Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections.

We investigated the impact of antiviral treatment on the emergence of SARS-CoV-2 resistance during persistent infections in immunocompromised patients (n=15). All patients received remdesivir and some also received nirmatrelvir-ritonavir or monoclonal antibodies. Sequence analysis showed that nine patients carried viruses with mutations in the nsp12 (RNA dependent RNA polymerase), while four had viruses with nsp5 (3C protease) mutations. Infectious SARS-CoV-2 with a double mutation in nsp5 (T169I) and nsp12 (V792I) was recovered from respiratory secretions 77 days after initial COVID-19 diagnosis from a patient treated with remdesivir and nirmatrelvir-ritonavir. In vitro characterization confirmed its decreased sensitivity to remdesivir and nirmatrelvir, which was overcome by combined antiviral treatment. Studies in golden Syrian hamsters demonstrated efficient transmission to contact animals. This study documents the isolation of SARS-CoV-2 carrying resistance mutations to both nirmatrelvir and remdesivir from a patient and demonstrates its transmissibility in vivo.

Towards IVDR-compliance by implementing quality control steps in a quantitative extracellular vesicle-miRNA liquid biopsy assay for response monitoring in patients with classic Hodgkin lymphoma.

Previously, we showed that quantification of lymphoma-associated miRNAs miR-155-5p, -127-3p and let-7a-5p levels in plasma extracellular vesicles (EVs) report treatment response in patients with classic Hodgkin lymphoma (cHL). Prior to clinical implementation, quality control (QC) steps and validation are required to meet international regulatory standards. Most published EV-based diagnostic assays have yet to meet these requirements. In order to advance the assay towards regulatory compliance (e.g., IVDR 2017/746), we incorporated three QC steps in our experimental EV-miRNA quantitative real-time reverse-transcription PCR (q-RT-PCR) assay in an ISO-13485 certified quality-management system (QMS). Liposomes encapsulated with a synthetic (nematode-derived) miRNA spike-in controlled for EV isolation by automated size-exclusion chromatography (SEC). Additional miRNA spike-ins controlled for RNA isolation and cDNA conversion efficiency. After deciding on quality criteria, in total 107 out of 120 samples from 46 patients passed QC. Generalized linear mixed-effect modelling with bootstrapping determined the diagnostic performance of the quality-controlled data at an area under the curve (AUC) of 0.84 (confidence interval [CI]: 0.76-0.92) compared to an AUC of 0.87 (CI: 0.80-0.94) of the experimental assay. After the inclusion of QC steps, the accuracy of the assay was determined to be 78.5% in predicting active disease status in cHL patients during treatment. We demonstrate that a quality-controlled plasma EV-miRNA assay is technically robust, taking EV-miRNA as liquid biopsy assay an important step closer to clinical evaluation.

Malaria Diagnosis at the Pediatric Emergency Unit of a Teaching Hospital in Makurdi, North Central Nigeria.

Background: Globally, there were 241 million cases of malaria in 2020, with an estimated 627,000 deaths with Nigeria accounting for 27% of the global malaria cases. In sub-Saharan Africa, testing is low with only 28% of children with a fever receiving medical advice or a rapid diagnostic test in 2021. In Nigeria, there are documented reports of over-diagnosis and over-treatment of malaria in children. Therefore, this study examined the diagnosis of malaria at the Benue State University Teaching Hospital, Makurdi. Methods: A 5-year (2018-2022) retrospective study was carried out at the Emergency Pediatric Unit (EPU). Records of all children presenting to the EPU with an assessment of malaria were retrieved and reviewed. Data was analyzed using SPSS 23. Results: Out of 206 children reviewed, 128 (62.1%) were tested using either malaria RDT or microscopy while 78(37.9%) were not tested. Out of the number tested, 59(46.1%) were negative while 69(53.9%) tested positive, of which 14(20.3%) had uncomplicated malaria while 55(79.7%) had severe malaria. However, while 97.1% (n=67) of the positive cases were treated with IV artesunate, 69.5% (n=41) of those who tested negative and 88.5% (69) of those who were not tested also received IV artesunate. Moreover, while 85.5% (n=59) of those who tested positive received oral artemisinin-based combination therapy (ACT), 72.9% (n=43) of those who tested negative and 67.9% (53) of those who were not tested also received oral ACT. Conclusion: There was over-diagnosis of malaria, and subsequently, over-treatment. Hence continued emphasis on parasitological confirmation of malaria before treatment is recommended.

[Terminalia chebula water extract reduces joint inflammation by regulating cellular immunity in spleen cells of collagen-induced arthritis (CIA) rats through up-regulation of PD-1/PD-L1].

Objective To investigate the effect of Terminalia chebula water extract (TCWE) on the cellular immunity and PD-1/PD-L1 pathway in rats with collagen-induced arthritis (CIA). Methods SD rats were randomly divided into four groups: a control group, a CIA group, a TCWE group and a methotrexate (MTX) group, with 15 rats in each group. Except for the control group, SD rats in other groups were subcutaneously injected with type II collagen to establish the model of collagen-induced arthritis (CIA). The rats in the TCWE group were treated with 20 mg/(kg.d) TCWE and the rats in the MTX group were treated with 1.67 mg/(kg.d) MTX. After 14 days of treatment, the cartilage morphology was examined using hematoxylin-eosin (HE) staining, and splenic T lymphocyte apoptosis and Treg/Th17 cell ratio were detected by flow cytometry. The mRNA expressions of retinoid-related orphan nuclear receptor γt (RORγt), forkhead box P3 (FOXP3), PD-1 and PD-L1 in spleen were detected by reverse transcription PCR. The expression and localization of RORγt and FOXP3 were detected by immunohistochemical staining. The protein expressions of PD-1 and PD-L1 in splenic lymphocytes were detected by Western blot, and the levels of serum interleukin 17 (IL-17) and transforming growth factor ß (TGF-ß) in rats were detected by ELISA. Results Compared with CIA group, the pathological changes of cartilage and synovium were significantly alleviated in the TCWE group and the MTX group. Both the apoptosis rate of T lymphocytes in spleen and the ratio of Treg/Th17 cells increased. The expression of RORγt decreased, while the expressions of FOXP3, PD-1 and PD-L1 increased in spleen lymphocytes. The level of serum IL-17 decreased, while the level of serum TGF-ß increased. Conclusion TCWE treatment may activate PD-1/PD-L1 pathway in spleen cells to regulate cellular immunity, thus reducing cartilage injury in CIA rats.

Time profiles of energy balance in dairy cows in association with metabolic status, inflammatory status, and disease.

The early lactation period in dairy cows is characterized by complex interactions among energy balance (EB), disease, and alterations in metabolic and inflammatory status. The objective of this study was to cluster cows based on EB time profiles in early lactation and investigate the association between EB clusters and inflammatory status, metabolic status, oxidative stress, and disease. Holstein-Friesian dairy cows (n = 153) were selected and monitored for disease treatments during wk 1 to 6 in lactation. Weekly EB was calculated based on energy intake and energy requirements for maintenance and milk yield in wk 1 to 6 in lactation. Weekly plasma samples were analyzed for metabolic variables in wk 1 to 6, and inflammatory and oxidative stress variables in wk 1, 2, and 4 in lactation. Liver activity index (LAI) was computed from plasma albumin, cholesterol, and retino-binding protein concentration. First, cows were clustered based on time profiles of EB, resulting in 4 clusters (SP: stable positive; MN: mild negative; IN: intermediate negative; SN: severe negative). Cows in the SN cluster had higher plasma nonesterified fatty acids and ß-hydroxybutyrate concentrations, compared with cows in the SP cluster, with the MN and IN cluster being intermediate. Cows in the SN cluster had a higher milk yield, lower dry matter intake in wk 1, lower insulin concentration compared with cows in the SP cluster, and lower glucose and IGF-1 concentration compared with cows in the SP and MN clusters. Energy balance clusters were not related with plasma haptoglobin, cholesterol, albumin, paraoxonase, and liver activity index (LAI). Second, cows were grouped based on health status [IHP: cows with treatment for inflammatory health problem (endometritis, fever, clinical mastitis, vaginal discharge or retained placenta); OHP: cows with no IHP but treatment for other health problem (milk fever, cystic ovaries, claw, and leg problems, rumen and intestine problems or other diseases); NHP: cows with no treatments, in the first 6 weeks after calving]. Energy balance was not different among health status groups. The IHP cows had lower nonesterified fatty acids and greater insulin concentration in plasma compared with OHP. The IHP cows had lower plasma albumin concentration, lower LAI and higher haptoglobin concentration compared with OHP and NHP. Overall, EB time profiles were associated with the metabolic status of dairy cows in early lactation, but were only limitedly related with markers of inflammation and oxidative stress status. Inflammatory and metabolic status were related to disease events in early lactation and caused prolonged effects on liver metabolism.

Fibroblast Activation Protein-Directed Imaging Outperforms 18F-FDG PET/CT in Malignant Mesothelioma: A Prospective, Single-Center, Observational Trial.

The fibroblast activation protein (FAP) is highly expressed in tumor and stromal cells of mesothelioma and thus is an interesting imaging and therapeutic target. Previous data on PET imaging with radiolabeled FAP inhibitors (FAPIs) suggest high potential for superior tumor detection. Here, we report the data of a large malignant pleural mesothelioma cohort within a 68Ga-FAPI46 PET observational trial (NCT04571086). Methods: Of 43 eligible patients with suspected or proven malignant mesothelioma, 41 could be included in the data analysis of the 68Ga-FAPI46 PET observational trial. All patients underwent 68Ga-FAPI46 PET/CT, contrast-enhanced CT, and 18F-FDG PET/CT. The primary study endpoint was the association of 68Ga-FAPI46 PET uptake intensity and histopathologic FAP expression. Furthermore, secondary endpoints were detection rate and sensitivity, specificity, and positive and negative predictive values as compared with 18F-FDG PET/CT. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met, and the association between 68Ga-FAPI46 SUVmax or SUVpeak and histopathologic FAP expression was significant (SUVmax: r = 0.49, P = 0.037; SUVpeak: r = 0.51, P = 0.030).68Ga-FAPI46 and 18F-FDG showed similar sensitivity by histopathologic validation on a per-patient (100.0% vs. 97.3%) and per region (98.0% vs. 95.9%) basis. Per-region analysis revealed higher 68Ga-FAPI46 than 18F-FDG specificity (81.1% vs. 36.8%) and positive predictive value (87.5% vs. 66.2%). Conclusion: We confirm an association of 68Ga-FAPI46 uptake and histopathologic FAP expression in mesothelioma patients. Additionally, we report high sensitivity and superior specificity and positive predictive value for 68Ga-FAPI46 versus 18F-FDG.

Assessment of the Sensitivity of Foodborne Cronobacter spp. Strains and Other Enterobacteria to Temperature Stresses and Chlorine-Containing Biocides.

We examined the effects of elevated temperatures and biocides on survivability of food isolates of Cronobacter spp. (C. sakazakii) and concomitant enterobacteriaceae obtained in microbiological control of infant nutrition products. Increased resistance of certain strains of Cronobacter, Enterobacter cloacae, and Pantoea spp. to thermal processing was revealed. Salmonella, Pantoea, and Cronobacter bacteria were least sensitive to antimicrobial action of chlorine-containing agents. The above properties varied in the strains of the same species. Specifically, only two of three examined isolates of Cronobacter spp. demonstrated lower sensitivity to heat in comparison with the enterobacterial test-cultures of other species.

Genetic variation modulates susceptibility to aberrant DNA hypomethylation and imprint deregulation in naïve pluripotent stem cells.

Naïve pluripotent stem cells (nPSC) frequently undergo pathological and not readily reversible loss of DNA methylation marks at imprinted gene loci. This abnormality poses a hurdle for using pluripotent cell lines in biomedical applications and underscores the need to identify the causes of imprint instability in these cells. We show that nPSCs from inbred mouse strains exhibit pronounced strain-specific susceptibility to locus-specific deregulation of imprinting marks during reprogramming to pluripotency and upon culture with MAP kinase inhibitors, a common approach to maintain naïve pluripotency. Analysis of genetically highly diverse nPSCs from the Diversity Outbred (DO) stock confirms that genetic variation is a major determinant of epigenome stability in pluripotent cells. We leverage the variable DNA hypomethylation in DO lines to identify several trans-acting quantitative trait loci (QTLs) that determine epigenome stability at either specific target loci or genome-wide. Candidate factors encoded by two multi-target QTLs on chromosomes 4 and 17 suggest specific transcriptional regulators that contribute to DNA methylation maintenance in nPSCs. We propose that genetic variants represent candidate biomarkers to identify pluripotent cell lines with desirable properties and might serve as entry points for the targeted engineering of nPSCs with stable epigenomes. Highlights: Naïve pluripotent stem cells from distinct inbred mouse strains exhibit variable DNA methylation levels at imprinted gene loci.The vulnerability of pluripotent stem cells to loss of genomic imprinting caused by MAP kinase inhibition strongly differs between inbred mouse strains.Genetically diverse pluripotent stem cell lines from Diversity Outbred mouse stock allow the identification of quantitative trait loci controlling DNA methylation stability.Genetic variants may serve as biomarkers to identify naïve pluripotent stem cell lines that are epigenetically stable in specific culture conditions.

Bisphenol-A induced cyto-genotoxicity on retinal pigment epithelial cells is differentially modulated by a multi-supplement containing guarana, selenium, and L-carnitine.

Bisphenol A (BPA) may adversely affect human health by inducing oxidative stress and irreversible damage to cells. Bioactive compounds found in some functional foods, individually or in combination, can attenuate the negative effects of BPA exposure; an example is the multi-supplement containing guarana (Gua), selenium (Se), and L-carnitine (LC) -GSC- which has already demonstrated antioxidant, genoprotective, and immunomodulatory activities. This study aimed to determine the effect of GSC and its constituents on oxidative and genotoxic alterations triggered by BPA exposure in the retinal epithelial cell line. The cells exposed to BPA (0.001, 0.01, 0.1, 1, 3, and 10 µM) to determine the lowest concentration required to induce cyto-genotoxicity. ARPE-19 cells were then concomitantly exposed to the selected BPA concentration, GSC, and its components (Gua, 1.07 mg/mL; Se, 0.178 µg/mL; and LC, 1.43 mg/mL). Flow cytometry, biochemical assays, qRT-PCR, genotoxicity, apoptosis, and cellular proliferation. Based on our results, 10 µM of BPA could induce cyto-genotoxic and oxidative alterations. BPA did not alter the Bcl-2/BAX expression ratio but induced Casp3 and Casp8 overexpression, suggesting that apoptosis was induced mainly via the extrinsic pathway. GSC partially reversed the alterations triggered by BPA in ARPE-19 cells. However, Se had unexpected negative effects on ARPE-19 cells. The multi-supplement GSC may attenuate changes in oxidative and genotoxic markers related to exposure of ARPE-19 cells to BPA. our results revealed that the antioxidant, anti-apoptotic, and genoprotective properties of GSC were not universally shared by its individual, once Se did not exhibit any positive impact.

Exploring the experiences of UK-based private physiotherapists when running and progressing a physiotherapy business: a hermeneutic phenomenological study.

AIM: To explore the experiences of UK-based private physiotherapists when running and progressing a physiotherapy business. DESIGN: A hermeneutic phenomenological approach. PARTICIPANTS: Six UK-based private physiotherapy practice owners were recruited via purposive and snowball sampling. METHODS: In-depth, semi-structured video interviews (2 per participant), audio-recorded and transcribed. Field notes, respondent validation and a reflexive diary were used. Data underwent line-by-line analysis, identifying codes and themes. Constant comparison of data, codes and themes occurred throughout. Peer review was utilised, small sections of data and all emerging codes were independently reviewed. RESULTS: Three interconnecting themes. Working for myself: participants highlighted the freedom, flexibility and independence of business ownership, whilst acknowledging the additional pressures/challenges associated with this. Evolution of a practice: business growth was slow, requiring income supplementation initially. Successful growth often utilised luck and unexpected opportunities. Working with others: participants faced decisions regarding solo or joint ownership, when/what additional staff were required, whether staff should be employed or self-employed, and how to appropriately manage/support staff. CONCLUSIONS: Private practice ownership brings an array of benefits and challenges. Areas for future research include exploring the stresses of private roles and business ownership, the evolution of private physiotherapy practices, small-scale business partnerships, and employment vs self-employment. CONTRIBUTION OF THE PAPER.

Limited sensitivity of permafrost soils to heavy rainfall across Svalbard ecosystems.

Together with warming air temperatures, Arctic ecosystems are expected to experience increases in heavy rainfall events. Recent studies report accelerated degradation of permafrost under heavy rainfall, which could put significant amounts of soil carbon and infrastructure at risk. However, controlled experimental evidence of rainfall effects on permafrost thaw is scarce. We experimentally tested the impact and legacy effect of heavy rainfall events in early and late summer for five sites varying in topography and soil type on the High Arctic archipelago of Svalbard. We found that effects of heavy rainfall on soil thermal regimes are small and limited to one season. Thaw rates increased under heavy rainfall in a loess terrace site, but not in polygonal tundra soils with higher organic matter content and water tables. End-of-season active layer thickness was not affected. Rainfall application did not affect soil temperature trends, which appeared driven by timing of snowmelt and organic layer thickness, particularly during early summer. Late summer rainfall was associated with slower freeze-up and colder soil temperatures the following winter. This implies that rainfall impacts on Svalbard permafrost are limited, locally variable and of short duration. Our findings diverge from earlier reports of sustained increases in permafrost thaw following extreme rainfall, but are consistent with observations that maritime permafrost regions such as Svalbard show lower rainfall sensitivity than continental regions. Based on our experiment, no substantial in-situ effects of heavy rainfall are anticipated for thawing of permafrost on Svalbard under future warming. However, further work is needed to quantify permafrost response to local redistribution of active layer flow under natural rainfall extremes. In addition, replication of experiments across variable Arctic regions as well as long-term monitoring of active layers, soil moisture and local climate will be essential to develop a panarctic perspective on rainfall sensitivity of permafrost.

C-reactive protein as robust laboratory value associated with prognosis in patients with stage III non-small cell lung cancer (NSCLC) treated with definitive radiochemotherapy.

To evaluate the prognostic value of biomarkers from peripheral blood obtained as routine laboratory assessment for overall survival in a cohort of stage III non-small cell lung cancer (NSCLC) patients treated with definitive radiochemotherapy at a high-volume cancer center. Seven blood biomarkers from 160 patients treated with definitive radiochemotherapy for stage III NSCLC were analyzed throughout the course treatment. Parameters were preselected using univariable and multivariable proportional hazards analysis and were assessed for internal validity using leave-one-out cross validation. Cross validated classifiers including biomarkers in addition to important clinical parameters were compared with classifiers containing the clinical parameters alone. An increased C-reactive protein (CRP) value in the final week of radiotherapy was found as a prognostic factor for overall survival, both as a continuous (HR 1.099 (1.038-1.164), p < 0.0012) as well as categorical variable splitting data at the median value of 1.2 mg/dl (HR 2.214 (1.388-3.531), p < 0.0008). In the multivariable analysis, the CRP value-maintained significance with an HR of 1.105 (1.040-1.173) and p-value of 0.0012. The cross validated classifier using CRP at the end of radiotherapy in addition to clinical parameters separated equally sized high and low risk groups more distinctly than a classifier containing the clinical parameters alone (HR = 2.786 (95% CI 1.686-4.605) vs. HR = 2.287 (95% CI 1.407-3.718)). Thus, the CRP value at the end of radiation therapy has successfully passed the crucial cross-validation test. The presented data on CRP levels suggests that inflammatory markers may become increasingly important during definitive radiochemotherapy, particularly with the growing utilization of immunotherapy as a consolidation therapy for stage III NSCLC.

Effect of Magnetite Nanoparticles on Human Blood Components.

The qualitative composition and zeta potential of magnetite nanoparticles (size 4.2±1.2 nm) obtained by co-precipitation method were determined by X-ray and diffraction dynamic light scattering. The zeta potential of Fe3O4 particles was -15.1±4.5 mV. The possibility of interaction of magnetite nanoparticles with human blood plasma proteins and hemoglobin as well as with erythrocyte membranes was demonstrated by spectrophotometry, electrophoresis, and fluorescence methods. No changes in the sizes of hemoglobin molecules and plasma proteins after their modification by Fe3O4 particles were detected. The possibility of modifying the structural state of erythrocyte membranes in the presence of magnetite nanoparticles was demonstrated by means of fluorescent probe 1-anilinonaphthalene-8-sulfonate.

Application of a practical amniotic membrane ring made on-site for restoration of ocular surface health in dry eye disease.

PURPOSE: Dry eye disease (DED) is one of the most common ocular surface disorders worldwide. Despite different underlying pathogenic processes, DED is characterized by ocular surface inflammation, which in turn induces further damage to the corneal epithelium and its underlying structures. Amniotic membrane transplants are known to have potent anti-inflammatory effects and also have the ability to enhance epithelial healing. In this study, we aimed to evaluate the clinical efficacy of amniotic membrane ring (AMR) application in treating refractory dry eye disease. METHODS: A retrospective analysis of 22 patients treated with contact lens-like amniotic membrane rings was performed. This amniotic membrane ring was formed using an aspiration catheter covered by a large piece of amniotic membrane graft. The amniotic membrane was sutured to the catheter using eight sutures. In this way, a customized amniotic membrane ring was prepared for each patient. Patients' demographics, symptoms, use of medications, conjunctival inflammation, corneal staining, and visual acuity were compared before and after treatment. In addition, the amniotic membrane retention duration, the amniotic membrane's effect on ocular surface healing, follow-up time, and complications were evaluated. RESULTS: Twenty-eight eyes of 22 patients (18 females and 4 males) aged 53.32±13.36 (6-73) years were included. The AMR retention duration ranged from 5 to 16 days, with a mean of 11±3.09 days, at which time the amniotic membrane had dissolved or been removed inadvertently by the patient. Discomfort with the ring was seen in 1 of 28 eyes (3.6%). The patients reported symptomatic relief for a period of 3.64±1.25 months. Symptomatic relief was accompanied by a reduction of OSDI scores (from 63.39±17.24 to 33.19±12.45) (P<0.001), use of topical medications (from 4.21±1.03 to 2.42±0.50) (P<0.001), conjunctival hyperemia (from 1.57±1.19 to 0.35±0.48) (P<0.001), corneal staining (from 2.89±1.16 to 0.57±0.74) (P<0.001), and improvement in visual acuity (from 0.23±0.16 to 0.16±0.25 logMAR) (P=0.001). CONCLUSIONS: Amniotic membrane ring treatment might be used to treat refractory dry eye disease. This technique has an economic advantage over other commercially available amniotic bandage tissues and can be easily removed and replaced during a follow-up examination.

Isolated Roux-en-Y versus single loop pancreaticojejunal reconstruction after pancreaticoduodenectomy - a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Pancreaticoduodenectomy is a complex intra-abdominal operation used for the treatment of benign and malignant disease of the pancreatic head or periampullary region. Despite developments in surgical techniques, pancreaticoduodenectomy is still associated with high rate of postoperative complications. We performed this systematic review and meta-analysis to compare the surgical outcomes of isolated Roux-en-Y pancreaticojejunostomy (IRYPJ), and conventional pancreaticojejunostomy(CPJ). METHODS: We performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We searched the following electronic databases - PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Clinical-Trials.gov. Published trials comparing the efficacy and safety of IRYPJ and CPJ after pancreaticoduodenectomy were evaluated. The search terms were "pancreaticoduodenectomy," "Whipple," "pylorus-preserving pancreaticoduodenectomy," "pancreaticojejunostomy," "Roux-en-Y," and "isolated Roux loop pancreaticojejunostomy." Only randomised controlled trials comparing outcome of IRYPJ and CPJ after pancreaticoduodenectomy were included. The analysed outcome measures were postoperative pancreatic fistula (POPF), clinically relevant POPF (CR-POPF), bile leak and delayed gastric emptying (DGE). RESULTS: The initial search yielded 342 results but only four randomised control trials fulfilled the inclusion criteria and were included for data synthesis and meta-analysis. Meta-analysis of POPF revealed that IRYPJ is associated with less POPF compared to CPJ but the difference was not statistically significant (risk ratio = 0.58, p = 0.56). A similar finding was also observed with CR-POPF (risk ratio = 0.17, p = 0.87) and DGE (risk ratio = 0.74, p = 0.46). CONCLUSION: Isolated Roux-en-Y pancreaticojejunostomy is not associated with a superior outcome when compared to CPJ.

Spatiotemporal and seasonal transmission dynamics of Schistosoma haematobium and snail infectivity in Ase River catchment, Delta State, Nigeria.

Bulinus are intermediate snail hosts of Schistosoma haematobium. Despite their vectorial role, the transmission dynamics and infectivity of these intermediate snail hosts remain understudied in the Ase River. This longitudinal study evaluated the geospatial and seasonal transmission patterns and infectivity of three S. haematobium vectors between November 2020 and October 2022 in the Ase River catchment, Delta State, Nigeria. Eleven (11) geospatial water contact coordinates were mapped for monthly spatiotemporal collection of Bulinus species along the Ase River and its catchment, for two years. Snail sampling was performed for 45 min at each study site using scooping/hand-picking techniques and subsequently counted, identified and recorded. Snails of the Bulinus genus were individually placed in a beaker containing distilled water and exposed to light to shed cercariae which were identified to be human schistosome type. The number of infected snails for each month and season was also documented to analyze the spatiotemporal and seasonal transmission dynamics of infectivity. Out of the 2345 Bulinus snails collected, a total of 41.45% were found to be infected with S. haematobium. The monthly infectivity of Bulinus snails varied significantly (P < 0.05) throughout the study period (P = < 0.0001; F = 23.11; df = 11). Further analysis showed a strong significant association (χ2 = 23.57; df = 11; p = 0.015) between the study years. The Principal Component Analysis (PCA) results suggest that Bulinus infectivity within the Ase River catchment area was primarily associated with the months of February and January. B. truncatus consistently had the highest transmission potential, followed by B. globosus and B. senegalensis. ANOVA confirms that the monthly/study site infectivity and transmission potential in B. truncates, B. globosus and S. senegalensis were statistically, significant (P < 0.05). These results demonstrated a clear distinction in the patterns and relationships between the different months in terms of snail infectivity and seasonal transmission potential. This understanding will help in the continuous monitoring and targeted interventions to control schistosomiasis transmission in Ase River.

[Brain-derived neurotrophic factor in the acute and early recovery period of ischemic stroke: the role of nocturnal hypoxemia]. / Mozgovoi neirotroficheskii faktor pri ishemicheskom insul'te v ostrom i rannem vosstanovitel'nom periodakh: rol' nochnoi gipoksemii.

OBJECTIVE: To study the relationship between brain-derived neurotrophic factor (BDNF) and the severity of nocturnal hypoxemia in patients in the acute and early recovery period of ischemic stroke (IS). MATERIAL AND METHODS: We enrolled 44 patients (27 men, 17 women), aged 18-85 years, in the acute phase of IS. At 3-month follow-up, 35 people were examined (21 men and 14 women). In the acute period, in addition to routine diagnostic procedures, respiratory monitoring was carried out, and the serum level of BDNF was measured by enzyme-linked immunosorbent assay. BDNF level was also evaluated at 3-month follow-up visit. Neurological status and its dynamics in the acute period of stroke were assessed as part of the clinical routine according to the National Institutes of Health Stroke Scale (NIHSS) at admission and discharge. RESULTS: We found a direct correlation between the duration of hypoxemia with SpO2 less than 90% (r=0.327, p=0.035) and less than 85% (r=0.461, p=0.003) and BDNF level in the acute phase of IS. BDNF level in the acute period of IS was negatively correlated with the minimum saturation value (r=-0.328, p=0.034). There was a direct relationship between BDNF level in the early recovery period and the duration of hypoxemia with SpO2 less than 85% (r=-0.389, p=0.028). A regression model showed that BDNF level was associated with the minimum SpO2 level. No significant associations were found with indicators of sleep-disordered breathing severity, such as the apnea-hypopnea index and the oxygen desaturation index. CONCLUSION: The severity of nocturnal hypoxemia is associated with the increase in BDNF levels both in the acute and recovery periods of IS, regardless of the presence of concomitant breathing disorders during sleep.

Open-source device for high sensitivity magnetic particle spectroscopy, relaxometry, and hysteresis loop tracing.

Magnetic nanoparticles (MNPs) are used extensively across numerous disciples, with applications including Magnetic Particle Imaging (MPI), targeted hyperthermia, deep brain stimulation, immunoassays, and thermometry. The assessment of MNPs, especially those being designed for MPI, is performed with magnetic particle spectrometers, relaxometers, loop tracers, or similar devices. Despite the many applications and the need for particle assessment, there are few consolidated resources for designing or building such a MNP assessment system. Here, we describe the design and performance of an open-source device capable of spectroscopy, relaxometry, and loop tracing. We show example measurements from the device and quantify the detection sensitivity by measuring a dilution series of Synomag-D 70 nm (from 0.5 mg Fe/ml to 7 ng Fe/ml) with a 10 mT drive field at 23.8 kHz. The device measures 260 pg Fe with SNR = 1 and 1.3 ng at SNR = 5 in spectroscopy mode in under one second of measurement time. The system has a dynamic range of 60 µg to 260 pg Fe without changing the hardware configuration. As an example application, we characterize Synomag-D's relaxation time constant for drive fields 2-18 mT and compare the magnetization responses of two commonly used MNPs.