CSF proteomics identifies early changes in autosomal dominant Alzheimer's disease.

In this high-throughput proteomic study of autosomal dominant Alzheimer's disease (ADAD), we sought to identify early biomarkers in cerebrospinal fluid (CSF) for disease monitoring and treatment strategies. We examined CSF proteins in 286 mutation carriers (MCs) and 177 non-carriers (NCs). The developed multi-layer regression model distinguished proteins with different pseudo-trajectories between these groups. We validated our findings with independent ADAD as well as sporadic AD datasets and employed machine learning to develop and validate predictive models. Our study identified 137 proteins with distinct trajectories between MCs and NCs, including eight that changed before traditional AD biomarkers. These proteins are grouped into three stages: early stage (stress response, glutamate metabolism, neuron mitochondrial damage), middle stage (neuronal death, apoptosis), and late presymptomatic stage (microglial changes, cell communication). The predictive model revealed a six-protein subset that more effectively differentiated MCs from NCs, compared with conventional biomarkers.

Capturing the fusion of two ancestries and kinship structures in Merovingian Flanders.

The Merovingian period (5th to 8th cc AD) was a time of demographic, socioeconomic, cultural, and political realignment in Western Europe. Here, we report the whole-genome shotgun sequence data of 30 human skeletal remains from a coastal Late Merovingian site of Koksijde (675 to 750 AD), alongside 18 remains from two Early to Late Medieval sites in present-day Flanders, Belgium. We find two distinct ancestries, one shared with Early Medieval England and the Netherlands, while the other, minor component, reflecting likely continental Gaulish ancestry. Kinship analyses identified no large pedigrees characteristic to elite burials revealing instead a high modularity of distant relationships among individuals of the main ancestry group. In contrast, individuals with >90% Gaulish ancestry had no kinship links among sampled individuals. Evidence for population structure and major differences in the extent of Gaulish ancestry in the main group, including in a mother-daughter pair, suggests ongoing admixture in the community at the time of their burial. The isotopic and genetic evidence combined supports a model by which the burials, representing an established coastal nonelite community, had incorporated migrants from inland populations. The main group of burials at Koksijde shows an abundance of >5 cM long shared allelic intervals with the High Medieval site nearby, implying long-term continuity and suggesting that similarly to Britain, the Early Medieval ancestry shifts left a significant and long-lasting impact on the genetic makeup of the Flemish population. We find substantial allele frequency differences between the two ancestry groups in pigmentation and diet-associated variants, including those linked with lactase persistence, likely reflecting ancestry change rather than local adaptation.

Glycan-Imprinted Nanoparticle as Artificial Neutralizing Antibody for Efficient HIV-1 Recognition and Inhibition.

The HIV-1 envelope is a heavily glycosylated class 1 trimeric fusion protein responsible for viral entry into CD4+ immune cells. Developing neutralizing antibodies against the specific envelope glycans is an alternative method for antiviral therapies. This work presents the first-ever development and characterization of artificial neutralizing antibodies using molecular imprinting technology to recognize and bind to the envelope protein of HIV-1. The prepared envelope glycan-imprinted nanoparticles (GINPs) can successfully prevent HIV-1 from infecting target cells by shielding the glycans on the envelope protein. In vitro experiments showed that GINPs have strong affinity toward HIV-1 (Kd = 36.7 ± 2.2 nM) and possess high anti-interference and specificity. GINPs demonstrate broad inhibition activity against both tier 1 and tier 2 HIV-1 strains with a pM-level IC50 and exhibit a significant inhibitory effect on long-term viral replication by more than 95%. The strategy provides a promising method for the inhibition and therapy of HIV-1 infection.

Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS).

Surgery is the standard of care for patients with primary renal cell carcinoma. Stereotactic body radiotherapy (SBRT) is a novel alternative for patients who are medically inoperable, technically high risk, or who decline surgery. Evidence for using SBRT in the primary renal cell carcinoma setting is growing, including several rigorously conducted prospective clinical trials. This systematic review was performed to assess the safety and efficacy of SBRT for primary renal cell carcinoma. Review results then formed the basis for the practice guidelines described, on behalf of the International Stereotactic Radiosurgery Society. 3972 publications were screened and 36 studies (822 patients) were included in the analysis. Median local control rate was 94·1% (range 70·0-100), 5-year progression-free survival was 80·5% (95% CI 72-92), and 5-year overall survival was 77·2% (95% CI 65-89). These practice guidelines addressed four key clinical questions. First, the optimal dose fractionation was 25-26 Gy in one fraction, or 42-48 Gy in three fractions for larger tumours. Second, routine post-treatment biopsy is not recommended as it is not predictive of patient outcome. Third, SBRT for primary renal cell carcinoma in a solitary kidney is safe and effective. Finally, guidelines for post-treatment follow-up are described, which include cross-axial imaging of the abdomen including both kidneys, adrenals, and surveillance of the chest initially every 6 months. This systematic review and practice guideline support the practice of SBRT for primary renal cell carcinoma as a safe and effective standard treatment option. Randomised trials with surgery and invasive ablative therapies are needed to further define best practice.

Genome wide analysis of carotenoid cleavage oxygenases (CCO) gene family in Arachis hypogaea (peanut) under biotic stress.

Carotenoid cleavage oxygenases (CCOs) enzymes play a vital role in plant growth and development through the synthesis of apocarotenoids and their derivative. These chemicals are necessary for flower and fruit coloration, as well as the manufacture of plant hormones such as abscisic acid (ABA) and strigolactones, which control a variety of physiological processes. The CCOs gene family has not been characterized in Arachis hypogaea. Genome mining of A. hypogaea identifies 24 AhCCO gene members. The AhCCO gene family was divided into two subgroups based on the recent study of the Arabidopsis thaliana CCO gene family classification system. Twenty-three AhCCO genes, constituting 95.8% of the total, were regulated by 29 miRNAs, underscoring the significance of microRNAs (miRNAs) in governing gene expression in peanuts. AhCCD19 is the only gene that lacks a miRNA target site. The physicochemical characteristics of CCO genes and their molecular weights and isoelectric points were studied further. The genes were then characterized regarding chromosomal distribution, structure, and promoter cis-elements. Light, stress development, drought stress, and hormone responsiveness were discovered to be associated with AhCCO genes, which can be utilized in developing more resilient crops. The investigation also showed the cellular location of the encoded proteins and discovered that the peanut carotenoid oxygenase gene family's expansion was most likely the result of tandem, segmental, and whole-genome duplication events. The localization expresses the abundance of genes mostly in the cytoplasm and chloroplast. Expression analysis shows that AhCCD7 and AhCCD14 genes show the maximum expression in the apical meristem, lateral leaf, and pentafoliate leaf development, while AhNCED9 and AhNCED13 express in response to Aspergillus flavus resistance. This knowledge throws light on the evolutionary history of the AhCCO gene family and may help researchers better understand the molecular processes behind gene duplication occurrences in plants. An integrated synteny study was used to find orthologous carotenoid oxygenase genes in A. hypogaea, whereas Arabidopsis thaliana and Beta vulgaris were used as references for the functional characterization of peanut CCO genes. These studies provide a foundation for future research on the regulation and functions of this gene family. This information provides valuable insights into the genetic regulation of AhCCO genes. This technology could create molecular markers for breeding programs to develop new peanut lines.

Harmonization of CSF and imaging biomarkers in Alzheimer's disease: Need and practical applications for genetics studies and preclinical classification.

In Alzheimer's disease (AD) research, cerebrospinal fluid (CSF) Amyloid beta (Aß), Tau and pTau are the most accepted and well validated biomarkers. Several methods and platforms exist to measure those biomarkers, leading to challenges in combining data across studies. Thus, there is a need to identify methods that harmonize and standardize these values. We used a Z-score based approach to harmonize CSF and amyloid imaging data from multiple cohorts and compared GWAS results using this approach with currently accepted methods. We also used a generalized mixture model to calculate the threshold for biomarker-positivity. Based on our findings, our normalization approach performed as well as meta-analysis and did not lead to any spurious results. In terms of dichotomization, cutoffs calculated with this approach were very similar to those reported previously. These findings show that the Z-score based harmonization approach can be applied to heterogeneous platforms and provides biomarker cut-offs consistent with the classical approaches without requiring any additional data.

Clinical trials and recent progress in HIV vaccine development.

The greatest obstacle for scientists is to develop an effective HIV vaccine. An effective vaccine represents the last hope for halting the unstoppable global spread of HIV and its catastrophic clinical consequences. Creating this vaccine has been challenging due to the virus's extensive genetic variability and the unique role of cytotoxic T lymphocytes (CTL) in containing it. Innovative methods to stimulate CTL have demonstrated significant therapeutic advantages in nonhuman primate model systems, unlike traditional vaccination techniques that are not expected to provide safe and efficient protection against HIV. Human clinical trials are currently evaluating these vaccination strategies, which involve plasmid DNA and live recombinant vectors. This review article covers the existing vaccines and ongoing trial vaccines. It also explores the different approaches used in developing HIV vaccines, including their molecular mechanisms, target site effectiveness, and potential side effects.

Monoallelic and bi-allelic variants in NCDN cause neurodevelopmental delay, intellectual disability, and epilepsy.

Neurochondrin (NCDN) is a cytoplasmatic neural protein of importance for neural growth, glutamate receptor (mGluR) signaling, and synaptic plasticity. Conditional loss of Ncdn in mice neural tissue causes depressive-like behaviors, impaired spatial learning, and epileptic seizures. We report on NCDN missense variants in six affected individuals with variable degrees of developmental delay, intellectual disability (ID), and seizures. Three siblings were found homozygous for a NCDN missense variant, whereas another three unrelated individuals carried different de novo missense variants in NCDN. We assayed the missense variants for their capability to rescue impaired neurite formation in human neuroblastoma (SH-SY5Y) cells depleted of NCDN. Overexpression of wild-type NCDN rescued the neurite-phenotype in contrast to expression of NCDN containing the variants of affected individuals. Two missense variants, associated with severe neurodevelopmental features and epilepsy, were unable to restore mGluR5-induced ERK phosphorylation. Electrophysiological analysis of SH-SY5Y cells depleted of NCDN exhibited altered membrane potential and impaired action potentials at repolarization, suggesting NCDN to be required for normal biophysical properties. Using available transcriptome data from human fetal cortex, we show that NCDN is highly expressed in maturing excitatory neurons. In combination, our data provide evidence that bi-allelic and de novo variants in NCDN cause a clinically variable form of neurodevelopmental delay and epilepsy, highlighting a critical role for NCDN in human brain development.

Improved chickpea growth, physiology, nutrient assimilation and rhizoremediation of hydrocarbons by bacterial consortia.

BACKGROUND: Soil pollution by petroleum hydrocarbons (PHCs) reduces yield by changing the physico-chemical properties of soil and plants due to PHCs' biotoxicity and persistence. Thus, removing PHCs from the soil is crucial for ecological sustainability. Microbes-assisted phytoremediation is an economical and eco-friendly solution. The current work aimed to develop and use bacterial consortia (BC) for PHCs degradation and plant growth enhancement in hydrocarbon-contaminated soil. Initially, the enriched microbial cultures (that were prepared from PHCs-contaminated soils from five distinct regions) were obtained via screening through microcosm experiments. Afterward, two best microbial cultures were tested for PHCs degradation under various temperature and pH ranges. After culture optimization, isolation and characterization of bacterial strains were done to construct two BC. These constructed BC were tested in a pot experiment for hydrocarbons degradation and chickpea growth in PHCs contaminated soil. RESULTS: Findings revealed that PHCs exerted significant phytotoxic effects on chickpea growth and physiology when cultivated in PHCs contaminated soil, reducing agronomic and physiological traits by 13-29% and 12-43%, respectively. However, in the presence of BC, the phytotoxic impacts of PHCs on chickpea plants were reduced, resulting in up to 24 - 35% improvement in agronomic and physiological characteristics as compared to un-inoculated contaminated controls. Furthermore, the bacterial consortia boosted chickpea's nutritional absorption and antioxidant mechanism. Most importantly, chickpea plants phytoremediated 52% of the initial PHCs concentration; however, adding BC1 and BC2 with chickpea plants further increased this removal and remediated 74% and 80% of the initial PHCs concentration, respectively. CONCLUSION: In general, BC2 outperformed BC1 (with few exceptions) in promoting plant growth and PHCs elimination. Therefore, using multi-trait BC for PHCs degradation and plant growth improvement under PHCs stress may be an efficient and environmentally friendly strategy to deal with PHCs pollution and toxicity.

Enhanced wheat productivity in saline soil through the combined application of poultry manure and beneficial microbes.

BACKGROUND: Soil salinity is one of the major menaces to food security, particularly in dealing with the food demand of the ever-increasing global population. Production of cereal crops such as wheat is severely affected by soil salinity and improper fertilization. The present study aimed to examine the effect of selected microbes and poultry manure (PM) on seedling emergence, physiology, nutrient uptake, and growth of wheat in saline soil. A pot experiment was carried out in research area of Institute of Soil and Environmental Sciences, University of Agriculture, Faisalabad, Pakistan. Saline soil (12 dS m- 1 w/w) was developed by spiking using sodium chloride, and used in experiment along with two microbial strains (i.e., Alcaligenes faecalis MH-2 and Achromobacter denitrificans MH-6) and PM. Finally, wheat seeds (variety Akbar-2019) were sown in amended and unamended soil, and pots were placed following a completely randomized design. The wheat crop was harvested after 140 days of sowing. RESULTS: The results showed a 10-39% increase (compared to non-saline control) in agronomic, physiological, and nutritive attributes of wheat plants when augmented with PM and microbes. Microbes together with PM significantly enhanced seedling emergence (up to 38%), agronomic (up to 36%), and physiological (up to 33%) in saline soil as compared to their respective unamended control. Moreover, the co-use of microbes and PM also improved soil's physicochemical attributes and enhanced N (i.e., 21.7%-17.1%), P (i.e., 24.1-29.3%), and K (i.e., 28.7%-25.3%) availability to the plant (roots and shoots, respectively). Similarly, the co-use of amendments also lowered the Na+ contents in soil (i.e., up to 62%) as compared to unamended saline control. This is the first study reporting the effects of the co-addition of newly identified salt-tolerant bacterial strains and PM on seedling emergence, physiology, nutrient uptake, and growth of wheat in highly saline soil. CONCLUSION: Our findings suggest that co-using a multi-trait bacterial culture and PM could be an appropriate option for sustainable crop production in salt-affected soil.

Xanthan gum-based edible coating effectively preserve postharvest quality of 'Gola' guava fruits by regulating physiological and biochemical processes.

BACKGROUND: Guava is a fruit prone to rapid spoilage following harvest, attributed to continuous and swift physicochemical transformations, leading to substantial postharvest losses. This study explored the efficacy of xanthan gum (XG) coatings applied at various concentrations (0.25, 0.5, and 0.75%) on guava fruits (Gola cultivar) over a 15-day storage period. RESULTS: The results indicated that XG coatings, particularly at 0.75%, substantially mitigated moisture loss and decay, presenting an optimal concentration. The coated fruits exhibited a modified total soluble soluble solids, an increased total titratable acidity, and an enhanced sugar-acid ratio, collectively enhancing overall quality. Furthermore, the XG coatings demonstrated the remarkable ability to preserve bioactive compounds, such as total phenolics, flavonoids, and antioxidants, while minimizing the levels of oxidative stress markers, such as electrolyte leakage, malondialdehyde, and H2O2. The coatings also influenced cell wall components, maintaining levels of hemicellulose, cellulose, and protopectin while reducing water-soluble pectin. Quantitative analysis of ROS-scavenging enzymes, including superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase, revealed significant increases in their activities in the XG-coated fruits compared to those in the control fruits. Specifically, on day 15, the 0.75% XG coating demonstrated the highest SOD and CAT activities while minimizing the reduction in APX activity. Moreover, XG coatings mitigated the activities of fruit-softening enzymes, including pectin methylesterase, polygalacturonase, and cellulase. CONCLUSIONS: This study concludes that XG coatings play a crucial role in preserving postharvest quality of guava fruits by regulating various physiological and biochemical processes. These findings offer valuable insights into the potential application of XG as a natural coating to extend the shelf life and maintain the quality of guava fruits during storage.

Alleviating salinity stress in canola (Brassica napus L.) through exogenous application of salicylic acid.

Canola, a vital oilseed crop, is grown globally for food and biodiesel. With the enormous demand for growing various crops, the utilization of agriculturally marginal lands is emerging as an attractive alternative, including brackish-saline transitional lands. Salinity is a major abiotic stress limiting growth and productivity of most crops, and causing food insecurity. Salicylic acid (SA), a small-molecule phenolic compound, is an essential plant defense phytohormone that promotes immunity against pathogens. Recently, several studies have reported that SA was able to improve plant resilience to withstand high salinity. For this purpose, a pot experiment was carried out to ameliorate the negative effects of sodium chloride (NaCl) on canola plants through foliar application of SA. Two canola varieties Faisal (V1) and Super (V2) were assessed for their growth performance during exposure to high salinity i.e. 0 mM NaCl (control) and 200 mM NaCl. Three levels of SA (0, 10, and 20 mM) were applied through foliar spray. The experimental design used for this study was completely randomized design (CRD) with three replicates. The salt stress reduced the shoot and root fresh weights up to 50.3% and 47% respectively. In addition, foliar chlorophyll a and b contents decreased up to 61-65%. Meanwhile, SA treatment diminished the negative effects of salinity and enhanced the shoot fresh weight (49.5%), root dry weight (70%), chl. a (36%) and chl. b (67%). Plants treated with SA showed an increased levels of both enzymatic i.e. (superoxide dismutase (27%), peroxidase (16%) and catalase (34%)) and non-enzymatic antioxidants i.e. total soluble protein (20%), total soluble sugar (17%), total phenolic (22%) flavonoids (19%), anthocyanin (23%), and endogenous ascorbic acid (23%). Application of SA also increased the levels of osmolytes i.e. glycine betaine (31%) and total free proline (24%). Salinity increased the concentration of Na+ ions and concomitantly decreased the K+ and Ca2+ absorption in canola plants. Overall, the foliar treatments of SA were quite effective in reducing the negative effects of salinity. By comparing both varieties of canola, it was observed that variety V2 (Super) grew better than variety V1 (Faisal). Interestingly, 20 mM foliar application of SA proved to be effective in ameliorating the negative effects of high salinity in canola plants.

Exogenous ascorbic acid as a potent regulator of antioxidants, osmo-protectants, and lipid peroxidation in pea under salt stress.

Pea (Pisum sativum L.), a globally cultivated leguminous crop valued for its nutritional and economic significance, faces a critical challenge of soil salinity, which significantly hampers crop growth and production worldwide. A pot experiment was carried out in the Botanical Garden, The Islamia University of Bahawalpur to alleviate the negative impacts of sodium chloride (NaCl) on pea through foliar application of ascorbic acid (AsA). Two pea varieties Meteor (V1) and Sarsabz (V2) were tested against salinity, i.e. 0 mM NaCl (Control) and 100 mM NaCl. Three levels of ascorbic acid 0 (Control), 5 and 10 mM were applied through foliar spray. The experimental design was completely randomized (CRD) with three replicates. Salt stress resulted in the suppression of growth, photosynthetic activity, and yield attributes in pea plants. However, the application of AsA treatments effectively alleviated these inhibitory effects. Under stress conditions, the application of AsA treatment led to a substantial increase in chlorophyll a (41.1%), chl. b (56.1%), total chl. contents (44.6%) and carotenoids (58.4%). Under salt stress, there was an increase in Na+ accumulation, lipid peroxidation, and the generation of reactive oxygen species (ROS). However, the application of AsA increased the contents of proline (26.9%), endogenous AsA (23.1%), total soluble sugars (17.1%), total phenolics (29.7%), and enzymatic antioxidants i.e. SOD (22.3%), POD (34.1%) and CAT (39%) in both varieties under stress. Salinity reduced the yield attributes while foliarly applied AsA increased the pod length (38.7%), number of pods per plant (40%) and 100 seed weight (45.2%). To sum up, the application of AsA alleviated salt-induced damage in pea plants by enhancing photosynthetic pigments, both enzymatic and non-enzymatic activities, maintaining ion homeostasis, and reducing excessive ROS accumulation through the limitation of lipid peroxidation. Overall, V2 (Sarsabz) performed better as compared to the V1 (Meteor).

Advanced High-Energy All-Solid-State Hybrid Supercapacitor with Nickel-Cobalt-Layered Double Hydroxide Nanoflowers Supported on Jute Stick-Derived Activated Carbon Nanosheets.

Developing efficient, lightweight, and durable all-solid-state supercapacitors is crucial for future energy storage systems. The study focuses on optimizing electrode materials to achieve high capacitance and stability. This study introduces a novel two-step pyrolysis process to synthesize activated carbon nanosheets from jute sticks (JAC), resulting in an optimized JAC-2 material with a high yield (≈24%) and specific surface area (≈2600 m2 g-1). Furthermore, an innovative in situ synthesis approach is employed to synthesize hybrid nanocomposites (NiCoLDH-1@JAC-2) by integrating JAC nanosheets with nickel-cobalt-layered double hydroxide nanoflowers (NiCoLDH). These nanocomposites serve as positive electrode materials and JAC-2 as the negative electrode material in all-solid-state asymmetric hybrid supercapacitors (HSCs), exhibiting remarkable performance metrics. The HSCs achieve a specific capacitance of 750 F g-1, a specific capacity of 209 mAh g-1 (at 0.5 A g-1), and an energy density of 100 Wh kg-1 (at 250 W kg-1) using PVA/KOH solid electrolyte, while maintaining outstanding cyclic stability. Importantly, a density functional theory framework is utilized to validate the experimental findings, underscoring the potential of this novel approach for enhancing HSC performance and enabling the large-scale production of transition metal-based layered double hydroxides.

Se-p Orbitals Induced "Strong d-d Orbitals Interaction" Enable High Reversibility of Se-Rich ZnSe/MnSe@C Electrode as Excellent Host for Sodium-Ion Storage.

The heterostructure of transition-metal chalcogenides is a promising approach to boost alkali ion storage due to fast charge kinetics and reduction of activation energy. However, cycling performance is a paramount challenge that is suffering from poor reversibility. Herein, it is reported that Se-rich particles can chemically interact with local hexagonal ZnSe/MnSe@C heterostructure environment, leading to effective ions insertion/extraction, enabling high reversibility. Enlightened by theoretical understanding, Se-rich particles endow high intrinsic conductivities in term of low energy barriers (1.32 eV) compared with those without Se-rich particles (1.50 eV) toward the sodiation process. Moreover, p orbitals of Se-rich particles may actively participate and further increase the electronegativity that pushes the Mn d orbitals (dxy and dx2-y2) and donate their electrons to dxz and dyz orbitals, manifesting strong d-d orbitals interaction between ZnSe and MnSe. Such fundamental interaction will adopt a well-stable conducive electronic bridge, eventually, charges are easily transferred from ZnSe to MnSe in the heterostructure during sodiation/desodiation. Therefore, the optimized Se-rich ZnSe/MnSe@C electrode delivered high capacity of 576 mAh g-1 at 0.1 A g-1 after 100 cycles and 384 mAh g-1 at 1 A g-1 after 2500 cycles, respectively. In situ and ex situ measurements further indicate the integrity and reversibility of the electrode materials upon charging/discharging.

Unraveling Clinical Glycoproteome by Integrating Affinity Enrichment with Nanopore Sequencing.

This prospect explores the integration of enrichment strategies with nanopore detection to advance clinical glycoproteomics. Glycoproteins, crucial for understanding biological processes, pose challenges due to their low abundance and structural diversity. Enrichment techniques using lectin affinity, boronate affinity, and hydrazide chemistry and especially molecular imprinted polymers may selectively and specifically isolate glycoproteins from complex samples, while nanopore technology enables label-free, real-time, and single-molecule analysis. This approach holds promise for disease-related glycosylation studies, biomarker discovery, personalized medicine, and streamlined clinical analysis. Standardization, optimization, and data analysis remain challenges, requiring interdisciplinary collaborations and technological advancements. Overall, this integration may offer transformative potential for clinical glycoproteomics and innovative diagnostic and therapeutic strategies.

Early Endophthalmitis Incidence and Risk Factors after Glaucoma Surgery in the Medicare Population from 2016 to 2019.

PURPOSE: To determine early endophthalmitis incidence and risk factors after glaucoma surgeries in the Medicare population. DESIGN: Retrospective, longitudinal study. PARTICIPANTS: Medicare Fee-for-Service (FFS) and Medicare Advantage beneficiaries in the United States aged 65 years or older undergoing glaucoma surgery. METHODS: Medicare claims were used to identify all patients who underwent glaucoma, cataract, or combined cataract/glaucoma surgery from 2016 to 2019. Endophthalmitis cases within 42 days of the index surgery were identified using the diagnostic codes. Multivariable logistic regression models were used to evaluate factors associated with postoperative endophthalmitis. MAIN OUTCOME MEASURES: The 42-day postoperative endophthalmitis incidence and risk factors associated with endophthalmitis after glaucoma surgery. RESULTS: There were 466 928 glaucoma surgeries, of which 310 823 (66.6%) were combined with cataract surgery. Cataract surgeries alone (n = 8 460 360) served as a reference group. Microinvasive glaucoma surgeries constituted most glaucoma procedures performed (67.8%), followed by trabeculectomy (14.0%), tube shunt (10.9%), and other procedures (7.3%). There were 572 cases of endophthalmitis identified after all glaucoma surgeries. Endophthalmitis incidence after glaucoma, combined cataract/glaucoma, and cataract surgeries alone was 1.5 (95% confidence interval [CI], 1.3-1.7), 1.1 (95% CI, 1.0-1.2), and 0.8 (95% CI, 0.8-0.8) per 1000 procedures, respectively. The median day of diagnosis of endophthalmitis was later for glaucoma surgeries (16.5 days) compared with combined cataract/glaucoma or cataract surgeries alone (8 and 6 days, respectively). Compared with microinvasive glaucoma surgery (MIGS), tube shunts were the only surgery type to be a significant risk factor for endophthalmitis for both stand-alone (adjusted odds ratio [aOR], 1.8, P = 0.002) and combined surgery (aOR 1.8, P = 0.047). The other risk factor for both stand-alone (aOR 1.1, P = 0.001) and combined (aOR 1.06, P = 0.049) surgeries was the Charlson Comorbidity Index (CCI). Age (aOR 1.03, P = 0.004) and male gender (1.46, P = 0.001) were significant risk factors for combined cataract and glaucoma surgeries. CONCLUSIONS: Compared with cataract surgery, early endophthalmitis incidence was higher for both glaucoma and combined cataract/glaucoma surgeries, with the highest incidence among tube shunts. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Biosensors with left ventricular assist devices.

Heart failure imposes a significant global health burden, standing as a primary contributor to mortality. Various indicators and physiological shifts within the body may hint at distinct cardiac conditions. Specific biosensors have the capability to identify these changes. Integrating or embedding these biosensors into mechanical circulatory support devices (MCSDs), such as left ventricular assist devices (LVADs), becomes crucial for monitoring alterations in biochemical and physiological factors subsequent to an MCSD implantation. Detecting abnormal changes early in the course of disease progression will allow for improved patient outcomes and prognosis following an MCSD implantation. The aim of this review is to explore the available biosensors that may be coupled or implanted alongside LVADs to monitor biomarkers and changes in physiological parameters. Different fabrication materials for the biosensors are discussed, including their advantages and disadvantages. This review also examines the feasibility of integrating feedback control mechanisms into LVAD systems using data from the biosensors. Challenges facing this emerging technology and future directions for research and development are outlined as well. The overarching goal is to provide an overview of how implanted biosensors may improve the performance and outcomes of LVADs through continuous monitoring and closed-loop control.

The effectiveness of sodium-glucose co-transporter 2 inhibitors on cardiorenal outcomes: an updated systematic review and meta-analysis.

BACKGROUND: The 2022 Canadian Cardiovascular Society (CCS) cardiorenal guideline provided clinical recommendations on sodium-glucose co-transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) use. Since then, additional trials of relevance for SGLT2i have been published. This update re-evaluates the clinical recommendations for using SGLTi and their indirect comparison with existing evidence on GLP-1RA as compared to the standard of care to reduce cardiorenal morbidity and mortality. METHODS: We updated our existing search and screening of the literature from September 2021 to April 2023 for randomized controlled trials of SGLT2i and GLP-1RA with placebo control. We conducted risk of bias assessment, data extraction and updated our meta-analysis of studies with similar interventions and components. The certainty of the evidence was determined using GRADE. RESULTS: Evidence from three new trials and additional results from an updated existing trial on SGLT2i met our inclusion criteria after an updated search. Across all the included studies, the total sample size was 151,023 adults, with 90,943 in SGLT2i trials and 60,080 in GLP-1 RA trials. The mean age ranged from 59.9 to 68.4 years. Compared with standard care, the use of SGLT2i and GLP-1 RA showed significant reductions in the outcomes of cardiovascular (CV) mortality (14% & 13%), any-cause mortality (12% & 12%), major adverse CV events (MACE) (11% & 14%), heart failure (HF) hospitalization (30% & 9%), CV death or HF hospitalization (23% & 11%), and kidney composite outcome (32% & 22%). In participants with T2D, both classes demonstrated significant cardiorenal protection. But, only GLP-1RA showed a reduction in non-fatal stroke (16%) and only SGLT2i showed a reduction in HF hospitalization (30%) in this population of people living with T2D. CONCLUSIONS: This updated and comprehensive meta-analysis substantiates and strengthens the clinical recommendations of the CCS cardiorenal guidelines.

Molecular insights into antimicrobial resistant Staphylococcus aureus strains: A potential zoonosis of goat origin.

Antimicrobial-resistant (AMR) Staphylococcus aureus (S. aureus) strains have attained global attention due to their life-threatening zoonotic nature. Being a member of ESKAPE group, S. aureus has an ability to escape the biocidal action of antimicrobial drugs. The current study investigated the prevalence and molecular characterization of methicillin-resistant S. aureus (MRSA), ß-lactam-resistant S. aureus (BRSA), aminoglycoside-resistant S. aureus (ARSA), tetracycline-resistant S. aureus (TRSA), and fluoroquinolones-resistant S. aureus (FRSA) associated with goat subclinical mastitis (SCM). Furthermore, the antimicrobial resistance and susceptibility profile of various antibiotics and non-antibiotics (NSAIDs, nisin, N-acetylcysteine, vitamin-C) along with their possible role in modulating the antibiotic resistance of MDR isolates was also investigated. A total of 768 goat milk samples were subjected to California mastitis test for SCM followed by bacteriological and molecular characterization of S. aureus. Moreover, in-vitro susceptibility of resistant antibiotics, non-antibiotics, and their combination against MDR S. aureus were conducted through well diffusion and broth microdilution assays. The results depicted that 55.47 % and 26.82 % of milk samples were positive for SCM and S. aureus, respectively. The molecular assay confirmed 35.92 % of isolates as MRSA, 45.63 % as BRSA, 50.49 % as ARSA, and 32.52 % but no isolate was confirmed as FRSA on molecular basis. The multidrug resistance was observed in 62.13 % and 47.09 % isolates, respectively. Molecular characterized MDR S. aureus revealed high homology of study isolates with the isolates of neighboring countries like India, Korea, Iran, and China. Antimicrobial susceptibility trials on well diffusion assay showed higher efficacy of different non-antibiotics with resistant antibiotics as penicillin with ketoprofen and gentamicin with flunixin meglumine while oxytetracycline with N-acetylcystiene. The synergy testing by checkerboard assay revealed synergistic activity of penicillin with ketoprofen, gentamicin with flunixin meglumine, and oxytetracycline with N-acetylcysteine. The current study highlighted the emergence and spread of AMR S. aureus strains from goat SCM and provided insights into possible drug repurposing of various non-antibiotics to modulate the multidrug resistance of S. aureus which will be helpful in devising the therapeutic options and control measures for this pathogen.