Cortical microtubules contribute to division plane positioning during telophase in maize.

Cell divisions are accurately positioned to generate cells of the correct size and shape. In plant cells, the new cell wall is built in the middle of the cell by vesicles trafficked along an antiparallel microtubule and a microfilament array called the phragmoplast. The phragmoplast expands toward a specific location at the cell cortex called the division site, but how it accurately reaches the division site is unclear. We observed microtubule arrays that accumulate at the cell cortex during the telophase transition in maize (Zea mays) leaf epidermal cells. Before the phragmoplast reaches the cell cortex, these cortical-telophase microtubules transiently interact with the division site. Increased microtubule plus end capture and pausing occur when microtubules contact the division site-localized protein TANGLED1 or other closely associated proteins. Microtubule capture and pausing align the cortical microtubules perpendicular to the division site during telophase. Once the phragmoplast reaches the cell cortex, cortical-telophase microtubules are incorporated into the phragmoplast primarily by parallel bundling. The addition of microtubules into the phragmoplast promotes fine-tuning of the positioning at the division site. Our hypothesis is that division site-localized proteins such as TANGLED1 organize cortical microtubules during telophase to mediate phragmoplast positioning at the final division plane.

Structural and electronic trends of optical cycling centers in polyatomic molecules revealed by microwave spectroscopy of MgCCH, CaCCH, and SrCCH.

The unique optical cycling efficiency of alkaline earth metal-ligand molecules has enabled significant advances in polyatomic laser cooling and trapping. Rotational spectroscopy is an ideal tool for probing the molecular properties that underpin optical cycling, thereby elucidating the design principles for expanding the chemical diversity and scope of these platforms for quantum science. We present a comprehensive study of the structure and electronic properties in alkaline earth metal acetylides with high-resolution microwave spectra of 17 isotopologues of MgCCH, CaCCH, and SrCCH in their 2Σ+ ground electronic states. The precise semiexperimental equilibrium geometry of each species has been derived by correcting the measured rotational constants for electronic and zero-point vibrational contributions calculated with high-level quantum chemistry methods. The well-resolved hyperfine structure associated with the 1,2H, 13C, and metal nuclear spins provides further information on the distribution and hybridization of the metal-centered, optically active unpaired electron. Together, these measurements allow us to correlate trends in chemical bonding and structure with the electronic properties that promote efficient optical cycling essential to next-generation experiments in precision measurement and quantum control of complex polyatomic molecules.

Warming-induced monsoon precipitation phase change intensifies glacier mass loss in the southeastern Tibetan Plateau.

Glaciers are key components of the mountain water towers of Asia and are vital for downstream domestic, agricultural, and industrial uses. The glacier mass loss rate over the southeastern Tibetan Plateau is among the highest in Asia and has accelerated in recent decades. This acceleration has been attributed to increased warming, but the mechanisms behind these glaciers' high sensitivity to warming remain unclear, while the influence of changes in precipitation over the past decades is poorly quantified. Here, we reconstruct glacier mass changes and catchment runoff since 1975 at a benchmark glacier, Parlung No. 4, to shed light on the drivers of recent mass losses for the monsoonal, spring-accumulation glaciers of the Tibetan Plateau. Our modeling demonstrates how a temperature increase (mean of 0.39 ∘C ⋅dec-1 since 1990) has accelerated mass loss rates by altering both the ablation and accumulation regimes in a complex manner. The majority of the post-2000 mass loss occurred during the monsoon months, caused by simultaneous decreases in the solid precipitation ratio (from 0.70 to 0.56) and precipitation amount (-10%), leading to reduced monsoon accumulation (-26%). Higher solid precipitation in spring (+18%) during the last two decades was increasingly important in mitigating glacier mass loss by providing mass to the glacier and protecting it from melting in the early monsoon. With bare ice exposed to warmer temperatures for longer periods, icemelt and catchment discharge have unsustainably intensified since the start of the 21st century, raising concerns for long-term water supply and hazard occurrence in the region.

Direct Probes of π-Delocalization in Prototypical Resonance-Stabilized Radicals: Hyperfine-Resolved Microwave Spectroscopy of Isotopic Propargyl and Cyanomethyl.

Delocalization of the unpaired electron in π-conjugated radicals has profound implications for their chemistry, but direct and quantitative characterization of this electronic structure in isolated molecules remains challenging. We apply hyperfine-resolved microwave rotational spectroscopy to rigorously probe π-delocalization in propargyl, CH2CCH, a prototypical resonance-stabilized radical and key reactive intermediate. Using the spectroscopic constants derived from the high-resolution cavity Fourier transform microwave measurements of an exhaustive set of 13C- and 2H-substituted isotopologues, together with high-level ab initio calculations of zero-point vibrational effects, we derive its precise semiexperimental equilibrium geometry and quantitatively characterize the spatial distribution of its unpaired electron. Our results highlight the importance of considering both spin-polarization and orbital-following contributions when interpreting the isotropic hyperfine coupling constants of π radicals. These physical insights are strengthened by a parallel analysis of the isoelectronic species cyanomethyl, CH2CN, using new 13C measurements also reported in this work. A detailed comparison of the structure and electronic properties of propargyl, cyanomethyl, and other closely related species allows us to correlate trends in their chemical bonding and electronic structure with critical changes in their reactivity and thermochemistry.

Focal adhesion is associated with lithium response in bipolar disorder: evidence from a network-based multi-omics analysis.

Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (Phypergeometric = 1.28E-09 and 4.10E-18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.

Timely Completion of Direct Access Colonoscopy Is Noninferior to Office Scheduled for Screening and Surveillance.

GOALS: We aimed to evaluate whether direct access colonoscopy (DAC) is noninferior to office-scheduled colonoscopy (OSC) for achieving successful colonoscopy. BACKGROUND: DAC may improve access to colonoscopy. We developed an algorithm assessing eligibility, risk for inadequate preparation, and need for nursing/navigator assistance. STUDY: This was a retrospective, single-center study of DAC and OSC patients from June 5, 2018, to July 31, 2019. Patients were 45 to 75 years old with an indication of screening or surveillance. A successful colonoscopy met 3 criteria: complete colonoscopy (cecum, anastomosis, or ileum), adequate preparation (Boston Score ≥2/segment), and performed <90 days from initial patient contact. Unsuccessful colonoscopy did not meet ≥1 criteria. Secondary end points included days to successful colonoscopy, preparation quality, polyp detection, and 10-year recall rate. Noninferiority against risk ratio value of 0.85 was tested using 1-sided alpha of 0.05. RESULTS: A total of 1823 DAC and 828 OSC patients were eligible. DAC patients were younger, with a greater proportion of black patients and screening indications. For the outcome of successful colonoscopy, DAC was noninferior to OSC (DAC vs. OSC: 62.7% vs. 57.1%, RR 1.16, 95% LCL 1.09, P=0.001). For DAC, days to colonoscopy were fewer, and likelihood of 10-year recall after negative screening greater. Boston Score and polyp detection were similar for groups. Black patients were less likely to achieve successful colonoscopy; otherwise, groups were similar. For unsuccessful colonoscopies, proportionally more DAC patients canceled or no-showed while more OSC patients scheduled >90 days. DAC remained noninferior to OSC at 180 days. CONCLUSIONS: DAC was noninferior to OSC for achieving successful colonoscopy, comparing similarly in quality and efficiency outcomes.

Corallococcus senghenyddensis sp. nov., a myxobacterium with potent antimicrobial activity.

AIM: Corallococcus species are diverse in the natural environment with 10 new Corallococcus species having been characterized in just the last 5 years. As well as being an abundant myxobacterial genus, they produce several secondary metabolites, including Corallopyronin, Corramycin, Coralmycin, and Corallorazine. We isolated a novel strain Corallococcus spp RDP092CA from soil in South Wales, UK, using Candida albicans as prey bait and characterized its predatory activities against pathogenic bacteria and yeast. METHODS AND RESULTS: The size of the RDP092CA genome was 8.5 Mb with a G + C content of 71.4%. Phylogenetically, RDP092CA is closely related to Corallococcus interemptor, C. coralloides, and C. exiguus. However, genome average nucleotide identity and digital DNA-DNA hybridization values are lower than 95% and 70% when compared to those type strains, implying that it belongs to a novel species. The RDP092CA genome harbours seven types of biosynthetic gene clusters (BGCs) and 152 predicted antimicrobial peptides. In predation assays, RDP092CA showed good predatory activity against Escherichia coli, Pseudomonas aeruginosa, Citrobacter freundii, and Staphylococcus aureus but not against Enterococcus faecalis. It also showed good antibiofilm activity against all five bacteria in biofilm assays. Antifungal activity against eight Candida spp. was variable, with particularly good activity against Meyerozyma guillermondii DSM 6381. Antimicrobial peptide RDP092CA_120 exhibited potent antibiofilm activity with >50% inhibition and >60% dispersion of biofilms at concentrations down to 1 µg/ml. CONCLUSIONS: We propose that strain RDP092CA represents a novel species with promising antimicrobial activities, Corallococcus senghenyddensis sp. nov. (=NBRC 116490T =CCOS 2109T), based on morphological, biochemical, and genomic features.

ENGOT-EN20/GOG-3083/XPORT-EC-042 - A phase III, randomized, placebo-controlled, double-blind, multicenter trial of selinexor in maintenance therapy after systemic therapy for patients with p53 wild-type, advanced, or recurrent endometrial carcinoma: rationale, methods, and trial design.

BACKGROUND: Patients with advanced/recurrent endometrial cancer have a poor prognosis and limited treatment options. Biomarkers such as tumor protein 53 (TP53) in endometrial cancer can integrate novel strategies for improved and individualized treatment that could impact patient outcomes. In an exploratory analysis of the phase III ENGOT-EN5/GOG-3055/SIENDO study of selinexor maintenance monotherapy 80 mg in advanced/recurrent endometrial cancer, a pre-specified subgroup of patients with TP53 wild type (wt) endometrial cancer showed preliminary activity at long-term follow-up with a generally manageable safety profile (median progression-free survival 27.4 months vs 5.2 months placebo, HR=0.41). PRIMARY OBJECTIVE: To evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer. STUDY HYPOTHESIS: Selinexor administered at 60 mg weekly as maintenance therapy will show manageable safety and maintain efficacy in patients with TP53wt advanced/recurrent endometrial cancer after systemic therapy versus placebo. TRIAL DESIGN: This is a prospective, multicenter, double-blind, placebo-controlled, randomized phase III study designed to evaluate the efficacy and safety of selinexor as a maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have histologically confirmed endometrial cancer, TP53wt confirmed by next-generation sequencing, completed at least 12 weeks of platinum-based therapy with or without immunotherapy, with confirmed partial response or complete response, and primary Stage IV disease or at first relapse. PRIMARY ENDPOINT: The primary endpoint is investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the intent-to-treat population. SAMPLE SIZE: A total of 220 patients will be enrolled. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual is expected to be completed in 2024 with presentation of results in 2025. TRIAL REGISTRATION: NCT05611931.

Deepfake Histologic Images for Enhancing Digital Pathology.

A pathologist's optical microscopic examination of thinly cut, stained tissue on glass slides prepared from a formalin-fixed paraffin-embedded tissue blocks is the gold standard for tissue diagnostics. In addition, the diagnostic abilities and expertise of pathologists is dependent on their direct experience with common and rarer variant morphologies. Recently, deep learning approaches have been used to successfully show a high level of accuracy for such tasks. However, obtaining expert-level annotated images is an expensive and time-consuming task, and artificially synthesized histologic images can prove greatly beneficial. In this study, we present an approach to not only generate histologic images that reproduce the diagnostic morphologic features of common disease but also provide a user ability to generate new and rare morphologies. Our approach involves developing a generative adversarial network model that synthesizes pathology images constrained by class labels. We investigated the ability of this framework in synthesizing realistic prostate and colon tissue images and assessed the utility of these images in augmenting the diagnostic ability of machine learning methods and their usability by a panel of experienced anatomic pathologists. Synthetic data generated by our framework performed similar to real data when training a deep learning model for diagnosis. Pathologists were not able to distinguish between real and synthetic images, and their analyses showed a similar level of interobserver agreement for prostate cancer grading. We extended the approach to significantly more complex images from colon biopsies and showed that the morphology of the complex microenvironment in such tissues can be reproduced. Finally, we present the ability for a user to generate deepfake histologic images using a simple markup of sematic labels.

Prognostic utility of RECIP 1.0 with manual and AI-based segmentations in biochemically recurrent prostate cancer from [68Ga]Ga-PSMA-11 PET images.

PURPOSE: This study aimed to (i) validate the Response Evaluation Criteria in PSMA (RECIP 1.0) criteria in a cohort of biochemically recurrent (BCR) prostate cancer (PCa) patients and (ii) determine if this classification could be performed fully automatically using a trained artificial intelligence (AI) model. METHODS: One hundred ninety-nine patients were imaged with [68Ga]Ga-PSMA-11 PET/CT once at the time of biochemical recurrence and then a second time a median of 6.0 months later to assess disease progression. Standard-of-care treatments were administered to patients in the interim. Whole-body tumour volume was quantified semi-automatically (TTVman) in all patients and using a novel AI method (TTVAI) in a subset (n = 74, the remainder were used in the training process of the model). Patients were classified as having progressive disease (RECIP-PD), or non-progressive disease (non RECIP-PD). Association of RECIP classifications with patient overall survival (OS) was assessed using the Kaplan-Meier method with the log rank test and univariate Cox regression analysis with derivation of hazard ratios (HRs). Concordance of manual and AI response classifications was evaluated using the Cohen's kappa statistic. RESULTS: Twenty-six patients (26/199 = 13.1%) presented with RECIP-PD according to semi-automated delineations, which was associated with a significantly lower survival probability (log rank p < 0.005) and higher risk of death (HR = 3.78 (1.96-7.28), p < 0.005). Twelve patients (12/74 = 16.2%) presented with RECIP-PD according to AI-based segmentations, which was also associated with a significantly lower survival (log rank p = 0.013) and higher risk of death (HR = 3.75 (1.23-11.47), p = 0.02). Overall, semi-automated and AI-based RECIP classifications were in fair agreement (Cohen's k = 0.31). CONCLUSION: RECIP 1.0 was demonstrated to be prognostic in a BCR PCa population and is robust to two different segmentation methods, including a novel AI-based method. RECIP 1.0 can be used to assess disease progression in PCa patients with less advanced disease. This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000608561) on 11 June 2015.

Rapid Detection of Lithium Concentrations in Oral Fluid.

BACKGROUND: Lithium medication is considered to be the first-line treatment for bipolar disorder as a monotherapy, and for treatment-resistant depression with lithium augmentation. However, because of potential toxicity, lithium levels must be monitored frequently. Recent studies have demonstrated a significant correlation between lithium levels measured in serum and those detected in oral fluid, suggesting that oral fluid analysis may represent an easy, noninvasive means to monitor lithium levels. The aim of this study was to evaluate the analytical performance of rapid assays for lithium measurements in oral fluid. METHODS: Levels of lithium in oral fluid from psychiatric patients (n = 108 in total) taking lithium medications were quantified using 2 rapid techniques: an automated clinical chemistry analyzer and a novel, commercially available colorimetric lithium assay. These results were compared with those obtained using inductively coupled plasma optical emission spectrometry (ICP-OES). RESULTS: The mean and median oral fluid lithium levels in this cohort were 1.43-1.61 mM and 1.32-1.52 mM, respectively, depending on the method, with the overall range, across all methods, being 0.213-4.42 mM. Linear regression analysis showed excellent agreement between the oral fluid values measured using ICP-OES and the colorimetric method (r 2 value = 0.926; P < 0.0001; slope = 1.084 ± 0.038). Similarly, excellent agreement was observed between ICP-OES and the automated method (r 2 = 0.872; P < 0.0001; slope = 1.019 ± 0.057). CONCLUSIONS: These results demonstrate that lithium levels in oral fluid can be rapidly and reliably quantified using colorimetric approaches. These findings may facilitate the development of point-of-care lithium monitoring systems for use in oral fluid.

Laboratory-based testing for hepatitis C infection using dried blood spot samples: A systematic review and meta-analysis of diagnostic accuracy.

The use of dried blood spot (DBS) samples can facilitate the implementation of reflex testing by circumventing the need for centrifugation and freezing of venous blood samples. This systematic review assessed the accuracy of using DBS samples to diagnose chronic hepatitis C virus (HCV) infection. A comprehensive search was undertaken to identify articles published up to July 2020 evaluating the diagnostic accuracy of anti-HCV, HCV-RNA and HCV core antigen tests using DBS. Screening, data extraction, quality appraisal and Grading of Recommendations, Assessment, Development and Evaluations certainty of the evidence assessment were performed independently by two reviewers. Meta-analysis, meta-regression and sensitivity analyses were conducted. The evidence demonstrates that laboratory-based anti-HCV and HCV-RNA tests using DBS samples have high diagnostic accuracy. All comparisons were between DBS and venous samples. For the detection of anti-HCV, sensitivity was 95% (95% CI: 92%-97%) and specificity was 99% ([95% CI: 98%-99%]; n = 25; I2  = 81%; moderate certainty). For the detection of HCV-RNA, the sensitivity was 95% (95% CI: 93%-97%) and specificity was 97% ([95% CI: 94%-98%]; n = 20; I2  = 52%; moderate certainty). The sensitivity of HCV core antigen tests was 86% (95% CI: 79%-91%) and specificity was 98% ([95% CI: 94%-99%]; n = 5; I2  = 37%; low certainty) compared with HCV-RNA (the gold standard for detecting chronic HCV). DBS samples could facilitate diagnosis of chronic HCV infection as the necessary sequential tests (anti-HCV and then HCV-RNA or HCV core antigen) can be undertaken using the same blood sample. This could reduce loss of patient follow-up and support international efforts towards HCV elimination in both high and low prevalence settings.

Low-Temperature Gas-Phase Kinetics of Ethanol-Methanol Heterodimer Formation.

The structures of gas-phase noncovalently bound clusters have long been studied in supersonic expansions. This method of study, while providing a wealth of information about the nature of noncovalent bonds, precludes observation of the formation of the cluster, as the clusters form just after the orifice of the pulsed valve. Here, we directly observe formation of ethanol-methanol dimers via microwave spectroscopy in a controlled cryogenic environment. Time profiles of the concentration of reagents in the cell yielded gas-phase reaction rate constants of kMe-g = (2.8 ± 1.4) × 10-13 cm3 molecule-1 s-1 and kMe-t = (1.6 ± 0.8) × 10-13 cm3 molecule-1 s-1 for the pseudo-second-order ethanol-methanol dimerization reaction at 8 K. The relaxation cross section between the gauche and trans conformers of ethanol was also measured using the same technique. In addition, thermodynamic relaxation between conformers of ethanol over time allowed for selection of conformer stoichiometry in the ethanol-methanol dimerization reaction, but no change in the ratio of dimer conformers was observed with changing ethanol monomer stoichiometry.

The state of evidence for social and emotional learning: A contemporary meta-analysis of universal school-based SEL interventions.

This article provides a systematic review and meta-analysis of the current evidence for universal school-based (USB) social and emotional learning (SEL) interventions for students in kindergarten through 12th grade available from 2008 through 2020. The sample includes 424 studies from 53 countries, reflecting 252 discrete USB SEL interventions, involving 575,361 students. Results endorsed that, compared to control conditions, students who participate in USB SEL interventions experienced significantly improved skills, attitudes, behaviors, school climate and safety, peer relationships, school functioning, and academic achievement. Significant heterogeneity in USB SEL content, intervention features, context, and implementation quality moderated student experiences and outcomes. Strengths and limitations of this evidence and implications for future USB SEL research, policy, and practice are discussed.

Impact of compliance to oral cysteamine treatment on the costs of Kidney failure in patients with nephropathic cystinosis in the United Kingdom.

BACKGROUND: Nephropathic Cystinosis (NC), a rare disease characterised by intra-lysosomal accumulation of cystine, results in progressive kidney failure (KF). Compliance to lifelong oral cysteamine, the only therapy, is often compromised. The relationship between compliance and costs of NC has not been previously formally assessed. The present study evaluates the impact of compliance on lifetime (direct) costs of treating KF in NC patients in the United Kingdom. METHODS: A three-state (KF-free, post-KF, death) partitioned survival model was developed for hypothetical 'Good Compliance' (GC) and 'Poor Compliance' (PC) cohorts. Survival in the KF-free state was determined by a published regression function of composite compliance score (CCS). The CCS is a summation of annual compliance scores (ACS) over treatment duration prior to KF. ACSs are indexed on annual (average) leukocyte cystine levels (LCL). The Poor Compliance cohort was defined to reflect NC patients in a previous study with a mean LCL of 2.35 nmols nmol half-cystine/mg protein over the study period - and an estimated mean ACS of 1.64 over a 13.4 year treatment duration. The Good Compliance cohort was assumed to have an ACS of 2.25 for 21 years. Major KF costs were evaluated - i.e., dialysis, kidney transplants, and subsequent monitoring. RESULTS: The mean CCS was 47 for the GC and 22 for the PC cohort respectively, corresponding to estimated lifetime KF costs of £92,370 and £117,830 respectively - i.e., a cost saving of £25,460/patient, or £1,005/patient for every 1-unit improvement in CCS. CONCLUSION: This analysis indicates that lifetime costs of KF in NC can be reduced through improved treatment compliance with oral cysteamine.

Disagreement about perceptions of patient disability between the stroke patient and caregiver: a cross sectional study exploring the association to patient and caregiver quality of life.

OBJECTIVES: This study explored the association of disagreement in the perception of patient disability between patients and family caregivers with physical and psychological quality of life (QOL) in both parties. METHODS: A cross-sectional analysis of data collected from male stroke patients and family caregivers was conducted. Physical and psychological QOL in patients and caregivers were measured using the WHOQOL BREF. Perceptions of patient disability were measured using the 12-item WHO Disability Assessment Schedule 2.0 (DAS). Using DAS scores reported independently by patients and caregivers, dyads were categorized into one of four groups representing agreement or disagreement about patient disability. Generalized estimating equations were used to examine the associations between WHOQOL scores in patients and caregivers and these four groups. RESULTS: Among 56 dyads enrolled, approximately 52% were categorized into 'agreement' groups and 48% were categorized into 'disagreement' groups. The disagreement in perception about patient disability were significantly associated with poor patient physical QOL. However, the disagreement in perception were not significantly associated with caregiver QOL. CONCLUSION: Findings suggest the association of disagreement with QOL differs between patients and caregivers. Further research is needed to carefully appraise the relationship and interaction between patient and caregiver.

Diverse rural caregivers for individuals with Alzheimer's disease or related dementias: analysis of health factors at the individual, interpersonal, and community level.

Objectives: Approximately 6.2 million Americans aged 65 or older have Alzheimer's disease or related dementias (ADRD). Unpaid family members and friends provide the bulk of caregiving for these individuals. Caregiving in rural areas adds unique challenges, particularly for ethnically/racially diverse caregivers. This study provides a profile of diverse, rural ADRD caregivers with an emphasis on multi-level factors that influence physical and mental health.Methods: A cross-sectional survey was conducted with 156 diverse rural ADRD caregivers.Results: 65% of participants identified as White/Non-Hispanic (WNH; n = 101) and 35% identified as ethnically/racially diverse (ERD; n = 55). The majority of participants reported economic deprivation. More ERD caregivers were uninsured and had at least one chronic health condition. Higher proportions of ERD caregivers smoked cigarettes, consumed alcohol regularly, and had not seen or talked to a doctor in the previous year. There were no ethnic/racial group differences in stress, anxiety, depressive symptoms, subjective health, or sleep quality.Conclusion: Rural caregivers, regardless of ethnicity/race, may benefit from extra supports in order to maintain optimal health. Further research is needed to disentangle the complex relationship between culture, caregiving, and health.

Systematic Review of the Evidence for Stroke Family Caregiver and Dyad Interventions.

Stroke family caregiver and dyad literature has expanded over the past few years. The purpose of this review was to build upon 2 prior systematic reviews to critique, analyze, and synthesize the evidence pertaining to the impact of family caregiver and dyad interventions on stroke survivor and family caregiver outcomes. CINAHL, PsychINFO, PubMed, and reference lists were searched from December 1, 2016 through March 31, 2021. Using PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), articles were identified that tested outcomes from stroke family caregiver or dyad interventions that targeted the health or well-being of family caregivers. Data from the articles were abstracted into tables for analysis, then compared with recommendations from the 2 prior systematic reviews. A total of 18 articles met inclusion criteria (10 caregiver interventions; 8 dyad interventions) representing sample sizes ranging from 7 to 349 caregivers or dyads. Most were randomized controlled trials (n=13); 2 were cluster randomized trials; and 3 were single-group quasi-experimental designs. Of the 18 studies, 8 had <50 caregivers or dyads and 5 were small feasibility studies that reported data trends rather than testing for significance. Only 6 studies reported significant survivor outcomes. Eleven studies reported significant caregiver outcomes, the most common being burden. A number of survivor and caregiver outcomes were not significant, or only significant for certain subgroups. The limited number of studies, small sample sizes, and conflicting results, made it difficult to draw firm conclusions regarding the impact of these interventions on outcomes. Based on the available evidence from these 18 studies, recommendations from the 2 prior reviews were generally supported. Well-designed and well-powered randomized controlled clinical trials are still needed to confirm efficacy of stroke family caregiver and dyad interventions.

Performance of the Cepheid Methicillin-Resistant Staphylococcus aureus/S. aureus Skin and Soft Tissue Infection PCR Assay on Respiratory Samples from Mechanically Ventilated Patients for S. aureus Screening during the Phase 2 Double-Blind SAATELLITE Study.

We investigated the performance of the Xpert methicillin-resistant Staphylococcus aureus (MRSA)/S. aureus skin and soft tissue (SSTI) quantitative PCR (qPCR) assay in SAATELLITE, a multicenter, double-blind, phase 2 study of suvratoxumab, a monoclonal antibody (MAb) targeting S. aureus alpha-toxin, for reducing the incidence of S. aureus pneumonia. The assay was used to detect methicillin-susceptible S. aureus (MSSA) and MRSA in lower respiratory tract (LRT) samples from mechanically ventilated patients. LRT culture results were compared with S. aureus protein A (spa) gene cycle threshold (CT) values. Receiver operating characteristic (ROC) and Youden index were used to determine the CT cutoff for best separation of culture-S. aureus-negative and S. aureus-positive patients. Of 720 screened subjects, 299 (41.5%) were S. aureus positive by qPCR, of whom 209 had culture data: 162 (77.5%) were S. aureus positive and 47 (22.5%) were S. aureus negative. Culture results were negatively affected by antibiotic use and cross-laboratory variability. An inverse linear correlation was observed between CT values and quantitative S. aureus culture results. A spa CT value of 29 (≈2 × 103 CFU/mL) served as the best cutoff for separation between culture-negative and culture-positive samples. The associated area under the ROC curve was 83.8% (95% confidence interval [CI], 78 to 90%). Suvratoxumab provided greater reduction in S. aureus pneumonia or death than placebo in subjects with low S. aureus load (CT ≥ 29; relative risk reduction [RRR], 50.0%; 90% CI, 2.7 to 74.4%) versus the total study population (RRR, 25.2%; 90% CI, -4.3 to 46.4%). The qPCR assay was easy to perform, sensitive, and standardized and provided better sensitivity than conventional culture for S. aureus detection. Quantitative PCR CT output correlated with suvratoxumab efficacy in reducing S. aureus pneumonia incidence or death in S. aureus-colonized, mechanically ventilated patients.

Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response: preliminary studies.

Bipolar disorder (BD) is a neuropsychiatric illness defined by recurrent episodes of mania/hypomania, depression and circadian rhythm abnormalities. Lithium is an effective drug for BD, but 30-40% of patients fail to respond adequately to treatment. Previous work has demonstrated that lithium affects the expression of "clock genes" and that lithium responders (Li-R) can be distinguished from non-responders (Li-NR) by differences in circadian rhythms. However, circadian rhythms have not been evaluated in BD patient neurons from Li-R and Li-NR. We used induced pluripotent stem cells (iPSCs) to culture neuronal precursor cells (NPC) and glutamatergic neurons from BD patients characterized for lithium responsiveness and matched controls. We identified strong circadian rhythms in Per2-luc expression in NPCs and neurons from controls and Li-R, but NPC rhythms in Li-R had a shorter circadian period. Li-NR rhythms were low amplitude and profoundly weakened. In NPCs and neurons, expression of PER2 was higher in both BD groups compared to controls. In neurons, PER2 protein levels were higher in BD than controls, especially in Li-NR samples. In single cells, NPC and neuron rhythms in both BD groups were desynchronized compared to controls. Lithium lengthened period in Li-R and control neurons but failed to alter rhythms in Li-NR. In contrast, temperature entrainment increased amplitude across all groups, and partly restored rhythms in Li-NR neurons. We conclude that neuronal circadian rhythm abnormalities are present in BD and most pronounced in Li-NR. Rhythm deficits in BD may be partly reversible through stimulation of entrainment pathways.