Community antibiotic prescribing in patients with COVID-19 across three pandemic waves: a population-based study in Scotland, UK.

OBJECTIVES: This study aims to examine community antibiotic prescribing across a complete geographical area for people with a positive COVID-19 test across three pandemic waves, and to examine health and demographic factors associated with antibiotic prescribing. DESIGN: A population-based study using administrative data. SETTING: A complete geographical region within Scotland, UK. PARTICIPANTS: Residents of two National Health Service Scotland health boards with SARS-CoV-2 virus test results from 1 February 2020 to 31 March 2022 (n=184 954). Individuals with a positive test result (n=16 025) had data linked to prescription and hospital admission data ±28 days of the test, general practice data for high-risk comorbidities and demographic data. OUTCOME MEASURES: The associations between patient factors and the odds of antibiotic prescription in COVID-19 episodes across three pandemic waves from multivariate binary logistic regression. RESULTS: Data included 768 206 tests for 184 954 individuals, identifying 16 240 COVID-19 episodes involving 16 025 individuals. There were 3263 antibiotic prescriptions ±28 days for 2395 episodes. 35.6% of episodes had a prescription only before the test date, 52.3% of episodes after and 12.1% before and after. Antibiotic prescribing reduced over time: 20.4% of episodes in wave 1, 17.7% in wave 2 and 12.0% in wave 3. In multivariate logistic regression, being female (OR 1.31, 95% CI 1.19 to 1.45), older (OR 3.02, 95% CI 2.50 to 3.68 75+ vs <25 years), having a high-risk comorbidity (OR 1.45, 95% CI 1.31 to 1.61), a hospital admission ±28 days of an episode (OR 1.58, 95% CI 1.42 to 1.77) and health board region (OR 1.14, 95% CI 1.03 to 1.25, board B vs A) increased the odds of receiving an antibiotic. CONCLUSION: Community antibiotic prescriptions in COVID-19 episodes were uncommon in this population and likelihood was associated with patient factors. The reduction over pandemic waves may represent increased knowledge regarding COVID-19 treatment and/or evolving symptomatology.

Improved survival outcomes with anakinra over etoposide-based therapies for the management of adults with hemophagocytic lymphohistiocytosis: a retrospective multicenter research network study.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening, hyperinflammatory syndrome for which etoposide-based regimens have historically been the standard of care. Recent reports have described positive outcomes with the utilization of ruxolitinib or anakinra although these studies are often limited to small samples. Objectives: We aimed to compare the efficacy of ruxolitinib, anakinra, and etoposide-based therapies for the management of HLH in adult patients. Design: We performed a population-based, multicenter, retrospective cohort study utilizing the TriNetX Networks database. Methods: Adult patients (⩾18 years) diagnosed with HLH who received first-line treatment with ruxolitinib, anakinra, or etoposide between 2008 and 2023 were analyzed. The primary endpoint was overall survival (OS) at 1 year. A 1:1 propensity-score matching analysis was utilized. Results: Anakinra (p = 0.020) but not ruxolitinib (p = 0.19) resulted in a significantly higher 1-year OS when compared with etoposide-based therapies. Conclusions: Anakinra is effective for the management of adult patients with HLH.

Genetic architecture of white striping in turkeys (Meleagris gallopavo).

White striping (WS) is a myopathy of growing concern to the turkey industry. It is rising in prevalence and has negative consequences for consumer acceptance and the functional properties of turkey meat. The objective of this study was to conduct a genome-wide association study (GWAS) and functional analysis on WS severity. Phenotypic data consisted of white striping scored on turkey breast fillets (N = 8422) by trained observers on a 0-3 scale (none to severe). Of the phenotyped birds, 4667 genotypic records were available using a proprietary 65 K single nucleotide polymorphism (SNP) chip. The SNP effects were estimated using a linear mixed model with a 30-SNP sliding window approach used to express the percentage genetic variance explained. Positional candidate genes were those located within 50 kb of the top 1% of SNP windows explaining the most genetic variance. Of the 95 positional candidate genes, seven were further classified as functional candidate genes because of their association with both a significant gene ontology and molecular function term. The results of the GWAS emphasize the polygenic nature of the trait with no specific genomic region contributing a large portion to the overall genetic variance. Significant pathways relating to growth, muscle development, collagen formation, circulatory system development, cell response to stimulus, and cytokine production were identified. These results help to support published biological associations between WS and hypoxia and oxidative stress and provide information that may be useful for future-omics studies in understanding the biological associations with WS development in turkeys.

Wallace's line structures seagrass microbiota and is a potential barrier to the dispersal of marine bacteria.

BACKGROUND: The processes that shape microbial biogeography are not well understood, and concepts that apply to macroorganisms, like dispersal barriers, may not affect microorganisms in the same predictable ways. To better understand how known macro-scale biogeographic processes can be applied at micro-scales, we examined seagrass associated microbiota on either side of Wallace's line to determine the influence of this cryptic dispersal boundary on the community structure of microorganisms. Communities were examined from twelve locations throughout Indonesia on either side of this theoretical line. RESULTS: We found significant differences in microbial community structure on either side of this boundary (R2 = 0.09; P = 0.001), and identified seven microbial genera as differentially abundant on either side of the line, six of these were more abundant in the West, with the other more strongly associated with the East. Genera found to be differentially abundant had significantly smaller minimum cell dimensions (GLM: t923 = 59.50, P < 0.001) than the overall community. CONCLUSION: Despite the assumed excellent dispersal ability of microbes, we were able to detect significant differences in community structure on either side of this cryptic biogeographic boundary. Samples from the two closest islands on opposite sides of the line, Bali and Komodo, were more different from each other than either was to its most distant island on the same side. We suggest that limited dispersal across this barrier coupled with habitat differences are primarily responsible for the patterns observed. The cryptic processes that drive macroorganism community divergence across this region may also play a role in the bigeographic patterns of microbiota.

From little things big things grow: enhancement of an acoustic telemetry network to monitor broad-scale movements of marine species along Australia's east coast.

BACKGROUND: Acoustic telemetry has become a fundamental tool to monitor the movement of aquatic species. Advances in technology, in particular the development of batteries with lives of > 10 years, have increased our ability to track the long-term movement patterns of many species. However, logistics and financial constraints often dictate the locations and deployment duration of acoustic receivers. Consequently, there is often a compromise between optimal array design and affordability. Such constraints can hinder the ability to track marine animals over large spatial and temporal scales. Continental-scale receiver networks have increased the ability to study large-scale movements, but significant gaps in coverage often remain. METHODS: Since 2007, the Integrated Marine Observing System's Animal Tracking Facility (IMOS ATF) has maintained permanent receiver installations on the eastern Australian seaboard. In this study, we present the recent enhancement of the IMOS ATF acoustic tracking infrastructure in Queensland to collect data on large-scale movements of marine species in the northeast extent of the national array. Securing a relatively small initial investment for expanding receiver deployment and tagging activities in Queensland served as a catalyst, bringing together a diverse group of stakeholders (research institutes, universities, government departments, port corporations, industries, Indigenous ranger groups and tourism operators) to create an extensive collaborative network that could sustain the extended receiver coverage into the future. To fill gaps between existing installations and maximise the monitoring footprint, the new initiative has an atypical design, deploying many single receivers spread across 2,100 km of Queensland waters. RESULTS: The approach revealed previously unknown broad-scale movements for some species and highlights that clusters of receivers are not always required to enhance data collection. However, array designs using predominantly single receiver deployments are more vulnerable to data gaps when receivers are lost or fail, and therefore "redundancy" is a critical consideration when designing this type of array. CONCLUSION: Initial results suggest that our array enhancement, if sustained over many years, will uncover a range of previously unknown movements that will assist in addressing ecological, fisheries, and conservation questions for multiple species.

Eastern Association for the Surgery of Trauma (EAST) vs Western Trauma Association (WTA): How a Level 1 Trauma Center Splits the Difference in Resuscitative Thoracotomy.

Background Resuscitative thoracotomy (RT) is performed in severe trauma cases as a final lifesaving effort. Prominent, yet differing, practice management guidelines exist from Eastern Association for the Surgery of Trauma (EAST) and Western Trauma Association (WTA). This study evaluates all RTs performed from 2012 to 2019 at an urban Level 1 trauma center for management guideline indication and subsequent outcomes. Methods Our trauma registry was queried to identify RT cases from 2012 to 2019. Data was collected on patient demographics, prehospital presentation, cardiopulmonary resuscitation (CPR) requirements, and resuscitation provided. Survival to the operating room, intensive care unit, and overall were recorded. Information was compared with regard to EAST and WTA criteria. Results Eighty-seven patients who underwent RTs were included. WTA guidelines were met in 78/87 (89.7%) of cases, comparatively EAST guidelines were met in every case. Within the EAST criteria, conditional and strong recommendations were met in 70/87 (80.4%) and 17/87 (19.5%) of cases, respectively. In nine cases (10.3%) indications were discordant, each meeting conditional indication by EAST and no indication by WTA. All patients that survived to the operating room (OR), ICU admission, and overall met EAST criteria. Conclusion All RTs performed at our Level 1 trauma center met indications provided by EAST criteria. WTA guidelines were not applicable in nine salvaging encounters due to the protracted duration of CPR before proceeding to RT. Furthermore, more patients that survived to OR and ICU admission met EAST guidelines suggesting an improved potential for patient survivability. As increased data is derived, management guidelines will likely be re-established for optimized patient outcomes.

Exploring Anti-Fibrotic Effects of Adipose-Derived Stem Cells: Transcriptome Analysis upon Fibrotic, Inflammatory, and Hypoxic Conditioning.

Autologous fat transfers show promise in treating fibrotic skin diseases, reversing scarring and stiffness, and improving quality of life. Adipose-derived stem cells (ADSCs) within these grafts are believed to be crucial for this effect, particularly their secreted factors, though the specific mechanisms remain unclear. This study investigates transcriptomic changes in ADSCs after in vitro fibrotic, inflammatory, and hypoxic conditioning. High-throughput gene expression assays were conducted on ADSCs exposed to IL1-ß, TGF-ß1, and hypoxia and in media with fetal bovine serum (FBS). Flow cytometry characterized the ADSCs. RNA-Seq analysis revealed distinct gene expression patterns between the conditions. FBS upregulated pathways were related to the cell cycle, replication, wound healing, and ossification. IL1-ß induced immunomodulatory pathways, including granulocyte chemotaxis and cytokine production. TGF-ß1 treatment upregulated wound healing and muscle tissue development pathways. Hypoxia led to the downregulation of mitochondria and cellular activity.

Analysing the effects of distance, taxon and biomass on vertebrate detections using bulk-collected carrion fly iDNA.

Invertebrate-derived DNA (iDNA) metabarcoding from carrion flies is a powerful, non-invasive tool that has value for assessing vertebrate diversity. However, unknowns exist around the factors that influence vertebrate detections, such as spatial limits to iDNA signals or if detections are influenced by taxonomic class or estimated biomass of the vertebrates of interest. Using a bulk-collection method, we captured flies from within a zoo and along transects extending 4 km away from this location. From 920 flies, we detected 28 vertebrate species. Of the 28 detected species, we identified 9 species kept at the zoo, 8 mammals and 1 bird, but no reptiles. iDNA detections were highly geographically localized, and only a few zoo animals were detected outside the zoo setting. However, due to the low number of detections in our dataset, we found no influence of the taxonomic group or the estimated biomass of animals on their detectability. Our data suggest that iDNA detections from bulk-collected carrion flies, at least in urban settings in Australia, are predominantly determined by geographic proximity to the sampling location. This study presents an important step in understanding how iDNA techniques can be used in biodiversity monitoring.

Ultrafast Photoinduced Phase Change in SnSe.

Time-resolved multiterahertz (THz) spectroscopy is used to observe an ultrafast, nonthermal electronic phase change in SnSe driven by interband photoexcitation with 1.55 eV pump photons. The transient THz photoconductivity spectrum is found to be Lorentzian-like, indicating charge localization and phase segregation. The rise of photoconductivity is bimodal in nature, with both a fast and slow component due to excitation into multiple bands and subsequent intervalley scattering. The THz conductivity magnitude, dynamics, and spectra show a drastic change in character at a critical excitation fluence of approximately 6 mJ/cm^{2} due to a photoinduced phase segregation and a macroscopic collapse of the band gap.

AOP report: Development of an adverse outcome pathway for deposition of energy leading to cataracts.

Cataracts are one of the leading causes of blindness, with an estimated 95 million people affected worldwide. A hallmark of cataract development is lens opacification, typically associated not only with aging but also radiation exposure as encountered by interventional radiologists and astronauts during the long-term space mission. To better understand radiation-induced cataracts, the adverse outcome pathway (AOP) framework was used to structure and evaluate knowledge across biological levels of organization (e.g., macromolecular, cell, tissue, organ, organism and population). AOPs identify a sequence of key events (KEs) causally connected by key event relationships (KERs) beginning with a molecular initiating event to an adverse outcome (AO) of relevance to regulatory decision-making. To construct the cataract AO and retrieve evidence to support it, a scoping review methodology was used to filter, screen, and review studies based on the modified Bradford Hill criteria. Eight KEs were identified that were moderately supported by empirical evidence (e.g., dose-, time-, incidence-concordance) across the adjacent (directly linked) relationships using well-established endpoints. Over half of the evidence to justify the KER linkages was derived from the evidence stream of biological plausibility. Early KEs of oxidative stress and protein modifications had strong linkages to downstream KEs and could be the focus of countermeasure development. Several identified knowledge gaps and inconsistencies related to the quantitative understanding of KERs which could be the basis of future research, most notably directed to experiments in the range of low or moderate doses and dose-rates, relevant to radiation workers and other occupational exposures.

Intact and Degenerate Diguanylate Cyclases regulate Shigella Cyclic di-GMP.

The intracellular human pathogen Shigella invades the colonic epithelium to cause disease. Prior to invasion, this bacterium navigates through different environments within the human body, including the stomach and the small intestine. To adapt to changing environments, Shigella uses the bacterial second messenger c-di-GMP signaling system, synthesized by diguanylate cyclases (DGCs) encoding GGDEF domains. Shigella flexneri encodes a total of 9 GGDEF or GGDEF-EAL domain enzymes in its genome, but 5 of these genes have acquired mutations that presumably inactivated the c-di-GMP synthesis activity of these enzymes. In this study, we examined individual S. flexneri DGCs for their role in c-di-GMP synthesis and pathogenesis. We individually expressed each of the 4 intact DGCs in an S. flexneri strain where these 4 DGCs had been deleted (Δ4DGC). We found that the 4 S. flexneri intact DGCs synthesize c-di-GMP at different levels in vitro and during infection of tissue-cultured cells. We also found that dgcF and dgcI expression significantly reduces invasion and plaque formation, and dgcF expression increases acid sensitivity, and that these phenotypes did not correspond with measured c-di-GMP levels. However, deletion of these 4 DGCs did not eliminate S. flexneri c-di-GMP, and we found that dgcE, dgcQ, and dgcN , which all have nonsense mutations prior to the GGDEF domain, still produce c-di-GMP. These S. flexneri degenerate DGC genes are expressed as multiple proteins, consistent with multiple start codons within the gene. We propose that both intact and degenerate DGCs contribute to S. flexneri c-di-GMP signaling.

Assessment of the impact of the vaccine pass policy on COVID-19 vaccine hesitancy and uptake among Chinese adults in Hong Kong.

BACKGROUND: Recognising the importance of attaining high vaccine coverage to mitigate the COVID-19 impact, a Vaccine Pass scheme was implemented during and after the first large Omicron wave with high mortality in older ages in Hong Kong in early 2022 requiring three doses by June 2022. We did not identify any studies evaluating the policy impact of vaccination mandates with vaccine uptake over whole policy period of time in a Chinese population. We aim to evaluate the impact of the Vaccine Pass policy on COVID-19 vaccine uptake in adults in a Chinese population in Hong Kong. METHODS: We analysed patterns in vaccine uptake and hesitancy using local data from population vaccine registry and 32 cross-sectional telephone surveys conducted from October 2021 to December 2022. The association of Vaccine Pass phases with vaccine uptake was examined using logistic regression analyses, taking into account covariates including self-risk perception, perceived self-efficacy in preventing COVID-19 and trust in government in pandemic control as well as physical distancing measures and demographics. RESULTS: The uptake of primary series and third doses was positively significantly associated with the successive stages of Vaccine Pass implementation (adjusted odds ratios ranged from 2.41 to 7.81). Other statistically significant drivers of uptake included age group, chronic condition, higher perceived personal susceptibility to COVID-19, higher trust in government, and higher educational attainment. CONCLUSION: Vaccine uptake in older adults was observed to have increased by a greater extent after the policy annoucement and implementation, under the contextual changes during and after a large Omicron wave with high mortality in Hong Kong in early 2022. Since the policy withdrawal the uptake of further booster doses has been very low in all ages. We suggest that improving voluntary booster uptake in older adults should be prioritized.

Correlation between oral and oropharyngeal resection subsites and impact of reconstruction on speech and swallowing function in head and neck cancer patients: A systematic review.

This review aims to provide a correlation between oral and oropharyngeal subsites and type of reconstruction used in the management of head and neck cancer patients. A literature search of PubMed, Embase and Web of Science was conducted. All study types describing long-term speech and swallow outcomes of adults following head and neck oncological reconstruction, which used a subsite classification, were included. Risk of bias was assessed using the Robbins-1 tool. A total of 2270 patients were found in 26 studies. The number of subsites/studies ranged from 2 to 18. Subsites were predominantly divided on an anatomical basis. Other classifications included functionally grouped subsites. Seven articles considered combinations, unilateral and bilateral defects. Base of tongue, FOM, and defects crossing the midline are negatively correlated with post-operative speech and swallow. Lateral distributions were associated with superior outcomes. The University of Washington Quality of Life Questionnaire (UW-QOL) was the most prevalent tool for speech and swallow assessment. Other factors that significantly affect speech and swallow outcomes include adjuvant therapy, size, type of reconstruction (free flap compared to pedicled or local). The role of neoadjuvant therapy remains unknown. A consistent and formalised approach including risk stratification for multiple contributing factors would be useful in clinical pre- and post-operative management.

Decreased risk of non-influenza respiratory infection after influenza B virus infection in children.

Previous studies suggest that influenza virus infection may provide temporary non-specific immunity and hence lower the risk of non-influenza respiratory virus infection. In a randomized controlled trial of influenza vaccination, 1 330 children were followed-up in 2009-2011. Respiratory swabs were collected when they reported acute respiratory illness and tested against influenza and other respiratory viruses. We used Poisson regression to compare the incidence of non-influenza respiratory virus infection before and after influenza virus infection. Based on 52 children with influenza B virus infection, the incidence rate ratio (IRR) of non-influenza respiratory virus infection after influenza virus infection was 0.47 (95% confidence interval: 0.27-0.82) compared with before infection. Simulation suggested that this IRR was 0.87 if the temporary protection did not exist. We identified a decreased risk of non-influenza respiratory virus infection after influenza B virus infection in children. Further investigation is needed to determine if this decreased risk could be attributed to temporary non-specific immunity acquired from influenza virus infection.

Rapid Genome Sequencing Shows Diagnostic Utility In Infants With Congenital Heart Defects.

Congenital heart disease (CHD) is the most common birth defect and a leading cause of infant mortality. CHD often has a genetic etiology and recent studies demonstrate utility in genetic testing. In clinical practice, decisions around genetic testing choices continue to evolve, and the incorporation of rapid genome sequencing (rGS) in CHD has not been well studied. Though smaller studies demonstrate the value of rGS, they also highlight the burden of results interpretation. We analyze genetic testing in CHD at two time-points, in 2018 and 2022-2023, across a change in clinical testing guidelines from chromosome microarray (CMA) to rGS. Analysis of 421 hospitalized infants with CHD demonstrated consistent genetic testing across time. Overall, after incorporation of rGS in 2022-2023, the diagnostic yield was 6.8% higher compared to 2018, and this pattern was consistent across all patient subtypes analyzed. In 2018, CMA was the most common test performed, with diagnostic results for CHD in 14.3%, while in 2022-2023, rGS was the most frequent test performed, with results diagnostic for CHD in 16.9%. Additionally, rGS identified 44% more unique genetic diagnoses than CMA. This is the largest study to highlight the value of rGS in CHD and has important implications for management.

Predictors of persistent opioid use in bladder cancer patients undergoing radical cystectomy: A SEER-Medicare analysis.

PURPOSE: To evaluate patient and provider characteristics that predict persistent opioid use following radical cystectomy for bladder cancer including non-opioid naïve patients. METHODS: Patients undergoing cystectomy between July 2007 and December 2015 were identified using the SEER-Medicare database. Opioid exposure was identified before and after cystectomy using Medicare Part D data. Multivariable analyses were used to identify predictors of the primary outcomes: persistent opioid use (prescription 3-6 months after surgery) and postoperative opioid prescriptions (within 30 days of surgery). Secondary outcomes included physician prescribing practices and rates of persistent opioid use in their patient cohorts. RESULTS: A total of 1,774 patients were included; 29% had prior opioid exposure. Compared to opioid-naïve patients, non-opioid naïve patients were more frequently younger, Black, and living in less educated communities. The percentage of persistent postoperative use was 10% overall and 24% in non-opioid naïve patients. Adjusting for patient factors, opioid naïve individuals were less likely to develop persistent use (OR 0.23) while a 50-unit increase in oral morphine equivalent per day prescribed following surgery nearly doubled the likelihood of persistent use (OR 1.98). Practice factors such as hospital size, teaching affiliation, and hospital ownership failed to predict persistent use. 29% of patients filled an opioid prescription postoperatively. Opioid naïve patients (OR 0.13) and those cared for at government hospitals (OR 0.59) were less likely to fill an opioid script along with those residing in the Northeast. Variability between physicians was seen in prescribing practices and rates of persistent use. CONCLUSIONS: Non-opioid naïve patients have higher rates of post-operative opioid prescription than opioid-naïve patients. Physician prescribing practices play a role in persistent use, as initial prescription amount predicts persistent use even in non-opioid naïve patients. Significant physician variation in both prescribing practices and rates of persistent use suggest a role for standardizing practices.

Open supraceliac aortic repair of an iatrogenic aortic partial ligation during laparoscopic nephrectomy.

Iatrogenic aortic injury is a rare complication of laparoscopic nephrectomy with potentially catastrophic complications. Delays in recognition and treatment contribute significantly to patient morbidity and mortality. We present the case of a patient with acute limb ischemia and mesenteric ischemia secondary to partial transection of the supraceliac aorta during laparoscopic nephrectomy with a staple ligature. The injury was successfully treated with resection of the stapled aorta and reconstruction of a thoracoabdominal aortic bypass with a jump graft to the celiac artery.

Azasulfur(iv) derivatives of sulfite and sulfinate esters by formal S-S bond insertion of dichloramines.

Azasulfur(vi) compounds such as sulfoximines and sulfonimidamides are attractive due to the unique properties of the S[double bond, length as m-dash]N bond. While the synthesis of these carbon-attached sulfonimidoyl derivatives is well-established, the situation is different for their heteroatom-bound counterparts. In this work, we propose azasulfur(iv) esters as platform chemicals that can be derivatized to obtain all types of SVI[double bond, length as m-dash]N functional groups, among these are the poorly accessible, all-heteroatom imidosulfate esters. Using a chloroamination workflow established here, S-S bond-containing structures such as elemental sulfur or diaryl disulfides can be transformed into imidothionyl or sulfinimidoyl chlorides, which are easily esterified or amidated. Thus, chloramines serve as a versatile [N] and [Cl+] source, and by using them in the context reported here, we advance the set of mild synthetic methods as the latest toolbox member to cover even more of the azasulfur(iv) and (vi) chemical space.

Molecular basis for the activation of the Fatty Acid Kinase complex of Staphylococcus aureus.

Gram-positive bacteria utilize a Fatty Acid Kinase (FAK) complex to harvest fatty acids from the environment. The complex, consisting of the fatty acid kinase, FakA, and an acyl carrier protein, FakB, is known to impact virulence and disease outcomes. However, FAK's structure and enzymatic mechanism remain poorly understood. Here, we used a combination of modeling, biochemical, and cell-based approaches to establish critical details of FAK activity. Solved structures of the apo and ligand-bound FakA kinase domain captured the protein state through ATP hydrolysis. Additionally, targeted mutagenesis of an understudied FakA Middle domain identified critical residues within a metal-binding pocket that contribute to FakA dimer stability and protein function. Regarding the complex, we demonstrated nanomolar affinity between FakA and FakB and generated computational models of the complex's quaternary structure. Together, these data provide critical insight into the structure and function of the FAK complex which is essential for understanding its mechanism.