BackgroundThis study assessed the potential cost-effectiveness of high (80–100%) vs low (21–35%) fraction of inspired oxygen (FiO2) at preventing surgical site infections (SSIs) after abdominal surgery in Nigeria, India, and South Africa.
Methods
Decision-analytic models were constructed using best available evidence sourced from unbundled data of an ongoing pilot trial assessing the effectiveness of high FiO2, published literature, and a cost survey in Nigeria, India, and South Africa. Effectiveness was measured as percentage of SSIs at 30 days after surgery, a healthcare perspective was adopted, and costs were reported in US dollars ($).
Results
High FiO2 may be cost-effective (cheaper and effective). In Nigeria, the average cost for high FiO2 was $216 compared with $222 for low FiO2 leading to a −$6 (95% confidence interval [CI]: −$13 to −$1) difference in costs. In India, the average cost for high FiO2 was $184 compared with $195 for low FiO2 leading to a −$11 (95% CI: −$15 to −$6) difference in costs. In South Africa, the average cost for high FiO2 was $1164 compared with $1257 for low FiO2 leading to a −$93 (95% CI: −$132 to −$65) difference in costs. The high FiO2 arm had few SSIs, 7.33% compared with 8.38% for low FiO2, leading to a −1.05 (95% CI: −1.14 to −0.90) percentage point reduction in SSIs.
Conclusion
High FiO2 could be cost-effective at preventing SSIs in the three countries but further data from large clinical trials are required to confirm this.

We present the experimental realization of plasmonic hyperdoped Si nanocrystals embedded in silica via a combination of sequential low energy ion implantation and rapid thermal annealing. We show that phosphorus dopants are incorporated into the nanocrystal cores at concentrations up to six times higher than P solid solubility in bulk Si by combining 3D mapping with atom probe tomography and analytical transmission electron microscopy. We shed light on the origin of nanocrystal growth at high P doses, which we attribute to Si recoiling atoms generated in the matrix by P implantation, which likely increase Si diffusivity and feed the Si nanocrystals. We show that dopant activation enables partial nanocrystal surface passivation that can be completed by forming gas annealing. Such surface passivation is a critical step in the formation of plasmon resonance, especially for small nanocrystals. We find that the activation rate in these small doped Si nanocrystals is the same as in bulk Si under the same doping conditions.

Land use changes profoundly affect the equilibrium of soil organic carbon (SOC) sequestration and greenhouse gas emissions. With the current global climatic changes, it is vital to understand the influence of ecological restoration and conservation management on the dynamics of SOC under different land uses, especially in erosion-endangered Loess soils. Therefore, we investigated changes in SOC through a suit of labile fractions, namely: light fraction organic C (LFOC), heavy fraction organic C (HFOC), coarse particulate organic C (CPOC), fine particulate organic C (FPOC), and dissolved organic C (DOC), from two forests i.e., Robinia pseudoacacia (RP) and Platycladus orientalis (PO), with different ages, in comparison with farmland (FL). The SOC and STN contents significantly increased over 42 years in the RP forest where the contents of CPOC and FPOC were significantly higher than in the FL. Moreover, total SOC and its labile fractions, in the studied land use types, significantly correlated with soil CaCO3, pH, and STN contents, indicating their key roles in SOC sequestration. The results reported here from different vegetation with different ages provide a better understanding of SOC and STN alterations at different stages of vegetation restoration. Our findings suggest that long-term natural vegetation restoration could be an effective approach for SOC sequestration and soil conservation on the Loess soil.

This study aims to investigate the effect of hydroethanolic extracts of leaf (CLHE) and flower (CFHE) on the hepatic histopathological lesions and functional biochemical changes induced by type 2 diabetes mellitus (T2DM). The rat model of T2DM was induced by intraperitoneal injection of streptozotocin (STZ) in a dose of 60 mg/kg for 15 minutes following nicotinamide (NA) (60 mg/kg). The rats were allocated into four groups: group 1 (negative control), group 2 (diabetic control), group 3 (diabetic rats supplemented with 100 mg/kg/day CLHE), and group 4 (diabetic rats supplemented with 100 mg/kg/day CFHE). Treatment with CLHE and CFHE, for the study duration of 28 days, significantly improved the deteriorated hepatic glycogen content, glycogen phosphorylase, glucose-6-phosphatase activities, serum fructosamine levels, lipid profile, aspartate transaminase activities, and alanine transaminase activities as well as serum insulin and C-peptide levels. The elevated liver lipid peroxidation and the decreased activities of superoxide dismutase and glutathione peroxidase were significantly alleviated. The elevated expression of the proinflammatory cytokine tumor necrosis factor- in the liver of diabetic rats was significantly reduced by treatments with CLHE and CFHE. NA/STZ-induced T2DM exhibited hepatic histopathological changes in the form of disordered hepatocytes, cytoplasm dissolution, and mononuclear leukocytic infiltration. The electron microscopic ultrastructure study revealed damaged mitochondria with ill-defined cristae and fragmentation of the rough endoplasmic reticulum. Treatments with CLHE and CFHE remarkably amended these histopathological and EM ultrastructural changes. In conclusion, both CLHE and CFHE may have antidiabetic and improvement effects on the liver function and structural integrity, which may be mediated, at least in part, suppression of inflammation and oxidative stress and enhancement of the antioxidant defence system.

Cernunnos deficiency is a rare genetic disorder characterized by immunodeficiency, microcephaly, growth retardation, bird-like facies, sensitivity to ionizing radiation, few autoimmune manifestations, premature aging of hematopoietic stem cells at an early age, and occasional myeloproliferative disease. Herein we present five Egyptian Cernunnos patients from 3 different families. We describe the patients' clinical phenotypes, their immunological profile as well as genetic results. Sequence analysis revealed three different mutations in the NHEJ1 gene: a nonsense variant c.532C > T; p.(Arg178Ter), an intronic variant c.178-1G > A and a frameshift insertion variant c.233dup; p.(Asn78LysfsTer14). In conclusion, Cernunnos deficiency can have a wide range of clinical features. The characteristic immune profile including a decrease in recent thymic emigrants and naive T cells, markedly elevated memory T cells together with normal to high IgM, and a decrease in IgG and IgA. This immune profile is highly suggestive of Cernunnos deficiency in T-B-NK + SCID patients especially surviving for older ages.

Sperm heterogeneity creates challenges for successful artificial insemination. Seminal plasma (SP) surrounding sperm is an excellent source for detecting reliable non-invasive biomarkers of sperm quality. Here, we isolated microRNAs (miRNAs) from SP-derived extracellular vesicles (SP-EV) of boars with divergent sperm quality statuses. Raw semen from sexually mature boars was collected for eight weeks. Sperm motility and normal morphology were analyzed, and the sperm was classified as poor- or good-quality based on standard cutoffs of 70% for the parameters measured. SP-EVs were isolated by ultracentrifugation and confirmed by electron microscopy, dynamic light scattering, and Western immunoblotting. The SP-EVs were subjected to total exosome RNA isolation, miRNA sequencing, and bioinformatics analysis. The isolated SP-EVs were round spherical structures approximately 30–400 nm in diameter expressing specific molecular markers. miRNAs were detected in both poor- (n = 281) and good (n = 271)-quality sperm, with fifteen being differentially expressed. Only three (ssc-miR-205, ssc-miR-493-5p, and ssc-miR-378b-3p) allowed gene targeting associated with cellular localization (nuclear and cytosol) and molecular functions (acetylation, Ubl conjugation, and protein kinase binding), potentially impairing sperm quality. PTEN and YWHAZ emerged as essential proteins for protein kinase binding. We conclude that SP-EV-derived miRNAs reflect boar sperm quality to enable therapeutic strategies to improve fertility.

Cattle and buffalo served as the first and second largest dairy animals, respectively, providing 96% milk products worldwide. Understanding the mechanisms underlying milk synthesis is critical to develop the technique to improve milk production. Thiolases, also known as acetyl-coenzyme A acetyltransferases (ACAT), are an enzyme family that plays vital roles in lipid metabolism, including ACAT1, ACAT2, ACAA1, ACAA2, and HADHB. Our present study showed that these five members were orthologous in six livestock species including buffalo and cattle. Transcriptomic data analyses derived from different lactations stages showed that displayed different expression patterns between buffalo and cattle. Immunohistochemistry staining revealed that ACAA1 were dominantly located in the mammary epithelial cells of these two dairy animals. Knockdown of inhibited mammary epithelial cell proliferation and triglyceride and β-casein secretion by regulating related gene expressions in cattle and buffalo. In contrast, overexpression promoted cell proliferation and triglyceride secretion. Finally, three novel SNPs (g.-681A>T, g.-23117C>T, and g.-24348G>T) were detected and showed significant association with milk production traits of Mediterranean buffaloes. In addition, g.-681A>T mutation located in the promoter region changed transcriptional activity significantly. Our findings suggested that play a key role in regulating buffalo and cattle milk synthesis and provided basic information to further understand the dairy animal lactation physiology.

Peroxisome injury occurs in the central nervous system (CNS) during multiple virus infections that result in neurological disabilities. We investigated host neuroimmune responses and peroxisome biogenesis factors during SARS-CoV-2 infection using a multiplatform strategy.|Brain tissues from COVID-19 (n=12) and other disease control (ODC) (n=12) patients, as well as primary human neural cells and Syrian hamsters, infected with a clinical variant of SARS-CoV-2, were investigated by ddPCR, RT-qPCR and immunodetection methods.|SARS-CoV-2 RNA was detected in the CNS of four patients with COVID-19 with viral protein (NSP3 and spike) immunodetection in the brainstem. Olfactory bulb, brainstem, and cerebrum from patients with COVID-19 showed induction of pro-inflammatory transcripts (IL8, IL18, CXCL10, NOD2) and cytokines (GM-CSF and IL-18) compared to CNS tissues from ODC patients (p<0.05). Peroxisome biogenesis factor transcripts (PEX3, PEX5L, PEX11β and PEX14) and proteins (PEX3, PEX14, PMP70) were suppressed in the CNS of COVID-19 patients compared to ODCs (p<0.05). SARS-CoV-2 infection of hamsters revealed viral RNA detection in the olfactory bulb at days 4 and 7 post-infection while inflammatory gene expression was upregulated in the cerebrum of infected animals by day 14 post-infection (p<0.05). Pex3 transcript levels together with catalase and PMP70 immunoreactivity were suppressed in the cerebrum of SARS-CoV-2 infected animals (p<0.05).|COVID-19 induced sustained neuroinflammatory responses with peroxisome biogenesis factor suppression despite limited brainstem SARS-CoV-2 neurotropism in humans. These observations offer insights into developing biomarkers and therapies, while also implicating persistent peroxisome dysfunction as a contributor to the neurological post-acute sequelae of COVID-19. This article is protected by copyright. All rights reserved.

BACKGROUND AND STUDY AIMS: Liver fibrosis is the underlying causeof hepatitis C virus (HCV)-related disease progression to endpoints such as cirrhosis, liver failure, and hepatocellular carcinoma. The aim of our study was to assess changes in hepatic fibrosis in patients with chronic HCV who had a fibrosis evaluation at two time points at least six months apart.

PATIENTS AND METHODS: This was a retrospective cohort study that included patients who had failed interferon therapy and received HCV retreatment with direct-acting antivirals (DAAs) at least six months later. Patients were evaluated previously for fibrosis according to liver biopsy and fibrosis biomarkers were evaluated before pegylated interferon and ribavirin (PEG/RBV) therapy. Fibrosis was re-evaluated with fibrosis-4 (FIB-4) scores before starting DAAs.

RESULTS: A total of 3,049 patients were included [age 43.47 ± 9.07 years, 55.20 % males] and baseline histopathology showed F1, F2, and F3 in 16.86 %, 46.21 %, and 36.93 %, respectively. The mean time interval between the last dose of previously failed IFN-therapy to the first dose of DAAs was 2.38 (±1.07) years. Overall, there was a significant increase in FIB-4 scores at retreatment times (from 11.71 ± 1.13 to 22.26 ± 1.68, p < 0.001). Patients with baseline FIB-4 < 1.45 (n = 1,569) and between 1.45 and 3.25 (n = 1,237) had significant increases in their FIB-4 at the retreatment time point [median difference; 0.41 (0.91) and 0.24 (1.5), p < 0.001, respectively], whereas patients with FIB-4 > 3.25 had significant reduction of their FIB-4 score at a retreatment timepoint [-0.98 (2.93), p ≤ 0.001].

CONCLUSION: Fibrosis progressed in most patients, even within six months for some patients, and this indicates retreatment of non-system vascular resistance patients even if they do not have significant fibrosis.