Cardiac Resynchronization Therapy for Patients with Mild to Moderately Reduced Ejection Fraction and Left Bundle Branch Block.

BACKGROUND: It is unknown if CRT would improve or halt the progression of heart failure (HF) in patients with mild-moderately reduced LVEF (HFmmrEF) and LBBB. OBJECTIVE: To investigate the outcomes of CRT in patients with HFmmrEF and LV conduction delay. METHODS: A prospective, randomized clinical trial sponsored by NHLBI included 76 patients who met the study inclusion criteria (LVEF 36-50% and LBBB). Patients received CRTP and were randomized to CRT-OFF (RV pacing 40bpm) or CRT-ON (BIV pacing 60-150bpm). At a 6-month follow-up, pacing programming was changed to the opposite settings. NYHA class, NT pro-BNP levels, and echocardiography were collected at baseline, 6-month, and 12-month. The primary study endpoint was the LV end-systolic volume (LVESV) change from baseline, and the primary randomized comparison was the comparison of 6-month to 12-month changes between randomized groups. RESULTS: The mean patient age was 68.4±9.8 years (male 71%). Baseline characteristics were similar between 2 randomized groups (all P>0.05). In patients randomized to CRT-OFF first, then ON, LVESV was reduced from baseline only after CRT-ON (baseline 116.1±36.5 mL, CRT-ON 87.6±26.0 mL, P<0.0001). The randomized analysis of LVEF showed a significantly better change from 6 to 12 months in the "OFF-ON" group, P=0.003. LVEF was improved by CRT (baseline 41.3±4.7%, CRT-ON 46.0±8.0%, P=0.002). In patients randomized to CRT-ON first, then OFF, LVESV was reduced both after CRT-ON and CRT-OFF (baseline 109.8±23.5 mL, CRT-ON 91.7±30.5 mL, P<0.0001; CRT-OFF 99.3±28.9 mL, P=0.012). However, the LVESV reduction effect became smaller between CRT-ON and OFF (P=0.027). LVEF improved both after CRT-ON and CRT-OFF (baseline 42.7±4.3%, CRT-ON 48.5±8.6%, P<0.001; CRT-OFF 45.9±7.7%, P=0.025). CONCLUSION: CRT for patients with HFmmrEF significantly improves LVEF and ventricular remodeling after 6 months of CRT. The study provides novel evidence that early CRT benefits patients with HFmmrEF with LBBB.

A user-friendly deep learning application for accurate lung cancer diagnosis.

BACKGROUND: Accurate diagnosis and subsequent delineated treatment planning require the experience of clinicians in the handling of their case numbers. However, applying deep learning in image processing is useful in creating tools that promise faster high-quality diagnoses, but the accuracy and precision of 3-D image processing from 2-D data may be limited by factors such as superposition of organs, distortion and magnification, and detection of new pathologies. The purpose of this research is to use radiomics and deep learning to develop a tool for lung cancer diagnosis. METHODS: This study applies radiomics and deep learning in the diagnosis of lung cancer to help clinicians accurately analyze the images and thereby provide the appropriate treatment planning. 86 patients were recruited from Bach Mai Hospital, and 1012 patients were collected from an open-source database. First, deep learning has been applied in the process of segmentation by U-NET and cancer classification via the use of the DenseNet model. Second, the radiomics were applied for measuring and calculating diameter, surface area, and volume. Finally, the hardware also was designed by connecting between Arduino Nano and MFRC522 module for reading data from the tag. In addition, the displayed interface was created on a web platform using Python through Streamlit. RESULTS: The applied segmentation model yielded a validation loss of 0.498, a train loss of 0.27, a cancer classification validation loss of 0.78, and a training accuracy of 0.98. The outcomes of the diagnostic capabilities of lung cancer (recognition and classification of lung cancer from chest CT scans) were quite successful. CONCLUSIONS: The model provided means for storing and updating patients' data directly on the interface which allowed the results to be readily available for the health care providers. The developed system will improve clinical communication and information exchange. Moreover, it can manage efforts by generating correlated and coherent summaries of cancer diagnoses.

Cryptic genetic variation shapes the fate of gene duplicates in a protein interaction network.

Paralogous genes are often redundant for long periods of time before they diverge in function. While their functions are preserved, paralogous proteins can accumulate mutations that, through epistasis, could impact their fate in the future. By quantifying the impact of all single-amino acid substitutions on the binding of two myosin proteins to their interaction partners, we find that the future evolution of these proteins is highly contingent on their regulatory divergence and the mutations that have silently accumulated in their protein binding domains. Differences in the promoter strength of the two paralogs amplify the impact of mutations on binding in the lowly expressed one. While some mutations would be sufficient to non-functionalize one paralog, they would have minimal impact on the other. Our results reveal how functionally equivalent protein domains could be destined to specific fates by regulatory and cryptic coding sequence changes that currently have little to no functional impact.

Orchestration of the Adipose Tissue Immune Landscape by Adipocytes.

Obesity is epidemic and of great concern because of its comorbid and costly inflammatory-driven complications. Extensive investigations in mice have elucidated highly coordinated, well-balanced interactions between adipocytes and immune cells in adipose tissue that maintain normal systemic metabolism in the lean state, while in obesity, proinflammatory changes occur in nearly all adipose tissue immune cells. Many of these changes are instigated by adipocytes. However, less is known about obesity-induced adipose-tissue immune cell alterations in humans. Upon high-fat diet feeding, the adipocyte changes its well-known function as a metabolic cell to assume the role of an immune cell, orchestrating proinflammatory changes that escalate inflammation and progress during obesity. This transformation is particularly prominent in humans. In this review, we (a) highlight a leading and early role for adipocytes in promulgating inflammation, (b) discuss immune cell changes and the time course of these changes (comparing humans and mice when possible), and (c) note how reversing proinflammatory changes in most types of immune cells, including adipocytes, rescues adipose tissue from inflammation and obese mice from insulin resistance.

Occupancy trends of overwintering coastal waterbird communities reveal guild-specific patterns of redistribution and shifting reliance on existing protected areas.

Climate change and anthropogenic stressors are redistributing species and altering community composition globally. Protected areas (PAs) may not sufficiently protect populations of species undergoing distributional shifts, necessitating that we evaluate existing PAs and identify areas for future protection to conserve biodiversity across regional and temporal scales. Coastal waterbirds are important indicators of marine ecosystem health, representing mobile, long-lived, higher trophic-level consumers. Using a 20-year citizen science dataset (1999-2019) with a before-after control-intervention sampling framework for habitat protection, we applied dynamic occupancy models to assess winter occupancy trends along the Pacific coast of Canada. Specifically, we sought to understand potential drivers of regional declines, spatial commonalities among guilds, and changes in habitat use before and after PA designation, as well as between PAs and non-PAs. Occupancy trends varied regionally, with greater declines in the south compared to the north. Regional differences underlined potential range shifts, particularly for species with traits linked to temperature tolerance, movement, and high productivity foraging, as cold-tolerant, migratory benthivores and piscivores wintered farther north relative to 20 years ago or retreated to cold-water fjords. While 21 of 57 (36.8%) species responded positively to PA designation (before-after), greater occupancy declines tended to occur in PAs established pre-1999 relative to non-PAs (control-intervention). Since PAs are currently concentrated in the south, negative associations were most apparent for species retreating northward, but existing PAs may have a stabilizing or transitory effect on southern wintering species shifting into the region from farther south. We emphasize that conservation strategies must balance persistence of current communities with preserving the climate-adapted biodiversity of tomorrow by accounting for community-level effects of species moving into and out of existing PAs. Incorporating range shifts into PA planning by predicting distributional changes will allow conservation practitioners to identify priority habitats, such as cold-water refugia, for persistent wildlife communities.

Le changement climatique et les facteurs de stress anthropiques redistribuent les espèces et modifient la composition des communautés à l'échelle mondiale. Les zones protégées (ZP) ne protègent peut-être pas suffisamment les populations d'espèces qui subissent des changements de répartition, ce qui nous oblige à évaluer les ZP existantes et à identifier les zones à protéger à l'avenir pour conserver la biodiversité à l'échelle régionale et temporelle. Les oiseaux côtiers sont des indicateurs importants de la santé des écosystèmes marins, car ils représentent des consommateurs mobiles, ont une longue durée de vie et représente le niveau trophique supérieur. En utilisant un ensemble de données de science participative sur 20 ans (1999-2019) avec un échantillonnage avant-après contrôle-intervention (AACI) pour la protection de l'habitat, nous avons appliqué des modèles d'occupation dynamiques pour évaluer les tendances de l'occupation hivernale le long de la côte pacifique du Canada. Plus précisément, nous avons cherché à comprendre les moteurs potentiels des déclins régionaux, les points communs spatiaux entre les guildes et les changements dans l'utilisation de l'habitat avant et après la désignation de le ZP, ainsi qu'entre les ZP et les non-ZP. Les tendances en matière d'occupation varient d'une région à l'autre, avec des déclins plus importants dans le sud que dans le nord. Les différences régionales soulignent les déplacements potentiels de l'aire de répartition, en particulier pour les espèces dont les caractéristiques sont liées à la tolérance à la température, aux déplacements et à la recherche de nourriture à rendement élevé, car les benthivores et les piscivores migrateurs tolérants au froid ont hiverné plus au nord qu'il y a 20 ans ou se sont retirés dans les fjords aux eaux froides. Alors que 21 des 57 (36,8 %) espèces ont réagi positivement à la désignation des aires protégées (avant-après), les baisses d'occupation ont eu tendance à être plus importantes dans les aires protégées créées avant 1999 que dans les aires non protégées (contrôle-intervention). Comme les aires protégées sont actuellement concentrées dans le sud, les associations négatives étaient plus évidentes pour les espèces qui se retirent vers le nord, mais les aires protégées existantes peuvent avoir un effet stabilisateur ou transitoire sur les espèces hivernant dans le sud qui se déplacent dans la région à partir d'une région plus au sud. Nous soulignons que les stratégies de conservation doivent trouver un équilibre entre la persistance des communautés actuelles et la préservation de la biodiversité adaptée au climat de demain, en tenant compte des effets au niveau des communautés des espèces qui entrent dans les aires protégées existantes ou qui en sortent. L'intégration des changements d'aire de répartition dans la planification des aires protégées en prédisant les changements de distribution permettra aux praticiens de la conservation d'identifier les habitats prioritaires, tels que les refuges d'eau froide, pour les communautés d'espèces sauvages persistantes.

Nonpharmacological Therapies for Musculoskeletal Injury in Military Personnel: A Systematic Review/Meta-Analysis.

INTRODUCTION: Musculoskeletal (MSK) injury is an inherent risk for military personnel that can potentially impact job performance, productivity, and military readiness. Evidence is needed to show the efficacy of nonpharmacological, self-managed therapies to reduce MSK symptoms at common injury sites that are feasible for use during expeditionary operations and home stations. This systematic review and meta-analysis identified, summarized, and synthesized available evidence from randomized and non-randomized trials on the effectiveness of self-managed, home-use therapies to improve pain, muscle strength, and physical performance in military personnel with MSK injuries, when compared to controls. METHODS: The electronic databases of MEDLINE ALL Ovid, Embase.com, Cochrane Library, Scopus, Clinicaltrial.gov, and CINAHL Complete via EBSCO were systematically searched for relevant reports published in English. Utilizing the Covidence platform and consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, multiple reviewers, using pre-determined data fields, screened for eligibility, assessed risk of bias (RoB), and performed data extraction. Evaluation of treatment effectiveness was determined using multilevel mixed-effects meta-analysis. RESULTS: The database and register search yielded 1,643 reports that were screened for eligibility. After screening of titles/abstracts and full texts, 21 reports were identified for evidence synthesis. Of these, two reports were excluded and two described the same study, resulting in a final list of 18 studies (19 reports). For quality assessment, the overall RoB for the 18 studies was categorized as 33.3% low risk, 55.6% with some concerns, and 11.1% high risk. Across the five domains of bias, 70% of the reports were classified as low risk. This systematic review found that the differences in interventions, outcome measures, and design between the studies were associated with a substantial degree of heterogeneity (I2 = 60.74%), with a small overall improvement in outcomes of the interventions relative to their specific control (standard mean difference 0.28; 95% CI, 0.12 to 0.45). There were varying degrees of heterogeneity for individual body regions. This was due, in part, to a small number of studies per bodily location and differences in the study designs. For the neck/shoulder, heterogeneity was moderate, with the clearest positive effect being for physical performance outcomes via other medical devices. For the back, there was substantial heterogeneity between studies, with modest evidence that pain was favorably improved by other medical devices and exercise interventions. For the leg, one study showed a clear large effect for other medical devices (shockwave treatment) on pain with substantial heterogeneity. The best evidence for positive effects was for the knee, with mainly negligible heterogeneity and some benefits from bracing, electrotherapy, and exercise. CONCLUSION: Evidence showed small beneficial effects in pain, strength, and physical performance by individual body regions for some interventions, compared to controls. The best evidence for a positive effect was for the knee. The findings suggest that some benefit may be obtained by including several treatments during deployment in austere environments and prolonged casualty care scenarios of military personnel with MSK injuries. Further research is warranted to better assess the potential benefits of using these treatments during deployments in austere environments as part of an individualized, multimodal approach for MSK injuries.

A simulation study on the radiosensitization properties of gold nanorods.

Objective. Gold nanorods (GNRs) have emerged as versatile nanoparticles with unique properties, holding promise in various modalities of cancer treatment through drug delivery and photothermal therapy. In the rapidly evolving field of nanoparticle radiosensitization (NPRS) for cancer therapy, this study assessed the potential of gold nanorods as radiosensitizing agents by quantifying the key features of NPRS, such as secondary electron emission and dose enhancement, using Monte Carlo simulations.Approach. Employing the TOPAS track structure code, we conducted a comprehensive evaluation of the radiosensitization behavior of spherical gold nanoparticles and gold nanorods. We systematically explored the impact of nanorod geometry (in particular size and aspect ratio) and orientation on secondary electron emission and deposited energy ratio, providing validated results against previously published simulations.Main results. Our findings demonstrate that gold nanorods exhibit comparable secondary electron emission to their spherical counterparts. Notably, nanorods with smaller surface-area-to-volume ratios (SA:V) and alignment with the incident photon beam proved to be more efficient radiosensitizing agents, showing superiority in emitted electron fluence. However, in the microscale, the deposited energy ratio (DER) was not markedly influenced by the SA:V of the nanorod. Additionally, our findings revealed that the geometry of gold nanoparticles has a more significant impact on the emission of M-shell Auger electrons (with energies below 3.5 keV) than on higher-energy electrons.Significance. This research investigated the radiosensitization properties of gold nanorods, positioning them as promising alternatives to the more conventionally studied spherical gold nanoparticles in the context of cancer research. With increasing interest in multimodal cancer therapy, our findings have the potential to contribute valuable insights into the perspective of gold nanorods as effective multipurpose agents for synergistic photothermal therapy and radiotherapy. Future directions may involve exploring alternative metallic nanorods as well as further optimizing the geometry and coating materials, opening new possibilities for more effective cancer treatments.

Biochemical and in silico characterization of glycosyltransferases from red sweet cherry (Prunus avium L.) reveals their broad specificity toward phenolic substrates.

Polyphenolic compounds are a class of phytonutrients that play important roles in plants and contribute to human health when incorporated into our diet through fruit consumption. A large proportion occur as glycoconjugates but the enzymes responsible for their glycosylation are poorly characterized. Here, we report the biochemical and structural characterization of two glycosyltransferases from sweet cherry named PaUGT1 and PaUGT2. Both are promiscuous glucosyltransferases active on diverse anthocyanidins and flavonols, as well as phenolic acids in the case of PaUGT1. They also exhibit weaker galactosyltransferase activity. The expression of the gene encoding PaUGT1, the most active of the two proteins, follows anthocyanin accumulation during fruit ripening, suggesting that this enzyme is the primary glycosyltransferase involved in flavonoid glycosylation in sweet cherry. It can potentially be used to synthesize diverse glycoconjugates of flavonoids for integration into bioactive formulations, and for generating new fruit cultivars with enhanced health-promoting properties using breeding methods.

The Impact of Rapid Handpump Repairs on Diarrhea Morbidity in Children: Cross-Sectional Study in Kwale County, Kenya.

BACKGROUND: Handpumps are used by millions of people as their main source of water. Although handpumps represent only a basic form of water provision, there have been continuous efforts to improve the performance of these systems as they are likely to remain in use for many years to come. The introduction of a professional maintenance service in southern Kenya has shown an order of magnitude improvement in operational performance over community-based management, with 90% of handpump faults repaired within 3 days of being reported. One driver behind these efforts is the assumption that a more reliable water supply will lead to a reduction in water-related disease. However, it is not clear if operational improvements lead to health gains. Despite limited empirical evidence, some modeling studies suggest that even short periods of drinking contaminated water can lead to disproportionate negative health impacts. OBJECTIVE: The aim of this study was to assess whether the improvements in operational performance from the rapid professional maintenance of rural handpumps lead to improved household health outcomes. METHODS: From a sample of households using handpumps as their primary water source in Kwale County, Kenya, we measured the 2-week prevalence of World Health Organization-defined diarrhea in children, reported by the adult respondent for each household. We compared the rates before and after a period during which the households' handpumps were being professionally maintained. We then conducted a cross-sectional analysis, fitting logistic regression models with reported diarrhea as the dependent variable and speed of repair as the independent exposure of interest, adjusting for household socioeconomic characteristics; dwelling construction; and Water, Sanitation, and Hygiene (WASH)-related factors. We fitted an additional model to examine select interactions between covariates. RESULTS: Reported diarrhea in children was lower in households whose pumps had been repaired within 24 hours (adjusted odds ratio 0.35, 95% CI 0.24-0.51). This effect was robust to the inclusion of multiple categories of covariates. No reduction was seen in households whose pump repairs took more than 24 hours. Analysis of interaction terms showed that certain interventions associated with improved WASH outcomes were only associated with reductions in diarrhea in conjunction with socioeconomic improvements. CONCLUSIONS: Only pump repairs consistently made within 24 hours of failure led to a reduction in diarrhea in the children of families using handpumps. While the efficacy of reduction in diarrhea is substantial, the operational challenges of guaranteeing same-day repairs limits the effectiveness of even best-in-class pump maintenance. Maintenance regimes that cannot bring handpump downtimes close to zero will struggle to generate health benefits. Other factors that reduce diarrhea prevalence have limited effect in isolation, suggesting that WASH interventions will be more effective when undertaken as part of more holistic poverty-reduction efforts.

Surgical Safety Does Not Happen By Accident: Learning From Perioperative Near Miss Case Studies.

Adverse surgical events cause negative patient health outcomes and harm that can often overshadow the safe and effective patient care provided daily by nurses as members of interprofessional healthcare teams. Near misses occur far more frequently than adverse events and are less visible to nurse leaders because patient harm is avoided due to chance, prevention, or mitigation. However, near misses have comparable root causes to adverse events and exhibit the same underlying patterns of failure. Reviewing near misses provides nurses with learning opportunities to identify patient care weaknesses and build appropriate solutions to enhance care. As the operating room is one of the most complex work settings in healthcare, identifying potential weaknesses or sources for errors is vital to reduce healthcare-associated risks for patients and staff. The purpose of this manuscript is to educate, inform, and stimulate critical thinking by discussing perioperative near miss case studies and the underlying factors that lead to errors. Our authors discuss 15 near miss case studies occurring across the perioperative patient experience of care and discuss barriers to near miss reporting. Nurse leaders can use our case studies to stimulate discussion among perioperative and perianesthesia nurses in their hospitals to inform comprehensive risk reduction programs.

Dissection of the role of a Src homology 3 domain in the evolution of binding preference of paralogous proteins.

Protein-protein interactions (PPIs) drive many cellular processes. Some interactions are directed by Src homology 3 (SH3) domains that bind proline-rich motifs on other proteins. The evolution of the binding specificity of SH3 domains is not completely understood, particularly following gene duplication. Paralogous genes accumulate mutations that can modify protein functions and, for SH3 domains, their binding preferences. Here, we examined how the binding of the SH3 domains of 2 paralogous yeast type I myosins, Myo3 and Myo5, evolved following duplication. We found that the paralogs have subtly different SH3-dependent interaction profiles. However, by swapping SH3 domains between the paralogs and characterizing the SH3 domains freed from their protein context, we find that very few of the differences in interactions, if any, depend on the SH3 domains themselves. We used ancestral sequence reconstruction to resurrect the preduplication SH3 domains and examined, moving back in time, how the binding preference changed. Although the most recent ancestor of the 2 domains had a very similar binding preference as the extant ones, older ancestral domains displayed a gradual loss of interaction with the modern interaction partners when inserted in the extant paralogs. Molecular docking and experimental characterization of the free ancestral domains showed that their affinity with the proline motifs is likely not the cause for this loss of binding. Taken together, our results suggest that a SH3 and its host protein could create intramolecular or allosteric interactions essential for the SH3-dependent PPIs, making domains not functionally equivalent even when they have the same binding specificity.

Advancing Readiness Through Military Programs: An Evidence-Based Practice Perspective.

INTRODUCTION: Military nurses comprise the largest percentage of military health care providers. In the current military health care system, they have two roles: (1) Patient care in military treatment facilities (MTFs) and (2) patient care during combat operations. Although in MTFs, the military nurse's roles are similar to those of their civilian counterpart, their roles are unique and varied in the combat operational environment. These combined roles lead to questions regarding readiness training to ensure that nurses are proficient in both MTFs and combat operational settings where treatment requirements may differ. The purpose of this paper is to (1) present the current state of educational readiness programs to maintain a ready medical force that entail formal teaching programs, military-civilian partnerships, and joint exercises of combat simulations, and (2) identify gaps as presented in an evidence-based practice educational panel. METHODS: On March 11, 2022, TriService Nursing Research Program hosted the virtual First Military Evidence-Based Practice Summit from the Uniformed Services University of the Health Sciences in Bethesda, MD. As part of the summit, an evidence-based practice education panel discussed the availability of current evidence-driven military medical readiness programs and identified gaps in the integration of military readiness for nursing personnel into the Defense Health Agency and Armed Services. RESULTS: The panel participants discussed the separate requirements for training within the MTFs and in combat operational settings. The available training programs identified by the panel were primarily those developed in local MTF settings to meet local needs. Although these programs support the MTFs' peacetime mission, competing roles, limited time, and limited funds contributed to limited preparation of nursing personnel in skills associated with combat-related injuries and illnesses. Prolonged casualty care has become an important focus for the Department of Defense as greater considerations are directed to wartime operations in austere expeditionary environments. Although there is some training available that is specific for prolonged casualty care, the focus has been the adaptation of combat casualty care during contingency operations. A keynote here was the concept that combat casualty care training must include both development of individual skills and integration of the team since maximal care can be achieved only when the individual and the team operate as a unit. A key point was the utility of central repositories for storing information related to training a ready medical force at individual and unit levels and that these repositories could also be used to collect and facilitate the accession of current evidence-based information. DISCUSSION: Optimal patient care at all levels of the military health system requires training that maximizes individual and unit skills specific to the environment at an MTF or in a combat operational setting. Training must be designed to incorporate evidence-driven knowledge in all military settings with guidance that is specific to the environment. CONCLUSION: Enhanced communication of evidence-based training and knowledge is an important component of maintaining a ready medical force for broader medical support of combat contingency operations.

Perioperative Pressure Injury Prevention Program in a Military Medical Treatment Facility: A Quality Improvement Project.

INTRODUCTION: The incidence of perioperative pressure injuries (PPIs) at a military medical treatment facility (MTF) increased from three PPI events in 2018 to five PPI events in the first half of 2019. The purpose of this quality improvement initiative was to determine whether an evidence-based PPI prevention program introduced during the second half of 2019 reduced pressure injuries compared to the previous 1.5 years that followed the standard of care for perioperative patient positioning. METHODS: We used a multidisciplinary quality improvement PPI prevention approach that included education, Scott Triggers® patient risk assessment, application of a five-layer silicone dressing to at-risk surgical position sites, and feedback via multidisciplinary postoperative rounding. RESULTS: There was an observed decrease in the rate of PPIs from 0.62 to 0.00 per 1,000 patient surgeries during the 26-month period that this protocol was implemented. CONCLUSION: This project was conducted at a major MTF using a multidisciplinary PPI prevention approach that may be of value in reducing PPIs in other settings. This approach seems worthy of further investigation and may be applicable to other military MTFs and in deployed settings.

Tidal modulation of very-low-frequency and ultra-low-frequency ambient noise levels.

Several years of continuous low-frequency underwater ambient noise data from 0.1 to 125 Hz have been made available for examination by the United Nations Comprehensive Nuclear Test Ban Treaty Organization. Narrow-band noise time records between 0.5 and 10 Hz were selected for study, chosen deliberately to address noise sources tied primarily to the environment. Power spectra of the variable narrow-band time records were found to display sharp spectral lines at fluctuation frequencies that match lunar and solar diurnal and semidiurnal ocean tides.

A single-site retrospective review of in-hospital stroke.

BACKGROUND: In-hospital stroke refers to a stroke arising in a patient during hospital admission for another condition. Between 2 and 17% of all inpatient strokes are in-hospital strokes. AIM: To compare the outcomes and performance on quality-of-care stroke measures of in-hospital stroke cases with community-onset strokes. METHODS: Data collected for the Irish Annual Audit of Stroke from an Irish university teaching hospital was analysed for a 2-year period from 1st January 2020 to 31st December 2021. A retrospective cohort study was conducted to compare baseline characteristics, outcomes, and performance on standardised quality-of-care measures between the cohorts. RESULTS: The rate of IHS was 15.6%. Median age was 73 years and 72 years for in-hospital and community-onset strokes respectively. Amongst in-hospital strokes, COVID-19 co-diagnosis (9.1% versus 1.3%; p = .0004), admission to intensive care (52.3% versus 5.3%; p < .0001), discharge to long term care (6.8% versus 2.3%; p = .04), mortality (12.5% versus 7.6%; p = .13), and modified Rankin score of two or more at discharge (58.0% versus 38.1%; p = .001), were more likely compared to community-onset strokes. Thrombolysis rates were lower (7.3% versus 12.0%; p = .22) and thrombectomy rates higher (9.8% versus 6.6;% p = .32), albeit non-significantly. Median time to thrombolysis was slower amongst in-hospital strokes (105 min versus 66 min; p = .03) and they were less likely to be admitted to the stroke unit (43.2% versus 78.5%; p < .0001). CONCLUSIONS: When compared with community-onset stroke, in-hospital stroke represents a distinct stroke subgroup with poorer outcomes and delays to thrombolysis emphasising the need for standardised approaches to evaluation and management.

Parallel Nonfunctionalization of CK1δ/ε Kinase Ohnologs Following a Whole-Genome Duplication Event.

Whole-genome duplication (WGD) followed by speciation allows us to examine the parallel evolution of ohnolog pairs. In the yeast family Saccharomycetaceae, HRR25 is a rare case of repeated ohnolog maintenance. This gene has reverted to a single copy in Saccharomyces cerevisiae where it is now essential, but has been maintained as pairs in at least 7 species post-WGD. In S. cerevisiae, HRR25 encodes the casein kinase 1δ/ε and plays a role in a variety of functions through its kinase activity and protein-protein interactions (PPIs). We hypothesized that the maintenance of duplicated HRR25 ohnologs could be a result of repeated subfunctionalization. We tested this hypothesis through a functional complementation assay in S. cerevisiae, testing all pairwise combinations of 25 orthologs (including 7 ohnolog pairs). Contrary to our expectations, we observed no cases of pair-dependent complementation, which would have supported the subfunctionalization hypothesis. Instead, most post-WGD species have one ohnolog that failed to complement, suggesting their nonfunctionalization or neofunctionalization. The ohnologs incapable of complementation have undergone more rapid protein evolution, lost most PPIs that were observed for their functional counterparts and singletons from post-WGD and non-WGD species, and have nonconserved cellular localization, consistent with their ongoing loss of function. The analysis in Naumovozyma castellii shows that the noncomplementing ohnolog is expressed at a lower level and has become nonessential. Taken together, our results indicate that HRR25 orthologs are undergoing gradual nonfunctionalization.

Norm in cultivated honey in Malaysia and concomitant effective dose to consumers.

Present study concerns the radiological character of Malaysian honey. A total of 18 samples (representative of the various most common types) were obtained from various honey bee farms throughout the country. Using a high-purity germanium γ-ray spectroscopic system, the samples were analysed for the naturally occurring radionuclides 226Ra, 228Ra and 40K. The respective range of activities (in Bq/kg) was: 3.49 ± 0.35 to 4.51 ± 0.39, 0.99 ± 0.37 to 1.74 ± 0.39 and 41.37 ± 3.26 to 105.02 ± 6.91. The estimated associated committed effective doses were derived from prevailing data on national consumption of honey, the annual dose being found low compared with the UNSCEAR reference dose limit of 290 µSv y-1. The estimated threshold consumption rate for honey indicates a maximum intake of 339 g/d, which poses an insignificant radiological risk to public health; however, the total dietary exposure may not, the guidance level of 290 µSv y-1 being applicable to dietary intake of all foodstuffs. The study is in support of the cultivation of a healthy lifestyle, acknowledging prevailing radioactivity within the environment.

Dosimetric and radiobiological comparison between conventional and hypofractionated breast treatment plans using the Halcyon system.

Purpose: The objective of this research is to compare the efficacy of conventional and hypofractionated radiotherapy treatment plans for breast cancer patients, with a specific focus on the unique features of the Halcyon system. Methods and materials: The study collected and analyzed dose volume histogram (DVH) data for two groups of treatment plans implemented using the Halcyon system. The first group consisted of 19 patients who received conventional fractionated (CF) treatment with a total dose of 50 Gy in 25 fractions, while the second group comprised 9 patients who received hypofractionated (HF) treatment with a total dose of 42.56 Gy in 16 fractions. The DVH data was used to calculate various parameters, including tumor control probability (TCP), normal tissue complication probability (NTCP), and equivalent uniform dose (EUD), using radiobiological models. Results: The results indicated that the CF plan resulted in higher TCP but lower NTCP for the lungs compared to the HF plan. The EUD for the HF plan was approximately 49 Gy (114% of its total dose) while that for the CF plan was around 53 Gy (107% of its total dose). Conclusions: The analysis suggests that while the CF plan is better at controlling tumors, it is not as effective as the HF plan in minimizing side effects. Additionally, it is suggested that there may be an optimal configuration for the HF plan that can provide the same or higher EUD than the CF plan.

Parallel nonfunctionalization of CK1δ/ε kinase ohnologs following a whole-genome duplication event.

Whole genome duplication (WGD) followed by speciation allows us to examine the parallel evolution of ohnolog pairs. In the yeast family Saccharomycetaceae, HRR25 is a rare case of repeated ohnolog maintenance. This gene has reverted to a single copy in S. cerevisiae where it is now essential, but has been maintained as pairs in at least 7 species post WGD. In S. cerevisiae, HRR25 encodes the casein kinase (CK) 1δ/ε and plays a role in a variety of functions through its kinase activity and protein-protein interactions (PPIs). We hypothesized that the maintenance of duplicated HRR25 ohnologs could be a result of repeated subfunctionalization. We tested this hypothesis through a functional complementation assay in S. cerevisiae, testing all pairwise combinations of 25 orthologs (including 7 ohnolog pairs). Contrary to our expectations, we observed no cases of pair-dependent complementation, which would have supported the subfunctionalization hypothesis. Instead, most post-WGD species have one ohnolog that failed to complement, suggesting their nonfunctionalization or neofunctionalization. The ohnologs incapable of complementation have undergone more rapid protein evolution, lost most PPIs that were observed for their functional counterparts and singletons from post and non-WGD species, and have non-conserved cellular localization, consistent with their ongoing loss of function. The analysis in N. castelli shows that the non-complementing ohnolog is expressed at a lower level and has become non-essential. Taken together, our results indicate that HRR25 orthologs are undergoing gradual nonfunctionalization.