bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic obstructive pulmonary disease combined with vertebral compression fracture increases the risk of temporomandibular disorder
Authors: Lee Kuei-Chen , Wu Yung-Tsan , Chen Liang-Cheng , Shen Chih-Hao , Chung Chi-Hsiang , Chien Wu-Chien , Shieh Yi-Shing
Published: September 2019

Vertebral compression fracture (VCF) is a common comorbidity of chronic obstructive pulmonary disease (COPD), and the coexistence of COPD and temporomandibular disorder (TMD) has been clinically noted. The present study aimed to investigate whether VCF increases the risk of TMD in patients with COPD.

With a follow-up period of 15 years, this retrospective, population-based longitudinal cohort study enrolled sex- and age-matched COPD patients with and without VCF (1:3) who were identified from Taiwan's National Health Insurance Research Database from 2000 to 2015. Multivariate Cox regression analysis was performed to determine the risk of TMD in COPD patients with and without VCF. The cumulative risk of TMD between groups was estimated using Kaplan–Meier analysis.

The risk factors for TMD in patients with COPD were VCF, osteoporosis, and winter season. The COPD with VCF group was more likely to develop TMD (adjusted hazard ratio = 3.011, P < .001) than the COPD without VCF group after adjustment for sex, age, variables, and comorbidities. In the subgroup analysis, the COPD with VCF group had a higher risk of TMD than the COPD without VCF group in almost all stratifications.

COPD patients with VCF are at a higher risk of developing TMD. Clinicians taking care of patients with COPD should be aware of the occurrence of TMD as a comorbidity.
Plate size reduction surgery for the Baerveldt 350-mm2 glaucoma implant for postoperative motor disturbance
Authors: Tanabe Hirotaka , Nakakura Shunsuke , Noguchi Asuka , Tabuchi Hitoshi , Kiuchi Yoshiaki
Published: September 2019

Rationale:

Diplopia due to ocular motility disturbance is a common complication after glaucoma drainage device (GDD) surgery. The treatment options include prescription prism glasses, strabismus surgery or GDD removal. However, to the best of our knowledge, GDD size reduction surgery has not been reported.

Patient concerns and diagnoses:

An 83-year-old woman diagnosed with primary open angle glaucoma was referred to Tsukazaki Hospital due to uncontrolled intraocular pressure (IOP) in December 2015. We performed an EXPRESS shunt surgery on both eyes in January 2016 and a needling procedure on the left eye in May 2017. Thereafter, because IOP in her left eye remained high, we performed Baerveldt 350-mm2 implantation in her inferotemporal area by placing the tube at the sulcus on December 3, 2017. The next day, 4Δ hypertropia (HT) was detected in the left eye in alternate cover testing in primary gaze, and diplopia in the inferotemporal direction was demonstrated. Although IOP was controlled well between 15 and 20 mmHg in her left eye, diplopia did not improve.

Interventions:

Three weeks later, we performed a plate size reduction surgery for the Baerveldt 350-mm2 implant. In this procedure, we cut and removed the plates placed beneath the lateral rectus muscle and inferior rectus muscle, which were thought to be responsible for diplopia.

Outcomes:

Diplopia improved subjectively, but there was no drastic objective change. We prescribed prism glasses (3Δ base down for the left eye) for remaining mild diplopia. On January 21, 2019, significant objective improvement (2Δ HT with less ocular motor dysfunction demonstrated in the Hess chart) was finally observed.

Lessons:

Early plate size reduction surgery, which was not immediately but ultimately effective in improving motor disturbance in our case, could be a potential option to relieve operation-induced motor disturbance. However, notably, tube shunt surgery has the risk of motility disturbances, which might require additional treatment.
Pooled analysis of efficacy and safety of ureteral stent removal using an extraction string
Authors: Sun Xujie , Dong Liying , Chen Tao , Huang Zhongyi , Zhang Xuebao , Wu Jitao , Lin Chunhua , Cui Yuanshan
Published: September 2019

Objective:

We conducted a Pooled analysis to investigate the efficacy and safety of ureteral stent removal using an extraction string.

Methods:

A systematic review was performed by using the Preferred Reporting Items for Systematic Reviews and Pooled analyses. The sources including EMBASE, MEDLINE, and the Cochrane Controlled Trials Register were retrieved to gather randomized controlled trials of ureteral stent removal using an extraction string. The reference of included literature was also searched.

Results:

Four randomized controlled trials containing a amount of 471 patients were involved in the analysis. We found that the ureteral stent removal using an extraction string group had a greater decrease of visual analog scale (VAS) (Mean difference (MD) −1.40, 95% confidence interval (CI) −1.99 to −0.81, P < .00001) compared with the no string group. The string group did not show a significant differences in Ureteric Stent Symptom Questionnaire (USSQ) (P = .15), general health (P = .77), stent dwell time (P = .06), and urinary tract infection (UTI) (P = .59) with exception of stent dislodgement (Odds Ratio (OR) 10.36, 95% CI 2.40 to 44.77, P = .002) compared with the no string group.

Conclusions:

Ureteral stent removal by string significantly provides less pain than those by cystoscope for patients without increasing stent-related urinary symptoms or UTI. However, this must be balanced against a risk of stent dislodgement and, hence, may not be a good option in all patients.
Clinical outcomes of comorbid cancer patients with venous thromboembolism
Authors: Jeong Jihwan , Jeong Min-Jae , Choi Kyunghak , Kim Min-Ju , Han Youngjin , Kwon Tae-Won , Cho Yong-Pil
Published: September 2019

In this single-center, retrospective study, we aimed to report the clinical outcomes, among Asian comorbid cancer patients with venous thromboembolism (VTE), and compare them with those of VTE patients without cancer.

Between January 2013 and December 2017, a total of 322 consecutive patients—diagnosed with acute VTE involving the leg, pelvis, or lung—were screened for inclusion. Comorbid cancer patients with VTE (n = 135, 41.9%) were included in this study and analyzed in comparison with VTE patients without cancer (n = 187, 58.1%). The study outcomes were the composite incidence of symptomatic and radiologically confirmed recurrence of VTE, or any-cause mortality.

The study outcome incidence was 62.2% (n = 84) during a mean follow-up period of 10 months: VTE recurrence in 7 patients and any-cause mortality in 83. Upon multivariate analysis, higher body mass index, diabetes mellitus, cancer stage IV, and radiotherapy were independently associated with study outcome incidence. VTE involving the inferior vena cava (hazard ratio [HR], 12.1; 95% confidence interval [CI], 1.20–120.80; P = .034), lung cancer (HR, 16.5; 95% CI, 2.32–117.50; P = .005), and use of vitamin K antagonists (HR, 36.4; 95% CI, 3.00–442.70; P = .005) were independent predictors of VTE recurrence. Compared with VTE patients without cancer, the study outcome incidence was significantly higher among comorbid cancer patients with VTE (62.2% vs 7.5%, P < .001), although there was no significant difference in VTE recurrence between the 2 groups (5.2% in patients with cancer vs 3.7% in patients without cancer, P = .531).

We found that various cancer-related and patient-related factors were associated with outcomes among comorbid cancer patients with VTE. The composite incidence of VTE recurrence or any-cause mortality was significantly higher among cancer patients with VTE than among VTE patients without cancer.
Quality Enhancement Research Initiative Implementation Roadmap
Authors: Kilbourne Amy M. , Goodrich David E. , Miake-Lye Isomi , Braganza Melissa Z. , Bowersox Nicholas W.
Published: September 2019

Background:

Learning Health Systems strive to continuously integrate innovations and evidence-based practices (EBPs) into routine care settings. Few models provide a specified pathway to accelerate adoption and spread of EBPs across diverse settings.

Objective:

The US Department of Veterans Affairs Quality Enhancement Research Initiative (QUERI) Implementation Roadmap facilitates uptake of EBPs in routine practice by aligning research and health system priorities.

Methods:

The Roadmap is based on earlier iterations of the QUERI translational research pipeline, incorporating recent advancements in quality improvement and implementation science. Progressive, dynamic phases were operationalized to form an implementation process that promoted a participatory approach which enables stakeholders (health care consumers, clinicians, administrators, and leaders) to systematically plan, deploy, evaluate, and sustain EBPs using implementation strategies within a Learning Health System framework.

Results:

The Roadmap consists of Preimplementation, Implementation, and Sustainment phases. Preimplementation identifies a high-priority need, selects EBPs to address the need, engages stakeholders to build implementation capacity, specifies needed EBP adaptions and evaluation goals, and activates leadership support. During Implementation, clinical and research leaders use implementation strategies to promote EBP technical competency and adaptive skills to motivate providers to own and sustain EBPs. Sustainment includes evaluation analyses that establish the EBP business case, and hand-off to system leadership to own EBP implementation maintenance over time.

Conclusions:

The QUERI Implementation Roadmap systematically guides identification, implementation, and sustainment of EBPs, demystifying implementation science for stakeholders in a Learning Health System to ensure that EBPs are more rapidly implemented into practice to improve overall consumer health.
The Collaborative Chronic Care Model for Mental Health Conditions
Authors: Bauer Mark S. , Weaver Kendra , Kim Bo , Miller Christopher , Lew Robert , Stolzmann Kelly , Sullivan Jennifer L. , Riendeau Rachel , Connolly Samantha , Pitcock Jeffery , Ludvigsen Stig M. , Elwy Anashua R.
Published: September 2019

Background:

Extensive evidence indicates that Collaborative Chronic Care Models (CCMs) improve outcome in chronic medical conditions and depression treated in primary care. Beginning with an evidence synthesis which indicated that CCMs are also effective for multiple mental health conditions, we describe a multistage process that translated this knowledge into evidence-based health system change in the US Department of Veterans Affairs (VA).

Evidence Synthesis:

In 2010, recognizing that there had been numerous CCM trials for a wide variety of mental health conditions, we conducted an evidence synthesis compiling randomized controlled trials of CCMs for any mental health condition. The systematic review demonstrated CCM effectiveness across mental health conditions and treatment venues. Cumulative meta-analysis and meta-regression further informed our approach to subsequent CCM implementation.

Policy Impact:

In 2015, based on the evidence synthesis, VA Office of Mental Health and Suicide Prevention (OMHSP) adopted the CCM as the model for their outpatient mental health teams.

Randomized Implementation Trial:

In 2015–2018 we partnered with OMHSP to conduct a 9-site stepped wedge implementation trial, guided by insights from the evidence synthesis.

Scale-Up and Spread:

In 2017 OMHSP launched an effort to scale-up and spread the CCM to additional VA medical centers. Seventeen facilitators were trained and 28 facilities engaged in facilitation.

Discussion:

Evidence synthesis provided leverage for evidence-based policy change. This formed the foundation for a health care leadership/researcher partnership, which conducted an implementation trial and subsequent scale-up and spread effort to enhance adoption of the CCM, as informed by the evidence synthesis.
Identifying Research Gaps and Prioritizing Psychological Health Evidence Synthesis Needs
Authors: Hempel Susanne , Gore Kristie , Belsher Bradley
Published: September 2019

Background:

Evidence synthesis is key in promoting evidence-based health care, but it is resource-intense. Methods are needed to identify and prioritize evidence synthesis needs within health care systems. We describe a collaboration between an agency charged with facilitating the implementation of evidence-based research and practices across the Military Health System and a research center specializing in evidence synthesis.

Methods:

Scoping searches targeted 15 sources, including the Veterans Affairs/Department of Defense Guidelines and National Defense Authorization Acts. We screened for evidence gaps in psychological health management approaches relevant to the target population. We translated gaps into potential topics for evidence maps and/or systematic reviews. Gaps amenable to evidence synthesis format provided the basis for stakeholder input. Stakeholders rated topics for their potential to inform psychological health care in the military health system. Feasibility scans determined whether topics were ready to be pursued, that is, sufficient literature exists, and duplicative efforts are avoided.

Results:

We identified 58 intervention, 9 diagnostics, 12 outcome, 19 population, and 24 health services evidence synthesis gaps. Areas included: posttraumatic stress disorder (PTSD) (19), suicide prevention (14), depression (9), bipolar disorder (9), substance use (24), traumatic brain injury (20), anxiety (1), and cross-cutting (14) synthesis topics. Stakeholder input helped prioritize 19 potential PTSD topics and 22 other psychological health topics. To date, 46 topics have undergone feasibility scans. We document lessons learned across clinical topics and research methods.

Conclusion:

We describe a transparent and structured approach to evidence synthesis topic selection for a health care system using scoping searches, translation into evidence synthesis format, stakeholder input, and feasibility scans.
Predictors of Dissociative Experiences Among Adolescents in Nepal
Authors: Sapkota Ram P. , Brunet Alain , Kirmayer Laurence J.
Published: September 2019

In recent years, many adolescents in Nepal have been affected by episodes of mass psychogenic illness, which seem to involve dissociative symptoms. To identify the potential contributors to dissociation, the present study examined correlates of dissociative experiences among adolescents in Nepal. In a cross-sectional survey, 314 adolescents were assessed with the Adolescent Dissociative Experiences Scale and measures of childhood trauma exposure, as well as cognitive and personality traits found to be associated with dissociation in studies on other populations. Path analysis confirmed that childhood trauma, cognitive and personality traits, and current distress each predicted dissociative experiences and behaviors. However, an integrated path model found that the effect of childhood trauma on dissociation was mediated either by posttraumatic stress symptoms or by cognitive failures. Future studies should develop and test multifactorial models of dissociation and multiple pathways.
Cervical Human Papillomavirus Testing With Two Home Self-Collection Methods Compared With a Standard Clinically Collected Sampling Method
Authors: McLarty Jerry W. , Williams Donna L. , Loyd Susan , Hagensee Michael E.
Published: September 2019

Background

The purpose of this study was to compare the outcomes of 2 self-collection methods to detect cervical human papillomavirus (HPV) DNA with outcomes from a standard clinical method. The standard method samples were collected by a clinician at a routine pelvic examination. Self-samples were taken at home and mailed to the clinical laboratory.

Methods

The 2 self-collection methods were a tampon-based method and a swab-based method using a commercial device, an Eve Medical HerSwab. All HPV samples were processed by a clinical laboratory using the Food and Drugs Administration approved Roche Cobase HPV method, which specifically identifies HPV 16, HPV 18, and a set of 12 other high-risk subtypes. Patients were recruited from 2 cancer screening clinics 2015 to 2017. All patients signed an informed consent. Screening outcomes, such as prevalence, percent agreement with standard, sensitivity, and specificity, were calculated for each self-collection method. Measures of similarity between self and standard collection outcomes, Cohen’s κ, percent concordance, McNemar equivalence, and others were tested statistically.

Results

One hundred seventy-four patients were randomized. The prevalence of 1 or more positive HPV high-risk subtypes from the standard clinical specimens was 13.5%. All clinical specimens were sufficient for valid HPV detection. For the tampon method, 15 (27%) of the specimens were insufficient quality. Only 1 (2%) swab specimen was insufficient. Only the swab self-collection method was found to be statistically noninferior to the clinical method. The tampon method had an unacceptably high rate of insufficient quality specimens and also failed the equivalency tests.

Conclusions

The swab home collection samples were equivalent to the clinical samples, but the tampon method had an unacceptably high rate of specimens insufficient for HPV detection.
The Vaginal Microbiota and Behavioral Factors Associated With Genital Candida albicans Detection in Reproductive-Age Women
Authors: Brown Sarah E. , Schwartz Jennifer A. , Robinson Courtney K. , O'Hanlon D. Elizabeth , Bradford L. Latéy , He Xin , Mark Katrina S. , Bruno Vincent M. , Ravel Jacques , Brotman Rebecca M.
Published: September 2019

Background

Vulvovaginal candidiasis is commonly diagnosed and has been associated in prospective studies with the acquisition of HIV. Little data is available on how the composition of the vaginal microbiota, and other risk factors, are associated with the molecular detection of Candida albicans—a common cause of vulvovaginal candidiasis.

Methods

In a cross-sectional study, self-collected vaginal swabs were obtained from 394 nonpregnant, reproductive-age women. C. albicans was detected using polymerase chain reaction targeting C. albicans ITS1/2 region. Vaginal microbiota was characterized by 16S rRNA gene amplicon sequencing of the V3 to V4 hypervariable regions and clustered into community state types (CSTs). Multiple logistic regression identified factors associated with C. albicans detection.

Results

Twenty-one percent had C. albicans detected and 46% reported vaginal symptoms in the prior 60 days. There was a 2-fold increase in the odds of C. albicans if a woman was in a L. crispatus-dominated CST compared to CSTs with low-Lactobacillus levels (adjusted odds ratio, 2.05; 95% confidence interval, 0.97–4.37). History of self-treatment with antifungals, L. crispatus relative abundance, and receptive oral sex were also significantly associated with C. albicans detection.

Conclusions

A L. crispatus-dominated vaginal microbiota is thought to protect women from both development of bacterial vaginosis and incidence of sexually transmitted infections; however, our data suggest that L. crispatus is associated with increased C. albicans detection. Receptive oral sex may also be a risk factor for vaginal C. albicans colonization.
Sexually Transmitted Infection Risk Reduction Strategies Among US Adolescents and Adults With Multiple Opposite-Sex Sex Partners or Perceived Partner Nonmonogamy, 2011–2017
Authors: Copen Casey E. , Leichliter Jami S. , Spicknall Ian H. , Aral Sevgi O.
Published: September 2019

Background

This study examined condom use and sexually transmitted infection (STI) testing among unmarried, non-cohabiting women and men who had multiple past-year partnerships or perceived their partner's involvement in another sexual relationship.

Methods

We identified 5868 and 5330 unmarried, non-cohabiting sexually active women and men aged 15 to 44 years using National Survey of Family Growth data for 2011 to 2017. To measure multiple partnerships, we created 4 dichotomous variables that included both past-year number of opposite-sex sex partners (1, 2 or more) and perceived partner nonmonogamy (PPNM) (yes, no). Results were stratified by relationship type at last sex (“steady” vs “casual”).

Results

Overall, 39.4% of women and 48.3% of men reported multiple partnerships and 23.4% and 24.0% reported PPNM. Lower condom use was seen for women and men who had 2 or more partners in the past year and PPNM than those with only 1 partner and no PPNM (women, 28.5%; 95% confidence interval [CI], 24.1–32.9 vs 39.3%; 95% CI, 36.6–41.9) (men, 37.7%; 33.5–41.8 vs 54.9%; 51.9–57.9). STI testing was higher for groups with PPNM. Men with a steady sex partner had higher prevalence of past-year STI testing if they reported PPNM than not (adjusted prevalence ratio, 2.00; 95% CI, 1.63–2.45).

Conclusions

Screening practices that include a standardized sexual risk assessment could identify those with multiple sex partners or PPNM and improve linkage to STI services. Availability of point-of-care tests and expedited partner therapy could provide targeted strategies that prioritize rapid diagnosis and effective partner treatment which may prevent further STI spread.
The Occurrence and Risk Factors of Inappropriately Deep Tip Position of Microcuff Pediatric Endotracheal Tube During PICU Stay: A Retrospective Cohort Pilot Study*
Authors: Matsuoka Wakato , Ide Kentaro , Matsudo Takahiro , Kobayashi Tohru , Nishimura Nao , Nakagawa Satoshi
Published: September 2019

Objectives:

Cuffed endotracheal tubes are being used increasingly for pediatric patients on mechanical ventilation. Appropriate placement of the tube tip for Microcuff (Kimberley-Clark, Roswell, GA) pediatric endotracheal tube is guided by the intubation depth mark on the device. However, inappropriately deep tip position is sometimes observed during PICU stay. The purpose of this study was to assess the occurrence and risk factors of inappropriately deep tip position of Microcuff pediatric endotracheal tube during PICU stay.

Design:

A retrospective cohort study.

Setting:

The PICU at the National Center for Child Health and Development, one of the largest tertiary pediatric hospitals in Japan.

Patients:

All patients on mechanical ventilation with Microcuff pediatric endotracheal tube admitted between February 1, 2015, and July 31, 2016, were enrolled.

Interventions:

None.

Measurements and Main Results:

The primary outcome was the occurrence of inappropriately deep tip position, defined as a position of the tube tip less than 5 mm above the carina on a chest radiograph. There were 179 cases (157 patients) requiring mechanical ventilation with Microcuff pediatric endotracheal tube during the study period. An inappropriately deep tip position was found in 42 cases (23.5%), including bronchial intubation in 13 cases (7.3%). In multivariate analysis, height in cm (odds ratio, 0.93; p < 0.001), history of abdominal disease or previous abdominal surgery (odds ratio, 4.38; p = 0.004), and oversized endotracheal tube (odds ratio, 2.93; p = 0.042) were found to be independent risk factors.

Conclusions:

The occurrence of inappropriately deep tip position of Microcuff pediatric endotracheal tube during PICU stay was 23.5%. The possibility of an inappropriately deep tip position should be considered whenever patients with the above risk factors, a history of abdominal disease or previous abdominal surgery, and small children are treated or when oversized endotracheal tubes are used.
HIV Risk and Prevention Outcomes in a Probability-Based Sample of Gay and Bisexual Men in the United States
Authors: Dodge Brian , Ford Jessie V. , Bo Na , Tu Wanzhu , Pachankis John , Herbenick Debby , Mayer Kenneth , Hatzenbuehler Mark L.
Published: September 2019

Background:

Although gay and bisexual men (GBM) represent the largest group of HIV-infected individuals in the United States, nearly all evidence on their HIV risk and prevention outcomes derive from nonprobability samples.

Setting:

A probability-based cohort of GBM (N = 502) from 45 states and Washington, DC.

Methods:

Cross-sectional survey.

Results:

Among HIV-negative/unknown/untested GBM, only 6.7% reported using pre-exposure prophylaxis (PrEP) in the past 6 months. Two-thirds (63.3%) of PrEP users reported daily adherence in the past week. Over half (54.2%) of GBM reported not using a condom during anal sex with their most recent male partner; of these men, 93.8% were not on PrEP. Most GBM had been tested for HIV (80.7%) and other sexually transmitted infections (67.1%) in their lifetime, with 45.2% having tested for HIV during the past year. Among those ever tested, 14.1% reported being HIV infected, whereas an additional 8.9% reported testing positive for at least one other sexually transmitted infection after their most recent test. All HIV-positive GBM reported being currently on antiretroviral treatment, and 94.7% reported an undetectable viral load, but nearly one-third (30.4%) reported not taking their medication every day during the past month. A majority of HIV-negative/unknown/untested GBM (64.3%) reported that they had never discussed HIV prevention with their primary health care provider.

Conclusions:

Our findings present a decidedly mixed picture regarding the success of the US National HIV/AIDS Strategy in meeting its stated goals of addressing HIV risk among the general population of GBM.
Benefits of Suture Reinforcement in Laparoscopic Sleeve Gastrectomy
Authors: Batman Burcin , Altun Hasan
Published: September 2019

Obesity is an increasing problem worldwide. Laparoscopic sleeve gastrectomy is gaining popularity. Although it has unique complications such as leakage, bleeding, and stenosis, it is a reliable procedure. A total of 1200 consecutive patients who underwent sleeve gastrectomy and omentopexy between March 2013 and December 2018 were enrolled in this retrospective study. Body mass index, age, sex, and postoperative complications were recorded in all patients. Of 1200 patients, 864 (72%) were female and 336 (28%) were male. The median age was 38 years (13 to 69 y). Preoperative median body mass index was found as 40.87 kg/m2 (30 to 88 kg/m2). Operative complications included strictures which occurred in 16 (1.33%) patients, bleeding in 7 (0.58%), stapler line leaks in 3 (0.25%), wound infection in 1 (0.08%), fat necrosis in 1 (0.08%), splenic arterial injury in 1 (0.08%), and intra-abdominal abscess in 1 (0.08%) patient. There was no mortality. Sleeve gastrectomy and omentopexy is a safe procedure with low complication rates.
Effects of a Mixed Reality-based Cognitive Training System Compared to a Conventional Computer-assisted Cognitive Training System on Mild Cognitive Impairment: A Pilot Study
Authors: Park Eunhee , Yun Byoung-Ju , Min Yu-Sun , Lee Yang-Soo , Moon Sung-Jun , Huh Jae-Won , Cha Hyunsil , Chang Yongmin , Jung Tae-Du
Published: September 2019

Background:

Mixed reality (MR) technology, which combines the best features of augmented reality and virtual reality, has recently emerged as a promising tool in cognitive rehabilitation therapy.

Objective:

To investigate the effectiveness of an MR-based cognitive training system for individuals with mild cognitive impairment (MCI).

Methods:

Twenty-one individuals aged 65 years and older who had been diagnosed with MCI were recruited for this study and were divided into two groups. Participants in the MR group (n=10, aged 70.5±4.2 years) received 30 minutes of training 3 times a week for 6 weeks using a newly developed MR-based cognitive training system. Participants in the control group (n=11, aged 72.6±5.3 years) received the same amount of training using a conventional computer-assisted cognitive training system. Both groups took the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD-K) both before and after intervention. To determine the effect of the intervention on cognitive function, we compared the difference in each group’s CERAD-K scores.

Results:

There was a statistically significant interaction between intervention (MR group vs control group) and time (before vs after intervention) as assessed by the Constructional Recall Test. The individuals with MCI who participated in the MR training showed significantly improved performance in visuospatial working memory compared with the individuals with MCI who participated in the conventional training.

Conclusion:

An MR-based cognitive training system can be used as a cognitive training tool to improve visuospatial working memory in individuals with MCI.
Relationship Between Cognitive-Behavioral Impairment and Clinical and Functional Parameters in ALS and Reliability of the Edinburgh Cognitive and Behavioural ALS Screen to Assess ALS: Preliminary Findings
Authors: Díaz Jose Luis , Mondragón Helena , Sancho Jesús , Aguilar Eduardo J. , Servera Emilio
Published: September 2019

Background:

Although it is widely recognized that a high percentage of individuals with amyotrophic lateral sclerosis (ALS) have cognitive and behavioral impairment, the associated clinical and functional parameters remain unknown. ALS is typically assessed via screening tests, such as the Edinburgh Cognitive and Behavioural ALS Screen (ECAS).

Objective:

To investigate the relationship between cognitive-behavioral impairment and other clinical and functional parameters and to compare the assessment results from a set of standardized neuropsychological tests with those from the ECAS.

Methods:

Forty individuals with ALS participated in the study. We assessed attention, memory and learning ability, and executive function using a set of standardized neuropsychological tests and the ECAS. Sociodemographic variables, time since onset of symptoms, time since diagnosis, and functional respiratory values were recorded.

Results:

No relationship was found between time since onset of symptoms and time since definitive diagnosis and either attention (P=0.206, 0.314, respectively), memory and learning ability (P=0.618, 0.692), or executive function (P=0.844, 0.583). The set of standardized neuropsychological tests identified an impairment in executive function in 29% of the participants, whereas the ECAS identified it in 89%.

Conclusions:

We found no relationship between cognitive-behavioral impairment and time since onset of symptoms nor time since ALS diagnosis. Because the ECAS does not correctly reflect the executive function of individuals with ALS, function-specific neuropsychological tests are preferred. Test selection must take into account individuals’ physical characteristics and their consequent ability to respond gesturally or orally.
Changes in Cognitive Performance With Age in Adults With Multiple Sclerosis
Authors: Baird Jessica F. , Cederberg Katie L.J. , Sikes E. Morghen , Jeng Brenda , Sasaki Jeffer E. , Sandroff Brian M. , Motl Robert W.
Published: September 2019

Background:

Cognitive impairment is one of the most common consequences of multiple sclerosis (MS), yet there is a shortage of data regarding how cognition changes during the life span of individuals with MS. This information is of increasing importance given the growing proportion of older adults with MS.

Objective:

To study possible changes in cognitive function in correlation with increasing age in individuals with MS.

Methods:

Participants (N=129) were recruited and a priori allocated into one of three age groups (young, middle-aged, and older). All participants completed the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) during a single laboratory testing session. The BICAMS measures cognitive processing speed as well as verbal and visuospatial learning and memory.

Results:

A multivariate analysis of variance indicated that cognitive function significantly differed by age group, and these differences were not explained by amount of physical activity, years of education, years since diagnosis, or race. Older adults displayed significantly worse cognitive processing speed than young and middle-aged adults. The older and middle-aged adults also demonstrated significantly worse visuospatial learning and memory than the younger adults. Effect sizes indicated that cognitive processing speed and verbal learning and memory were more affected in late adulthood than early adulthood, whereas visuospatial learning and memory was affected similarly in early and late adulthood.

Conclusions:

Older adults with MS demonstrated significant impairments in cognitive function compared to young and middle-aged adults with MS. Future studies should determine the predictors of cognitive decline in this age cohort.
Dyspareunia in their own words: A comprehensive qualitative description of endometriosis-associated sexual pain
Authors: Wahl Kate J , Imtiaz Shermeen , Joseph KS , Smith Kelly B , Yong Paul J. , Cox Susan M.
Published: September 2019

Background

Dyspareunia is a classic symptom of endometriosis but is neglected in research and clinical contexts. This study explored the experience of this endometriosis-associated sexual pain.

Methods

This was a qualitative descriptive study that included people who had experienced endometriosis-associated dyspareunia alone or with a partner. Data collection involved semi- structured interviews with a female researcher that began with an open-ended question about dyspareunia and included interview prompts related to the nature of sexual pain. Interviews were recorded, transcribed verbatim, and analysed for themes.

Results

17 participants completed interviews. The mean participant age was 33.3 (SD=7.2) and most participants identified as white (82%), were college-educated (71%), identified as heterosexual (65%), and were partnered (59%). Location, onset, and character emerged as important, interrelated features of endometriosis-associated dyspareunia, as did severity and impact. Dyspareunia occurred at the vaginal opening (n=7) and in the abdomen/pelvis (n=13). Pain at the vaginal opening began with initial penetration and had pulling, burning and stinging qualities. Pain in the pelvis was typically experienced with deep penetration or in certain position and was described as sharp, stabbing and/or cramping. Dyspareunia ranged from mild to severe, and for some participants had a marked psychosocial impact.

Conclusions

Dyspareunia is a heterogeneous symptom of endometriosis that ranges in severity and impact. Disaggregating dyspareunia into superficial and deep types may better reflect the etiologies of this pain, thereby improving outcome measurement in intervention studies and clinical care.
DCT4- a new member of the dicarboxylate transporter family in C4grasses
Authors: Weissmann Sarit , Huang Pu , Furuyama Koki , Wiechert Madeline A. , Taniguchi Mitsutaka , Schnable James C. , Brutnell Thomas P. , Mockler Todd C.
Published: September 2019

Malate transport shuttles atmospheric carbon into the Calvin-Benson cycle during NADP-ME C4photosynthesis. Previous characterizations of several plant dicarboxylate transporters (DCT) showed that they efficiently exchange malate across membranes. Here we identify and characterize a previously unknown member of theDCTfamily,DCT4, inSorghum bicolor. We show that SbDCT4 exchanges malate across membranes and its expression pattern is consistent with a role in malate transport during C4photosynthesis.SbDCT4is not syntenic to the characterized photosynthetic geneZmDCT2, and an ortholog is not detectable in the maize reference genome. We found that the expression patterns ofDCTfamily genes in the leaves ofZ. mays, andS. bicolorvaried by cell type. Our results suggest that sub-functionalization of members of theDCTfamily for the transport of malate into the bundle sheath (BS) plastids occurred during the process of independent recurrent evolution of C4photosynthesis in grasses of the PACMAD clade. This study confirms the value of using both syntenic information and gene expression profiles to assign orthology in evolutionarily related genomes.
Eye movements support behavioral pattern completion
Authors: Wynn Jordana S. , Ryan Jennifer D. , Buchsbaum Bradley R.
Published: September 2019

The ability to recall a detailed event from a simple reminder is supported by pattern completion, a cognitive operation performed by the hippocampus wherein existing mnemonic representations are retrieved from incomplete input. In behavioral studies, pattern completion is often inferred through the false endorsement of lure (i.e., similar) items as old. However, evidence that such a response is due to the specific retrieval of a similar, previously encoded item is severely lacking. We used eye movement (EM) monitoring during a partial-cue recognition memory task to index reinstatement of lure images behaviorally via the recapitulation of encoding-related EMs or, gaze reinstatement. Participants reinstated encoding-related EMs following degraded retrieval cues and this reinstatement was negatively correlated with accuracy for lure images, suggesting that retrieval of existing representations (i.e., pattern completion) underlies lure false alarms. Our findings provide novel evidence linking gaze reinstatement and pattern completion and advance a functional role for EMs in memory retrieval.
A Conserved Mechanism of APOBEC3 Relocalization by Herpesviral Ribonucleotide Reductase Large Subunits
Authors: Cheng Adam Z. , de Moraes Sofia Nóbrega , Attarian Claire , Yockteng-Melgar Jaime , Jarvis Matthew C. , Biolatti Matteo , Galitska Ganna , Dell’Oste Valentina , Frappier Lori , Bierle Craig J. , Rice Stephen A. , Harris Reuben S.
Published: September 2019

An integral part of the antiviral innate immune response is the APOBEC3 family of single-stranded DNA cytosine deaminases, which inhibits virus replication through deamination-dependent and -independent activities. Viruses have evolved mechanisms to counteract these enzymes such as HIV-1 Vif-mediated formation of a ubiquitin ligase to degrade virus-restrictive APOBEC3 enzymes. A new example is Epstein-Barr virus (EBV) ribonucleotide reductase (RNR)-mediated inhibition of cellular APOBEC3B (A3B). The large subunit of the viral RNR, BORF2, causes A3B relocalization from the nucleus to cytoplasmic bodies and thereby protects viral DNA during lytic replication. Here, we use co-immunoprecipitation and immunofluorescent microscopy approaches to ask whether this mechanism is shared with the closely related γ-herpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV) and the more distantly related α-herpesvirus, herpes simplex virus-1 (HSV-1). The large RNR subunit of KSHV, ORF61, co-precipitated multiple APOBEC3s including A3B and APOBEC3A (A3A). KSHV ORF61 also caused relocalization of these two enzymes to perinuclear bodies (A3B) and to oblong cytoplasmic structures (A3A). The large RNR subunit of HSV-1, ICP6, also co-precipitated A3B and A3A and was sufficient to promote the relocalization of these enzymes from nuclear to cytoplasmic compartments. HSV-1 infection caused similar relocalization phenotypes that required ICP6. However, unlike the infectivity defects previously reported for BORF2-null EBV, ICP6 mutant HSV-1 showed normal growth rates and plaque phenotypes. These results combine to indicate that both γ- and α-herpesviruses use a conserved RNR-dependent mechanism to relocalize A3B and A3A and, further, suggest that HSV-1 possesses at least one additional mechanism to neutralize these antiviral enzymes.

Importance

The APOBEC3 family of DNA cytosine deaminases constitutes a vital innate immune defense against a range of different viruses. A novel counter-restriction mechanism has recently been uncovered for the γ-herpesvirus EBV, in which a subunit of the viral protein known to produce DNA building blocks (ribonucleotide reductase) causes A3B to relocalize from the nucleus to the cytosol. Here, we extend these observations with A3B to include a closely related γ-herpesvirus, KSHV, and to a more distantly related α-herpesvirus, HSV-1. These different viral ribonucleotide reductases also caused relocalization of A3A, which is 92% identical to A3B. These studies are important because they suggest a conserved mechanism of APOBEC3 evasion by large double-stranded DNA herpesviruses. Strategies to block this host-pathogen interaction may be effective for treating infections caused by these herpesviruses.
Primary cilium-dependent cAMP/PKA signaling at the centrosome regulates neuronal migration
Authors: Stoufflet Julie , Chaulet Maxime , Doulazmi Mohamed , Fouquet Coralie , Dubacq Caroline , Metin Christine , Trembleau Alain , Vincent Pierre , Caille Isabelle
Published: September 2019

The primary cilium (PC) is a small centrosome-assembled organelle, protruding from the surface of most eukaryotic cells. It plays a key role in cell migration, but the underlying mechanisms are unknown. Here, we show that the PC regulates neuronal migration via cAMP production activating centrosomal Protein Kinase A (PKA). Biosensor live-imaging revealed a periodic cAMP hotspot at the centrosome of embryonic, postnatal and adult migrating neurons. Genetic ablation of the PC, or knock-down of ciliary Adenylate Cyclase 3, caused hotspot disappearance and migratory defects, with defective centrosome/nucleus coupling and altered nucleokinesis. Delocalization of PKA from the centrosome phenocopied the migratory defects. Our results show that the PC and centrosome form a single cAMP-signaling unit dynamically regulating migration, further highlighting the centrosome as a signaling hub.
A model Roseobacter employs a diffusible killing mechanism to eliminate competitors
Authors: Sharpe Garrett C. , Gifford Scott M. , Septer Alecia N.
Published: September 2019

The roseobacter clade is a group of α-proteobacteria that have diverse metabolic and regulatory capabilities. They are abundant in marine environments and have a substantial role in marine ecology and biogeochemistry. However, interactions between roseobacters and other bacterioplankton have not been extensively explored. In this study, we identify a killing mechanism in the model Roseobacter Ruegeria pomeroyi DSS-3 by competing it against a group of phylogenetically diverse bacteria. The killing mechanism involves an unidentified antimicrobial compound that is produced when cells are grown on both surfaces and in suspension and is dependent on cell density. A screen of random transposon mutants revealed the killing phenotype, as well as resistance to the antimicrobial, require genes within an ~8 kb putative γ-butyrolactone synthesis gene cluster, which resembles similar pheromone-sensing systems in actinomycetes that regulate secondary metabolite production. Transcriptomics revealed the gene cluster is highly upregulated in wild-type DSS-3 compared to a non-killer mutant when grown in liquid coculture with a roseobacter target. Our findings show that R. pomeroyi has the capability to eliminate closely- and distantly-related competitors, providing a mechanism to alter the community structure and function in its native habitats.
Sensitive Detection of Protein Binding to the Plasma Membrane with Dual-Color Z-Scan Fluorescence
Authors: Angert I. , Karuka S.R. , Hennen J. , Chen Y. , Albanesi J.P. , Mansky L.M. , Mueller J.D.
Published: September 2019

Delicate and transitory protein engagement at the plasma membrane (PM) is crucial to a broad range of cellular functions including cell motility, signal transduction, and virus replication. Here we describe a dual color (DC) extension of the fluorescence z-scan technique which has proven successful for quantification of peripheral membrane protein binding to the PM in living cells. We demonstrate that the co-expression of a second distinctly colored fluorescent protein provides a soluble reference species, which delineates the extent of the cell cytoplasm and lowers the detection threshold of z-scan PM binding measurements by an order of magnitude. DC z-scan generates an intensity profile for each detection channel that contains information on the axial distribution of the peripheral membrane and reference protein. Fit models for DC z-scan are developed and verified using simple model systems. Next, we apply the quantitative DC z-scan technique to investigate the binding of two peripheral membrane protein systems for which previous z-scan studies failed to detect binding: human immunodeficiency virus type 1 (HIV-1) matrix (MA) protein and lipidation-deficient mutants of the fibroblast growth factor receptor substrate 2α. Our findings show that these mutations severely disrupt PM association of fibroblast growth factor receptor substrate 2α but do not eliminate it. We further detected binding of HIV-1 MA to the PM using DC z-scan. Interestingly, our data indicate that HIV-1 MA binds cooperatively to the PM with a dissociation coefficient ofKd~16 μM and Hill coefficient ofn~2.

SIGNIFICANCE

Protein binding to the plasma membrane of cells plays an important role in a multitude of cell functions and disease processes. Quantitative binding studies of protein/membrane interactions are almost exclusively limited to in vitro systems and may produce results that poorly mimic the authentic interactions in living cells. We report quantitative measurements of plasma membrane binding directly in living cells by using dual color z-scan fluorescence, which improves the detection threshold by an order of magnitude compared to our previous single color technique. This advance allowed us to examine the role of mutations on binding affinity and identify the presence of cooperative binding in protein systems with relevance to HIV/AIDS and cancer biology.
Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice
Authors: Lang Veronika , Ferencik Sebastian , Ananthasubramaniam Bharath , Kramer Achim , Maier Bert
Published: September 2019

Local circadian clocks are active in most cells of our body. However, their impact on circadian physiology is still under debate. Mortality by endotoxic (LPS) shock is highly time-of-day dependent and local circadian immune function such as the cytokine burst after LPS challenge has been assumed to be causal for the large differences in survival. Here, we investigate the roles of light and myeloid clocks on mortality by endotoxic shock. Strikingly, mice in constant darkness (DD) show a three-fold increased susceptibility to LPS as compared to mice in light-dark conditions. Mortality by endotoxic shock as a function of circadian time is independent of light-dark cycles as well as myeloid CLOCK or BMAL1 as demonstrated in conditional knockout mice. Unexpectedly, despite the lack of a myeloid clock these mice still show rhythmic patterns of pro- and anti-inflammatory cytokines such as TNFα, MCP-1, IL-18 and IL-10 in peripheral blood as well as time-of-day and site dependent traffic of myeloid cells. We speculate that systemic time-cues are sufficient to orchestrate innate immune response to LPS by driving immune functions such as cell trafficking and cytokine expression.
Alternative catalytic residues in the active site of Esco acetyltransferases
Authors: Ajam Tahereh , De Inessa , Petkau Nikolai , Whelan Gabriela , Pena Vladimir , Eichele Gregor
Published: September 2019

Cohesin is a protein complex encircles the DNA and regulates the separation of sister chromatids during cell division. Following a catalytic mechanism that is insufficiently understood, Esco1 and Esco2 acetyltransferases acetylate Smc3 subunit of cohesin, thereby inducing a stabilization of cohesin on DNA. As a prerequisite for structure-guided investigation of enzymatic activity, we determine here the crystal structure of the mouse Esco2/CoA complex at 1.8 Å resolution. We reconstitute the entire cohesin as a tetrameric assembly and use it as a physiologically-relevant substrate for enzymatic assays in vitro. Furthermore, we employ cell-based complementation studies in mouse embryonic fibroblast deficient for Esco1 and Esco2, as a means to identify catalytically-important residues in vivo. These analyses demonstrate that D567/S566 and E491/S527, located on opposite sides of the MmEsco2 active site cleft, are critical for catalysis. Our experiments supports a catalytic mechanism of acetylation where residues D567 and E491 are general bases that deprotonate the ε-amino group of lysine substrate, via two nearby serine residues - S566 and S527-that possess a proton relay function.