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Abstract Background The CD133 antigen is a marker of radio- and chemo-resistant stem cell populations in glioblastoma (GBM). The O6-methylguanine DNA methyltransferase (MGMT) enzyme is related with temozolomide (TMZ) resistance. Our propose is to analyze the prognostic significance of the CD133 antigen and promoter methylation and protein expression of MGMT in a homogenous group of GBM patients uniformly treated with radiotherapy and TMZ. The possible connection between these GBM markers was also investigated. Methods Seventy-eight patients with GBM treated with radiotherapy combined with concomitant and adjuvant TMZ were analyzed for MGMT and CD133. MGMT gene promoter methylation was determined by methylation-specific polymerase chain reaction after bisulfite treatment. MGMT and CD133 expression was assessed immunohistochemically using an automatic quantification system. Overall and progression-free survival was calculated according to the Kaplan–Meier method. Results The MGMT gene promoter was found to be methylated in 34 patients (44.7%) and unmethylated in 42 patients (55.3%). A significant correlation was observed between MGMT promoter methylation and patients’ survival. Among the unmethylated tumors, 52.4% showed low expression of MGMT and 47.6% showed high-expression. Among methylated tumors, 58.8% showed low-expression of MGMT and 41.2% showed high-expression. No correlation was found between MGMT promoter methylation and MGMT expression, or MGMT expression and survival. In contrast with recent results, CD133 expression was not a predictive marker in GBM patients. Analyses of possible correlation between CD133 expression and MGMT protein expression or MGMT promoter methylation were negative. Conclusions Our results support the hypothesis that MGMT promoter methylation status but not MGMT expression may be a predictive biomarker in the treatment of patients with GBM. In addition, CD133 should not be used for prognostic evaluation of these patients. Future studies will be necessary to determine its clinical utility.

Abstract Introduction A unicornuate uterus with a rudimentary horn is the most uncommon uterine anomaly of the female genital tract. It has an estimated frequency of one in 100,000 among the fertile female population. This anomaly results from the abnormal maturation of one Müllerian duct with the normal development of the contralateral one. Case presentation We report here the case of a 14-year-old Caucasian girl who came to our hospital with intense dysmenorrhea. Imaging techniques revealed a unicornuate uterus with a rudimentary horn and a large hematosalpinx. We performed a laparoscopic removal of this uterine anomaly without any complication in the postoperative period. Conclusion In our case report, we demonstrate that laparoscopy is the best approach for the treatment of IIb Müllerian abnormalities. Laparoscopy resulted in anatomical and reproductive results equivalent to those offered by a laparotomic approach, but with the additional advantages of minimally invasive surgery, such as better cosmetic results and postoperative period, which are essential for very young patients.

This response supports previous findings by describing the experiences of the Wentham Developmental Center. This center found switching from Depakene to generic valproic acid was not associated with any change in the number of epileptic seizures. The occurrence of adverse gastrointestinal effects of valproic acid is addressed. (CR)

Malignant transformation of cells is typically associated with increased proliferation, loss of contact inhibition, acquisition of anchorage-independent growth potential, and the ability to form tumors in experimental animals(1). In NIH 3T3 cells, the Ras signal transduction pathway is known to trigger many of these events, what is known as Ras transformation. The introduction of an overexpressed gene in NIH 3T3 cells may promote morphological transformation and loss of contact inhibition, which can help determine the oncogenic potential of that gene of interest. An assay that provides a straightforward method to assess one aspect of the transforming potential of an oncogene is the Focus Formation Assay (FFA)(2). When NIH 3T3 cells divide normally in culture, they do so until they reach a confluent monolayer. However, in the presence of an overexpressed oncogene, these cells can begin to grow in dense, multilayered foci(1) that can be visualized and quantified by crystal violet or Hema 3 staining. In this article we describe the FFA protocol with retroviral transduction of the gene of interest into NIH 3T3 cells, and how to quantify the number of foci through staining. Retroviral transduction offers a more efficient method of gene delivery than transfection, and the use of an ecotropic murine retrovirus provides a biosafety control when working with potential human oncogenes.

A male infant of 2,900 g was born at term to a 19-year-old primigravida woman who had adequate prenatal care and no major complications detected during the pregnancy. The only reported medical event was an episode of urinary tract infection by E. coli one month before delivering, which resolved without complications using nitrofurantoin. There was no history of maternal herpes simplex infection and her serologic screening was negative for syphilis.

Primary sarcomas of the chest are rare. Although primitive neuroectodermal tumor (PNET) usually develops in the chest wall, it has been described as a primary pulmonary tumor. We present an unusual case of PNET arising in the lung of an 89-year-old man.

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We report acute Oropouche virus infections in 2 previously healthy women from a nonendemic region of Brazil outside the Amazon Basin. Infections rapidly progressed to hemorrhagic manifestations and fatal outcomes in 4–5 days. These cases highlight the critical need for enhanced surveillance to clarify epidemiology of this neglected disease.

Abstract Common single-nucleotide variants (SNVs) of eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) slightly increase the risk of disorders in the periphery and the central nervous system. EIF2AK3 encodes protein kinase RNA-like endoplasmic reticulum kinase (PERK), a key regulator of ER stress. Three exonic EIF2AK3 SNVs form the PERK-B haplotype, which is present in 28% of the global population. Importantly, the precise impact of these SNVs on PERK activity remains elusive. In this study, we demonstrate that PERK-B SNVs do not alter PERK expression or basal activity in vitro and in the novel triple knock-in mice expressing the exonic PERK-B SNVs in vivo. However, the kinase activity of PERK-B protein is higher than that of PERK-A in a cell-free assay and in mouse liver homogenates. Pancreatic tissue in PERK-B/B mice also exhibit increased susceptibility to apoptosis under acute ER stress. Monocyte-derived macrophages from PERK-B/B mice exhibit higher PERK activity than those from PERK-A/A mice, albeit with minimal functional consequences at acute timepoints. The subtle PERK-B-driven effects observed in liver and pancreas during acute stress implicate PERK as a contributor to disease susceptibility. The novel PERK-B mouse model provides valuable insights into ER stress-induced PERK activity, aiding the understanding of the genetic basis of disorders associated with ER stress.

Abstract Antenatal hydronephrosis (HN) impacts up to 5% of pregnancies and requires close, frequent follow-up monitoring to determine who may benefit from surgical intervention. To create an automated HN Severity Index (HSI) that helps guide clinical decision-making directly from renal ultrasound images. We applied a deep learning model to paediatric renal ultrasound images to predict the need for surgical intervention based on the HSI. The model was developed and studied at four large quaternary free-standing paediatric hospitals in North America. We evaluated the degree to which HSI corresponded with surgical intervention at each hospital using area under the receiver-operator curve, area under the precision-recall curve, sensitivity, and specificity. HSI predicted subsequent surgical intervention with > 90% AUROC, > 90% sensitivity, and > 70% specificity in a test set of 202 patients from the same institution. At three external institutions, HSI corresponded with AUROCs ≥ 90%, sensitivities ≥ 80%, and specificities > 50%. It is possible to automatically and reliably assess HN severity directly from a single ultrasound. The HSI stratifies low- and high-risk HN patients thus helping to triage low-risk patients while maintaining very high sensitivity to surgical cases. HN severity can be predicted from a single patient ultrasound using a novel image-based artificial intelligence system.

Abstract Cassava (Manihot esculenta Crantz) is a vital carbohydrate source for over 800 million people globally, yet its production in East Africa is severely affected by cassava brown streak disease (CBSD). Genebanks, through ex-situ conservation, play a pivotal role in preserving crop diversity, providing crucial resources for breeding resilient and disease-resistant crops. This study genotyped 234 South American cassava accessions conserved at the CIAT genebank, previously phenotyped for CBSD resistance by an independent group, to perform a genome-wide association analysis (GWAS) to identify genetic variants associated with CBSD resistance. Our GWAS identified 35 single nucleotide polymorphism (SNP) markers distributed across various chromosomes, associated with disease severity or the presence/absence of viral infection. Markers were annotated within or near genes previously identified with functions related to pathogen recognition and immune response activation. Using the SNP candidates, we screened the world’s largest cassava collection for accessions with a higher frequency of favorable genotypes, proposing 35 accessions with potential resistance to CBSD. Our results provide insights into the genetics of CBSD resistance and highlight the importance of genetic resources to equip breeders with the raw materials needed to develop new crop varieties resistant to pests and diseases.

Phylogenetic analyses showed that the virus responsible for a May 2024 Oropouche fever outbreak in Cuba was closely related to viruses from Brazil in 2023. Pools of Ceratopogonidae spp. biting midges and Culex quinquefasciatus mosquitoes were positive for Oropouche viral RNA. No cases were severe. Virus extension to new areas may increase case numbers and severity.

Abstract In this work, we use mass quadrupole spectroscopy to analyze the ion energy distribution function for C+ ions from different gas composition discharges (20, 40, 60, 80, and 90% Ne) + Ar in a plasma sputtering process. Carbon films were obtained for each gas composition discharge. The carbon bonding structure of films was analyzed by Raman spectroscopy using deconvolution fitting of the G and D Raman peaks. The C-sp3 content was correlated with the electrical and tribological properties of the carbon films. Our results further corroborate the enhancement of carbon ionization in HiPIMS processes by adding neon in conventional argon gas during the deposition process. Furthermore, we found that excessive levels of carbon ionization were detrimental in the formation of C-sp3 decreasing the resistivity, and indicating the decrement of the elastic modulus of the samples. In addition, the use of neon in the gas working mixture increased the deposition rate significantly compared to argon-only processes from 1.7 to 3.22 nm/min for the highest deposition rate cases. Tribology showed that an intermediate C-sp3 content in the carbon films developed desirable tribological behaviors with lower friction coefficients and wear rates, revealing that higher values of C-sp3 content are not necessarily for robust solid lubricious and wear resistance.

Abstract Benign prostatic hyperplasia (BPH) is a prevalent age-related condition often characterized by debilitating urinary symptoms. Its etiology is believed to stem from hormonal imbalance, particularly an elevated estradiol-to-testosterone ratio and chronic inflammation. Our previous studies using a mouse steroid hormone imbalance model identified a specific increase in macrophages that migrated and accumulated in the prostate lumen where they differentiated into lipid-laden foam cells in mice implanted with testosterone and estradiol pellets, but not in sham animals. The current study focused on further characterizing the cellular heterogeneity of the prostate in this model as well as identifying the specific transcriptomic signature of the recruited foam cells. Moreover, we aimed to identify epithelia-derived signals that drive macrophage infiltration and luminal translocation. Male C57BL/6J mice were implanted with slow-release testosterone and estradiol pellets (T + E2) or sham surgery was performed and the ventral prostates were harvested two weeks later for scRNA-seq analysis. We identified Ear2 + and Cd72 + macrophages that were elevated in response to steroid hormone imbalance, whereas a Mrc1 + resident macrophage population did not change. In addition, an Spp1 + foam cell cluster was almost exclusively found in T + E2 mice. Further markers of foam cells were also identified, including Gpnmb and Trem2, and GPNMB was confirmed as a novel histological marker with immunohistochemistry. Foam cells were also shown to express known pathological factors Vegf, Tgfb1, Ccl6, Cxcl16 and Mmp12. Intriguingly, a screen for chemokines identified the upregulation of epithelia-derived Cxcl17, a known monocyte attractant, in T + E2 prostates suggesting that it might be responsible for the elevated macrophage number as well as their translocation to the lumen. Our study identified macrophage subsets that responded to steroid hormone imbalance as well as further confirmed a potential pathological role of luminal foam cells in the prostate. These results underscore a potential pathological role of the identified prostate foam cells and suggests CXCL17-mediated macrophage migration as a critical initiating event.

Abstract Background The architecture and dynamics of T cell populations are critical in orchestrating the immune response to SARS-CoV-2. In our study, we used T Cell Receptor sequencing (TCRseq) to investigate TCR repertoires in 173 post-infection COVID-19 patients. Methods The cohort included 98 mild and 75 severe cases with a median age of 53. We amplified and sequenced the TCR β chain Complementary Determining Region 3 (CDR3b) and performed bioinformatic analyses to assess repertoire diversity, clonality, and V/J allelic usage between age, sex and severity groups. CDR3b amino acid sequence inference was performed by clustering structural motifs and filtering validated reactive CDR3b to COVID-19. Results Our results revealed a pronounced decrease in diversity and an increase in clonal expansion in the TCR repertoires of severe COVID-19 patients younger than 55 years old. These results reflect the observed trends in patients older than 55 years old (both mild and severe). In addition, we identified a significant reduction in the usage of key V alleles (TRBV14, TRBV19, TRBV15 and TRBV6-4) associated with disease severity. Notably, severe patients under 55 years old had allelic patterns that resemble those over 55 years old, accompanied by a skewed frequency of COVID-19-related motifs. Conclusions Present results suggest that severe patients younger than 55 may have a compromised TCR repertoire contributing to a worse disease outcome. Graphical Abstract

The female steroid, 17β-estradiol (E2), is important for pancreatic β-cell function and acts via at least three estrogen receptors (ER), ERα, ERβ, and the G-protein coupled ER (GPER). Using a pancreas-specific ERα knockout mouse generated using the Cre-lox-P system and a Pdx1-Cre transgenic line (PERαKO−/−), we previously reported that islet ERα suppresses islet glucolipotoxicity and prevents β-cell dysfunction induced by high fat feeding. We also showed that E2 acts via ERα to prevent β-cell apoptosis in vivo. However, the contribution of the islet ERα to β-cell survival in vivo, without the contribution of ERα in other tissues is still unclear. Using the PERαKO−/− mouse, we show that ERα mRNA expression is only decreased by 20% in the arcuate nucleus of the hypothalamus, without a parallel decrease in the VMH, making it a reliable model of pancreas-specific ERα elimination. Following exposure to alloxan-induced oxidative stress in vivo, female and male PERαKO−/− mice exhibited a predisposition to β-cell destruction and insulin deficient diabetes. In male PERαKO−/− mice, exposure to E2 partially prevented alloxan-induced β-cell destruction and diabetes. ERα mRNA expression was induced by hyperglycemia in vivo in islets from young mice as well as in cultured rat islets. The induction of ERα mRNA by hyperglycemia was retained in insulin receptor-deficient β-cells, demonstrating independence from direct insulin regulation. These findings suggest that induction of ERα expression acts to naturally protect β-cells against oxidative injury.

Fluid intelligence is important for successful functioning in the modern world, but much evidence suggests that fluid intelligence is largely immutable after childhood. Recently, however, researchers have reported gains in fluid intelligence after multiple sessions of adaptive working memory training in adults. The current study attempted to replicate and expand those results by administering a broad assessment of cognitive abilities and personality traits to young adults who underwent 20 sessions of an adaptive dual n-back working memory training program and comparing their post-training performance on those tests to a matched set of young adults who underwent 20 sessions of an adaptive attentional tracking program. Pre- and post-training measurements of fluid intelligence, standardized intelligence tests, speed of processing, reading skills, and other tests of working memory were assessed. Both training groups exhibited substantial and specific improvements on the trained tasks that persisted for at least 6 months post-training, but no transfer of improvement was observed to any of the non-trained measurements when compared to a third untrained group serving as a passive control. These findings fail to support the idea that adaptive working memory training in healthy young adults enhances working memory capacity in non-trained tasks, fluid intelligence, or other measures of cognitive abilities., Psychology

Se realizó un estudio en el departamento de Ginecología y Obstetricia del Hospital Nacional Edgardo Rebagliati Martins (HNERM) con el objetivo analizar la transmisión vertical del SARS-CoV-2 en mujeres embarazadas con COVID-19. Se incluyeron 12 gestantes que cumplían con los criterios de inclusión. Se realizaron pruebas diagnósticas de PCR en tiempo real (RT-PCR) para SARS-CoV-2 durante la admisión de cada gestante y se recolectaron muestras de placenta para su evaluación anatomopatológica. Los resultados mostraron que la transmisión vertical del virus fue poco común, con una tasa general de positividad baja en los recién nacidos. Aunque el estudio presenta limitaciones, como el número reducido de casos y la falta de análisis con microscopio electrónico, constituye el primer intento en Perú de evaluar la transmisión vertical. Se concluye que se necesita más investigación para comprender mejor la relación entre la infección por la COVID-19 y las complicaciones durante el embarazo.

Background: Rooms illuminated by “black light” (

Abstract Single-domain antibodies (sdAbs) or nanobodies have received widespread attention due to their small size (~ 15 kDa) and diverse applications in bio-derived therapeutics. As many modern biotechnology breakthroughs are applied to antibody engineering and design, nanobody thermostability or melting temperature (Tm) is crucial for their successful utilization. In this study, we present TEMPRO which is a predictive modeling approach for estimating the Tm of nanobodies using computational methods. Our methodology integrates various nanobody biophysical features to include Evolutionary Scale Modeling (ESM) embeddings, NetSurfP3 structural predictions, pLDDT scores per sdAb region from AlphaFold2, and each sequence’s physicochemical characteristics. This approach is validated with our combined dataset containing 567 unique sequences with corresponding experimental Tm values from a manually curated internal data and a recently published nanobody database, NbThermo. Our results indicate the efficacy of protein embeddings in reliably predicting the Tm of sdAbs with mean absolute error (MAE) of 4.03 °C and root mean squared error (RMSE) of 5.66 °C, thus offering a valuable tool for the optimization of nanobodies for various biomedical and therapeutic applications. Moreover, we have validated the models’ performance using experimentally determined Tms from nanobodies not found in NbThermo. This predictive model not only enhances nanobody thermostability prediction, but also provides a useful perspective of using embeddings as a tool for facilitating a broader applicability of downstream protein analyses.

Abstract The production of Paleolithic art represents one of the most intricate technical and cognitive endeavors of Homo sapiens, marked by its profound antiquity and vast temporal and spatial framework. Despite its significance, there have been no prior studies aimed at understanding the cognitive and motor skills linked to the creation of realistic images characteristic of this artistic cycle. This research integrates archaeology and experimental psychology, premised on the assumption that the neurological basis of Anatomically Modern Humans has not changed substantially since the Upper Paleolithic. This work employs an innovative interdisciplinary approach, utilizing psychometric tests and drawing and engraving tasks monitored by motion-sensing gloves, to compare the performance of experts and non-experts in visual arts when faced with challenges akin to those of Upper Paleolithic artistic production. The results revealed that expertise in visual arts is linked to enhanced spatial abilities and specific patterns in drawing from memory. Additionally, both experts and non-experts displayed similar motor skills when engraving using Paleolithic techniques, suggesting that these techniques required specialized training in the contemporary experts. In conclusion, this research deepens our understanding of the processes involved in Upper Paleolithic artistic production.

Abstract Non-contact methods are useful to improve the quality control of particle filtration media. The purpose of this paper is to investigate the correlation between the filtration efficiency of a porous sheet and its ultrasonic properties obtained using a non-contact technique. An air-coupled ultrasonic technique is used to obtain rapid measurements without affecting the integrity of the material. High frequencies (from 0.1 to 2.5 MHz) are used to improve technique sensitivity, and transmitted waves are measured to probe the internal properties of the material. Measurements of transmission coefficient spectra (amplitude and phase) and the corresponding ultrasound velocity and attenuation coefficient at different frequencies are obtained for a set of filtration media with well-characterized properties. Results show that the ultrasonic properties of filtration media vary as a function of basis weight, and therefore filtration efficiency, for a given charge state. However, the effect of electrostatic charge on ultrasonic propagation is almost negligible, as expected. We conclude that ultrasonic transmission may provide a valuable tool for the continuous online monitoring of material quality during fabrication and as a method to tease apart mechanical and electrostatic contributions to particle filtration.

Abstract Background Scientific evidence highlights the influence of biological sex on the relationship between stress and metabolic dysfunctions. However, there is limited understanding of how diet and stress concurrently contribute to metabolic dysregulation in both males and females. Our study aimed to investigate the combined effects of high-fat diet (HFD) induced obesity and repeated stress on fear-related behaviors, metabolic, immune, and hypothalamic outcomes in male and female mice. Methods To investigate this, we used a highly reliable rodent behavioral model that faithfully recapitulates key aspects of post-traumatic stress disorder (PTSD)-like fear. We subjected mice to footshock stressor followed by a weekly singular footshock stressor or no stressor for 14 weeks while on either an HFD or chow diet. At weeks 10 and 14 we conducted glucose tolerance and insulin sensitivity measurements. Additionally, we placed the mice in metabolic chambers to perform indirect calorimetric measurements. Finally, we collected brain and peripheral tissues for cellular analysis. Results We observed that HFD-induced obesity disrupted fear memory extinction, increased glucose intolerance, and affected energy expenditure specifically in male mice. Conversely, female mice on HFD exhibited reduced respiratory exchange ratio (RER), and a significant defect in glucose tolerance only when subjected to repeated stress. Furthermore, the combination of repeated stress and HFD led to sex-specific alterations in proinflammatory markers and hematopoietic stem cells across various peripheral metabolic tissues. Single-nuclei RNA sequencing (snRNAseq) analysis of the ventromedial hypothalamus (VMH) revealed microglial activation in female mice on HFD, while male mice on HFD exhibited astrocytic activation under repeated stress. Conclusions Overall, our findings provide insights into complex interplay between repeated stress, high-fat diet regimen, and their cumulative effects on health, including their potential contribution to the development of PTSD-like stress and metabolic dysfunctions, emphasizing the need for further research to fully understand these interconnected pathways and their implications for health.

Abstract Background Depression, anxiety, and insomnia are prevalent in older people and are associated with increased risk of mortality, dependency, falls and reduced quality of life. Prior to or whilst seeking treatment, older people often manage these symptoms or conditions using products purchased over the counter (OTC), such as medication or herbal products. This review aims to map the evidence available for OTC medications, herbal medicines and dietary supplements for depression, anxiety and insomnia in older adults. Methodology We carried out a scoping review, including searches of five databases to identify relevant randomised controlled trials (inception-Dec 2022). We took an inclusive approach to products to represent the wide range that may be available online. Trials were summarised according to condition and product. Results We included 47 trials and 10 ongoing trial protocols. Most targeted insomnia (n = 25), followed by depression (n = 20), and mixed conditions (n = 2). None evaluated products targeted at anxiety alone. Where reported, most products appeared to be safe for use, but studies rarely included people with multiple comorbidities or taking concomitant medication. Some types of melatonin for insomnia (n = 19) and omega-3 fatty acids for depression (n = 7) had more substantive evidence compared to the other products. Conclusion There is a substantial gap in evidence for OTC products for anxiety in older people. This should be addressed in future trials. Research should also focus on products that are widely used, and these need to be tested in older populations that are similar to those who would use them in practice.

Abstract Intrinsic and extrinsic factors, including lifestyle and sun exposure, can contribute to cell senescence, which impairs skin homeostasis, that may in turn lead to skin aging. Senescent cells have a specific secretome, called the senescence-associated secretory phenotype (SASP) that includes MMPs, CXCLs and S100A8/9. Reducing the SASP with senotherapeutics is a promising strategy to reduce skin aging. Here we evaluated the effect of a formula containing niacinamide and hyaluronic acid, which are known to limit senescence and skin aging. We conducted three different studies. (1) Ex vivo explants treated with the formula had more collagen and glycosaminoglycan. (2) In a clinical trial with forty-four women, two months of treatment improved fine lines, wrinkles, luminosity, smoothness, homogeneity, and plumpness. (3) In a third study on thirty women, we treated one arm for two months and took skin biopsies to study gene expression. 101 mRNAs and 13 miRNAs were differentially expressed. We observed a likely senomorphic effect, as there was a decrease in many SASP genes including MMP12 and CXCL9 and a significant downregulation of autocrine signaling genes: S100A8 and S100A9. These pharmaco-clinical results are the first to demonstrate the senomorphic properties of an effective anti-aging formula in skin.

Abstract Gut fungal imbalances, particularly increased Candida spp., are linked to obesity. This study explored the potential of Lactiplantibacillus plantarum cell-free extracts (postbiotics) to modulate the growth of Candida albicans and Candida kefyr, key members of the gut mycobiota. A minimal synthetic gut model was employed to evaluate the effects of Lactiplantibacillus plantarum postbiotics on fungal growth in mono- and mixed cultures. Microreactors were employed for culturing, fungal growth was quantified using CFU counting, and regression analysis was used to evaluate the effects of postbiotics on fungal growth. Postbiotics at a concentration of 12.5% significantly reduced the growth of both Candida species. At 24 h, both C. albicans and C. kefyr in monocultures exhibited a decrease in growth of 0.11 log CFU/mL. In contrast, mixed cultures showed a more pronounced antifungal effect, with C. albicans and C. kefyr reductions of 0.62 log CFU/mL and 0.64 log CFU/mL, respectively. Regression analysis using the Gompertz model supported the antifungal activity of postbiotics and revealed species-specific differences in growth parameters. These findings suggest that L. plantarum postbiotics have the potential to modulate the gut mycobiota by reducing Candida growth, potentially offering a therapeutic approach for combating fungal overgrowth associated with obesity.

Acute ischemic stroke of the posterior circulation presents a diagnostic and therapeutic challenge for all healthcare providers. The intervention window is slightly longer than that of the anterior circulation; however, approximately six hours after symptom onset, the patient's prognosis is poor. We report a case of a patient who presented to the emergency department with a two-hour history of altered consciousness. Magnetic resonance imaging (MRI) confirmed an acute right hemispheric cerebellar infarction in the posterior inferior cerebellar artery (PICA) territory with basilar artery occlusion. Mechanical thrombectomy, performed by a neurointerventional radiologist, achieved reperfusion of the ischemic area. The patient experienced complete neurological recovery without sequelae.

Abstract The influence of Hofmeister cations (NH4 +, Na+, Mg2+) and anions (H2PO4 −, CH3COO−, Cl− , NO3 −) on the thermostability of a GHG hydrogel was investigated. The combined results of UV circular dichroism (UVCD) and Small Amplitude Oscillatory Shear Rheology experiments reveal that the addition of salt reduces the stability of the gel phase and the underlying fibrils. In line with the cationic Hofmeister hierarchy, the chaotropic Mg2+ ions caused the greatest thermal destabilization of the gel phase with the gel → sol transition temperature T gs value lowered by 10 °C. In the absence of salt, the gel → sol transition probed by the storage modulus and microscopy is biphasic. In the presence of salt, it becomes monophasic. Contrary to expectations the presence of Hofmeister anions leads to a nearly identical reduction of the gel → sol transition temperatures. However, UVCD spectra suggest that they affect the ππ-stacking between imidazole groups to a different extent. We relate the absence of ion specificity regarding the solubility of fibrils (probed by UVCD) to the observed enthalpy-entropy compensation of the dissolution process. Our results combined show how CD spectroscopy and rheology combined yields a more nuanced picture of the processes underlying the gel → sol transition.

Abstract This study tested if a high-resolution, multi-modal, multi-scale retinal imaging instrument can provide novel information about structural abnormalities in vivo. The study examined 11 patients with very mild to moderate non-proliferative diabetic retinopathy (NPDR) and 10 healthy subjects using fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), adaptive optics scanning laser ophthalmoscopy (AO-SLO), adaptive optics OCT and OCTA (AO-OCT(A)). Of 21 eyes of 11 patients, 11 had very mild NPDR, 8 had mild NPDR, 2 had moderate NPDR, and 1 had no retinopathy. Using AO-SLO, capillary looping, inflections and dilations were detected in 8 patients with very mild or mild NPDR, and microaneurysms containing hyperreflective granular elements were visible in 9 patients with mild or moderate NPDR. Most of the abnormalities were seen to be perfused in the corresponding OCTA scans while a few capillary loops appeared to be occluded or perfused at a non-detectable flow rate, possibly because of hypoperfusion. In one patient with moderate NPDR, non-perfused capillaries, also called ghost vessels, were identified by alignment of corresponding en face AO-OCT and AO-OCTA images. The combination of multiple non-invasive imaging methods could identify prominent microscopic abnormalities in diabetic retinopathy earlier and more detailed than conventional fundus imaging devices.

Patients present a wide range of clinical severities in response severe acute respiratory syndrome coronavirus 2 infection, but the underlying molecular and cellular reasons why clinical outcomes vary so greatly within the population remains unknown. Here, we report that negative clinical outcomes in severely ill patients were associated with divergent RNA transcriptome profiles in peripheral immune cells compared with mild cases during the first weeks after disease onset. Protein–protein interaction analysis indicated that early-responding cytotoxic natural killer cells were associated with an effective clearance of the virus and a less severe outcome. This innate immune response was associated with the activation of select cytokine–cytokine receptor pathways and robust Th1/Th2 cell differentiation profiles. In contrast, severely ill patients exhibited a dysregulation between innate and adaptive responses affiliated with divergent Th1/Th2 profiles and negative outcomes. This knowledge forms the basis of clinical triage that may be used to preemptively detect high-risk patients before life-threatening outcomes ensue.

The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.

Background The dynamics of carbon (C), nitrogen (N), and phosphorus (P) in soils determine their fertility and crop growth in agroecosystems. These dynamics depend on microbial metabolism, which in turn depends on nutrient availability. Farmers typically apply either mineral or organic fertilizers to increase the availability of nutrients in soils. Phosphorus, which usually limits plant growth, is one of the most applied nutrients. Our knowledge is limited regarding how different forms of P impact the ability of microbes in soils to produce the enzymes required to release nutrients, such as C, N and P from different substrates. Methods In this study, we used the arable layer of a calcareous soil obtained from an alfalfa cropland in Cuatro Cienegas, México, to perform an incubation experiment, where five different phosphate molecules were added as treatments substrates: three organic molecules (RNA, adenine monophosphate (AMP) and phytate) and two inorganic molecules (calcium phosphate and ammonium phosphate). Controls did not receive added phosphorus. We measured nutrient dynamics and soil microbial activity after 19 days of incubation. Results Different P molecules affected potential microbial C mineralization (CO2-C) and enzyme activities, specifically in the organic treatments. P remained immobilized in the microbial biomass (Pmic) regardless of the source of P, suggesting that soil microorganisms were limited by phosphorus. Higher mineralization rates in soil amended with organic P compounds depleted dissolved organic carbon and increased nitrification. The C:N:P stoichiometry of the microbial biomass implied a change in the microbial community which affected the carbon use efficiency (CUE), threshold elemental ratio (TER), and homeostasis. Conclusion Different organic and inorganic sources of P affect soil microbial community structure and metabolism. This modifies the dynamics of soil C, N and P. These results highlight the importance of considering the composition of organic matter and phosphate compounds used in agriculture since their impact on the microbial activity of the soil can also affect plant productivity.