortality in AIH may be due lower retransplantation rate in this population.
Simultaneous local excision of synchronous rectal polyps by transanal endoscopic microsurgery
Authors: Issa Nida , Fenig Yaniv , Schmilovitz-Weiss Hemda , Khatib Muhammad , Nissim Bachar Gil , Gingold-Belfer Rachel , Yassin Mustafa
Published: October 2019

Background:

The approach to surgical resection of multiple rectal lesions when endoscopic polypectomy is unsuccessful has historically been radical rectal resection with total mesorectal excision. This approach is fraught with high morbidity and mortality. We explored the possibility of performing one transanal endoscopic microsurgery procedure to resect multiple synchronous rectal lesions.

Materials and methods:

A retrospective analysis of all adult patients undergoing transanal endoscopic microsurgery at a single institution between 2004 and 2015. Clinical, demographic, and pathologic data were analyzed for all patients with synchronous rectal lesions that were excised via one transanal endoscopic microsurgery procedure.

Results:

Of the 158 patients who underwent transanal endoscopic microsurgery during the study period, 14 (8.8%) had two or more synchronous rectal lesions resected. The mean tumor size was 2.5 cm (range 0.5–3.5). The mean distance from the anal verge for the upper/proximal lesions: 10 ± 2.5 cm, and for the lower/distal lesions: 7 ± 2 cm. Mean operative time was 112 minutes (range 75–170). Median hospitalization time was 3 days (range 2–4). Two patients had urinary retention. No other complications were noted. All the transanal endoscopic microsurgery specimens were with clear margins.

Conclusion:

Transanal endoscopic microsurgery is a safe and feasible procedure for patients with multiple rectal lesions. We demonstrate no increase in surgical time, completeness of specimen resection, no increase in complications or hospital length or stay when compared to patients undergoing transanal endoscopic microsurgery for a single lesion.
Response to Propoxyphene Market Withdrawal
Authors: Jeffery Molly M. , Morden Nancy E. , Larochelle Marc , Shah Nilay D. , Hooten W. Michael , Meara Ellen
Published: October 2019

Objective:

Experts cautioned that patients affected by the November 2010 withdrawal of the opioid analgesic propoxyphene might receive riskier prescriptions. To explore this, we compared drug receipts and outcomes among propoxyphene users before and aftermarket withdrawal.

Study Design:

Using OptumLabs data, we studied 3 populations: commercial, Medicare Advantage (MA) aged (age 65+ y) and MA disabled (age below 65 y) enrollees. The exposed enrollees received propoxyphene in the 3 months before market withdrawal (n=13,622); historical controls (unexposed) received propoxyphene 1 year earlier (n=9971). Regression models estimated daily milligrams morphine equivalent (MME), daily prescription acetaminophen dose, potentially toxic acetaminophen doses, nonopioid prescription analgesics receipt, emergency room visits, and diagnosed falls, motor vehicle accidents, and hip fractures.

Principal Findings:

Aged MA enrollees illustrate the experience of all 3 populations examined. Following the market withdrawal, propoxyphene users in the exposed cohort experienced an abrupt decline of 69% in average daily MME, compared with a 14% decline in the unexposed. Opioids were discontinued by 34% of the exposed cohort and 18% of the unexposed. Tramadol and hydrocodone were the most common opioids substituted for propoxyphene. The proportion of each group receiving ≥4 g of prescription acetaminophen per day decreased from 12% to 2% in the exposed group but increased from 6% to 8% among the unexposed. Adverse events were rare and not significantly different in exposed versus unexposed groups.

Conclusions:

After propoxyphene market withdrawal, many individuals experienced abrupt discontinuation of opioids. Policymakers might consider supporting appropriate treatment transitions and monitoring responses following drug withdrawals.
Thirty-Day Hospital Readmission Among Homeless Individuals With Medicaid in Massachusetts
Authors: Racine Melanie W. , Munson David , Gaeta Jessie M. , Baggett Travis P.
Published: October 2019

Background:

National efforts are underway to reduce hospital readmissions. Few studies have used administrative data to provide a global view of readmission among people experiencing homelessness, who often utilize multiple hospital systems.

Objective:

To examine the 30-day hospital readmission rate and factors associated with readmission following discharge among homeless Medicaid members in Massachusetts.

Methods:

We analyzed medical record and Medicaid administrative data for 1269 hospitalizations between 2013 and 2014 for 458 unique patients attributed to Boston Health Care for the Homeless Program. Generalized Estimating Equations were used to investigate factors associated with readmission.

Results:

Of all hospitalizations, 27% resulted in readmission, more than double the average national Medicaid readmission rate. Leaving against medical advice was associated with increased readmission, while having a Health Care for the Homeless primary care practitioner was associated with reduced readmission. Among the most frequently admitted individuals, being discharged to medical respite care was associated with reduced readmission.

Conclusions:

To break the readmission cycle, health care providers serving homeless individuals could focus on assuring access to medical respite care and extending outreach efforts that increase primary care engagement. This may be especially important for accountable care systems, as safety net providers increasingly assume financial risk for patients’ total cost and quality of care.
Exploring Use of Endoscopy Simulation in North American Pediatric Gastroenterology Fellowship Training Programs
Authors: Gabrani Aayush , Monteiro Iona M. , Walsh Catharine M.
Published: October 2019

Objectives:

Increasing evidence supports simulation‐based training; however, limited data exist regarding its use in pediatric gastroenterology (GI). We explored the use of simulation‐based endoscopy training in pediatric GI fellowship programs across North America.

Methods:

GI fellowship program directors (PDs) from the United States and Canada were surveyed between August to November 2018. The pretested, electronic survey comprised 3 sections: program demographics; details of current simulation‐based training; and PDs’ perceptions of endoscopy simulation. Responses were analyzed using descriptive statistics.

Results:

Forty‐three of 71 (61%) PDs responded (6 Canadian, 37 US). Programs were predominantly academic (95%) and enrolled 1.87 ± 1.01 fellows/yr. Twenty‐four programs (56%) reported using simulation for endoscopy training, whereas 8 (19%) used simulation for nonprocedural education. Only 2 programs (5%) used endoscopy simulation for assessment. Of those using simulation (n = 24), upper endoscopy and colonoscopy were trained most frequently, and mechanical simulators were used most commonly. Eight programs (33%) required simulation training prior to clinical performance. Although 10 programs (42%) provided protected training time, only 2 (8%) tracked hours. Three programs (13%) reported having an organized curriculum and 6 (25%) train their endoscopic trainers. Cost, time constraints, and lack of a standardized curriculum were perceived as key barriers to integration. Most PDs reported a need for endoscopy simulation to train both technical and nontechnical skills; however, they felt simulation cannot replace clinical experience.

Conclusion:

PDs recognize the potential importance of endoscopy simulation, particularly for novices; however, only 56% report using it. Perceived barriers indicate the need for inexpensive portable simulators and a validated pediatric simulation curriculum to promote uptake.
Immigrant Women's Experiences as Mothers in the United States
Authors: Oerther Sarah , Lach Helen W. , Oerther Daniel
Published: October 2019

Background:

Immigrant mothers are raising an increasing proportion of the population of children in the United States.

Purpose:

The purpose of this review was to explore existing research on immigrant women's experiences of being mothers in the United States and identify key concepts, gaps in the literature, and implications for future research that builds on the strengths of immigrant women while addressing their unique challenges.

Study Design and Methods:

In this scoping review, Ovid MEDLINE, CINAHL, SCOPUS, Web of Science, JUSTOR, and PsycINFO databases were searched using a combination of applicable key words.

Results:

Twenty-two articles were selected. Few studies were identified. Analyses revealed a broad array in purpose, populations, theoretical frameworks, settings, study instruments, and practices, making comparison difficult. Although mothering is a universal experience among women who have children, little is known about the broad experiences of immigrant women from different cultures.

Clinical Implications:

Immigrant mothers are not a monolithic group. More research is needed to provide a deeper understanding of strengths, challenges, and solutions of various immigrant groups, which can facilitate development of nursing interventions that support immigrant women and their children in the United States, and strengthen their families.
Examining the Beliefs of Skilled Nursing Facility Directors of Nursing Regarding BSN Completion and the Impact of Nurse Leader Education on Patient Outcomes
Authors: Holle Cynthia L. , Sundean Lisa J. , Dellefield Mary Ellen , Wong John , Lopez Ruth Palan
Published: October 2019

Research suggests that acute care patients cared for by baccalaureate-educated nurses have better outcomes. Directors of nursing (DONs) in skilled nursing facilities (SNFs) have lower rates of baccalaureate attainment than acute care nurses for unclear reasons. To understand the interest in advancing education, researchers surveyed SNF DONs in Connecticut to examine their beliefs about academic advancement and the impact of DON education on resident outcomes. Nearly 70% of participants with diplomas and associate degrees lacked interest in degree advancement and did not believe a baccalaureate degree is necessary for DONs or that DON level of education impacts resident outcomes. Alternatives to degree completion may include interventions to provide SNF DONs with skills for improving resident outcomes.
Ensuring Workplace Safety
Authors: Bromley Gail , Painter Susan
Published: October 2019

Healthcare workplace violence is a growing concern among nurses; however, nurse administrators and managers may not be fully aware of the level, frequency, or extent of the trauma that staff nurses experience. This information gap is influenced by nurses' failure to report violent incidents, their belief that they are expected to care for violent/assaultive patients, time required for extensive documentation about these incidents, and perceptions that minimal follow-up to mitigate future episodes will occur. This article describes the evidence-based structures, processes, and practices supported to minimize organizational risk and protect nurses and other staff from being physically or emotionally injured and/or traumatized in the workplace.
Population Level-Impact and Herd Effects Following the Introduction of Human Papillomavirus Vaccination Programmes: Updated Systematic Review and Meta-analysis
Authors: Drolet Mélanie , Bénard Élodie , Pérez Norma , Brisson Marc
Published: October 2019

(Abstracted from Lancet 2019;394:497–509)

To date, a total of 99 countries and territories have introduced population-level human papillomavirus (HPV) vaccination programs. Early adopting countries have served as models and produced observational and epidemiological data on the ability of such programs in preventing HPV-related infections and diseases.
Management of Preexisting Diabetes in Pregnancy: A Review
Authors: Alexopoulos Anastasia-Stefania , Blair Rachel , Peters Anne L.
Published: October 2019

(Abstracted from JAMA 2019;321(18):1811–1819)

Preexisting diabetes complicates 0.9% of pregnancies in the US and increases the risk of adverse maternal and neonatal outcomes, specifically linked to preeclampsia, congenital anomalies, preterm delivery, and stillbirth. With type 1 and type 2 diabetes becoming more common, clinicians need to review planning and optimization of glycemic control with patients before pregnancy to mitigate the risk associated with diabetes.
Preimplantation Genetic Testing for Aneuploidy by Microarray Analysis of Polar Bodies in Advanced Maternal Age: A Randomized Clinical Trial
Authors: Verpoest Willem , Staessen Catherine , Bossuyt Patrick M. , Goossens Veerle , Altarescu Gheona , Bonduelle Maryse , Devesa Martha , Eldar-Geva Talia , Gianaroli Luca , Griesinger Georg , Kakourou Georgia , Kokkali Georgia , Liebenthron Jana , Magli Maria-Cristina , Parriego Monica , Schmutzler Andreas G. , Tobler Monica , van der Ven Katrin , Geraedts Joep , Sermon Karen
Published: October 2019

(Abstracted from Human Reproduction 2018;33(9):1767–1776)

Preimplantation genetics for aneuploidy (PGT-A) has shown mixed results on pregnancy rates when applied at the cleavage stage of development due to a high rate of mosaicism and limitations of the comprehensive chromosomal screening technology, FISH, which was available at the time. A pilot study aiming to address this found that array comparative genomic hybridization (aCGH) analysis of both polar bodies possessed 94% concordance with the chromosome analysis of the resulting fertilized oocytes.
MUC4 Expression in Angiomatoid Fibrous Histiocytoma
Authors: Abrahao-Machado Lucas F. , Bacchi Livia M. , Fernandes Igor L. , Costa Felipe D’Almeida , Bacchi Carlos E.
Published: October 2019

Angiomatoid fibrous histiocytoma (AFH) is a rarely metastasizing neoplasm that typically occurs in the deep dermis and subcutis of the extremities of young patients, characterized by a t(2;22) translocation involving EWSR1 and CREB1. Because of its distinctive histologic features, the diagnosis of AFH is generally straightforward, although the immunohistochemistry (IHC) findings are relatively nonspecific. We recently encountered a case of primary cranial AFH that showed strong MUC4 IHC expression, which has not yet been reported previously. Prompted by this surprising finding, we investigated MUC4 expression in a series of AFH to evaluate this potential diagnostic pitfall. The expression of ALK by IHC, recently discovered in AFH, was also assessed in this study. We also analyzed EWSR1 rearrangement by fluorescence in situ hybridization using a dual color break-apart probe to confirm the diagnosis. The results showed MUC4 expression in 22.2% of AFH cases (4/18 cases), demonstrating a variable intensity of cytoplasmic staining. Most notably, one of the positive cases showed strong and diffuse expression. ALK IHC expression was observed in 17 of 18 cases (94.4%), usually in a diffuse and strong cytoplasmic pattern. EWSR1 rearrangement was demonstrated by fluorescence in situ hybridization in 81.2% of cases (13 of 16), including all the MUC4-positive cases. Our results indicate that although the significance of MUC4 expression in AFH is unknown, it is important to be aware that a subset of AFH can express the protein by IHC, expanding a variety of MUC4-positive mesenchymal tumors.
FDG PET/CT of Cervical Gout With Spinal Cord Compression
Authors: Emsen Berivan , Fitoussi Alexandre , Chalaye Julia , Adam Clovis , Itti Emmanuel
Published: October 2019

We report FDG PET/CT images of a 63-year-old woman referred for characterization of osteolytic lesions of the cervical spine. This patient with chronic renal failure had a history of follicular thyroid carcinoma with undifferentiated cells, treated by a total thyroidectomy, completed by radioactive iodine in 2017. Because of cancer history, a FDG PET/CT was performed and showed multiple moderately hypermetabolic osteolytic lesions of the spine from C3 to T1, with joint erosion on CT. A laminectomy was performed for cervical spinal cord decompression and revealed a gouty tophus.
A New Suture Technique for Peritoneal Flap Closure in TAPP: A Prospective Randomized Controlled Trial
Authors: Zhu Yilin , Liu Yuchen , Wang Minggang
Published: October 2019

Purpose:

To facilitate the suture step, we describe a new suture method for laparoscopic closure of the peritoneal flap in transabdominal preperitoneal (TAPP). A prospective randomized controlled trial was carried out to evaluate the efficacy of the new suture method compared with the conventional method.

Methods:

Eighty patients who presented to our hospital in May 2019 with primary unilateral inguinal hernia were randomized into the conventional suture method group and the new suture group for TAPP repairs. The primary outcome was the suture time to complete the peritoneal flap closure. Secondary outcomes included the number of cases of peritoneum tearing, need for additional suture, and suture line breaking.

Results:

The suture time in the new suture method group was significantly shorter than that of the conventional group (715.3±132.4 s vs. 840.71±137.9 s, P<0.001); furthermore, there were significantly less number of cases of peritoneal tearing in the new suture method group than in the conventional suture method group (4 vs. 11, P<0.01).

Conclusions:

The new suture method is relatively easy to learn for beginners performing TAPP procedures, as compared with the conventional method, and less peritoneal tearing is encountered when using this method for peritoneal flap closure.
Mechanisms and treatment of bone pain in multiple myeloma
Authors: Davies Matthew Philip , Fingas Sam , Chantry Andrew
Published: October 2019

Purpose of review

Multiple myeloma is a haematological malignancy of differentiated B lymphocytes, known as plasma cells. The disease is common in the UK (incidence of 9 cases per 100 000 people) and the most frequent presentation is bone pain caused by skeletal damage. Patients with myeloma also experience neuropathic pain induced by chemotherapy. The management of pain in multiple myeloma is frequently demanding and often sub-optimally addressed. This review seeks to summarize a rational approach to the management of pain experienced by multiple myeloma patients.

Recent findings

Bone pain has a dramatic detrimental impact on a patient's physical capacity, and therefore, quality of life. Various mechanisms of bone pain have been elucidated; however, neuropathic bone pain in multiple myeloma is not completely understood. Potential mechanisms for this phenomenon; namely increased intraosseous pressure and the acidity of the bone marrow in the disease state will be interrogated. The current analgesic pathways used to treat multiple myeloma bone pain and new advances in therapies that may confer future benefit to patients will briefly be reviewed.

Holistic care and the provision of an array of pain relief methods is required to achieve effective pain control in multiple myeloma bone pain and requires a concerted effort from the healthcare team to be realized.
Functional Fitness in Older Adults
Authors: Yang Ya-Ping , Lin Hsiu-Ching , Chen Kuei-Min
Published: October 2019

Background:

Using multiple interventions can increase muscle strength in older adults. A functional fitness test is a useful instrument to identify the effectiveness of physical functioning among older adults. However, the results in previous studies with regard to improvements in their physical function are inconsistent.

Aim:

To synthesize the intensity and interval of the effective interventions on physical functioning in community-dwelling older adults.

Methods:

A systematic review and meta-analysis on the related literature was conducted. The databases searched were PubMed, EBSCO, and Cochrane Trials. Papers published from January 1, 2013, to December 31, 2017, were subjected to a computerized search. The inclusion criteria were that the randomized controlled trials examined a healthy and community-dwelling older adult population, and the instrument used to evaluate functional fitness was based on “functional fitness” or “senior fitness.” Two reviewers independently assessed the methodological quality of each trial, including study participants, allocation, blinding, data analysis, duration of follow-up and loss to follow-up, intervention, inclusion criteria, outcome measurements, and other biases.

Results:

Among the 218 trials, only 5 randomized control trials were synthesized in this systematic review. These works examined the effects of the intensity, interval, and duration of intervention programs based on elastic band exercise, aerobic training and combined aerobic and resistance training, Tai Chi with TheraBand resistance exercise, and Tai Chi and Thai Yoga exercise.

Conclusions:

A 1-hour intervention program, including 10 to 15 minutes of warm-up, 30 to 40 minutes of main exercise, and 5 to 10 minutes of cool-down stages, for 2 to 3 sessions per week, and continuing for 12 to 16 weeks, was the effect intervention for community-dwelling healthy older adults to enhance their upper body strength, lower body flexibility, and agility balance.
Effects of Tai Chi Combined With Theraband Training on Physical Fitness, Psychological Well-being, and Pain in Older Sedentary Office Workers
Authors: Qi Meiling , Moyle Wendy , Jones Cindy , Weeks Benjamin
Published: October 2019

Objectives:

The aim of this study was to compare the effectiveness of Tai Chi combined with Theraband training with Tai Chi exercise–only on physical fitness, psychological well-being, and pain in older sedentary office workers.

Materials and Methods:

Forty sedentary office workers older than 55 years were recruited and randomly assigned to an intervention or control group. Both groups received Tai Chi exercise for 12 weeks, 3 times per week, whereas participants in the intervention group also held a Theraband using 2 hands when practicing Tai Chi. Physical and psychological measurements and pain scores were collected at baseline, week 6, and week 12.

Results and Conclusions:

The results showed a significant improvement in lower-limb and right upper-limb strength after the Tai Chi combined with Theraband intervention. Future research might extend the length of the intervention.
The small RNA microRNA-212 regulates sirtuin 2 expression in a cellular model of oxygen-glucose deprivation
Authors: Zhao Guangming , He Juan , Wang Zhiguang , Bao Leri , Cong Ribo , An Wenrui , Zhao Xueliang , Liu Guiying
Published: October 2019

MicroRNA-212 has been found to play an important role in several types of diseases, but the functional and potential mechanisms of microRNA-212 in ischemic brain injury are still unclear. The aims of this study were to investigate the potential role of microRNA-212 in ischemic brain injury and to reveal potential molecular mechanisms. The rat oxygen-glucose deprivation and simulated reperfusion model was established to study the role of microRNA-212 in ischemic brain injury. The expression of microRNA-212 in oxygen-glucose deprivation and simulated reperfusion model and its effect on cell proliferation were measured by quantitative reverse transcription PCR and Cell Counting Kit-8 assay, respectively. The relationships between microRNA-212 and sirtuin 2 were confirmed by luciferase-reporter assay. We observed that microRNA-212 was downregulated after oxygen-glucose deprivation and simulated reperfusion treatment. Besides, the cells viabilities were increased/decreased in oxygen-glucose deprivation and simulated reperfusion model after transfection with microRNA-212 agomir (agonist of microRNA-212 action) and microRNA-212 antagomir (inhibitor of microRNA-212 action). In addition, luciferase and western blot experiments showed that microRNA-212 directly regulated sirtuin 2 changes. Furthermore, promotion of neuronal survival by microRNA-212 was blocked by overexpression of sirtuin 2, whereas the neuronal death induced by microRNA-212 inhibition was rescued by sirtuin 2 inhibition. Taken together, our study revealed that the role of miR-212 in the modulation of ischemic brain injury might be achieved by regulating sirtuin 2, which provides potential biomarkers and candidates for the treatment of cerebral ischemia.
Bihemispheric changes associated with cognition in patients with chronic brainstem stroke
Authors: Ahn Dahyun , Kyeong Sunghyon , Kang Hyunkoo , Kim Dae Hyun
Published: October 2019

Objective:

We aimed to identify brain changes associated with preserved cognitive function in patients with chronic brainstem stroke.

Methods:

Twelve patients with chronic brainstem stroke and 24 age-matched healthy controls were included in this retrospective study. All participants underwent T1-weighted, diffusion tensor, and resting-state functional MRI. Gray matter density, fractional anisotropy, and mean diffusivity maps from diffusion tensor imaging and seven cognition-related independent component maps from resting-state functional MRI were used to identify differences in brain volume, structural connectivity, and functional connectivity. Independent t-tests were used to determine the statistical significance of changes in gray matter density, fractional anisotropy, mean diffusivity, and inter-network functional connectivity maps.

Results:

Bilateral cerebellum volumes and structural connectivity of the diffuse bilateral cerebral hemispheres were significantly lower in the patient than in the control group. However, patients exhibited increased gray matter volume and increased structural connectivity of the temporal lobe in the contra-lesional hemisphere and basal forebrain, compared with healthy controls. Furthermore, the intra-network functional connectivity in the frontal and temporal lobes was significantly higher in patients than in controls (P
FWE < 0.05).

Conclusion:

In the patient group, the brain regions mainly associated with the cholinergic system exhibited increased volume, structural connectivity, and functional connectivity. In contrast, the regions connected with the brainstem via cortico-ponto-cerebellar fibers exhibited decreased volume or structural connectivity. Cognitive function may be preserved in patients with brainstem stroke due to significant increases in frontal and temporal inter-network connectivity.
PheWAS-ME: A web-app for interactive exploration of multimorbidity patterns in PheWAS
Authors: Strayer Nick , Shirey-Rice Jana K , Shyr Yu , Denny Joshua C. , Pulley Jill M. , Xu Yaomin
Published: October 2019

Electronic health records (EHRs) linked with a DNA biobank provide unprecedented opportunities to use big data for biomedical research in precision medicine. The Phenome-wide association study (PheWAS) is a widely used technique for high-throughput evaluation of relationships between a set of genetic variants and a large collection of clinical phenotypes recorded in EHRs. PheWAS analyses are typically presented as static tables and charts of summary statistics obtained from statistical tests of association between pairs of a genetic variant and individual phenotypes. Comorbidities are common and typically lead to complex, multivariate gene-disease association signals that are challenging to interpret. Discovering and interrogating multimorbidity patterns and their influence in PheWAS is difficult and time-consuming. Here, we present a web application to visualize individual-level genotype and phenotype data side-by-side with PheWAS analysis results in an interactive dashboard, allowing researchers to explore multimorbidity patterns and their associations with a genetic variant of interest. We expect this application to enrich PheWAS analyses by illuminating clinical multimorbidity patterns present in the data.

Availability

A demo PheWAS-ME application is publicly available at https://prod.tbilab.org/phewas_me/. A sample simulated-dataset is provided for exploration with the option to upload custom PheWAS results and corresponding individual-level data. The source code is available as an R package on GitHub (https://github.com/tbilab/multimorbidity_explorer).
Co-circulation and misdiagnosis led to underestimation of the 2015-2017 Zika epidemic in the Americas
Authors: Oidtman Rachel J. , España Guido , Perkins T. Alex
Published: October 2019

During the 2015-2017 Zika epidemic, dengue and chikungunya – two other viral diseases with the same vector as Zika – were also in circulation. Clinical presentation of these diseases can vary from person to person in terms of symptoms and severity, making it difficult to differentially diagnose them. Under these circumstances, it is possible that numerous cases of Zika could have been misdiagnosed as dengue or chikungunya, or vice versa. Given the importance of surveillance data for informing epidemiological analyses, our aim was to quantify the potential extent of misdiagnosis during this epidemic. Using basic principles of probability and empirical estimates of diagnostic sensitivity and specificity, we generated revised estimates of Zika incidence that accounted for the accuracy of diagnoses made on the basis of clinical presentation with or without molecular confirmation. Applying this method to weekly incidence data from 43 countries throughout Latin America and the Caribbean, we estimated that 1,062,821 (95% CrI: 1,014,428-1,104,794) Zika cases occurred during this epidemic, which is 56.4% (95% CrI: 49.3-62.6%) more than the 679,743 cases diagnosed as Zika. Our results imply that misdiagnosis was more common in countries with proportionally higher incidence of dengue and chikungunya, such as Brazil.
Comprehensive molecular characterization of pediatric treatment-induced high-grade glioma: A distinct entity despite disparate etiologies with defining molecular characteristics and potential therapeutic targets
Authors: DeSisto John , Lucas John T. , Xu Ke , Donson Andrew , Lin Tong , Sanford Bridget , Wu Gang , Tran Quynh T. , Hedges Dale , Hsu Chih-Yang , Armstrong Gregory T. , Arnold Michael , Bhatia Smita , Flannery Patrick , Lemma Rakeb , Hardie Lakotah , Schüller Ulrich , Hoffman Lindsey M. , Dorris Kathleen , Levy Jean Mulcahy , Hankinson Todd C. , Handler Michael , Liu Arthur , Foreman Nicholas , Vibhakar Rajeev , Jones Kenneth , Allen Sariah , Zhang Jinghui , Baker Suzanne J. , Merchant Thomas E. , Orr Brent A. , Green Adam L.
Published: October 2019

Treatment-induced high-grade gliomas (TIHGGs) are an incurable late complication of cranial radiation therapy or combined radiation/chemotherapy used to treat pediatric cancer. We assembled a cohort of 33 TIHGGs from multiple institutions. The primary antecedent malignancies were medulloblastoma, acute lymphoblastic leukemia, astrocytoma, and ependymoma. We performed methylation profiling, RNA-seq, and genomic sequencing (whole-genome or whole-exome) on TIHGG samples. Methylation profiling revealed that TIHGGs cluster primarily with the pediatric receptor tyrosine kinase I subtype (26/31 samples). Common TIHGG copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, Ch. 4 loss, Ch. 6q loss, and Ch. 13 and Ch. 14 loss; focal alterations include PDGFRA and CDK4 gain and loss of CDKN2A and BCOR. Relative to de novo pediatric high-grade glioma (pHGG), BCOR loss (p=0.004) and CDKN2A loss (p=0.005) were significantly increased. Transcriptomic analysis identified two distinct TIHGG subgroups, one with a lesser mutation burden (0.12 mut/Mb), Ch. 1p loss/1q gain (5/6 samples), and stem cell characteristics, and one with a greater mutation burden (1.08 mut/Mb, p<0.0002), depletion of DNA repair pathways, and inflammatory characteristics. We observed increased chromothripsis in TIHGG versus pHGG (67% vs. 31%, p=0.036), which was associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. In vitro drug screening in one primary, patient-derived TIHGG cell line from each expression subgroup identified microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors as potentially effective therapies. This study provides a comprehensive molecular profile of TIHGG, including mechanistic insights to TIHGG oncogenesis, and identifies potentially effective therapeutic modalities for further investigation.
Pan-cancer computational histopathology reveals mutations, tumor composition and prognosis
Authors: Fu Yu , Jung Alexander W , Torne Ramon Viñas , Gonzalez Santiago , Vöhringer Harald , Shmatko Artem , Yates Lucy , Jimenez-Linan Mercedes , Moore Luiza , Gerstung Moritz
Published: October 2019

The diagnosis of cancer is typically based on histopathological assessment of tissue sections, and supplemented by genetic and other molecular tests1–6. Modern computer vision algorithms have high diagnostic accuracy and potential to augment histopathology workflows7–9. Here we use deep transfer learning to quantify histopathological patterns across 17,396 hematoxylin and eosin (H&E) stained histopathology slide images from 28 cancer types and correlate these with matched genomic, transcriptomic and survival data. This approach accurately classifies cancer types and provides spatially resolved tumor and normal distinction. Automatically learned computational histopathological features correlate with a large range of recurrent genetic aberrations pan-cancer. This includes whole genome duplications, which display universal features across cancer types, individual chromosomal aneuploidies, focal amplifications and deletions as well as driver gene mutations. There are wide-spread associations between bulk gene expression levels and histopathology, which reflect tumour composition and enables localising transcriptomically defined tumour infiltrating lymphocytes. Computational histopathology augments prognosis based on histopathological subtyping and grading and highlights prognostically relevant areas such as necrosis or lymphocytic aggregates. These findings demonstrate the large potential of computer vision to characterise the molecular basis of tumour histopathology and lay out a rationale for integrating molecular and histopathological data to augment diagnostic and prognostic workflows.
Head motion during fMRI tasks is reduced in children and adults if participants take breaks
Authors: Meissner Tobias W. , Walbrin Jon , Nordt Marisa , Koldewyn Kami , Weigelt Sarah
Published: October 2019

Head motion remains a challenging confound in functional magnetic resonance imaging (fMRI) studies of both children and adults. Most pediatric neuroimaging labs have developed experience-based, child-friendly standards concerning e.g. the maximum length of a session or the time between mock scanner training and actual scanning. However, it is unclear which factors of child-friendly neuroimaging approaches are effective in reducing head motion. Here, we investigate three main factors including (i) time lag of mock scanner training to the actual scan, (ii) prior scan time, and (iii) task engagement in a dataset of 77 children (aged 6-13) and 64 adults (aged 18-35) using a multilevel modeling approach. In children, distributing fMRI data acquisition across multiple same-day sessions reduces head motion. In adults, motion is reduced after inside-scanner breaks. Despite these positive effects of splitting up data acquisition, motion increases over the course of a study as well as over the course of a run in both children and adults. Our results suggest that splitting up fMRI data acquisition is an effective tool to reduce head motion in general. At the same time, different ways of splitting up data acquisition benefit children and adults.

Highlights

In children, fMRI data acquisition split into multiple sessions reduces head motion

In adults, fMRI data acquisition split by inside-scanner breaks reduces head motion

In both children and adults, motion increases over the duration of a study

In both children and adults, motion increases over the duration of a run
Two Receptor-Like Kinases Required For Arabidopsis Endodermal Root Organisation Shape The Rhizosphere Microbiome
Authors: Durr Julius , Reyt Guilhem , Spaepen Stijn , Hilton Sally , Meehan Cathal , Qi Wu , Kamiya Takehiro , Flis Paulina , Dickinson Hugh G. , Feher Attila , Bending Gary D. , Schulze-Lefert Paul , Salt David , Gutierrez-Marcos Jose
Published: October 2019

The Casparian Strip (CS) constitutes a physical diffusion barrier to water and nutrients in plant roots, and is formed by the polar deposition of lignin polymer in the endodermis. This precise pattern of lignin deposition is thought to be mediated by the scaffolding activity of membrane-bound Casparian Strip domain proteins (CASPs). However, we show that endodermis-specific receptor-like kinase 1 (ERK1) and ROP Binding Kinase1 (RBK1) are also involved in this intricate process, with the former playing an essential role both in the localization of CASP1 and in lignin deposition. We further characterised ERK1 and determined its subcellular localisation in the cytoplasm and nucleus of the endodermis, as well as provide evidence for its involvement in a signalling pathway together with the circadian clock regulator, Time for Coffee (TIC). We also show that disruption to CS organisation and increased suberisation in the endodermis due to loss of function of eitherERK1orTICcollectively leads to an altered root microbiome composition. Thus, our work reveals additional players in the complex cascade of signalling events operating in the root endodermis to establish both the CS diffusion barrier and the microbial composition of the rhizosphere.
Male genital lobe morphology affects the chance to copulate inDrosophila pachea
Authors: Lefèvre Bénédicte M. , Catté Diane , Courtier-Orgogozo Virginie , Lang Michael
Published: October 2019

Introduction

Male genitalia are thought to ensure transfer of sperm through direct physical contact with female during copulation. However, little attention has been given to their pre-copulatory role with respect to sexual selection and sexual conflict. Males of the fruitflyDrosophila pacheahave a pair of asymmetric external genital lobes, which are primary sexual structures and stabilize the copulatory complex of female and male genitalia. We wondered if genital lobes inD. pacheamay have a role before or at the onset of copulation, before genitalia contacts are made.

Results

We tested this hypothesis with aD. pacheastock where males have variable lobe lengths. In 92 mate competition trials with a single female and two males, females preferentially engaged into a first copulation with males that had a longer left lobe and that displayed increased courtship vigor. In 53 additional trials with both males having partially amputated left lobes of different lengths, we observed a weaker and non-significant effect of left lobe length on copulation success. Courtship durations significantly increased with female age and when two males courted the female simultaneously, compared to trials with only one courting male. In addition, lobe length did not affect sperm transfer once copulation was established.

Conclusion

Left lobe length affects the chance of a male to engage into copulation. The morphology of this primary sexual trait may affect reproductive success by mediating courtship signals or by facilitating the establishment of genital contacts at the onset of copulation.