bluuebunny/crossref_metadata_2025 huggingface dataset:
A high mutation rate of immunoglobulin heavy chain variable region gene associates with a poor survival and chemotherapy response of mantle cell lymphoma patients
Authors: Li Xianqian , Wu Ning , Li Bin
Published: May 2019

Immunoglobulin heavy chain variable region (IGHV) gene mutation status is a biomarker for the prognosis of chronic lymphocytic leukemia, whether it is associated with the diagnosis, staging, and prognosis of patients with mantle cell lymphoma (MCL) remains to be determined.

The IGHV gene mutations of 52 MCL patients were determined by DNA sequencing and compared with published IGHV germline sequences.

DNA sequence alignment of IGHV variable regions with published IGHV germline sequences showed that the coincidence rate was 94% to 100%. Ten cases (21%) were significantly mutated with the rate of 96.9% to 94.0%. The overall survival time of patients was negatively correlated with the degree of IGHV gene mutation. Further survival analysis with log-rank test demonstrated that the patients with significant IGHV gene mutations showed a trend towards poor survival.

The mutation rate of the IGHV variant region may be determined to assess the prognosis and overall survival time of MCL patients.
The association between occupational stress and psychosomatic wellbeing among Chinese nurses
Authors: Gu Bo , Tan Qiling , Zhao Shangping
Published: May 2019

Occupational stress impairs nurses’ psychosomatic wellbeing, which includes anxiety, depression, sleep quality, and somatic symptoms; however, few studies have focused on the associations between the subdimensions of occupational stress [workload and time pressure (WTP), professional and career issues (PC), patient care and interaction (PCI), interpersonal relationships and management problems (IRMP), resource and environment problem (REP)] and psychosomatic wellbeing among nurses in China. This study thus examined these associations using a cross-sectional survey in Sichuan, China. An online application was devised to collect data, with the scales of sociodemographic and occupational variables, Nurse Job Stressor Questionnaire, the 9- and 15-item Patient Health Questionnaires, the 7-item Generalized Anxiety Disorder scale, and the Pittsburgh Sleep Quality Index. Investigation was completed by 2889 nurses (96.7% women; mean age = 31.20 ± 6.72 years). Relationships were identified by correlation and multivariate regression analyses. Most (68.3%) nurses had high levels of occupational stress. The multivariate analyses revealed that WTP was correlated with anxiety (P = .003). PC was associated with depression (P = .033) and sleep quality (P = .078). PCI was correlated with anxiety (P = .031) and somatic symptoms (P = .005). IRMP was associated with anxiety (P = .018), depression (P = .001), and somatic symptoms (P = .025). Lastly, REPs had nonsignificant relationships with depression, anxiety, sleep quality, and somatic symptoms. In sum, nurses had high levels of occupational stress; therefore, a series of strategies should be implemented to help nurses cope with the above issues, which could promote nurses’ psychosomatic wellbeing, and have a buffering effect on nurses’ depression, anxiety, poor sleep quality, and somatic symptoms.
A meta-analysis of the diagnostic value of microRNA-1246 for malignant tumors
Authors: Xie Chunlin , Huang Tao , Teng Zhaowei , Xu Shuanglan , Bu Junhui , Li Mengzhou , Zhang Yibing , Zhang Jing
Published: May 2019

Background:

Cancer morbidity and mortality are growing rapidly worldwide. There have been an increasing number of studies on the correlation between miRNA1246 expression in circulating blood and tumors; however, no comprehensive conclusion has been reached. Therefore, this meta-analysis was carried out to systematically evaluate the diagnostic value of blood levels of microRNA-1246 for malignant tumors.

Methods:

We searched PubMed, MEDLINE, Embase, The Cochrane Library, the China National Knowledge Internet (CNKI), and Wanfang databases from the inception of each database until November 2018. The quality of the included literature was evaluated using the quality assessment tool called Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The data were pooled using Stata14 and Meta-DiSc 1.4 software.

Results:

Seven studies were included. The pooled sensitivity (SENS) was 0.80 (95% CI 0.65–0.89), the pooled specificity (SPEC) was 0.77 (95% CI 0.70–0.83), the pooled positive likelihood ratio (PLR) was 3.55 (95% CI 2.53–4.99), the pooled negative likelihood ratio (NLR) was 0.26 (95% CI 0.16–0.47), the pooled diagnostic odds ratio (DOR) was 13.78 (95% CI 5.84–32.5), and the area under the curve (AUC) was 0.83 (95% CI 0.79–0.86). The result of Deeks’ funnel plot was P = 0.31, indicating a lack of publication bias.

Conclusion:

MicroRNA-1246 in the blood can be used as a good indicator for the diagnosis of malignant tumor diseases and has a moderate diagnostic accuracy for the differentiation of patients with malignant tumors from healthy people.
Typical manifestations of Hürthle cell adenoma of the thyroid on contrast-enhanced CT
Authors: Deng Dayong , Chen Xi , Wang Hongru , Wu Haidi
Published: May 2019

Rationale:

Hürthle cell adenoma (HCA) of the thyroid is a rare thyroid tumor, and there are limited studies on the contrast-enhanced computed tomography (CT).

Patient concerns:

We report the case of a 63-year-old woman with gradual enlargement of the thyroid over 10 years.

Diagnoses:

Preoperative contrast-enhanced CT revealed typical lesion characteristics of HCA, confirmed by postoperative pathology.

Interventions:

Left thyroidectomy and partial right thyroidectomy were performed on the patient after general anesthesia.

Outcomes:

At follow-up of 12 months after surgery, the patient was in good health without recurrence.

Lessons:

The typical imaging features of HCA on contrast-enhanced CT are helpful for the early diagnosis of thyroid eosinophilic adenoma. This will provide an important basis for the preoperative diagnosis and treatment strategy of HCA of the thyroid in future.
Increased risk of gallstones after gastrectomy
Authors: Kim So Young , Bang Woo Jin , Lim Hyun , Lim Man Sup , Kim Miyoung , Choi Hyo Geun
Published: May 2019

This study sought to evaluate the association between gastrectomy and the occurrence of gallstones using a national sample cohort from Korea.

Data from 2002 to 2013 were collected for individuals ≥20 years of age in the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC). We extracted data for patients who had undergone gastrectomy (n = 1998) and a 1:4 matched control group (n = 7992) and then analyzed the occurrence of gallstones. The patients were matched according to age, sex, income, region of residence, hypertension, diabetes mellitus, and history of dyslipidemia. Gastrectomies were identified using operation codes (Q2533-Q2537, Q2594-Q2596, and Q2598). Gallstones were diagnosed if the corresponding International Classification of Disease-10 code (K80) was reported ≥2 times. Crude (simple) and adjusted hazard ratios (HRs) were analyzed using Cox proportional hazard models, and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed based on age and sex.

The adjusted HR for gallstones was 1.77 (95% CI = 1.34–2.35, P < .001) in the gastrectomy group compared to control. Consistent HRs were found in the analyses of all of the subgroups determined using age and sex.

The occurrence of gallstones was increased in the patients who had undergone gastrectomy compared to their matched control group.
Post-stroke rehabilitation
Authors: Rakesh Neal , Boiarsky Daniel , Athar Ammar , Hinds Shaliesha , Stein Joel
Published: May 2019

The aim of this study was to examine predictors of discharge of hospitalized stroke patients to either an acute inpatient rehabilitation facility (IRF) or subacute skilled nursing facility (SNF).

A retrospective cohort study was done in a large multicampus urban academic medical center of individuals hospitalized for stroke between January 1, 2015 and December 31, 2015 and who were discharged to either an IRF (n = 84) or SNF (n = 59). A set of characteristics and scales were collected on each patient and assessed using univariate and multivariate regression analyses.

Although univariate analyses revealed multiple measures were associated with discharge destination, the most predictive multivariate logistic regression model for discharge to SNF incorporated age (odds ratio [OR] = 1.09, 95% confidence interval [CI], 1.05–1.13), premorbid physical disability (OR 7.52, 95% CI 1.66–34.14), and inability to ambulate before discharge (OR 5.84, 95% CI 2.01–16.92) with an overall c-statistic of 0.85.

Increasing age, premorbid physical disability, and inability to ambulate increase the overall likelihood of discharge to a SNF. These findings need to be replicated in larger samples to determine whether they are generalizable.
Ultra-low-dose chest computed tomography for interstitial lung disease using model-based iterative reconstruction with or without the lung setting
Authors: Hata Akinori , Yanagawa Masahiro , Honda Osamu , Miyata Tomo , Tomiyama Noriyuki
Published: May 2019

The aim of this study was to assess the effects of reconstruction on the image quality and quantitative analysis for interstitial lung disease (ILD) using filtered back projection (FBP) and model-based iterative reconstruction (MBIR) with the lung setting and the conventional setting on ultra-low-dose computed tomography (CT).

Fifty-two patients with known ILD were prospectively enrolled and underwent CT at an ultra-low dose (0.18 ± 0.02 mSv) and a standard dose (7.01 ± 2.66 mSv). Ultra-low-dose CT was reconstructed using FBP (uFBP) and MBIR with the lung setting (uMBIR-Lung) and the conventional setting (uMBIR-Stnd). Standard-dose CT was reconstructed using FBP (sFBP). Three radiologists subjectively evaluated the images on a 3-point scale (1 = worst, 3 = best). For objective image quality analysis, regions of interest were placed in the lung parenchyma and the axillary fat, and standard deviation (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were evaluated. For 32 patients with clinically diagnosed idiopathic interstitial pneumonia, quantitative measurements including total lung volume (TLV) and the percentage of ILD volume (%ILDV) were obtained. The medians of 3 radiologists’ scores were analyzed using the Wilcoxon signed-rank test and the objective noise was analyzed using the paired t test. The Bonferroni correction was used for multiple comparisons. The quantitative measurements were analyzed using the Bland-Altman method.

uMBIR-Lung scored better than uMBIR-Stnd and worse than sFBP (P < .001), except for noise and streak artifact in subjective analysis. The SD decreased significantly in the order of uMBIR-Stnd, uMBIR-Lung, sFBP, and uFBP (P < .001). The SNR and CNR increased significantly in the order of uMBIR-Stnd, uMBIR-Lung, sFBP, and uFBP (P < .001). For TLV, there was no significant bias between ultra-low-dose MBIRs and sFBP (P > .3). For %ILDV, there was no significant bias between uMBIR-Lung and sFBP (p = 0.8), but uMBIR-Stnd showed significantly lower %ILDV than sFBP (P = .013).

uMBIR-Lung provided more appropriate image quality than uMBIR-Stnd. Although inferior to standard-dose CT for image quality, uMBIR-Lung showed equivalent CT quantitative measurements to standard-dose CT.
Therapeutic effects of acupuncture plus fire needle versus acupuncture alone in lateral epicondylitis
Authors: Wu Szu-Ying , Lu Cheng-Nan , Chung Chia-Jung , Kuo Chun-En , Sheen Jer-Ming , Hsueh Tun-Pin , Chen Ching-Chih , Bi Kuo-Wei
Published: May 2019

Background:

The aim of this study was to compare the short-term and intermediate-term efficacy of acupuncture plus fire needle therapy with that of acupuncture alone in the treatment of lateral epicondylitis (LE).

Methods:

Thirty-eight patients with LE who had persisted for at least 2 months were enrolled in this prospective, assessor-blinded, randomized controlled pilot trial. Twenty-one patients were randomized to the acupuncture plus fire needle group and 17 to the acupuncture-only group. The primary outcome was the visual analog scale pain score for the previous 24 hours and the secondary outcomes were the maximum grip strength, Patient-rated Forearm Evaluation Questionnaire score, and Medical Outcomes Study 36-Item Short-form Health Survey score. The values at baseline (pretreatment), at the end of treatment, and at 3 months after treatment were used to assess the short-term and intermediate-term effects of treatment. The data were analyzed using the Chi-square test and t test.

Results:

Within-group analyses showed better results for acupuncture plus fire needle therapy in the short term and intermediate term. Differences in the severity of pain and secondary outcomes were significant in the intermediate term in the acupuncture group. At the end of treatment, none of the differences in outcome scores were significant, except for maximum grip strength in the affected hand in the acupuncture group. No significant between-group differences in short-term or intermediate-term outcomes were observed.

Conclusion:

Acupuncture plus fire needle therapy was effective in the short term in patients seeking improvement of LE. Twelve treatments were effective for relieving pain and improving disability in the intermediate term in patients with chronic LE in both study groups. The findings of the pilot study confirm the feasibility of proceeding to a larger randomized controlled study of the longer-term effects of acupuncture plus fire needle therapy in patients with LE.
All-Cause Mortality and Cardiovascular Outcomes With Non-Vitamin K Oral Anticoagulants Versus Warfarin in Patients With Heart Failure in the Food and Drug Administration Adverse Event Reporting System
Authors: von Lueder Thomas G. , Atar Dan , Agewall Stefan , Jensen Jesper K. , Hopper Ingrid , Kotecha Dipak , Mentz Robert J. , Kim Moo Hyun , Serebruany Victor L.
Published: May 2019

Background:

Many patients with heart failure (HF) are treated with warfarin or non-vitamin K oral anticoagulants (NOACs). Randomized outcome-driven comparisons of different anticoagulant strategies in HF are lacking. Data from international, government-mandated registries may be useful in understanding the real-life use of various anticoagulants and how they are linked to outcomes.

Study Question:

To assess 2015 annual all-cause mortality, myocardial infarction, and stroke rates co-reported for warfarin and NOACs in subjects with and without HF in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Study Design:

We extracted and examined outcome cases in subjects with HF and on warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban and stratified these according to anticoagulants.

Measures and Outcomes:

Annual all-cause mortality, myocardial infarction, and stroke in FAERS.

Analysis Method:

Odds ratio (OR) and χ2

JOURNAL/ajthe/04.03/00045391-201912000-00001/inline-formula1/v/2023-09-17T022715Z/r/image-tiff

for oral anticoagulants from FAERS with and without HF among complete primary reports issued in 2015.

Results:

FAERS reported 137,026 HF cases, with death co-reported in 42,942 (31.3%). In total, 11,278 (8.2%) HF patients were treated with anticoagulants, with more prescribed warfarin (n = 8260) than all NOACs combined (n = 3018). Very few reports for edoxaban were available. Warfarin consistently displayed a signal for excess adverse events compared to NOACs: OR (95% confidence interval) for the composite of mortality, myocardial infarction, and stroke were 1.91 (1.76–2.07) versus apixaban, 1.92 (1.81–2.03) versus dabigatran, 4.09 (3.38–4.37) versus rivaroxaban, and 2.64 (2.53–2.76) versus all NOACs combined (all P < 0.001). Warfarin, compared to all NOACs combined, demonstrated higher rates of all-cause mortality [OR = 2.69 (95% confidence interval, 2.49–2.90)], myocardial infarction [5.30 (4.17–6.74)], stroke [OR = 8.85 (6.61–11.84)], and ischemic stroke [OR = 12.73 (8.87–18.27); all P < 0.001].

Conclusions:

Annual 2015 FAERS profiles in HF patients reveal that warfarin was numerically dominant. Warfarin was associated with higher risk of death, myocardial infarction, and stroke compared to NOACs. These observational data provide real-world insight into a potential safety benefit of NOACs over warfarin in the setting of HF.
High-density lipoprotein: our elusive friend
Authors: Asztalos Bela F. , Niisuke Katrin , Horvath Katalin V.
Published: May 2019

Purpose of review

Despite advances in the research on HDL composition (lipidomics and proteomics) and functions (cholesterol efflux and antioxidative capacities), the relationship between HDL compositional and functional properties is not fully understood. We have reviewed the recent literature on this topic and pointed out the difficulties which limit our understanding of HDL's role in cardiovascular disease (CVD).

Recent findings

Though current findings strongly support that HDL has a significant role in CVD, the underlying mechanisms by which HDL mitigates CVD risk are not clear. This review focuses on studies that investigate the cell-cholesterol efflux capacity and the proteomic and lipidomic characterization of HDL and its subfractions especially those that analyzed the relationship between HDL composition and functions.

Recent studies on HDL composition and HDL functions have greatly contributed to our understanding of HDL's role in CVD. A major problem in HDL research is the lack of standardization of both the HDL isolation and HDL functionality methods. Data generated by different methods often produce discordant results on the particle number, size, lipid and protein composition, and the various functions of HDL.
Management of pseudohypoparathyroidism
Authors: Germain-Lee Emily L.
Published: May 2019

Purpose of review

This review is timely given the 2018 publication of the first international Consensus Statement for the diagnosis and management of pseudohypoparathyroidism (PHP) and related disorders. The purpose of this review is to provide the knowledge needed to recognize and manage PHP1A, pseudopseudohypoparathyroidism (PPHP) and PHP1B – the most common of the subtypes – with an overview of the entire spectrum and to provide a concise summary of management for clinical use. This review will draw from recent literature as well as personal experience in evaluating hundreds of children and adults with PHP.

Recent findings

Progress is continually being made in understanding the mechanisms underlying the PHP spectrum. Every year, through clinical and laboratory studies, the phenotypes are elucidated in more detail, as are clinical issues such as short stature, brachydactyly, subcutaneous ossifications, cognitive/behavioural impairments, obesity and metabolic disturbances. Headed by a European PHP consortium, experts worldwide published the first international Consensus that provides detailed guidance in a systematic manner and will lead to exponential progress in understanding and managing these disorders.

As more knowledge is gained from clinical and laboratory investigations, the mechanisms underlying the abnormalities associated with PHP are being uncovered as are improvements in management.
The future of HIV Organ Policy Equity Act is now: the state of HIV+ to HIV+ kidney transplantation in the United States
Authors: Boyarsky Brian J. , Bowring Mary Grace , Shaffer Ashton A. , Segev Dorry L. , Durand Christine M.
Published: May 2019

Purpose of review

We report the current state of HIV+ to HIV+ kidney transplantation in the United States and remaining challenges in implementing this practice nationally.

Recent findings

The HIV Organ Policy Equity (HOPE) Act, which was the first step in unlocking the potential of HIV+ organ donors, mandates clinical research on HIV+ to HIV+ transplantation. As of March 2019, there have been 57 HOPE donors, including both true and false positive HOPE donors resulting in more than 120 transplants.

The HOPE Act, signed in 2013, reversed the federal ban on the transplantation of organs from HIV+ donors into HIV+ recipients. Ongoing national studies are exploring the safety, feasibility, and efficacy of both kidney and liver transplantation in this population. If successfully and fully implemented, HIV+ to HIV+ transplantation could attenuate the organ shortage for everyone waiting, resulting in a far-reaching public health impact.
Novel therapeutic strategies for renal graft preservation and their potential impact on the future of clinical transplantation
Authors: Juriasingani Smriti , Akbari Masoud , Luke Patrick , Sener Alp
Published: May 2019

Purpose of review

The current review aims to examine recent evidence about improvements, therapeutics and novel approaches for renal graft preservation along with presenting a pragmatic outlook on their potential for clinical translation.

Recent findings

Modifying established cold preservation methods (4 °C) with oxygenation, gene therapies and gasotransmitters such as hydrogen sulfide has been shown to improve renal graft outcomes with minimum modifications to current protocols. These strategies have also shown promise in the context of normothermic preservation (34–37 °C), which circumvents the damage caused by cold preservation. Although normothermic machine perfusion (NMP) is being evaluated in clinical trials, it is limited by high cost, the use of blood and the lack of standardized protocols. Recent studies confirmed that preservation at subnormothermic temperatures (∼20 °C) is effective with approved preservation solutions and, in conjunction with exogenous hydrogen sulfide therapy, this approach may expedite a static preservation alternative to NMP.

Progress has been made in investigating improvements and alternatives to cold preservation. Promising therapeutic strategies have also been studied in the context of cold, subnormothermic and normothermic preservation. Further research is needed to optimize clinical renal graft preservation.
Factors That Influence Home Care Case Managers' Work and Workload
Authors: Fraser Kimberly , Baird Lisa Garland , Laing Daley , Lai Jonathan , Punjani Neelam Saleem
Published: May 2019

Background:

Home care services are increasing across Canada and in other developed nations. There has been increased pressure on home care programs to not only accept more clients more rapidly but also work more efficiently. Case management is an approach through which clients access and receive home care. With both rising numbers of clients and growing complexity among them, case managers' work and workload are also increasing. The demands on case managers and expansion in caseloads are happening without an increase in resources or funding. With case manager work increasing steadily, an understanding of the factors that influence their work and workload is vital.

Purpose:

The purpose of this study was to explore what factors influence case managers' work and workload.

Methods:

This study used an ethnographic approach. It took place in Alberta, Canada, in 3 home care offices in urban and suburban geographic areas. Purposive sampling was used, and participants included 28 home care case managers with predominantly long-term clients (>3 months on home care), 3 site managers, and 1 project lead. Data collection methods included semistructured interviews, nonparticipant observation, participant journaling, and focus groups.

Results:

Case manager works were portrayed in 2 key ways: the number and type of tasks a case manager was required to complete and the amount of time and energy needed to complete a task. The factors that influence case manager work and workload fall into 3 overarching categories: structural, operational, or individual factors.

Discussion:

The 3 overarching categories, as well as interactions between various factors, contribute to what is known about case managers' work and workload. Participants found it difficult to discuss the factors in isolation because the interaction and “messiness” of the factors were inherent in their actions and stories about their work and workload. Workload includes not only the easily captured work such as direct care and specific activities such as assessment but also diverse forms of invisible work such as problem solving, rapport building, and caseload management, as well as emotional work such as coping, stress management, and team support.

Implications for Case Management:

Case managers' work and workload in home care are important phenomena. In a climate of budgetary restraint and an aging population, which seemingly prefer home care as much as the system desires to provide it as a main option for care, it is important to capture, recognize, and legitimize an understanding of case managers' work and workload. Increased knowledge in this area could, in turn, transforms both home care and case management.
Changes in Patient Visits After the Implementation of Insurance Billing at a Sexually Transmitted Diseases Clinic in a Medicaid Expansion State
Authors: Jin Harry , Marshall Brandon D.L. , Raifman Julia , Montgomery Madeline , Maynard Michaela A. , Chan Philip A.
Published: May 2019

Background

Medicaid expansion has led to unique opportunities for sexually transmitted disease (STD) clinics to improve the sustainability of services by billing insurance. We evaluated changes in patient visits after the implementation of insurance billing at a STD clinic in a Medicaid expansion state.

Methods

The Rhode Island STD Clinic offered HIV/STD screening services at no cost to patients until October 2016, when insurance billing was implemented. Care for uninsured patients was still provided for free. We compared the clinic visits in the preinsurance period with the postinsurance period using t-tests, Poisson regressions, and a logistic regression.

Results

A total of 5560 patients were seen during the preinsurance (n = 2555) and postinsurance (n = 3005) periods. Compared with the preinsurance period, the postinsurance period had a significantly higher average number of patient visits/month (212.9 vs. 250.4, P = 0.0016), including among patients who were black (36.8 vs. 50.3, P = 0.0029), Hispanic/Latino (50.8 vs. 65.8, P = 0.0018), and insured (106.3 vs. 130.1, P = 0.0025). The growth rate of uninsured (+0.10 vs. +4.11, P = 0.0026) and new patients (−4.28 vs. +1.07, P = 0.0007) also increased between the two periods. New patients whose first visit was before the billing change had greater odds (adjusted odds ratio, 2.68, 95% confidence interval, 2.09–3.44; P < 0.0001) of returning compared with new patients whose first visit was after the billing change.

Conclusions

Implementation of insurance billing at a publicly funded STD clinic, with free services provided to uninsured individuals, was associated with a modest increase in patient visits and a decline in patients returning for second visits.
Management of Small Intestinal Bacterial Overgrowth in Adult Patients
Authors: Rasmussen Jamie , Duriancik David M.
Published: May 2019

The human gastrointestinal tract is a complex system of digestive pathways aided by mechanical processes, enzymes, transport molecules, and colonic bacteria. Occasionally, these bacterial components transplant to atypical locations due to various gastrointestinal imbalances or anatomical structural issues. This may lead to bacterial overgrowth of the small intestine, where minimal or no bacteria are normally found. Symptoms of small intestinal bacterial overgrowth may mimic those of various functional gastrointestinal diseases. Small intestinal bacterial overgrowth is typically diagnosed through hydrogen breath tests or jejunal aspirate culture. Current recommendations indicate antibiotics as the first-line treatment to eradicate or modify the bacterial overgrowth to a more favorable state. Nutritional support is also indicated to correct deficiencies and aid in symptom alleviation. As small intestinal bacterial overgrowth is common in other conditions, much of the research for this area is based on findings in codisease states rather than independent disease research. To provide accurate recommendations for small intestinal bacterial overgrowth, more targeted research is needed.
The role of psychological support interventions in trauma patients on mental health outcomes: A systematic review and meta-analysis
Authors: Pham Christopher H. , Fang Mike , Nager Jacqueline , Matsushima Kazuhide , Inaba Kenji , Kuza Catherine M.
Published: May 2019

BACKGROUND

The recovery and rehabilitation of trauma survivors may be long and challenging. Patients may be prone to psychiatric disorders, cognitive impairments, and decreased quality of life. The objective of this review was to determine whether there is a role for psychological interventions in reducing the incidence and severity of psychiatric sequelae in trauma survivors.

METHODS

MEDLINE, PubMed, SCOPUS, and Google Scholar were searched for published articles. We searched for articles published between 1990 and 2018 with adult subjects, and limited our search to articles published in English. Randomized controlled trials that evaluated various psychiatric interventions in trauma patients on the effects of psychiatric outcomes were included for analysis. The articles were independently reviewed for eligibility by two different reviewers. A meta-analysis was performed on nine studies with similar interventions, outcomes measured, and patient populations.

RESULTS

Nine hundred thirty-four articles were identified [830 articles identified through database search, and 107 through article references]. Sixty-nine full-text articles were reviewed for eligibility. Of these, 33 were included for qualitative analysis. Thirteen studies evaluating the effect of cognitive behavioral therapy (CBT)-based interventions on the severity of posttraumatic stress disorder (PTSD), anxiety, and depression symptoms underwent meta-analysis. While CBT-treated patients experienced clinically significant decreases in symptom severity, there were no statistically significant differences between treatment and control groups at follow-up for PTSD, anxiety, and depression.

CONCLUSION

Compared with usual care, CBT-based interventions may not be effective in decreasing or preventing PTSD, anxiety, or depression symptoms in trauma survivors.

LEVEL OF EVIDENCE

Systematic Review, level III.
Sympatric and allopatric differentiation delineates population structure in free-living terrestrial bacteria
Authors: Chase Alexander B. , Arevalo Philip , Brodie Eoin L. , Polz Martin F. , Karaoz Ulas , Martiny Jennifer B.H.
Published: May 2019

In free-living bacteria and archaea, the equivalent of the biological species concept does not exist, creating several barriers to the study of the processes contributing to microbial diversification. As such, microorganisms are often operationally defined using conserved marker genes (i.e., 16S rRNA gene) or whole-genome measurements (i.e., ANI) to interpret intra-specific processes. However, as in eukaryotes, investigations into microbial populations must consider the potential for interacting genotypes among individuals that are subjected to similar environmental selective pressures. Therefore, we isolated 26 strains within a single bacterial ecotype (equivalent to a eukaryotic species definition) from a common habitat (leaf litter) across a regional climate gradient and asked whether the genetic diversity in a free-living soil bacterium (Curtobacterium) was consistent with patterns of allopatric or sympatric differentiation. By examining patterns of gene flow, our results indicate that microbial populations are delineated by gene flow discontinuities and exhibit evidence for population-specific adaptation. We conclude that the genetic structure within this bacterium is due to both adaptation within localized microenvironments (isolation-by-environment) as well as dispersal limitation between geographic locations (isolation-by-distance).
Repetitive subconcussive head impacts and changes in sensory processing for balance control
Authors: Caccese Jaclyn B. , Santos Fernando V. , Anson Eric , Buckley Thomas A. , Yamaguchi Felipe , Gongora Mariana , Jeka John J.
Published: May 2019

Background

Repetitive subconcussive head impacts (RHI) may be associated with current and future detrimental neurological effects. However, the effects of RHI on sensory processing for balance control is unknown and may have significant clinical implications if athletes are still participating in sport despite impairments.

Research Question

Are there changes in sensory processing for balance control during standing and walking following RHI?

Methods

Thirty healthy, adult, amateur soccer players (15 males, 15 females, 21.8±2.8 years, 69.9±11.5 kg, 171.4±8.2 cm) volunteered for the standing balance assessment (i.e., experiment 1). A distinct cohort of twenty healthy, adult, amateur soccer players (10 males, 10 females, 22.3±4.5 years, 70.0±10.5 kg, 170.5±9.8 cm) volunteered for the walking balance assessment (i.e., experiment 2). We used a repeated measures design across three time points (pre-heading, 0-hours post-heading, 24-hours post-heading). Participants were randomly assigned to an experimental (i.e., performed 10 soccer headers in 10 minutes) or a control group (i.e., did not perform any soccer heading between sessions). In experiment 1, participants stood in a virtual reality cave while experiencing simultaneous perturbations to their visual, vestibular, and proprioceptive systems. In experiment 2, participants walked blindfolded along a foam walkway and experienced a vestibular perturbation on the second heel strike of the right foot. Changes in sensory processing were assessed using repeated measures ANOVAs.

Results

There were no changes in sensory reweighting during experiment 1 and no changes in balance responses to the vestibular stimulus in experiment 2.

Significance

Although the cumulative effects of RHI may result in later-life cognitive, behavioral, and mood impairments, a single episode of repeated soccer headers does not appear to be associated with acute impairments in sensory processing for balance control.
Alpha1-Adrenergic Receptor Mediated Long-Term Depression at CA3-CA1 Synapses Can be Induced via Accumulation of Endogenous Norepinephrine and is Preserved Following Noradrenergic Denervation
Authors: Dyer-Reaves Katie , Goodman Anthoni M. , Nelson Amy R. , McMahon Lori L.
Published: May 2019

Locus coeruleus (LC) provides the sole source of noradrenergic (NA) innervation to hippocampus, and it undergoes significant degeneration early in Alzheimer’s disease (AD). Norepinephrine (NE) modulates synaptic transmission and plasticity at hippocampal synapses which likely contributes to hippocampus dependent learning and memory. We previously reported that pharmacological activation of α1 adrenergic receptors (α1ARs) induces long-term depression (LTD) at CA3-CA1 synapses. Here we investigated whether accumulation of endogenous NE via pharmacological blockade of NE transporters (NET) and the NE degradative enzyme, monoamine oxidase (MAO), can induce α1AR LTD, as these inhibitors are used clinically. Further, we sought to determine how degeneration of hippocampal NA innervation, as occurs in AD, impacts α1AR function and α1AR LTD. Bath application of NET and MAO inhibitors in slices from control rats reliably induced α1AR LTD when β adrenergic receptors were inhibited. To induce degeneration of LC-NA innervation, rats were treated with the specific NA neurotoxin DSP-4 and recordings performed 1-3 weeks later when NA axon degeneration had stabilized. Even with 85% loss of hippocampal NA innervation, α1AR LTD was successfully induced using either the α1AR agonist phenylephrine or the combined NET and MAO inhibitors, and importantly, the LTD magnitude was not different from saline-treated control. These data suggest that despite significant decreases in NA input to hippocampus, the mechanisms necessary for the induction of α1AR LTD remain functional. Furthermore, we posit that α1AR activation could be a viable therapeutic target for pharmacological intervention in AD and other diseases involving malfunctions of NA neurotransmission.
JARID2 facilitates transcriptional reprogramming in glioblastoma in response to standard treatment
Authors: Rippaus Nora , F-Bruns Alexander , Tanner Georgette , Taylor Claire , Droop Alastair , Brüning-Richardson Anke , Care Matthew A. , Wilkinson Joseph , Jenkinson Michael D. , Brodbelt Andrew , Chakrabarty Aruna , Ismail Azzam , Short Susan , Stead Lucy F.
Published: May 2019

Background

Glioblastoma (GBM) is a fatal and incurable brain cancer with a dismal prognosis. In order to impact on this disease, we need to understand how infiltrating, non resectable tumour cells resist chemoradiation and facilitate disease recurrence. To this end, we generated or acquired bulk tumour RNA sequencing data from 45 paired primary and locally recurrent GBM tumours (split into original and validation cohorts) from patients that received standard treatment. We also generated DNA methylation profiles for 9 pairs and sequenced RNA from single cells isolated from a patient derived GBM spheroid model at different timepoints following in vitro chemoradiation.

Results

We have identified a set of genes with Jumonji and AT-Rich Interacting Domain 2 (JARID2) binding sites in their promoters that are universally dysregulated in post-standard treatment recurrent GBMs compared to the primary tumour. The direction of dysregulation is patient-dependent and not associated with differential promoter DNA methylation. Our in vitro experiments suggest that this dysregulation occurs dynamically following treatment as opposed to resulting from selection of cells with specific expression profiles.

Conclusion

JARID2 is an accessory protein to a chromatin remodeling complex, responsible for histone modifications observed during cell state transitions in both normal brain and GBM. We propose that JARID2 facilitates GBM recurrence following treatment by indirect transcriptional reprogramming of surviving cells in whichever manner is needed to reproduce the phenotypic heterogeneity required for tumour regrowth in vivo. The mechanism of this reprogramming may present a therapeutic vulnerability for more effective treatment of GBM.
Single-cell transcriptional diversity is a hallmark of developmental potential
Authors: Gulati Gunsagar S. , Sikandar Shaheen S. , Wesche Daniel J. , Manjunath Anoop , Bharadwaj Anjan , Berger Mark J. , Ilagan Francisco , Kuo Angera H. , Hsieh Robert W. , Cai Shang , Zabala Maider , Scheeren Ferenc A. , Lobo Neethan A. , Qian Dalong , Yu Feiqiao B. , Dirbas Frederick M. , Clarke Michael F. , Newman Aaron M.
Published: May 2019

Single-cell RNA-sequencing (scRNA-seq) is a powerful approach for reconstructing cellular differentiation trajectories. However, inferring both the state and direction of differentiation without prior knowledge has remained challenging. Here we describe a simple yet robust determinant of developmental potential—the number of detectably expressed genes per cell— and leverage this measure of transcriptional diversity to develop a new framework for predicting ordered differentiation states from scRNA-seq data. When evaluated on ~150,000 single-cell transcriptomes spanning 53 lineages and five species, our approach, called CytoTRACE, outperformed previous methods and ~19,000 molecular signatures for resolving experimentally-confirmed developmental trajectories. In addition, it enabled unbiased identification of tissue-resident stem cells, including cells with long-term regenerative potential. When used to analyze human breast tumors, we discovered candidate genes associated with less-differentiated luminal progenitor cells and validated GULP1 as a novel gene involved in tumorigenesis. Our study establishes a key RNA-based correlate of developmental potential and provides a new platform for robust delineation of cellular hierarchies (https://cytotrace.stanford.edu).
Elimination of galanin synthesis in noradrenergic neurons reduces galanin in select brain areas and promotes active coping behaviors
Authors: Tillage Rachel P. , Sciolino Natale R. , Plummer Nicholas W. , Lustberg Daniel , Liles L. Cameron , Hsiang Madeline , Powell Jeanne M. , Smith Kathleen G. , Jensen Patricia , Weinshenker David
Published: May 2019

Accumulating evidence indicates that disruption of galanin signaling is associated with neuropsychiatric disease, but the precise functions of this neuropeptide remain largely unresolved due to lack of tools for experimentally disrupting its transmission in a cell type-specific manner. To examine the function of galanin in the noradrenergic system, we generated and crossed two novel knock-in mouse lines to create animals lacking galanin specifically in noradrenergic neurons (GalcKO-Dbh). We observed reduced levels of galanin peptide in pons, hippocampus, and prefrontal cortex of GalcKO-Dbh mice, indicating that noradrenergic neurons are a significant source of galanin to those brain regions, while midbrain and hypothalamic galanin levels were comparable to littermate controls. In these same brain regions, we observed no change in levels of norepinephrine or its major metabolite at baseline or after an acute stressor, suggesting that loss of galanin does not affect noradrenergic synthesis or turnover. GalcKO-Dbh mice had normal performance in tests of depression, learning, and motor-related behavior, but had an altered response in some anxiety-related tasks. Specifically, GalcKO-Dbh mice showed increased marble and shock probe burying and had a reduced latency to eat in a novel environment, indicative of a more proactive coping strategy. Together, these findings indicate that noradrenergic neurons provide a significant source of galanin to discrete brain areas, and noradrenergic-specific galanin opposes adaptive coping responses.
miRDriver: A Tool to Infer Copy Number Derived miRNA-Gene Networks in Cancer
Authors: Bose Banabithi , Bozdag Serdar
Published: May 2019

Copy number aberration events such as amplifications and deletions in chromosomal regions are prevalent in cancer patients. Frequently aberrated copy number regions include regulators such as microRNAs (miRNAs), which regulate downstream target genes that involve in the important biological processes in tumorigenesis and proliferation. Many previous studies explored the miRNA-gene interaction networks but copy number-derived miRNA regulations are limited. Identifying copy number-derived miRNA-target gene regulatory interactions in cancer could shed some light on biological mechanisms in tumor initiation and progression. In the present study, we developed a computational pipeline, called miRDriver which is based on the hypothesis that copy number data from cancer patients can be utilized to discover driver miRNAs of cancer. miRDriver integrates copy number aberration, DNA methylation, gene and miRNA expression datasets to compute copy number-derived miRNA-gene interactions in cancer. We tested miRDriver on breast cancer and ovarian cancer data from the Cancer Genome Atlas (TCGA) database. miRDriver discovered some of the known miRNAs, such as miR-125b, mir-320d, let-7g, and miR-21, which are known to be in copy number aberrated regions in breast cancer. We also discovered some potentially novel miRNA-gene interactions. Also, several miRNAs such as miR-127, miR-139 and let-7b were found to be associated with tumor survival and progression based on Cox proportional hazard model. We compared the enrichment of known miRNA-gene interactions computed by miRDriver with the enrichment of interactions computed by the state-of-the-art methods and miRDriver outperformed all the other methods.

CCS CONCEPTS

Bioinformatics

Computational Genomics

Biological Networks
Large-scale Analyses of Disease Biomarkers and Apremilast Pharmacodynamic Effects
Authors: Medvedeva Irina V. , Stokes Matthew E. , Eisinger Dominic , LaBrie Samuel T. , Ai Jing , Trotter Matthew W. B. , Schafer Peter , Yang Robert
Published: May 2019

Finding biomarkers that provide shared link between disease severity, drug-induced pharmacodynamic effects and response status in human trials can provide number of values for patient benefits: elucidating current therapeutic mechanism-of-action, and, back-translating to fast-track development of next-generation therapeutics. Both opportunities are predicated on proactive generation of human molecular profiles that capture longitudinal trajectories before and after pharmacological intervention. Here, we present the largest plasma proteomic biomarker dataset available to-date and the corresponding analyses from placebo-controlled Phase III clinical trials of the phosphodiesterase type 4 inhibitor apremilast in psoriasis (PSOR), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) from 526 subjects overall. Using approximately 150 plasma analytes tracked across three time points, we identified IL-17A and KLK-7 as biomarkers for disease severity and apremilast pharmacodynamic effect in psoriasis patients. Combined decline rate of KLK-7, PEDF, MDC and ANGPTL4 by Week 16 represented biomarkers for the responder subgroup, shedding insights into therapeutic mechanisms. In ankylosing spondylitis patients, IL-6 and LRG-1 were identified as biomarkers with concordance to disease severity. Apremilast-induced LRG-1 increase was consistent with the overall lack of efficacy in ankylosing spondylitis. Taken together, these findings expanded the mechanistic knowledge base of apremilast and provided translational foundations to accelerate future efforts including compound differentiation, combination, and repurposing.
A fitness cost resulting fromHamiltonella defensainfection is associated with altered probing and feeding behaviour inRhopalosiphum padi
Authors: Leybourne Daniel. J. , Valentine Tracy. A. , Bos Jorunn. I. B. , Karley Alison. J.
Published: May 2019

Aphids frequently associate with facultative endosymbiotic bacteria which influence aphid physiology in myriad ways. Endosymbiont infection can increase aphid resistance against parasitoids and pathogens, modulate plant responses to aphid feeding, and promote aphid virulence. These endosymbiotic relationships can also decrease aphid fitness in the absence of natural enemies or when feeding on less suitable plant types. Here, we use the Electrical Penetration Graph (EPG) technique to monitor feeding behaviour of four genetically-similar clonal lines of a cereal-feeding aphid,Rhopalosiphum padi, differentially infected (+/−) with the facultative protective endosymbiont,Hamiltonella defensa, to understand how physiological processes at the aphid-plant interface are affected by endosymbiont infection. Endosymbiont-infected aphids exhibited altered probing and feeding patterns compared with uninfected aphids, characterised by a two-fold increase in the number of plant cell punctures, a 50% reduction in the duration of each cellular puncture, and a greater probability of achieving sustained ingestion of plant phloem. Feeding behaviour was altered further by host plant identity: endosymbiont-infected aphids spent less time probing into plant tissue, required twice as many probes into plant tissue to reach plant phloem, and showed a 44% reduction in phloem ingestion when feeding on the partially-resistant wild relative of barley,Hordeum spontaneum5, compared with a commercial barley cultivar. These observations might explain reduced growth ofH. defensa-infected aphids on the former host plant. This study is the first to demonstrate a physiological mechanism at the aphid-plant interface contributing to endosymbiont effects on aphid fitness on different quality plants through altered aphid feeding behaviour.

Reduced performance of aphids infected with a common facultative endosymbiont on poor quality plants may be explained by changes in aphid probing behaviour and decreased phloem sap ingestion.