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Objective Chronic skin wounds are one of the most devastating complications in diabetic patients due to the formation of advanced glycation end products (AGEs) resulting from non-enzymatic glycation of proteins and lipids in hyperglycemia. AGEs, upon binding their receptors (RAGEs), trigger pro-inflammatory signals that impair wound healing in diabetes and contribute to the pathology of chronic skin wounds. Approach We previously developed a recombinant fusion protein containing the binding domain of RAGE (vRAGE) linked to elastin-like polypeptides (ELPs) that acts as a competitive inhibitor of AGEs, and another ELP fusion protein containing stromal cell-derived factor 1 (SDF1) that promotes revascularization. Herein, we report the effects of protein coacervates incorporating both vRAGE-ELP and SDF1-ELP on wound healing in an in vitro diabetes-mimicking cell culture system, and in in vivo in full-thickness wounds on diabetic mice. Results The combination of vRAGE-ELP and SDF1-ELP increased cell metabolic activity in AGE-stimulated endothelial cells, promoted in vitro tube formation and accelerated healing in an in vitro cell migration assay. When used in a single topical application on full-thickness excisional skin wounds in diabetic mice, wound closure in the combination groups reached almost 100% on post-wounding day 35, compared to 62% and 85% on the same days in animals treated with fibrin gel control and vehicle control consisting of ELP alone. Innovation To our knowledge, this is the first study that attempts to reverse the AGE-RAGE-mediated signaling as well as to promote cell proliferation and vascularization in one single treatment. Conclusion The co-delivery of vRAGE-ELP and SDF1-ELP has potential for the treatment of diabetic wounds.

Objective Police officers typically face multiple potentially traumatic events and consequently have a higher conditional probability of developing PTSD. Although most police officers with PTSD benefit from first-line treatment, it is unknown whether recommended intensification of treatment for low responders is effective and which factors contribute to response. This study aimed to examine the treatment response of a day clinic for police officers with PTSD and identify predictors of treatment response. Method Between 2009 and 2019, routine outcome monitoring measurements consisting of PTSD symptom severity and general psychological distress were administered at two timepoints among 102 patients undergoing a day clinic treatment consisting of trauma-focused therapy, sociotherapy, and psychomotor therapy. Hierarchical regression was used to assess whether change in PTSD symptom severity was associated with baseline PTSD and depression severity, gender, age, and eligibility for a recognition procedure. Results Significant improvements in PTSD symptom severity were found over the course of the treatment (d = .59), with 47% of patients showing statistically reliable improvement in their symptoms. The only significant predictor of treatment response was eligibility for a recognition procedure, with the total model explaining approximately 10% of the variation in treatment response. Conclusions Intensifying treatment for police officers with PTSD who do not respond to previous trauma-focused treatment appears beneficial for a substantial number of patients. However, eligibility for a recognition procedure may negatively impact treatment response. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Low voltage shielded cable serves critical roles in controlling and measuring advanced power systems to ensure their reliability and safety. As a consequence, monitoring of the cable is significant, yet conventional monitoring techniques are limited for non-operating power systems for safety causes which eventually affects the reliability of the power system and brings economical loss. In this paper, a contactless signal communication approach via inductive coupler is applied to stepped frequency waveform reflectometry (SFWR) for monitoring operating power systems. Additionally, a long short-term memory (LSTM) based neural network model is adapted for compensating non-linear distortion of the signals yielded by the couplers. Compared to conventional approaches, LSTM has advantages to restore non-linearities of the couplers since it can respond to various non-linear factors such as the dimension of the coupler, the length of the cable, or the position of the signal application. The proposed reflectometry system for monitoring live shielded cable is tested on 75m 2-core shielded cable with two cases of fault emulation, and the efficacy of the proposed technique in real fields is also verified.

Background Theta burst stimulation (TBS), a patterned repetitive transcranial magnetic stimulation (rTMS) protocol with shorter simulation duration and lower stimulus intensity, could be a better protocol for individuals with autism spectrum disorder (ASD). Our study aimed to explore the impacts of intermittent TBS (iTBS) over the bilateral posterior superior temporal sulcus (pSTS) on intellectually able adults with ASD. Material and methods In this randomized, single-blinded, sham-controlled crossover trial, 13 adults with ASD completed iTBS for 5 consecutive days over the bilateral pSTS and inion (as a sham control) in a 16-weeks interval and in a randomly assigned order. The neuropsychological function was measured with the Wisconsin Card Sorting Test (WCST) for cognitive flexibility while the clinical outcomes were measured with both self-rate and parents-rate Autism Spectrum Quotient (AQ) before and after 5-day iTBS interventions. Results The results revealed significantly immediate effects of multi-session iTBS over the bilateral pSTS on parent-rate autistic symptoms in adults with ASD. The post-hoc analysis revealed the impacts of multi-session iTBS on cognitive flexibility were affected by baseline social-communicative impairment and baseline cognitive performance. Besides, the impacts of multi-session iTBS on clinical symptoms was affected by the concurrent psychotropic medication use and baseline autistic symptoms. Conclusions Given the caveat of the small sample size and discrepancy of multiple informants, this pilot study suggests the therapeutic potential of 5-day multi-session iTBS over the pSTS in adults with ASD. Individual factors modulating the response to rTMS should be explicitly considered in the future trial.

Background A lack of scientific information regarding the risk factors and diagnosis of peri-implant atypical femoral fracture (PI-AFF) exists. We report a case series of developed PI-AFF with a nail or plate construct wherein prior femoral fractures were already healed after osteosynthesis. This study aimed to identify the cause and risk factors of PI-AFF and to devise a preventive method based on this. Methods We identified 11 PI-AFFs displaying features of AFFs. All patients were ambulant females (mean age, 74.9 years). The mean T-score of the femur measured by DEXA (Dual Energy X-ray Absorptiometry) scan was 3.5. Osteosynthesis was performed with a plate and an intramedullary nail in six and five patients, respectively. Possible risk factors were investigated, including the used implant, the medication of bisphosphonate, the characteristics of previous fracture (AFF or non-AFF), and the co-existence of AFF on the contralateral side. Results The PI-AFFs developed at an average of 6.6 years from the time of prior fracture. All fractures were located at the screw through the plate or nail. Regarding anatomic locations, seven and four fractures were at the subtrochanteric area and diaphysis, respectively. Diaphyseal PI-AFFs occurred in plating cases, all of which were associated with excessive femoral bowing. Subtrochanteric PI-AFFs included all five patients with nail fixation, which occurred near a proximal interlocking screw. Six of the 11 patients were on bisphosphonate treatment before or at the time of fracture. The duration of bisphosphonate treatment was 6 years on average. Concerning the previous femoral fractures, seven and four patients were AFF and non-AFF, respectively. Considering the pathology on the contralateral leg, eight had suffered diaphyseal AFF. Four patients were treated nonoperatively. Seven patients needed an operation; 6 of them healed after reconstruction nailing, and one needed hip arthroplasty because of the associated displaced femoral neck fracture. Conclusions PI-AFFs may develop through the screw hole at the subtrochanteric or diaphyseal area due to femoral fragility and stress riser effect of the implant. An improved osteosynthesis strategy may be necessary to avoid PI-AFFs when fixing osteoporotic femoral fractures.

The containment building Kori Unit 1 may require sequential steps for full decommissioning. This study assumes that the containment building is to be used as an auxiliary building that handles nuclear power systems and materials during decommissioning before conversion into a greenfield. Through the derivation of guidelines and dose evaluation, it was confirmed whether the radiation workers were satisfied with the ALARA decision. The specific modeling of the external radiation exposure was performed based on the facility investigation procedures. The external radiation specific derived concentration guideline levels (DCGLs) for radiation workers in containment building were obtained using the RESRAD-BUILD code and were applied to the VISIPLAN 3D ALARA Planning Tool code to calculate the working dose and check worker safety. The derivation of site-specific and realistic DCGLs and dose evaluation via 3D modeling can contribute to the scenario development for the decommission and remediation of containment building.

BACKGROUND: Epidemiological studies from Europe and North America report an increasing incidence of microscopic colitis (MC) in the late twentieth century followed by a plateau. This population-based study assessed recent incidence trends and the overall prevalence of MC over the past decade. METHODS: Residents of Olmsted County, Minnesota diagnosed with collagenous colitis (CC) or lymphocytic colitis (LC) between January 1, 2011 and December 31, 2019 were identified using the Rochester Epidemiology Project. Clinical variables were abstracted by chart review. Incidence rates were age- and sex-adjusted to the 2010 US population. Associations between incidence and age, sex, and calendar periods were evaluated using Poisson regression analyses. RESULTS: A total of 268 incident cases of MC were identified with a median age at diagnosis of 64 years (range, 19–90); 207 (77%) were women. The age- and sex-adjusted incidence of MC was 25.8 (95% confidence interval [CI] 22.7–28.9) cases per 100,000 person-years. The incidence of LC was 15.8 (95% CI, 13.4–18.2) and CC 9.9 (95% CI, 8.1–11.9) per 100,000 person-years. A higher MC incidence was associated with increasing age and female sex (p

Osteoarthritis, the most common degenerative joint disease, occurs more frequently in joints that have sustained injury. Currently, osteoarthritis is diagnosed with imaging that finds radiographic changes after the disease has already progressed to multiple tissues. The primary objective of this study was to compare potential metabolomic biomarkers of joint injury between the synovial fluid and serum in a mouse model of post-traumatic osteoarthritis. The secondary objective was to gain insight into the pathophysiology of osteoarthritis by examining metabolomic profiles after joint injury. 12-week-old adult female C57BL/6 mice (n=12) were randomly assigned to control, day 1 post injury, or day 8 post injury groups. Randomly selected stifle (i.e., knee) joints were placed into a non-invasive injury apparatus and subjected to a single dynamic axial compression causing anterior translation of the tibia relative to the femur to tear the anterior cruciate ligament. At days 1 and 8 post injury, serum was extracted then mice were immediately euthanized prior to synovial fluid collection. Metabolites were extracted and analyzed by liquid chromatography coupled to mass spectrometry. We detected ~2500 metabolites across serum and synovial fluid. Of these metabolites 179 were positively correlated and 51 were negatively correlated between synovial fluid and serum, indicating potential for the development of metabolomic biomarkers. Synovial fluid appeared to capture differences in metabolomic profiles between injured mice at both day 1 and 8 after injury whereas serum did not. However, synovial fluid and serum were distinct at both days 1 and 8 after injury. In the synovial fluid, pathways of interest across different time points mapped to amino acid synthesis and degradation, bupropion degradation, and the tRNA charging pathway. In the serum, notable pathways across time points were amino acid synthesis and degradation, the phospholipase pathway, and nicotine degradation. These results provide a rich picture of the injury response at early time points following traumatic joint injury. Furthermore, the correlations between synovial fluid and serum metabolites suggest that there is potential to gain insight into intra-articular pathophysiology through analysis of serum metabolites.

We hypothesized that combining adoptively transferred autologous T cells with a cancer vaccine strategy would enhance therapeutic efficacy by adding antimyeloma idiotype (Id)–keyhole limpet hemocyanin (KLH) vaccine to vaccine-specific costimulated T cells. In this randomized phase 2 trial, patients received either control (KLH only) or Id-KLH vaccine, autologous transplantation, vaccine-specific costimulated T cells expanded ex vivo, and 2 booster doses of assigned vaccine. In 36 patients (KLH, n = 20; Id-KLH, n = 16), no dose-limiting toxicity was seen. At last evaluation, 6 (30%) and 8 patients (50%) had achieved complete remission in KLH-only and Id-KLH arms, respectively (P = .22), and no difference in 3-year progression-free survival was observed (59% and 56%, respectively; P = .32). In a 594 Nanostring nCounter gene panel analyzed for immune reconstitution (IR), compared with patients receiving KLH only, there was a greater change in IR genes in T cells in those receiving Id-KLH relative to baseline. Specifically, upregulation of genes associated with activation, effector function induction, and memory CD8+ T-cell generation after Id-KLH but not after KLH control vaccination was observed. Similarly, in responding patients across both arms, upregulation of genes associated with T-cell activation was seen. At baseline, all patients had greater expression of CD8+ T-cell exhaustion markers. These changes were associated with functional Id-specific immune responses in a subset of patients receiving Id-KLH. In conclusion, in this combination immunotherapy approach, we observed significantly more robust IR in CD4+ and CD8+ T cells in the Id-KLH arm, supporting further investigation of vaccine and adoptive immunotherapy strategies. This trial was registered at www.clinicaltrials.gov as #NCT01426828.

Covid-19 has drawn renewed focus to the importance of resilience, both among practitioners and in academia, as companies struggle to cope with the rapid swings, changing patterns, and disruptions in supply and demand. This article identifies and delineates a way forward for companies to support resilience, particularly by companies recognizing the wider communities they are nested in and resources that exist there. To identify such productive resources, known as ‘capitals’, we provide a novel and actionable Integrated Capitals Framework. This framework integrates ten existing frameworks drawn from both practice and academia, and is comprised of nine different forms of capital: financial, physical, social, natural, human, cultural, public, political, and, crucially, health. Businesses can leverage and contribute to these resources to support resilience. We provide insights into how businesses can use this framework in practice, providing a way for companies to achieve resilience through this useful, yet underutilized, path.

Background Clinical manifestations of coronavirus disease 2019 (COVID19) can vary from asymptomatic to profusely symptomatic due to many factors. Having data on the clinical characteristics of the affected patients is important for the screening and diagnosis of COVID-19. Main objective of this study is to evaluate the clinical and epidemiological characteristics and outcomes of patients with COVID-19 admitted to six treatment centres in Sri Lanka. Methods For the specific epidemic situation of COVID-19, we chose to conduct a descriptive retrospective study from six treatment centres in the country between March 10, 2020 and May 30, 2020. Results The study included 431 laboratory confirmed patients with COVID-19. Of them, 335 (78.2%) were males and their mean age was 37 years. Most patients (373: 86.5%) had had close contact with COVID-19 positive patients. The majority were asymptomatic (243: 56.3%) and of the symptomatic patients, the most common symptom was sore throat (81, 19%), followed by cough (72, 17%), headache (72, 17%), fever (50, 12%), and nasal discharge (36, 8%). Eight patients required either high dependency care or intensive unit care two of them succumbed to the illness (0.5%). Hydroxychloroquine (HCQ) was used as a treatment in 248 patients and they had a significantly longer (17.6 days) duration of hospital stays compared those who were not treated (13.6 days) with HCQ. When the HCQ was not used as a treatment, asymptomatic individuals had significantly shorter durations of hospital (11.1 days) stays compared to symptomatic individuals (14.3 days). Conclusions The majority of patients remained asymptomatic during the course of illness. The most common symptom was sore throat, seen in one fifth of patients, followed by cough, and headache. Our study also indicated the possibility of reduced viral clearance and hence longer duration of hospital stays with HCQ.

Halide perovskites, fascinating memristive materials owing to mixed ionic-electronic conductivity, have been attracting great attention as artificial synapses recently. However, polycrystalline nature in thin film form and instability under ambient air hamper them to be implemented in demonstrating reliable neuromorphic devices. Here, we successfully fabricated vertically aligned 2D halide perovskite films (V-HPs) for active layers of artificial synapses, showing moisture stability for several months. Unlike random-oriented HPs, which exhibit negligible current hysteresis, the V-HPs possess multilevel analog memristive characteristics, programmable potentiation and depression with distinguished multi-states, long-short-term plasticity, paired-pulse facilitation, and even spike-timing-dependent plasticity. Furthermore, high classification accuracy is obtained with implementation in deep neural networks. These remarkable improvements are attributed to the vertically well-aligned lead iodide octahedra acting as the ion transport channel, confirmed by first-principles calculations. This study paves the way for understanding HPs nanophysics and demonstrating their potential utility in neuromorphic computing systems.

Objective To evaluate long-term reproductive outcomes in couples who were enrolled in a large randomized controlled trial that studied optimal treatment for unexplained infertility. Design Telephone survey, administered between March 2019 and February 2020. Setting Large urban university-affiliated fertility center. Patient(s) Couples who enrolled in the Fast Track and Standard Treatment Trial (FASTT). Intervention(s) None. Main Outcomes Measure(s) Number of live births, methods of conception, adoption, and satisfaction regarding family size. Result(s) Of the 503 couples enrolled in FASTT, 311 (61.8%) were contacted and 286 (56.9%) consented to participate. The mean age and follicle-stimulating hormone level at the time of enrollment in FASTT were 33.1 ± 3.2 years and 6.8 ± 2.2 mIU/mL, respectively, for those who participated in this study. The mean age at follow-up was 49.5 ± 3.4 years. Of the 286 women, 194 (67.8%) had a live birth during the trial and 225 (78.7%) continued to try to conceive after FASTT. Of those who tried to conceive without treatment, 101 of 157 (64.3%) had a successful live birth, whereas 12 (5.3%) women had a live birth via intrauterine insemination and 82 (36.4%) via autologous oocyte in vitro fertilization. Overall, 182 (80.9%) women achieved a live birth after FASTT. Conclusion(s) The majority of couples were able to achieve a live birth after FASTT. Only 19 (6.6%) never achieved a live birth during their reproductive years. Moving to treatment sooner allows the opportunity to achieve >1 live birth, which is associated with increased satisfaction regarding family size. This further supports access to care and insurance coverage for infertility treatment.

Next-generation sequencing (NGS) of rearranged Ig genes is an effective technology for identifying pathologic clonal cells in multiple myeloma (MM) and tracking minimal residual disease. The clinical effect of implementing NGS in Ig gene clonality analysis was evaluated via a retrospective chart review. A total of 312 patients diagnosed with MM were enrolled in the study. Ig gene clonality was determined by fragment analysis using BIOMED-2 multiplex PCR assays and by NGS using the LymphoTrack IGH FR1 Assay and LymphoTrack IGK Assay. The clonality detection rates in diagnostic samples obtained using fragment analysis and NGS were 96.7% and 95.4%, respectively (statistically nonsignificant difference; P = 0.772). Among samples of patients in complete remission, the clonality detection rates obtained using fragment analysis and NGS were 33.3% and 60.3%, respectively (statistically significant difference; P = 0.034). Progression-free survival was significantly longer in negative than positive patients by NGS analysis (P = 0.03). Clonality detection by NGS-based methods using IGH FR1 and IGK assays in routine clinical practice is feasible, provides good clonality detection rates in diagnostic samples, and allows monitoring of samples in MM patients with significant prognostic value.

Background Seroprevalence studies of coronavirus disease 2019 (COVID-19) cases, including asymptomatic and past infections, are important to estimate the scale of the disease outbreak and to establish quarantine measures. We evaluated the clinical performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays available in Korea for use in seroprevalence studies. Methods The sensitivity, specificity, cross-reactivity, and interference of five SARS-CoV-2 antibody assays were evaluated using the following: 398 serum samples from confirmed COVID-19 patients, 510 negative control samples from before 2018 (pre-pandemic), 163 serum samples from patients with SARS, Middle East respiratory syndrome (MERS), and other viral infections, and five samples for the interference study. Results The sensitivities of the five assays ranged from 92.2% to 98%, and their specificities, including cross-reactivity and interference, ranged from 97.5% to 100%. The agreement rates were excellent (kappa >0.9). Adjustment of the cutoff values could be considered through ROC curve analysis. The positive predictive values of the individual assays varied from 3.5% to 100% at a 0.1% prevalence but were as high as ≥95% when two assays were combined. Conclusions The prevalence of COVID-19 in Korea is considered to be exceptionally low at present; thus, we recommend using a combination of two or more SARS-CoV-2 antibody assays rather than a single assay. These results could help select SARS-CoV-2 antibody assays for COVID-19 seroprevalence studies in Korea.

Objectives: We examined the use and long-term outcomes of vaginal hysterectomy for women with early-stage endometrial cancer. Methods: The Surveillance, Epidemiology, and End Results-Medicare database was used to identify women with stage I-II endometrial cancer treated with primary hysterectomy from 2000-2015. Multivariable models were developed to examine clinical, demographic, and pathologic factors associated with performance of TVH. The association between route of hysterectomy and cancer specific and overall survival was examined using multivariable Cox proportional hazards models. Results: A total of 19,212 patients including 837 (4.6%) who underwent TVH were identified. Performance of vaginal hysterectomy declined from 4.5% in 2000 to 2.2% in 2015 (P 80 years old (aRR=1.60; 95% CI, 1.30-1.97) were more likely to undergo TVH. There was no association between either overall co-morbidity (Charlson index) or any individual comorbidities and performance of TVH. Women with high grade tumors were less likely to undergo TVH. Five-year survival was 78.4% (95% CI: 77.6-79.2) in those who underwent abdominal hysterectomy, 83.3% (95% CI: 82.1-84.4) in those who had a laparoscopic hysterectomy and 80.9% (95% CI: 77.8-83.5) in those who underwent TVH. In multivariable models, there was no adverse impact between TVH and either overall (HR=1.06; 95% CI, 0.94-1.19) or cancer-specific (HR=0.95; 95% CI, 0.70-1.28) survival. Download : Download high-res image (83KB) Download : Download full-size image Conclusions: Use of vaginal hysterectomy for stage I/II endometrial cancer has decreased in the U.S. Chronologic age is the greatest predictor of performance of TVH. Performance of TVH does not negatively impact survival for women with early-stage endometrial cancer.

Purpose: Advances in the diagnosis and treatment of prostate cancer have increased the patients’ stress level and decreased the quality of life. A variety of instruments are currently available to evaluate patients with prostate cancer. However, only a few tools are available to assess Korean patients, and therefore we demonstrated a linguistic validation of Korean Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP).Methods: EPIC-CP was translated into Korean and the linguistic validation was evaluated. The evaluation process includes permission for translation, forward translation, reconciliation, backward translation, cognitive debriefing, and proofreading. Two bilingual translators independently translated the original questionnaire, discussed the feasibility and naturalness of initial translation, followed by revision to the reconciled version. Another translator then performed a backward translation into English. Ten patients with prostate cancer completed the translated questionnaire and performed cognitive debriefing.Results: The original EPIC-CP was translated into 2 Korean versions. The different wording in both versions and the ordinary words in the initial translations were changed considering the nuances and meanings of medical terms. During the backward translation, the panels made slight changes to clarify the meaning and nuances of the translated questionnaire. During cognitive debriefing, 10 patients answered the questionnaire and offered their opinions regarding comprehensibility and naturalness. Most patients agreed that the translation was comprehensible in general.Conclusions: Our study provides a successful linguistic validation of the EPIC-CP questionnaire. The translation is a helpful diagnostic tool to ensure the quality of life of patients with prostate cancer attending crowded clinics.

OBJECTIVES Patients with microscopic colitis may have subtle macroscopic findings on colonoscopy such as erythema, edema, or altered vascular pattern; however, radiographic abnormalities on cross-sectional imaging have not been investigated. We aimed at identifying the abdominopelvic radiographic abnormalities in patients with microscopic colitis, as well as possible correlation with endoscopic findings and the need for extended duration of treatment. MATERIALS AND METHODS This was a retrospective study of patients with biopsy-proven microscopic colitis at two tertiary centers between 1 January 2010 and 30 April 2020. Patients underwent computed tomography scan or magnetic resonance imaging within 30 days of a diagnostic flexible sigmoidoscopy or colonoscopy. Patients with colon ischemia and other causes of colitis were excluded. Radiographic abnormalities from imaging reports included bowel wall thickening, mucosal hyperenhancement and mesenteric fat stranding. Univariate and multivariable logistic regression models were used to identify predictors of radiographic abnormalities. RESULTS 498 patients with microscopic colitis underwent abdominopelvic cross-sectional imaging within 30 days of flexible sigmoidoscopy/colonoscopy. Lymphocytic colitis was diagnosed in 54.6% of patients, and collagenous colitis in 45.4%. Endoscopic and radiographic abnormalities were identified in 16.1% and 12.4% of patients, respectively. Radiographic abnormalities were associated with the need for budesonide therapy (p = .029) and budesonide therapy long-term (p = .0028). Budesonide therapy long-term (p = .047) was associated with radiographic abnormalities in multivariate analysis. CONCLUSIONS Radiographic abnormalities may be present on abdominopelvic cross-sectional imaging in a minority of patients with biopsy-proven microscopic colitis, suggesting cross-sectional imaging has low clinical value in the evaluation and treatment of this disease.

AIM Vision impairment (VI) and hearing impairment (HI), alone or in combination (dual sensory impairment [DSI]), are common in older adults. We determined (i) the association of vision and hearing, and of VI only, HI only and DSI, with three psychosocial variables (social network, loneliness, depressive symptoms) and with quality of life (QoL), and (ii) whether the considered psychosocial variables mediate the association of VI only, HI only and DSI with QoL among older adults. METHODS Cross-sectional survey data for 4077 older adults (≥60 years) from Singapore were analyzed. Those with self-reported fair or poor vision and hearing were considered to have an impairment in that sense. Standard scales were used to assess the psychosocial variables and QoL. Regression and mediation models were used. RESULTS Those with fair and poor vs. good, vision and hearing generally had poorer psychosocial outcomes and lower QoL. VI only, HI only and DSI were all associated with lower social network, more depressive symptoms and lower QoL. VI only and DSI were associated with more loneliness. Social network, loneliness and depressive symptoms partially mediated the association of VI only, HI only and DSI with QoL, with depressive symptoms being the strongest mediator. CONCLUSIONS VI and HI, particularly in combination, are associated with poorer psychosocial status and QoL among older adults. Older adults with VI or HI should be screened for depressive symptoms and social risks. Improving social network, loneliness and depressive symptoms among older adults with sensory impairments may enhance their QoL. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2021; ••: ••-••.

Rationale Two distinct subphenotypes have been identified in acute respiratory distress syndrome (ARDS), but the presence of subgroups in ARDS associated with COVID-19 is unknown. The objective of this study was to identify clinically relevant, novel subgroups in COVID-19-related ARDS, and compare them to previously described ARDS subphenotypes. Methods Eligible participants were adults with COVID-19 and ARDS at Columbia University Irving Medical Center. Latent class analysis (LCA) was used to identify subgroups with baseline clinical, respiratory, and laboratory data serving as partitioning variables. A previously-developed machine learning model was used to classify patients as the hypoinflammatory and hyperinflammatory subphenotypes. Baseline characteristics and clinical outcomes were compared between subgroups. Heterogeneity of treatment effect (HTE) for corticosteroid-use in subgroups was tested. Measurements and Main Results From 3/2-4/30/2020, 483 patients with COVID-19-related ARDS met study criteria. A two-class LCA model best fit the population (p=0.0075). Class 2 (23%) had higher pro-inflammatory markers, troponin, creatinine and lactate, lower bicarbonate and lower blood pressure than Class 1 (77%). 90-day mortality was higher in Class 2 versus Class 1 (75% vs 48%; p

PURPOSE Pain is among the most common and consequential symptoms of cancer, particularly in the context of lung cancer. Māori have extremely high rates of lung cancer, and there is evidence that Māori patients with lung cancer are less likely to receive curative treatment and more likely to receive palliative treatment and to wait longer for their treatment than non-Māori New Zealanders. The extent to which Māori patients with lung cancer are also less likely to have access to pain medicines as part of their supportive care remains unclear. METHODS Using national-level Cancer Registry and linked health records, we describe access to subsidized pain medicines among patients with lung cancer diagnosed over the decade spanning 2007-2016 and compare access between Māori and non-Māori patients. Descriptive and logistic regression methods were used to compare access between ethnic groups. RESULTS We observed that the majority of patients with lung cancer are accessing some form of pain medicine and there do not appear to be strong differences between Māori and non-Māori in terms of overall access or the type of pain medicine dispensed. However, Māori patients appeared more likely than non-Māori to first access pain medicines within 2 weeks before their death and commensurately less likely to access them more than 24 weeks before death. CONCLUSION Given the plausibility that there are differences in first access to pain medicines (particularly opioid medicines) among Māori approaching end of life, further investigation of the factors contributing to this disparity is required.

Gastric cancer is the third most common cause of cancer deaths worldwide. Despite evidence-based recommendation for treatment, the current treatment patterns for all stages of gastric cancer remain largely unexplored. This study investigates trends in the treatments and survival of gastric cancer. The National Cancer Database was used to identify gastric adenocarcinoma patients from 2004&ndash, 2016. Chi-square tests were used to examine subgroup differences between disease stages: Stage I, II/III and IV. Multivariate analyses identified factors associated with the receipt of guideline concordant care. The Kaplan&ndash, Meier method was used to assess three-year overall survival. The final cohort included 108,150 patients: 23,584 Stage I, 40,216 Stage II/III, and 44,350 Stage IV. Stage specific guideline concordant care was received in only 73% of patients with Stage I disease and 51% of patients with Stage II/III disease. Patients who received guideline consistent care had significantly improved survival compared to those who did not. Overall, we found only moderate improvement in guideline adherence and three-year overall survival during the 13-year study time period. This study showed underutilization of stage specific guideline concordant care for stage I and II/III disease.

Introduction The Blood First Assay Screening Trial is an ongoing open-label, multicohort study, prospectively evaluating the relationship between blood-based next-generation sequencing (NGS) detection of actionable genetic alterations and activity of targeted therapies or immunotherapy in treatment-naive advanced or metastatic NSCLC. We present data from the ALK-positive cohort. Methods Patients aged more than or equal to 18 years with stage IIIB or IV NSCLC and ALK rearrangements detected by blood-based NGS using hybrid capture technology (FoundationACT) received alectinib 600 mg twice daily. Asymptomatic or treated central nervous system (CNS) metastases were permitted. Primary end point was investigator-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors version 1.1). Secondary end points were independent review facility-assessed ORR, duration of response, progression-free survival (PFS), overall survival, and safety. Exploratory end points were investigator-assessed ORR in patients with baseline CNS metastases and relationship between circulating biomarkers and response. Results In total, 2219 patients were screened and blood-based NGS yielded results in 98.6% of the cases. Of these, 119 patients (5.4%) had ALK-positive disease; 87 were enrolled and received alectinib. Median follow-up was 12.6 months (range: 2.6–18.7). Confirmed ORR was 87.4% (95% confidence interval [CI]: 78.5–93.5) by investigator and 92.0% (95% CI: 84.1–96.7) by independent review facility. Investigator-confirmed 12-month duration of response was 75.9% (95% CI: 63.6–88.2). In 35 patients (40%) with baseline CNS disease, investigator-assessed ORR was 91.4% (95% CI: 76.9–98.2). Median PFS was not reached; 12-month investigator-assessed PFS was 78.4% (95% CI: 69.1–87.7). Safety data were consistent with the known tolerability profile of alectinib. Conclusions These results reveal the clinical application of blood-based NGS as a method to inform clinical decision-making in ALK-positive NSCLC.

INTRODUCTIONSARS-CoV-2 testing is one of the options to combat COVID-19 in Kenya. In the first COVID-19 year there was limited tapping of the private sectors potential to scale up testing in Kenya. In April 2020, we initiated a unique public-private partnership (PPP) project in Kisumu County connecting the private sector to centralized testing supported by the ministry of health (MoH), COVID-Dx, to accelerate the local response to COVID-19. Within COVID-Dx, we aimed to demonstrate this PPPs performance as a replicable model for effective public-private collaboration in responding to the COVID-19 pandemic in similar settings. METHODSKEMRI, Department of Health Kisumu County, PharmAccess Foundation, and local faith-based and private healthcare facilities collaborated in COVID-Dx. COVID-Dx was implemented from June 01, 2020, to March 31, 2021, in Kisumu County, Kenya. Trained laboratory technologists in participating healthcare facilities collected nasopharyngeal and oropharyngeal samples from patients meeting the MoH COVID-19 case definition. Samples were tested at the central laboratory in KEMRI via SARS-CoV-2 RT-PCR. Healthcare workers in participating facilities collected data using the digitized MoH COVID-19 Case Identification Form. We shared aggregated results from these data via (semi-) live dashboard to all relevant stakeholders. We did descriptive statistical analyses using Stata 16 to inform project processes. RESULTSNine facilities participated in the project. A total of 4,324 PCR tests for SARS-CoV-2 were done, with 425 positives. We noted differences in positivity rates between the facilities. Healthcare workers were the largest group tested in the project, 1009, representing 43% of the Kisumu healthcare workforce. CONCLUSIONCOVID-Dx can serve as a model for PPPs scale-up testing, especially LMICs, and digitizing the MoH case report form improved reporting efficiency, demonstrating that digital is the way forward. The COVID-Dx PPP has led to another collaboration with Kisumu County aimed towards extending the COVID-Dx model to other counties. SUMMARY BOX O_TEXTBOXWhat is already known?O_LIIn sub-Saharan Africa, COVID-19 responses are mainly rolled out through the public healthcare sector, even though the private sector plays a significant role in health service delivery C_LIO_LIThe challenge is to combine private and public efforts in healthcare delivery in a mutually supportive and collaborative manner, especially during large outbreaks such as COVID-19. C_LI What are the new findings?O_LIThe development of a public-private partnership (COVID-Dx) at the start of a global pandemic - COVID-19 - is challenging, but PPPs are essential for epidemic preparedness. C_LIO_LIThe development of a digital app with a corresponding dashboard, ensures transparency and efficiency. It has shown to enable data-driven decision-making and provides insight into how to prioritize funding streams. C_LI What do the new findings imply?O_LIThis PPP model is replicable and can serve as an example of PPPs for epidemic preparedness in similar settings in LMICs. C_LIO_LIDigital is the way going forward when combatting large outbreaks in the future, especially in LMICs C_LI C_TEXTBOX

In this paper, we propose the tilted milling method for the fabrication of the precise microlens array (MLA) by eliminating the influence of tool error. In the conventional milling process, the sur...

BackgroundKlebsiella pneumoniae is a critically important pathogen in the Philippines. Isolates are commonly resistant to at least two classes of antibiotics, yet mechanisms and spread of its resistance are not well studied.MethodsA retrospective sequencing survey was performed on carbapenem-, extended spectrum beta-lactam- and cephalosporin-resistant Klebsiella pneumoniae isolated at 20 antimicrobial resistance (AMR) surveillance sentinel sites from 2015-2017. We characterized 259 isolates using biochemical methods, antimicrobial susceptibility testing, and whole genome sequencing (WGS). Known AMR mechanisms were identified. Potential outbreaks were investigated by detecting clusters from epidemiologic, phenotypic and genome-derived data.ResultsPrevalent AMR mechanisms detected include blaCTX-M-15 (76.8%) and blaNDM-1 (37.5%). An epidemic IncFII(Yp) plasmid carrying blaNDM-1 was also detected in 46 isolates from 6 sentinel sites and 14 different sequence types (ST). This plasmid was also identified as the main vehicle of carbapenem resistance in 2 previously unrecognized local outbreaks of ST348 and ST283 at 2 different sentinel sites. A third local outbreak of ST397 was also identified but without the IncFII(Yp) plasmid. Isolates in each outbreak site showed identical STs, K- and O-loci, and similar resistance profiles and AMR genes. All outbreak isolates were collected from blood of children aged ConclusionWGS provided an in-depth understanding of the epidemiology of AMR in the Philippines, which was not possible with only phenotypic and epidemiologic data. The identification of three previously unrecognized Klebsiella outbreaks highlights the utility of WGS in outbreak detection, as well as its importance in public health and in implementing infection control programs.summaryWhole genome sequencing identified three distinct previously unrecognized local outbreaks in a retrospective study in the Philippines, along with an epidemic plasmid carrying antimicrobial resistance genes, highlighting its importance in antimicrobial resistance surveillance, outbreak detection and infection control.

Performing whole genome sequencing (WGS) for the surveillance of antimicrobial resistance offers the ability to determine not only the antimicrobials to which rates of resistance are increasing, but also the evolutionary mechanisms and transmission routes responsible for the increase at local, national, and global scales. To derive WGS-based outputs, a series of processes are required, beginning with sample and metadata collection, followed by nucleic acid extraction, library preparation, sequencing, and analysis. Throughout this pathway there are many data-related operations required (informatics) combined with more biologically focused procedures (bioinformatics). For a laboratory aiming to implement pathogen genomics, the informatics and bioinformatics activities can be a barrier to starting on the journey; for a laboratory that has already started, these activities may become overwhelming. Here we describe these data bottlenecks and how they have been addressed in laboratories in India, Colombia, Nigeria, and the Philippines, as part of the National Institute for Health Research Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance. The approaches taken include the use of reproducible data parsing pipelines and genome sequence analysis workflows, using technologies such as Data-flo, the Nextflow workflow manager, and containerization of software dependencies. By overcoming barriers to WGS implementation in countries where genome sampling for some species may be underrepresented, a body of evidence can be built to determine the concordance of antimicrobial sensitivity testing and genome-derived resistance, and novel high-risk clones and unknown mechanisms of resistance can be discovered.

The rollout of antiretroviral therapy globally has increased life expectancy across Southern Africa, where 20.6 million people now live with human immunodeficiency virus (HIV). We aimed to determine the prevalence of age-related osteoporosis and sarcopenia, and investigate the association between HIV, bone mineral density (BMD), muscle strength and lean mass, and gait speed. A cross-sectional community-based study of individuals aged 20-80 years in rural South Africa collected demographic and clinical data, including HIV status, grip strength, gait speed, body composition, and BMD. Sarcopenia was defined by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) guidelines, and osteoporosis as BMD T-score ≤ -2.5 (if age ≥50 years). The mean ± standard deviation (SD) age of 805 black South African participants was 44.6 ± 14.8 years, 547 (68.2%) were female; 34 (13.2%) were men, and 129 (23.6%) women had HIV, with 88% overall taking anti-retroviral therapy. A femoral neck T-score ≤ -2.5, seen in four of 95 (4.2%) men and 39 of 201 (19.4%) women age ≥50 years, was more common in women with than without HIV (13/35 [37.1%] versus 26/166 [15.7%]; p = 0.003). Although no participant had confirmed sarcopenia, probable sarcopenia affected more men than women (30/258 [11.6%] versus 24/547 [4.4%]; p = .001]. Although appendicular lean mass (ALM)/height2 index was lower in both men and women with HIV, there were no differences in grip strength, gait speed, or probable sarcopenia by HIV status. Older age, female sex, lower ALM/height2 index, slower gait speed, and HIV infection were all independently associated with lower femoral neck BMD. In conclusion, osteoporosis rather than sarcopenia is the common musculoskeletal disease of aging in rural South Africa; older women with HIV may experience greater bone losses than women without HIV. Findings raise concerns over future fracture risk in Southern Africa, where HIV clinics should consider routine bone health assessment, particularly in aging women. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Cognitive behavioral therapy, first introduced by Beck in the 1950s to treat depression by integrating cognitive and behavioral therapies, is now an established psychotherapy technique used to treat insomnia, chronic pain, and anxiety. Currently, cognitive behavioral therapy is widely used to treat tinnitus in European countries, and the efficacy and safety of the treatment have been proven through randomized clinical trials and meta-analyses. Although interest in cognitive behavioral therapy for tinnitus is increasing in Korea, there are limited reports. Because many studies so far have targeted patients in Western countries, it is difficult to apply the same to domestic patients due to cultural and linguistic differences, the absence of standardized guidelines, and limitations in clinic hours. We experienced various cases in which tinnitus was effectively treated simultaneously with pharmacotherapy and cognitive behavioral therapy, so here we report an introduction to the program along with a literature review. Cognitive behavioral therapy was performed as a 4-week program in our hospital, and progress was evaluated through Visual Analogue Scales (VAS) and tinnitus handicap inventory (THI). After each weekly 20-minute individual counseling session, a take-home writing task was given to the patient. The main goal was to guide the patient to discover and correct automatic thoughts related to their tinnitus symptoms. This paper aimed to introduce a specific scheme on how to perform cognitive behavioral therapy for domestic tinnitus patients.

Over the last few years data from our group have indicated that α-synuclein is important in development of immune cells as well as potentially erythrocytes and platelets. The latter is important since this protein may work as negative regulator of granule release. Thus, we sought to begin to understand the structure of this protein in platelets. Flow cytometric analysis of this protein using region-specific (N-terminus, central region and C-terminus) monoclonal antibodies was performed. Antibody to the central region gave the strongest shift among all three antibodies, with the C-terminus having intermediate shift and N-terminus minimal shift. Western blotting using the same antibodies showed similar binding of all antibodies to α-synuclein. These results suggest a similar arrangement of this protein in platelets as seen in neurons. Future studies ought to look at the role that each protein region plays in platelets.

OBJECTIVE While there are a number of benefits to minimally invasive surgery (MIS) for women with ovarian cysts, there is an increased risk of ovarian capsule rupture during the procedure, which could potentially seed the abdominal cavity with malignant cells. We developed a decision model to compare the risks, benefits, effectiveness and cost of MIS versus laparotomy in women with ovarian masses. DESIGN Cost-effectiveness study POPULATION: Hypothetical cohort of 10 000 women with ovarian masses who were undergoing surgical management. METHODS The initial decision point in the model was performance of surgery via laparotomy or a MIS approach. Model probabilities, costs and utility values were derived from published literature and administrative data sources. Extensive sensitivity analyses were conducted to assess the robustness of the findings. MAIN OUTCOME MEASURES The primary outcome was the cost-effectiveness of MIS versus laparotomy for women with a pelvic mass measured by incremental cost-effectiveness ratios (ICERs). RESULTS MIS was the least costly strategy at $7,732 per women on average, compared with $17,899 for laparotomy. In our hypothetical cohort of 10 000 women, there were 64 cases of ovarian rupture in the MIS group and 53 in the laparotomy group, while there were 26 cancer-related deaths in the MIS group and 25 in the laparotomy group. MIS was more effective than laparotomy (188 462 QALYs for MIS versus 187 631 quality adjusted life years [QALYs] for laparotomy). Thus, MIS was a dominant strategy, being both less costly and more effective than laparotomy. These results were robust in a variety of sensitivity analyses. CONCLUSION MIS constitutes a cost-effective management strategy for women with suspicious ovarian masses. TWEETABLE ABSTRACT MIS is a cost-effective management strategy for women with suspicious ovarian masses.

Varicella is a highly contagious disease caused by the varicella-zoster virus (VZV). Given its tendency to cluster geographically, spatial analyses may provide a better understanding of the pattern of varicella transmission. We investigated the spatial characteristics of varicella in Korea and the risk factors for varicella at a national level. Using national surveillance and demographic data, we examined the spatial distribution of incidence rates and their spatial autocorrelation and calculated Moran's index. Spatial regression analysis was used to identify sociodemographic predictors of varicella incidence at the district level. An increasing tendency in the annual incidence of varicella was observed over a 12-year period (2006-2018), with a surge in 2017. There was a clear positive spatial autocorrelation of the varicella incidence rate during the surveillance period. During 2006-2014, High-High (HH) clusters were mostly confined to the northeast region and neighboring districts. The spatial error model showed that population density had a negative coefficient and childhood percentage, percentage of children under 12 years of age among the total population, had positive coefficient, whereas vaccine coverage was insignificant. The varicella incidence according to geographic region varied with population density, childhood percentage, suggesting the importance of community-level surveillance and monitoring strategies.

Substance use disorders (SUDs) are moderately to highly heritable and are in part cross-transmitted genetically, as observed in twin and family studies. We performed exome-focused genotyping to examine the cross-transmission of four SUDs: alcohol use disorder (AUD, n = 4487); nicotine use disorder (NUD, n = 4394); cannabis use disorder (CUD, n = 954); and nonmedical prescription opioid use disorder (NMPOUD, n = 346) within a large nationally representative sample (n = 36,309), the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III). All diagnoses were based on in-person structured psychiatric interview (AUDADIS-5). SUD cases were compared alone and together to 3959 "super controls" who had neither a SUD nor a psychiatric disorder using an exome-focused array assaying 363,496 SNPs, yielding a representative view of within-disorder and cross-disorder genetic influences on SUDs. The 29 top susceptibility genes for one or more SUDs overlapped highly with genes previously implicated by GWAS of SUD. Polygenic scores (PGS) were computed within the European ancestry (EA) component of the sample (n = 12,505) using summary statistics from each of four clinically distinct SUDs compared to the 3959 "super controls" but then used for two distinctly different purposes: to predict SUD severity (mild, moderate, or severe) and to predict each of the other 3 SUDs. Our findings based on PGS highlight shared and unshared genetic contributions to the pathogenesis of SUDs, confirming the strong cross-inheritance of AUD and NUD as well as the distinctiveness of inheritance of opioid use disorder.

Background Exercise may improve clinical and quality of life outcomes for men with prostate cancer. No randomized controlled trials (RCTs) have examined the feasibility, safety, and acceptability of remote exercise training in men with metastatic castrate‐resistant prostate cancer (mCRPC). Methods We conducted a pilot RCT (1:1:1 aerobic or resistance exercise 3x/week or usual care) to determine the feasibility, safety, and acceptability of remotely monitored exercise over 12 weeks in 25 men with mCRPC. A prescribed exercise program was based on baseline testing including high‐ and moderate‐intensity aerobic exercise or resistance exercise completed at a local exercise facility. Feasibility was based on attendance, adherence, and tolerance; safety on adverse events; and acceptability on participant interviews. Results Between March 2016 and March 2020, 25 patients were randomized (8 aerobic, 7 resistance, and 10 control). Twenty‐three men (82%) completed the 12‐week study. Men who completed the remote intervention attempted 90% and 96% of prescribed aerobic and resistance training sessions, respectively, and 86% and 88% of attempted sessions were completed as or more than prescribed. We observed changes in performance tests that corresponded with the exercise prescription. No safety concerns were identified. Ninety percent of participants interviewed were satisfied with the program and would recommend it to others. Conclusions Remotely monitored exercise training is feasible, safe, and acceptable in men with mCRPC; there was no difference in these outcomes by mode of exercise. Through this research, we provide direction and rationale for future studies of exercise and clinical outcomes in patients with metastatic prostate cancer., We conducted a 3‐arm pilot randomized controlled trial to determine the feasibility, safety, and acceptability of two modes of remotely monitored exercise (resistance or aerobic) over 12 weeks compared to usual care in 25 men with metastatic castrate‐resistant prostate cancer (mCRPC). We report that remotely monitored exercise training is feasible, safe, and acceptable in this patient population, with a high satisfaction rate. Through this research we provide direction and rationale for future studies of exercise and clinical outcomes for people with metastatic cancer.

Antimicrobial resistance (AMR) is considered a global threat, and novel drug discovery needs to be complemented with systematic and standardized epidemiological surveillance. Surveillance data are currently generated using phenotypic characterization. However, due to poor scalability, this approach does little for true epidemiological investigations. There is a strong case for whole-genome sequencing (WGS) to enhance the phenotypic data. To establish global AMR surveillance using WGS, we developed a laboratory implementation approach that we applied within the NIHR Global Health Research Unit (GHRU) on Genomic Surveillance of Antimicrobial Resistance. In this paper, we outline the laboratory implementation at 4 units: Colombia, India, Nigeria, and the Philippines. The journey to embedding WGS capacity was split into 4 phases: Assessment, Assembly, Optimization, and Reassessment. We show that on-boarding WGS capabilities can greatly enhance the real-time processing power within regional and national AMR surveillance initiatives, despite the high initial investment in laboratory infrastructure and maintenance. Countries looking to introduce WGS as a surveillance tool could begin by sequencing select Global Antimicrobial Resistance Surveillance System (GLASS) priority pathogens that can demonstrate the standardization and impact genome sequencing has in tackling AMR.

Due to its high-dimensional data characteristics, the channel state information (CSI) of Wi-Fi signals has become a strong candidate for use in indoor localization. In addition, machine learning techniques can improve the accuracy of indoor localization systems using multiview CSI data received at multiple access points (APs). However, in complex environments, most CSI views collected at APs in non-line-of-sight (NLoS) configurations relative to a transmitter may lose so much useful data information as to become nonsalient. In this paper, we propose a practical machine learning approach named unsupervised view-selective deep learning (UVSDL), in which only the most salient CSI view is selected in an unsupervised manner to be applied in regression for localization. In an experiment in a complex building, our variational deep learning (VDL)-based regression method with the most salient CSI view achieves a localization accuracy of 1.36 m, significantly outperforming the best-known system BiLoc by 25 %.

The administration and governance of grant funding across global health organizations presents enormous challenges. Meeting these challenges is crucial to ensuring that funds are used in the most effective way to improve health outcomes, in line with the United Nations’ Sustainable Development Goal 3, “Ensure healthy lives and promote well-being for all at all ages.” The Good Financial Grant Practice (GFGP) Standard (ARS 1651) is the world’s first and, currently, only international standard for the financial governance and management of grant funding. Through consensus building and global harmonization between both low- and middle-income and high-income country players, the GFGP Standard has achieved a leveling impact: GFGP applies equally to, and can be implemented by, all types of organization, regardless of location, size, or whether they predominantly give or receive funding.GFGP can be used as a tool for addressing some of the challenges of the current funding model. Here, we describe our experiences and lessons learned from implementing GFGP across 4 diverse research institutions in India, Nigeria, Colombia, and the Philippines as part of our National Institute for Health Research Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance.

Over 30% of adults with congenital heart disease (CHD) experience depression.To evaluate the effectiveness of Rational Emotive Behavior Therapy (REBT) in reducing depressive symptoms in adults with CHD.Forty-two adults with CHD were recruited from an outpatient clinic and randomized to a study group (n = 21), which comprised 8-weekly group-based counseling sessions, or a control group (n = 21), which received usual care. REBT effectiveness was examined using the Hamilton Depression Rating Scale, Beck Depression Inventory, Shorten General Attitude and Belief Scale, and salivary cortisol levels before therapy, after the last session, and at follow-up 4 weeks later.Average participant ages were 30.1 ± 7.58 and 33.3 ± 7.1 years in study and control groups, respectively; 52.4% of participants in each group were female. After REBT, depression (p 0.001), irrational beliefs (p 0.001), and salivary cortisol levels (p = 0.006) were significantly lower in the study group than in the control group. Effects of REBT in the study group remained consistent at the 4-week follow-up.REBT may be effective in reducing depression in adults with CHD.

Tyrosine kinase inhibitors (TKIs) have been widely used to treat various malignancies, dramatically improving survival. The use of these treatments has been limited by adverse effects. Ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, has been associated with increased prevalence of atrial fibrillation (AF) in approximately 5%–16% of patients, especially those with prior history of AF,1 and often leads to treatment discontinuation in a significant proportion of patients. Management of AF in this patient population also presents a unique challenge. Current guidelines recommend rate control as the primary strategy,2,3 which can be challenging, since pharmacological management is limited by significant drug interactions with cancer therapies as well as potential side effects. Additionally, the need for anticoagulation in this strategy is challenged by increased risk of bleeding owing to inhibition of collagen-induced platelet aggregation by ibrutinib.4 Recent studies document the long-term benefits of catheter ablation in maintaining sinus rhythm in the general population. We present a case of ibrutinib-associated symptomatic AF, which was successfully treated with ablation therapy, and allowed the patient to return to ibrutinib therapy for adequate management of his cancer (Figure 1). Open in a separate window Figure 1 Timeline showing cardiovascular and hematologic disease and treatment course. AF = atrial fibrillation; CLL = chronic lymphocytic leukemia; AAD = antiarrhythmic drug; OAC = oral anticoagulant. (Figure created with BioRender.com.)

Background To investigate the impact of programmed death‐ligand 1 (PD‐L1) polymorphisms on the prognosis of non‐small cell lung cancer (NSCLC) patients treated with curative radiotherapy. Methods Four single nucleotide polymorphisms (SNPs) (rs822336G>C, rs822337T>A, rs822338C>T, and rs2297136A>G) in the PD‐L1 gene were evaluated in 124 NSCLC patients. Clinical stage was I in 28, II in 17, and III in 79 patients. Fifty‐seven patients received radiotherapy alone, including 28 patients who received stereotactic body radiotherapy. Sixty‐seven patients received sequential or concurrent chemoradiotherapy. Risk factors for survival outcomes were analyzed with the log‐rank test and multivariate Cox proportional hazards models. Results The rs822336GC+CC genotype was associated with better overall survival (OS) (hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.37–0.97, p = 0.036) and regional failure‐free survival (RFFS) (HR = 0.32, 95% CI = 0.14–0.76, p = 0.009), compared with rs822336GG genotype. The rs822337TA+AA genotype was associated with better OS (HR =0.54, 95% CI = 0.34–0.88, p = 0.014), progression‐free survival (PFS) (HR = 0.64, 95% CI = 0.41–0.99, p = 0.046), and RFFS (HR = 0.38, 95% CI = 0.17–0.81, p = 0.013), compared with rs822337TT genotype. Three SNPs (rs822336, rs822337, and rs822338) were in linkage disequilibrium. Combined GTC and GTT (GT*) haplotype was associated with significantly worse OS (p = 0.018), PFS (p = 0.044), and RFFS (p = 0.038), compared with those with other combined haplotypes. Patients with diplotypes of two GT* haplotypes showed significantly worse OS (p = 0.023) and RFFS (p = 0.014) than those with other diplotypes. Conclusions These findings suggest that PD‐L1 polymorphisms could be predictive markers for NSCLC patients receiving radiotherapy., Genotypes of two SNPs (rs822336G>C and rs822337T>A) and the risk groups of diplotypes of rs822336‐rs822337‐rs822338 haplotypes in the PD‐L1 gene were significantly associated with overall survival. These genotypes were related to regional failure‐free survival in terms of patterns of initial failure.

Summary Objective To explore how systemic factors that modify knee osteoarthritis risk are connected to ‘whole-joint’ structural changes by evaluating the effects of high-fat diet and wheel running exercise on synovial fluid (SF) metabolomics. Methods Male mice were fed a defined control or high-fat (60% kcal fat) diet from 6 to 52 weeks of age, and half the animals were housed with running wheels from 26 to 52 weeks of age (n = 9–13 per group). Joint tissue structure and osteoarthritis pathology were evaluated by histology and micro-computed tomography. Systemic metabolic and inflammatory changes were evaluated by body composition, glucose tolerance testing, and serum biomarkers. SF metabolites were analyzed by high performance-liquid chromatography mass spectrometry. We built correlation-based network models to evaluate the connectivity between systemic and local metabolic biomarkers and osteoarthritis structural pathology within each experimental group. Results High-fat diet caused moderate osteoarthritis, including cartilage pathology, synovitis and increased subchondral bone density. In contrast, voluntary exercise had a negligible effect on these joint structure components. 1,412 SF metabolite features were detected, with high-fat sedentary mice being the most distinct. Diet and activity uniquely altered SF metabolites attributed to amino acids, lipids, and steroids. Notably, high-fat diet increased network connections to systemic biomarkers such as interleukin-1β and glucose intolerance. In contrast, exercise increased local joint-level network connections, especially among subchondral bone features and SF metabolites. Conclusion Network mapping showed that obesity strengthened SF metabolite links to blood glucose and inflammation, whereas exercise strengthened SF metabolite links to subchondral bone structure.

PURPOSE: We examined the demographic and clinicopathological parameters associated with the time to convert from active surveillance to treatment among men with prostate cancer. MATERIALS AND METHODS: A multi-institutional cohort of 7,279 patients managed with active surveillance had data and biospecimens collected for germline genetic analyses. RESULTS: Of 6,775 men included in the analysis, 2,260 (33.4%) converted to treatment at a median followup of 6.7 years. Earlier conversion was associated with higher Gleason grade groups (GG2 vs GG1 adjusted hazard ratio [aHR] 1.57, 95% CI 1.36–1.82; ≥GG3 vs GG1 aHR 1.77, 95% CI 1.29–2.43), serum prostate specific antigen concentrations (aHR per 5 ng/ml increment 1.18, 95% CI 1.11–1.25), tumor stages (cT2 vs cT1 aHR 1.58, 95% CI 1.41–1.77; ≥cT3 vs cT1 aHR 4.36, 95% CI 3.19–5.96) and number of cancerous biopsy cores (3 vs 1–2 cores aHR 1.59, 95% CI 1.37–1.84; ≥4 vs 1–2 cores aHR 3.29, 95% CI 2.94–3.69), and younger age (age continuous per 5-year increase aHR 0.96, 95% CI 0.93–0.99). Patients with high-volume GG1 tumors had a shorter interval to conversion than those with low-volume GG1 tumors and behaved like the higher-risk patients. We found no significant association between the time to conversion and self-reported race or genetic ancestry. CONCLUSIONS: A shorter time to conversion from active surveillance to treatment was associated with higher-risk clinicopathological tumor features. Furthermore, patients with high-volume GG1 tumors behaved similarly to those with intermediate and high-risk tumors. An exploratory analysis of self-reported race and genetic ancestry revealed no association with the time to conversion.

In this work, we demonstrate that t-tubule remodeling occurs in the atrophied left ventricle as well as the overloaded right ventricle after right-side heart failure. Moreover, we identify that t-tubule remodeling in both ventricles is linked to sarcoplasmic reticulum remodeling as indicated by decreased labeling periodicity of both the Ca2+ release channel, RyR2, and the cardiac junction-forming protein, JPH2, that forms a link between the sarcoplasmic reticulum and sarcolemma. Studies developing treatments for right-sided heart failure should consider effects on both the right and left ventricle.

Despite the expanding clinical application of hydroxychloroquine in dermatology, the overall data on hydroxychloroquine use among dermatologists are limited. With retrospective review of the medical records of the 790 patients who were prescribed hydroxychloroquine, we classified the diagnoses into 12 disease categories, the lupus erythematosus group being the largest. The lupus erythematosus group had the longest prescription duration (median, 6.2 months), whereas the photodermatitis group had a significantly shorter prescription duration (median, 0.5 months). The overall good response rate was 77.1%. The photodermatitis group had the best response (88.7%), followed by the lupus panniculitis (85.1%) and lichen planus (84.4%). In conclusion, hydroxychloroquine has proven utility for various inflammatory skin diseases, including but not limited to cutaneous lupus erythematosus.