Illuminating Polysulfide Distribution in Lithium Sulfur Batteries; Tracking Polysulfide Shuttle Using Operando Optical Fluorescence Microscopy.

High-energy-density lithium sulfur (Li-S) batteries suffer heavily from the polysulfide shuttle effect, a result of the dissolution and transport of intermediate polysulfides from the cathode, into the electrolyte, and onto the anode, leading to rapid cell degradation. If this primary mechanism of cell failure is to be overcome, the distribution, dynamics, and degree of polysulfide transport must first be understood in depth. In this work, operando optical fluorescence microscope imaging of optically accessible Li-S cells is shown to enable real-time qualitative visualization of the spatial distribution of lithium polysulfides, both within the electrolyte and porous cathode. Quantitative determinations of spatial concentration are also possible at a low enough concentration. The distribution throughout cycling is monitored, including direct observation of polysulfide shuttling to the anode and consequent dendrite formation. This was enabled through the optimization of a selective fluorescent dye, verified to fluoresce proportionally with concentration of polysulfides within Li-S cells. This ability to directly and conveniently track the spatial distribution of soluble polysulfide intermediates in Li-S battery electrolytes, while the cell operates, has the potential to have a widespread impact across the field, for example, by enabling the influence of a variety of polysulfide mitigation strategies to be assessed and optimized, including in this work the LiNO3 additive.

Prices and complications in hospital-based and freestanding surgery centers.

OBJECTIVES: To quantify differences in prices paid and procedural complications incurred in hospital outpatient departments (HOPDs) and freestanding ambulatory surgery centers (ASCs). STUDY DESIGN: Observational study using deidentified 2019-2020 insurance claims from Blue Cross Blue Shield insurance plans nationally, with information on prices paid and complications incurred for colonoscopy, knee or shoulder arthroscopy, and cataract removal surgery. METHODS: The data include 1,662,183 patients who received a colonoscopy, 53.5% of whom were treated in HOPDs; 259,200 patients who underwent arthroscopy, 61.0% of whom were treated in HOPDs; and 173,664 patients who had cataract removal surgery, 34.7% of whom were treated in HOPDs. Multivariable linear regression methods were used to identify the associations between HOPD and ASC site of care, prices, and complications after adjusting for patient demographics, risk, and geographic market location. RESULTS: After adjusting for patient characteristics, risk, and geographic market location, prices paid in HOPDs were 54.9% higher than those charged in ASCs for colonoscopy (95% CI, 53.6%-56.1%), 44.4% higher for arthroscopy (95% CI, 43.0%-45.8%), and 44.0% higher for cataract removal surgery (95% CI, 42.9%-45.5%). Adjusted rates of complications were slightly higher in HOPDs than ASCs for colonoscopy over a 90-day interval but similar over the 7- and 30-day intervals. Rates were statistically and clinically similar between the 2 sites of care for arthroscopy and cataract removal. CONCLUSIONS: The higher prices charged in HOPDs for the 3 ambulatory procedures were not balanced by better quality-as measured by rates of procedural complications-compared with procedures performed in nonhospital ASCs.

Altered COVID-19 immunity in children with asthma by atopic status.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a spectrum of clinical outcomes that may be complicated by severe asthma. Antiviral immunity is often compromised in patients with asthma; however, whether this is true for SARS-CoV-2 immunity and children is unknown. Objective: We aimed to evaluate SARS-CoV-2 immunity in children with asthma on the basis of infection or vaccination history and compared to respiratory syncytial viral or allergen (eg, cockroach, dust mite)-specific immunity. Methods: Fifty-three children from an urban asthma study were evaluated for medical history, lung function, and virus- or allergen-specific immunity using antibody or T-cell assays. Results: Polyclonal antibody responses to spike were observed in most children from infection and/or vaccination history. Children with atopic asthma or high allergen-specific IgE, particularly to dust mites, exhibited reduced seroconversion, antibody magnitude, and SARS-CoV-2 virus neutralization after SARS-CoV-2 infection or vaccination. TH1 responses to SARS-CoV-2 and respiratory syncytial virus correlated with antigen-respective IgG. Cockroach-specific T-cell activation as well as IL-17A and IL-21 cytokines negatively correlated with SARS-CoV-2 antibodies and effector functions, distinct from total and dust mite IgE. Allergen-specific IgE and lack of vaccination were associated with recent health care utilization. Reduced lung function (forced expiratory volume in 1 second ≤ 80%) was independently associated with (SARS-CoV-2) peptide-induced cytokines, including IL-31, whereas poor asthma control was associated with cockroach-specific cytokine responses. Conclusion: Mechanisms underpinning atopic and nonatopic asthma may complicate the development of memory to SARS-CoV-2 infection or vaccination and lead to a higher risk of repeated infection in these children.

Wild fish consumption can balance nutrient retention in farmed fish.

Wild fish used as aquafeeds could be redirected towards human consumption to support sustainable marine resource use. Here we use mass-balance fish-in/fish-out ratio approaches to assess nutrient retention in salmon farming and identify scenarios that provide more nutrient-rich food to people. Using data on Norway's salmon farms, our study revealed that six of nine dietary nutrients had higher yields in wild fish used for feeds, such as anchovies and mackerel, than in farmed salmon production. Reallocating one-third of food-grade wild feed fish towards direct human consumption would increase seafood production, while also retaining by-products for use as aquafeeds, thus maximizing nutrient utilization of marine resources.

Satisfactory 5-year functional outcomes following primary ACL reconstructions from the UK National Ligament Registry.

PURPOSE: The aim of this study was to describe the 10-year findings from the UK National Ligament Registry (NLR). METHODS: A retrospective review was performed for prospectively collected data on the NLR between January 2013 and December 2022. All patients who underwent primary ACL reconstruction (ACLR) on the registry were included. Surgical characteristics were analysed, including surgeon grade and case volume, concomitant knee procedures, venous thromboembolic prophylaxis, graft characteristics, femoral and tibial tunnel drilling, and fixation methods. Clinical outcomes were collected preoperatively and at 6 months, 1 year, 2 years and 5 years following the index procedure. RESULTS: During the study period, 17,492 unilateral ACLR procedures were recorded. Autograft was used in 98%, most commonly a combined semitendinosus and gracilis graft (77%) or patella tendon graft (31%). Allograft was used in only 1% of the patients. In 52% of cases, ACLR was associated with an additional procedure, with isolated medial meniscal surgery being the most common (21%). Femoral tunnel drilling was mostly performed through an anteromedial portal (73%) and tibial tunnel drilling using an outside-in technique (92%). The most common method of femoral graft fixation was with an Endobutton fixed loop suspensory device (77%), while interference screws predominated for tibial tunnel fixation (86%). Patients who underwent ACLR surgery showed significant improvement in their functional outcome scores at six months, 1 year, 2 years and 5 years postoperatively. CONCLUSION: Data from the NLR shows a detailed description of the current trends and evolution of ACLR in the United Kingdom over the last 10 years. Satisfactory functional outcomes were observed 5 years postoperatively. This study provides useful information on the prevalence of ACL-associated injuries and current surgical techniques with the aim of improving the quality of clinical care and patients' outcomes. Moreover, it provides surgeons with a benchmark against which to compare current practices and functional outcomes following ACLR across the United Kingdom. LEVEL OF EVIDENCE: Level III.

Isometry of anteromedial reconstructions mimicking the deep medial collateral ligament depends on the femoral insertion.

PURPOSE: This study aimed to investigate the length change patterns of the native deep medial collateral ligament (dMCL) and potential anteromedial reconstructions (AMs) that might be added to a reconstruction of the superficial MCL (sMCL) to better understand the control of anteromedial rotatory instability (AMRI). METHODS: Insertion points of the dMCL and potential AM reconstructions were marked with pins (tibial) and eyelets (femoral) in 11 cadaveric knee specimens. Length changes between the pins and eyelets were then tested using threads in a validated kinematics rig with muscle loading of the quadriceps and iliotibial tract. Between 0° and 100° knee flexion, length change pattern of the anterior, middle and posterior part of the dMCL and simulated AM reconstructions were analysed using a rotary encoder. Isometry was tested using the total strain range (TSR). RESULTS: The tibiofemoral distance of the anterior dMCL part lengthened with flexion (+12.7% at 100°), whereas the posterior part slackened with flexion (-12.9% at 100°). The middle part behaved almost isometrically (maximum length: +2.8% at 100°). Depending on the femoral position within the sMCL footprint, AM reconstructions resulted in an increase in length as the knee flexed when a more centred position was used, irrespective of the tibial attachment position. Femoral positioning in the posterior aspect of the sMCL footprint exhibited <4% length change and was slightly less tight in flexion (min TSR = 3.6 ± 1.5%), irrespective of the tibial attachment position. CONCLUSION: The length change behaviour of potential AM reconstructions in a functionally intact knee is mainly influenced by the position of the femoral attachment, with different tibial attachments having a minimal effect on length change. Surgeons performing AM reconstructions to control AMRI would be advised to choose a femoral graft position in the posterior part of the native sMCL attachment to optimise graft length change behaviour. Given the high frequency of MCL injuries, sufficient restoration of AMRI is essential in isolated and combined ligamentous knee injuries. LEVEL OF EVIDENCE: There is no level of evidence as this study was an experimental laboratory study.

Ten-year results from the UK National Ligament Registry: Patient characteristics and factors predicting nonresponders for completion of outcome scores.

PURPOSE: The aim of this study was to report the demographic and mechanism of injury data in the UK National Ligament Registry (NLR) at 10 years and determine factors leading to poor compliance with completion of Patient-Reported Outcome Scores (PROMs). METHODS: A retrospective review was performed for prospectively collected data on the NLR between January 2013 and December 2022. All patients who underwent primary anterior cruciate ligament reconstruction (ACLR) were included. Patient demographics, mechanism of injury and patient compliance with completing PROMs were analysed. Patient characteristics were further analysed in relation to compliance with completing the different PROMs at the predefined time points. Patients were identified as nonresponders if they had not completed either 1- or 2-year postoperative Knee injury and Osteoarthritis Outcome Score (KOOS). RESULTS: A total of 17,492 patients were included in this study. The average age for patients undergoing ACLR between 2013 and 2022 was 29.4 (SD, 10.3). Seventy percent were men and 30% women. Football was the most common activity associated with an ACL injury. Patient compliance with recording PROMs was 55% preoperatively and 37%, 32% and 24% at 1-, 2- and 5-year postoperative follow-up, respectively. Nonresponders represented 54% of eligible patients. Multivariate analyses showed that sex, age, smoking, time interval between injury and surgery and low socioeconomic status were associated with low compliance with postoperative PROM completion (p < 0.001). CONCLUSION: This study reports the demographic characteristics for patients on the NLR since 2013. Male sex, young age, increased waiting time between injury and surgery, smoking and lower socioeconomic class were predictors of low compliance with completion of postoperative PROMs on the UK NLR. Understanding the factors that affect patient compliance with PROMs improves our ability to provide targeted interventions and information to specific patient populations with the aim of enhancing inclusiveness and representation of population in the registry. LEVEL OF EVIDENCE: Level III.

Multicomponent Synthesis of α-Branched Amines via a Zinc-Mediated Carbonyl Alkylative Amination Reaction.

Methods for the synthesis of α-branched alkylamines are important due to their ubiquity in biologically active molecules. Despite the development of many methods for amine preparation, C(sp3)-rich nitrogen-containing compounds continue to pose challenges for synthesis. While carbonyl reductive amination (CRA) between ketones and alkylamines is the cornerstone method for α-branched alkylamine synthesis, it is sometimes limited by the sterically demanding condensation step between dialkyl ketones and amines and the more restricted availability of ketones compared to aldehydes. We recently reported a "higher-order" variant of this transformation, carbonyl alkylative amination (CAA), which utilized a halogen atom transfer (XAT)-mediated radical mechanism, enabling the streamlined synthesis of complex α-branched alkylamines. Despite the efficacy of this visible-light-driven approach, it displayed scalability issues, and competitive reductive amination was a problem for certain substrate classes, limiting applicability. Here, we report a change in the reaction regime that expands the CAA platform through the realization of an extremely broad zinc-mediated CAA reaction. This new strategy enabled elimination of competitive CRA, simplified purification, and improved reaction scope. Furthermore, this new reaction harnessed carboxylic acid derivatives as alkyl donors and facilitated the synthesis of α-trialkyl tertiary amines, which cannot be accessed via CRA. This Zn-mediated CAA reaction can be carried out at a variety of scales, from a 10 µmol setup in microtiter plates enabling high-throughput experimentation, to the gram-scale synthesis of medicinally-relevant compounds. We believe that this transformation enables robust, efficient, and economical access to α-branched alkylamines and provides a viable alternative to the current benchmark methods.

Biomechanical Comparison of All-Suture, All-Inside Meniscus Repair Devices in a Human Cadaveric Meniscus Model.

OBJECTIVE: Newer all-suture, all-inside meniscus repair devices utilize soft suture anchors. The purpose of this study was to compare the biomechanical performance of 4 meniscus repair devices in human cadaver menisci: the JuggerStitch (all-suture, all-inside), the FiberStitch (all-suture, all-inside), a polyether ether ketone (PEEK) all-inside, and an inside-out device. DESIGN: Forty human cadaver menisci were tested after creating 20 mm longitudinal tears in the posterior meniscus. Each knee was randomized to 1 of 4 meniscus repair groups: JuggerStitch (all-suture, all-inside), FiberStitch (all-suture, all-inside), FAST-FIX 360 (PEEK-based anchor all-inside), and inside-out (with BroadbandTM tape meniscus needles). For each meniscus, 2 devices were used to prepare vertical mattress repair construct. The specimens were tested by pre-conditioning 20 cycles between 5 N and 30 N and then the tear diastasis was measured, followed by distraction to failure phase after imposing a displacement at a rate of 0.5 mm/s. RESULTS: Ten menisci were tested in each of the 4 groups. After pre-conditioning, there was no significant difference in the gap formation among groups (P = 0.212). The average failure load for the JuggerStitch, FiberStitch, PEEK all-inside, and inside-out was 384 N, 311 N, 207 N, and 261 N, respectively, with a significant difference between groups (P = 0.034). Post hoc analysis showed the JuggerStitch failure load was higher than the PEEK all-inside and inside-out (P = 0.005, and P = 0.045, respectively). There was no significant difference between the failure load of the JuggerStitch and FiberStitch (P = 0.225). CONCLUSION: The JuggerStitch all-suture device, FiberStitch all-suture device, PEEK all-inside, and inside-out devices have similar biomechanical properties for gapping and stiffness. The JuggerStitch all-suture, all-inside device has superior failure load compared with the PEEK all-inside and inside-out repair for longitudinal meniscus tear repair.

Facilitating knowledge transfer to policy makers and front-line workers during a pandemic: Implementation, impact and lessons learned.

BACKGROUND: Stakeholders working on the COVID-19 pandemic response needed access to evidence, requiring a systematic approach to identify and disseminate relevant research. OBJECTIVES: Outline the stages of development of a COVID-19 Literature Digest; demonstrate the impact the Digest had on decision-making and knowledge gain; identify the lessons learned. METHODS: A standardised process was developed to identify and select papers. The main sources for content were PubMed, bioRxiv and medRxiv. A shared EndNote library was used to deduplicate and organise papers. Three user surveys obtained feedback from subscribers to determine if the Digest remained valuable, and explore the benefits to individuals. RESULTS: 40-60 papers were summarised each week. 211 Digests were produced from March 2020 to March 2022, with around 10,000 papers included altogether. Survey results suggest benefits of the Digest were gaining new knowledge, saving time and contributing to evidence-based decision making. DISCUSSION: Digest procedures constantly evolved and were adapted in response to survey feedback. Lessons identified: learn from failure, communication is key, measure your impact, work collaboratively, reflect and be flexible. CONCLUSION: The Digest was successfully produced within the limits of available resource. The learning from this Digest will inform evidence monitoring, selection and dissemination for future health crises.

A new method to identify key match-play behaviours of young soccer players: Development of the Hull Soccer Behavioural Scoring Tool.

The aim of this research was to assess the validity and reliability of a newly developed scoring tool, designed for monitoring youth soccer players during match-play performance to support coaches/scouts with the talent identification process. The method used to design the Hull Soccer Behavioural Scoring Tool comprised of a five-stage process of (i) conducting an initial literature review to establish content validity (ii) gaining content validity through a cross sectional online survey (iii) establishing face validity via expert coach feedback (iv) conducting inter-rater reliability tests and (v) intra-rater reliability tests. In stage two, twenty-two soccer academy practitioners completed an online survey, which revealed that player behaviours such as resilience, competitiveness, and decision making were all valued as the most important behavioural characteristics by practitioners (90.9%), whilst X-factor was valued as least important by a significant amount (27.2%). Stages three to five of the testing procedure included a sample of four academy coaches not involved in the preceding stage. Twenty male collegiate soccer players (under-16 to under-18) involved in the study took part in four versus four small-sided games (SSG) in a 'round-robin' tournament across three weeks which accumulated 14 SSG's, 100-140 minutes of playing time and 70-98 individual player grades. Two of the four academy coaches watched the SSG's and used the Hull Soccer Behavioural Scoring Tool to assess live evidence of desirable player behaviours, which was subsequently followed by retrospective video analysis for intra-rater reliability testing. The remaining two academy coaches watched the same SSG retrospective video footage to test for inter-rater reliability. Reliability results revealed an acceptable level of agreement with scores between 81.25%-89.9% for inter-rater whilst intra-rater provided scores between 80.35%-99.4%. Preliminary evidence here suggests that the Hull Soccer Behavioural Scoring Tool is both a valid and reliable method to assess desirable player behaviours during talent identification processes. Thus, youth soccer practitioners and researchers should seek to test and further validate the tool in order to confirm its utility as a means of measuring behavioural characteristics of youth soccer players.

Hospital Prices for Physician-Administered Drugs for Patients with Private Insurance.

BACKGROUND: Hospitals can leverage their position between the ultimate buyers and sellers of drugs to retain a substantial share of insurer pharmaceutical expenditures. METHODS: In this study, we used 2020-2021 national Blue Cross Blue Shield claims data regarding patients in the United States who had drug-infusion visits for oncologic conditions, inflammatory conditions, or blood-cell deficiency disorders. Markups of the reimbursement prices were measured in terms of amounts paid by Blue Cross Blue Shield plans to hospitals and physician practices relative to the amounts paid by these providers to drug manufacturers. Acquisition-price reductions in hospital payments to drug manufacturers were measured in terms of discounts under the federal 340B Drug Pricing Program. We estimated the percentage of Blue Cross Blue Shield drug spending that was received by drug manufacturers and the percentage retained by provider organizations. RESULTS: The study included 404,443 patients in the United States who had 4,727,189 drug-infusion visits. The median price markup (defined as the ratio of the reimbursement price to the acquisition price) for hospitals eligible for 340B discounts was 3.08 (interquartile range, 1.87 to 6.38). After adjustment for drug, patient, and geographic factors, price markups at hospitals eligible for 340B discounts were 6.59 times (95% confidence interval [CI], 6.02 to 7.16) as high as those in independent physician practices, and price markups at noneligible hospitals were 4.34 times (95% CI, 3.77 to 4.90) as high as those in physician practices. Hospitals eligible for 340B discounts retained 64.3% of insurer drug expenditures, whereas hospitals not eligible for 340B discounts retained 44.8% and independent physician practices retained 19.1%. CONCLUSIONS: This study showed that hospitals imposed large price markups and retained a substantial share of total insurer spending on physician-administered drugs for patients with private insurance. The effects were especially large for hospitals eligible for discounts under the federal 340B Drug Pricing Program on acquisition costs paid to manufacturers. (Funded by Arnold Ventures and the National Institute for Health Care Management.).

Barriers to Office Hysteroscopy in Fellowship Education and Practice.

STUDY OBJECTIVE: To identify the top 3 perceived barriers to performing office hysteroscopy (OH) by minimally invasive gynecologic surgery (MIGS) faculty and fellows and identify opportunities for education on this key topic that will be most effective in fellowship training and MIGS practice. DESIGN: Cross-sectional survey study targeted at all American Association of Gynecologic Laparoscopists-accredited Fellowship in Minimally Invasive Gynecologic Surgery fellows, program directors, and associate program directors in February to April 2022. The survey was designed by faculty who have extensive experience in OH procedures. In addition, a literature search was performed to aid with question design. SETTING, PATIENTS, AND INTERVENTIONS: This was a REDCap electronic survey administered through the Fellowship in Minimally Invasive Gynecologic Surgery listserv. No additional follow-up was performed after survey completion. The 15-minute survey was sent to 60 program directors, 92 assistant program directors, and 158 fellows, including the incoming class of 2024 and the 2022 fellowship graduates. MEASUREMENTS AND MAIN RESULTS: A total of 93 responses were received; 67% of respondents performed OH but 73% of those performed 5 procedures or less per month. Most participants controlled pain with nonsteroidal anti-inflammatory drugs +/- paracervical block. The most common perceived barrier to performing OH was concern over pain management. Other commonly cited concerns were equipment costs, sterilization costs, and office staff training; 37% to 44% of respondents also cited lack of departmental support and insufficient clinic time, respectively, as barriers, and 56% indicated they are interested in educational materials on OH. CONCLUSION: Our study suggests general interest in, but a low volume of, OH among MIGS fellows and faculty. The most common perceived barrier was concern regarding pain management. This has been well studied in the literature and likely presents an area for greater education to improve OH utilization. We also uncovered concerns regarding systemic barriers, such as equipment costs, departmental support, and clinic structure. This is an area for further research and advocacy efforts to address barriers to OH on a system level.

Passive antibody transfer from pregnant women to their fetus are maximized after SARS-CoV-2 vaccination irrespective of prior infection.

Background: Pregnancy is associated with a higher risk of adverse symptoms and outcomes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for both mother and neonate. Antibodies can provide protection against SARS-CoV-2 infection and are induced in pregnant women after vaccination or infection. Passive transfer of these antibodies from mother to fetus in utero may provide protection to the neonate against infection. However, it is unclear whether the magnitude or quality and kinetics of maternally derived fetal antibodies differs in the context of maternal infection or vaccination. Objective: We aimed to determine whether antibodies transferred from maternal to fetus differed in quality or quantity between infection- or vaccination-induced humoral immune responses. Methods: We evaluated 93 paired maternal and neonatal umbilical cord blood plasma samples collected between October 2020 and February 2022 from a birth cohort of pregnant women from New Orleans, Louisiana, with histories of SARS-CoV-2 infection and/or vaccination. Plasma was profiled for the levels of spike-specific antibodies and induction of antiviral humoral immune functions, including neutralization and Fc-mediated innate immune effector functions. Responses were compared between 4 groups according to maternal infection and vaccination. Results: We found that SARS-CoV-2 vaccination or infection during pregnancy increased the levels of antiviral antibodies compared to naive subjects. Vaccinated mothers and cord samples had the highest anti-spike antibody levels and antiviral function independent of the time of vaccination during pregnancy. Conclusions: These results show that the most effective passive transfer of functional antibodies against SARS-CoV-2 in utero is achieved through vaccination, highlighting the importance of vaccination in pregnant women.

Fifty novel HLA-DPB1 alleles identified in a UK cohort of unrelated hematopoietic cell donors and recipients.

HLA-DPB1 is the classical HLA class II genes with the least recorded variation on the IPD-IMGT/HLA Database, suggesting the full extent of its diversity is perhaps yet to be characterized. Here, a full-gene typing strategy was employed to genotype a UK cohort of 1470 HCT recipients (n = 744) and donors (n = 726). In total, 2940 full-length HLA-DPB1 sequences were generated, comprising 193 distinct alleles. Of these, 107 sequences contained novel variation, totaling 49 unique intronic HLA-DPB1 alleles, and one coding variant (HLA-DPB1*1188:01). Full-gene sequencing resulted in zygosity changes for 129 individuals by identifying two distinct intronic variants of the same coding allele. We verified the existence of nine unconfirmed alleles and extended the sequence of two existing alleles on the IPD-IMGT/HLA Database.

The impact of bariatric surgery on liver enzymes in people with obesity: A 5-year observational study.

BACKGROUND AND PURPOSE: Non-alcoholic fatty liver disease (NAFLD) has increasing worldwide prevalence, fuelled by rising obesity rates, and weight reduction is the mainstay of its management. We sought to study the effect of bariatric surgery, the most effective long-term treatment for obesity and associated metabolic disorders, on liver function in people with obesity. METHODS: We performed a retrospective longitudinal cohort study of 511 patients who had undergone bariatric surgery (71 sleeve gastrectomy and 440 gastric bypass) over 60 months of follow-up. Patients were stratified into groups based on their baseline alanine aminotransferase (ALT) into Group A (ALT < 40 U/L) and Group B (ALT > 40 U/L). Postoperative follow-up weight loss, liver function tests, HbA1c, blood pressure and lipid profiles were collected. FINDINGS: Bariatric surgery resulted in nadir total weight loss of 33.1% by 24 months (p < 0.001) with no significant difference between groups. In people with raised baseline ALT (Group B), ALT and gamma glutamyl transferase (GGT) levels decreased significantly by 4 months postoperatively (p < 0.001) and sustained over 60 months of follow-up. There was also significant and sustained reduction in HbA1c, blood pressure, total cholesterol, and non-HDL cholesterol overall with no differences between groups. CONCLUSIONS: Bariatric surgery results in significant weight loss, improves liver function tests and metabolic outcomes in people with obesity. Bariatric surgery could be a therapeutic consideration for patients with NAFLD associated with severe obesity who have otherwise been unresponsive to conservative management.

Prenatal Infection by Respiratory Viruses Is Associated With Immuno-Inflammatory Responses in the Fetus.

RATIONALE: Respiratory viral infections can be transmitted from pregnant women to their offspring, but frequency, mechanisms, and postnatal outcomes remain unclear. OBJECTIVES: This prospective cohort study compared frequencies of transplacental transmission of respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), analyzed the concentrations of inflammatory mediators in maternal and fetal blood, and assessed clinical consequences. METHODS: We recruited pregnant women who developed upper respiratory infections or tested positive for SARS-CoV-2. Maternal and cord blood samples were collected at delivery. Study questionnaires and electronic medical records were used to document demographic and medical information. RESULTS: From October 2020 to June 2022, droplet digital (dd)PCR was used to test blood mononuclear cells of 103 mother-baby dyads. Twice more newborns in our sample were vertically infected with RSV compared to SARS-CoV-2 (25.2% (26/103) versus 11.9% (12/101), p = 0.019). Multiplex ELISA measured significantly increased concentrations of several inflammatory cytokines and chemokines in maternal and cord blood from newborns with evidence of viral exposure in utero compared to the control dyads group. Prenatal infection was associated with significantly lower birth weight and postnatal weight growth. CONCLUSIONS: Data suggest a higher frequency of vertical transmission for RSV than SARS-CoV-2. Intrauterine exposure is associated with fetal inflammation driven by soluble inflammatory mediators with expression profiles dependent on the virus type and affecting the rate of viral transmission. Virus-induced inflammation may have pathological consequences already in the first days of life, as shown by its effects on birth weight and postnatal weight growth. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Quantifying energy and nutrient fluxes in coral reef food webs.

The movement of energy and nutrients through ecological communities represents the biological 'pulse' underpinning ecosystem functioning and services. However, energy and nutrient fluxes are inherently difficult to observe, particularly in high-diversity systems such as coral reefs. We review advances in the quantification of fluxes in coral reef fishes, focusing on four key frameworks: demographic modelling, bioenergetics, micronutrients, and compound-specific stable isotope analysis (CSIA). Each framework can be integrated with underwater surveys, enabling researchers to scale organismal processes to ecosystem properties. This has revealed how small fish support biomass turnover, pelagic subsidies sustain fisheries, and fisheries benefit human health. Combining frameworks, closing data gaps, and expansion to other aquatic ecosystems can advance understanding of how fishes contribute to ecosystem functions and services.

Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastoma.

Circular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution of drug resistance and poor patient outcomes. Applying computational methods for the detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma tumors from 465 patients, we identify circular ecDNA in 82 patients (18%). Patients with ecDNA-positive medulloblastoma were more than twice as likely to relapse and three times as likely to die within 5 years of diagnosis. A subset of tumors harbored multiple ecDNA lineages, each containing distinct amplified oncogenes. Multimodal sequencing, imaging and CRISPR inhibition experiments in medulloblastoma models reveal intratumoral heterogeneity of ecDNA copy number per cell and frequent putative 'enhancer rewiring' events on ecDNA. This study reveals the frequency and diversity of ecDNA in medulloblastoma, stratified into molecular subgroups, and suggests copy number heterogeneity and enhancer rewiring as oncogenic features of ecDNA.