Background: Several hereditary-familial syndromes associated with various types of tumors have been identified to date, evidencing that hereditary cancers caused by germline mutations account for 5-10% of all tumors. Advances in genetic technology and the implementation of Next Generation Sequencing (NGS) have accelerated the discovery of several susceptibility cancer genes, allowing the detection of cancer-predisposing mutations in a larger number of cases. The aim of this study is to highlight how the application of an NGS-multi gene panel to a group of oncological patients subsequently leads to the improvement of healthy pathogenic variants/likely pathogenic variants (PVs/LPVs) carriers' identification and prevention of the disease in these cases. Methods: Starting from a total of 110 cancer patients carrying PVs/LPVs in genes involved in cancer susceptibility detected by a customized NGS panel of 27 cancer-associated genes, we enrolled 250 healthy collateral family members from January 2020 to July 2022. The specific PVs/LPVs identified in each proband were tested in healthy collateral family members by Sanger sequencing. Results: 131 out of the 250 cases (52%) weren’t carriers of the mutation detected in the affected relative, while 119 were carriers. Of these, 81/250 patients carried PVs/LPVs on BRCA1/2 (33%), 35/250 harbored PVs/LPVs on other genes beyond BRCA1 and BRCA2 (14%), and 3/250 (1%) were PVs/LPVs carriers both on BRCA1/2 and on another susceptibility gene. Conclusion: Our results show that the analysis of BRCA1/2 genes only would have resulted in a missed diagnosis in a number of cases and in the lack of prevention of the disease in a considerable percentage of healthy carriers with a genetic mutation (14%).

Hemolysin II (HlyII) – one of the pathogenic factors of Bacillus cereus, a pore-forming β-barrel toxin – possesses a C-terminal extension of 94 amino acid residues, designated as the C-terminal domain of HlyII (HlyIICTD), which plays an important role in the functioning of the toxin. Our previous work described a monoclonal antibody (HlyIIC-20), capable of strain-specific inhibi-tion of hemolysis caused by HlyII, and demonstrated the dependence of the efficiency of hemol-ysis on the presence of proline at position 324 in HlyII outside the conformational antigenic de-terminant. In this work, we studied 16 mutant forms of HlyIICTD. Each of the mutations, ob-tained by multiple site-directed mutagenesis leading to the replacement of amino acid residues lying on the surface of the 3D structure of HlyIICTD, led to a decrease in the interaction of HlyIIC-20 with the mutant form of the protein. Changes in epitope structure confirm the high conformational mobility of HlyIICTD required for the functioning of HlyII. Comparison of the effect of the introduced mutations on the effectiveness of interaction between HlyIICTD and HlyIIC-20 and a control antibody recognizing a non-overlapping epitope enabled identifying the amino acid residues N339, K340 included in the conformational antigenic determinant rec-ognized by HlyIIC-20.

Background: There is limited data on gender-based differences in atrial fibrillation (AF) treatment and prognosis. Our aim was to examine gender-related differences in medical attention in emergency department (ED) and follow-up (FU) among patients diagnosed with an AF episode and to determine whether there are gender-related differences in clinical characteristics, therapeutic strategies and long-term adverse events in this population. Methods: We performed a retrospective observational study of patients who presented to a tertiary hospital ER for AF from 2010-2015, with a minimum FU of one year. Data on medical attention received, mortality and other adverse outcomes were collected and analyzed. Results: Among the 2 013 patients selected, 1232 (60%) was female. Women were less likely than men to be evaluated by a cardiologist during the ED visit (11.5% vs. 16.6%, p=0.001) and were less likely to be admitted (5.9% vs. 9.5%, p<0.05). Electrical cardioversion was performed more frequently in men, both during the first episode (3.4% vs. 1.2%, p=0.001) and during FU (15.9% vs. 10.6%, p<0.001), in spite of a lower AF recurrence rate in women (9.9% vs 18.1%). During FU, women had more hospitalizations for heart failure (26.2% vs. 16.1%, p<0.001). Conclusions: In patients with AF, although no gender differences in mortality, there were significant differences in clinical outcomes, medical attention received, and therapeutic strategies. Women underwent fewer attempts at cardioversion, had a lower probability of being evaluated by cardiologists and showed a higher probability of hospitalization for heart failure. Being alert to these iniquities should facilitate to adopt measures to correct them.

Four leather substrates from different animals were treated by dispersions containing hydrophilic composite silica-hyperbranched poly(ethylene imine) xerogels. Antimicrobial activity was introduced by incorporating silver nanoparticles and /or benzalkonium chloride. The gel precursor solutions were also infused before gelation to titanium oxide powders typically employed for induction of self-cleaning properties. The dispersions from these biomimetically premade xerogels integrate environmentally friendly materials with short coating times. Scanning electron microscopy (SEM) provided information on the powder distribution onto the leathers. Substrate and coating composition were estimated by infrared spectroscopy (IR) and ener-gy-dispersive X-ray spectroscopy (EDS). Surface hydrophilicity and water permeability were assessed by water-contact angle experiments. The diffusion of the leather's initial components and xerogel additives into the water were measured by Ultraviolet-Visible (UV-Vis) spectroscopy. Protection against GRAM- bacteria was tested for Escherichia coli, Pseudomonas aeruginosa, and Klebsiella Pneumoniae against GRAM+ bacteria for Staphylococcus aureus, and Enterococcus faecalis and against fungi for Candida albicans. Antibiofilm capacity experiments were performed against Staphylococcus aureus, Klebsiella Pneumoniae, Enterococcus faecalis, and Candida albicans. The application of xerogel dispersions proved an adequate and economically feasible alternative to the direct gel formation into the substrate’s pores for the preparation of leathers intended for medical uses

Image analysis is widely applied in plant science for phenotyping and monitoring botanic and agricultural species. Although a lot of software is available, tools integrating image analysis and statistical assessment of seedling growth in large groups of plants are limited or absent, and do not cover the needs of the researchers. In this study, we developed Morley, a free, open-source graphical user interface written in Python. Morley automates the following workflow: (1) group-wise analysis of a few thousand seedlings from multiple images; (2) recognition of seeds, shoots and roots in seedling images; (3) calculation of shoot and root lengths and surface areas, (4) evaluation of statistically significant differences between plant groups, (5) calculation of germination rates, (6) visualization and interpretation. Morley is designed for laboratory studies of biotic effects on seedling growth, when molecular mechanisms underlying morphometric changes are analyzed. Performance was tested using cultivars of T. aestivum, P. sativum on seedlings of up to 1 week old. Accuracy of the measured morphometric parameters was comparable with the ones obtained using ImageJ and manual measurements. Dose-dependent laboratory tests for germination affected by new bioactive compounds and fertilizers, assuming extraction of seedlings from a substrate and/or dissection are among the suggested applications.

(1) Background: This case report focuses on a 46-year-old female patient diagnosed with a rare and aggressive form of breast cancer known as rapidly growing, ulcerated breast cancer. The patient exhibited rapid progression of the disease, experiencing discomfort and noticeable changes in the size and texture of the affected breast over a short period of time; (2) Methods: An intensive neoadjuvant chemotherapy regimen was employed as the primary treatment approach. The patient's response to this treatment was closely monitored and assessed. Various diagnostic tests and imaging techniques were utilized to evaluate the extent of the disease and track its response to the chemotherapy; (3) Results: The patient's response to the neoadjuvant chemotherapy regimen was remarkable, resulting in a complete pathologic response. This outcome, although unusual in rapidly growing, ulcerated breast cancers, highlights the effectiveness of neoadjuvant chemotherapy in managing large, locally advanced breast cancers; (4) Conclusions: The multidisciplinary approach employed in managing this complex breast cancer case proved to be crucial to the patient's favorable outcome. Despite the aggressive nature of the disease and the challenges posed by the rapid growth and ulceration, the patient achieved a positive result. This case contributes to the limited clinical literature on such unusual and aggressive breast cancer cases, providing valuable insights for future clinical practice.8

Background: Areca nut and betel quid (ANBQ) chewing is a widespread carcinogenic habit. The BENIT (ClinicalTrials.gov - NCT02942745) is the first known randomized trial designed for ANBQ chewers. Methods: We compared intensive behavioral treatment intervention condition (IC) with control condition (CC) in the BENIT and included a 5-stage early stopping rule. We report the primary analysis at stage 3. English literate adults in Guam and Saipan who self-identified as ANBQ chewers with tobacco were enrolled between August 2016 and August 2020. IC participants (n=88) received five in-person sessions over 22 days and a brochure containing quitting advice. CC participants (n=88) received only the brochure. Participants were assessed at baseline and day-22 follow-up. Self-reported chewing status at day-22 was determined by a composite of two survey items with disparate wording and response options for cross-verification. Results: Cessation rates were 38.6% (IC) and 9.1% (CC). Proportional hazards regression revealed a p=0.0058, which met the Stage 3 criteria for significance and an estimated reduction in ANBQ chewing for IC compared to the CC of 71% (95% CI: 41%-88%). Conclusion: Robust self-reported intervention effects at day-22 suggests that intensive cessation programs such as BENIT should be further developed and implemented on a larger scale.

In neuroendocrine neoplasms (NENs), the use of new radiopharmaceuticals has improved the accuracy of diagnosis and staging, refined surveillance approaches, and introduced specific and personalized radiation therapies. Nuclear medicine has therefore acquired a crucial role in the management of NENs patients by improving their risk stratification and personalized therapies. Artificial intelligence (AI) and radiomics can enable physicians to further improve the overall efficiency and accuracy of the use of these tools in both di-agnostic and therapeutic settings by improving the prediction of tumor grade, differential diagnosis from other malignancies, assessment of tumor behavior and aggressiveness, and prediction of treatment response. This systematic review aims to describe the state-of-the-art on AI and radiomics applications in molecular imaging of NENs.

Background: In trials using normofractionated regimen, the radiation-induced lymphocyte apoptosis (RILA) and the chromosomal damage assays (CDA) have shown prognostic roles of radiation-induced adverse events. The main objectives here were to validate RILA and CDA in extreme and moderate hypofractionation regimens for breast (FAST) and prostate (CHHiP) cancers. Methods: Blood samples were collected from 400 volunteers included in FAST and CHHiP trials. The primary endpoints (PE) were first change in photographic breast appearance and first grade ≥2 RTOG bladder or bowel toxicity (BBT) in FAST and CHHiP, respectively. The secondary endpoints was first grade ≥2 breast clinical changes (BCC) in FAST and BBT using different scales in CHHiP. Results: 103 FAST and 297 CHHiP patients with lab and clinical data were included. In FAST trial, no significant association of RILA with the primary endpoint was observed. A significant association of higher RILA levels with lower risk of any RIAE was found. The risk of developing grade ≥2 RIAE decreased significantly for patients with RILA≥24% compared to those with RILA≤16% with a HR of 0.50 (95%CI 0.25-1.00, p=0.012). Concerning chromosomic aberrations, no significant associations were found with change in photographic breast appearance nor with the secondary endpoint of any RIAE. In CHHiP trial, a decreased risk of grade≥2 RTOG bladder or bowel RIAE was observed for increasing values of RILA (HR 0.97, 95%CI 0.94-1.01, p=0.11) but did not reach statistical significance. Concerning chromosomic aberrations, we found significant association of higher levels of micronuclei per cell with lower risk of gr2+ RTOGAE (p=0.021 for trend test across tertiles; p=0.023 for upper vs lower tertile). Conclusions: This study is the first to evaluate RILA and CDA as predictors of late effects after breast and prostate RT in the “hypofractionation” era. Development of toxicity biomarkers whatever the RT fractionation are urgently needed.

Headstarting is a conservation approach that suggests offering an advantage to a population by improving egg production, survival of embryos and/or juveniles. In this article, we are providing the quantitative data obtained during 10-years for different stages of headstarting (production of eggs per pair, hatching and fledging rates) and the resulting impact (survival to maturity, philopatry rate, sex ratio, apparent survival, growth/decline rate) on the local population of the critically endangered spoon-billed sandpiper. We have shown that headstarting gain is reduced over time from fledging to long-term recruitment to the local breeding population. The possible reasons for this reduction are suggested and discussed. The unexpected finding was a drastic difference in sex ratios of the new recruits which was about even for headstaring, but strongly male-biased for wild reared birds. We suggest that to happen due to increased mortality of female chicks in nature. We have also shown only headstarting could stop the global decline of the species, particularly once the suggested improvements are implemented and the number of pairs involved is scaled up. Headstarting also had a significant social effect due to involvement of in-creasing numbers of people both in the local communities in Chukotka and from many countries on the flyway into searching for marked birds and learning about waders, raising awareness about ecological problems on the East Asian-Australasian Flyway, thus, making the need for conservation actions on the flyway more obvious and sensible.

Hepatitis B virus (HBV) is a major global health challenge. Emerging evidence suggests that poor knowledge and stigma are impacting HBV control efforts in sub-Saharan Africa (SSA), however their role is not well understood. We conducted a cross-sectional study of adults aged ≥ 18 years in a community and pharmacy setting in Freetown, Sierra Leone. A structured questionnaire was used to assess knowledge, stigmatizing attitudes, and health-seeking behaviors regarding HBV. Logistic regression was used to identify predictors of HBV knowledge and related stigma. A total of 306 adult participants were enrolled (50.7% male, 7.5% HBV positive and 11.7% vaccinated). Overall, 52.2% had comprehensive HBV knowledge and 49.3% expressed a stigmatizing attitude towards people with HBV. Notwithstanding, 72.2% stated they would receive the HBV vaccine if offered, 80.4% would take anti-HBV medication and 78.8% would be willing to attend clinic regularly. Comprehensive HBV knowledge was associated with HBV positive status (aOR 4.41; p = 0.029) and being vaccinated against HBV (aOR 3.30; p = 0.034). HBV-related stigma was associated with secondary or higher level of education (aOR 2.36; p &lt; 0.001), good HBV knowledge (aOR 2.05; p = 0.006) and pharmacy setting (aOR 1.74, p = 0.037). These findings suggest that education and stigma reduction may benefit HBV elimination efforts in SSA.

Acute kidney injury (AKI) caused by ischemia followed by reperfusion (I/R) is characterized by intense anion superoxide (O2•-) production and oxidative damage. We investigated whether extracellular vesicles secreted by adipose tissue mesenchymal cells (EVs) administrated during reperfusion can suppress the exacerbated mitochondrial O2•- formation after I/R. We used Wistar rats submitted to bilateral renal arterial clamping (30 min) followed by 24 h of reperfusion. The animals received EVs (I/R+EVs group) or saline, I/R group) in the kidney subcapsular space. The 3rd group was of the false-operated rats (SHAM). Mitochondria were isolated from proximal tubule cells and immediately used. Amplex Red™ was used to measure mitochondrial O2•- formation and MitoTracker® Orange to evaluate Δψ. In vitro studies were carried out by using human renal proximal tubular cells (HK-2) co-cultured or not with EVs under hypoxia conditions. Administration of EVs restored O2•- formation to SHAM levels in all mitochondrial functional conditions. The expression of catalase and superoxide dismutase remained unmodified; transcription of heme oxygenase-1 (HO-1) was upregulated. The co-cultures of HK-2 cells with EVs revealed an intense decrease in apoptosis. We conclude that the mechanisms by which EVs recover the renal structure and function after I/R are related to the normalization of the mitochondrial redox environment. The intravesicular catalase is central in the preservation mechanisms that, with the aid of the upregulated antioxidant HO-1/Nuclear factor erythroid 2-related factor 2 system, depress early processes of cell death after I/R and open new vistas for the treatment of AKI.

The purpose of the study was to describe and compare the pharmacokinetics of five commercial edible marijuana products, determine the influence of body composition on pharmacokinetics, and, in light of epidemiology suggesting marijuana may offer diabetes protection, explore the influence of edible marijuana on glucose tolerance. Seven regular users of marijuana self-administered five edible products in a randomized crossover design; each product contained 10mg of delta-9-tetrahydrocannabinol (THC). 30-minutes following marijuana ingestion, participants imbibed a 75g glucose beverage. Time-to-peak plasma THC concentration ranged between 35 and 90 minutes; maximal plasma THC concentration (Cmax) ranged between 3.2 and 5.5 ng/mL. Differences between products in plasma THC concentration during the first 20-to-30 minutes were detected (P=0.019). Relations were identified between body composition and pharmacokinetic parameters for some products; however, none of these body composition characteristics were consistently related to pharmacokinetics across all five of the products. Edible marijuana had no effect on oral glucose tolerance compared with a marijuana-free control (Matsuda Index; P>0.395). Commercially available edible marijuana products evoke different plasma THC concentrations shortly after ingestion, but do not appear to influence acute glucose regulation. These data may allow marijuana users to make informed decisions pertaining to rates of edible marijuana ingestion and avoid overdose.

There are uncertainties associated with every phase of the stock assessment process, ranging from the collection of data, assessment model choice, model assumptions and interpretation of risk to the implementation of management advice. The dynamics of fish populations are complex, and our incomplete understanding of those dynamics (and limited observations of important mechanisms) necessitate that models are simpler than nature. The aim is for the model to capture enough of the dynamics to accurately estimate trends and abundance and to provide advice to managers about sustainable harvests. The \textit{status quo} approach to assessment modelling has been to identify the `best' model, based on diagnostics and model selection criteria, and to generate advice from that model, mostly ignoring advice from other model configurations regardless of how closely they performed relative to the chosen model. We review the suitability of the ensemble modelling paradigm to more fully capture uncertainty in stock assessment model building and the provision of advice. We recommend further research to evaluate potential gains in modelling performance and advice from the use of ensemble modelling, while also suggesting revisions to the formal process for reviewing models and providing advice to management bodies.

Background: This study tested the hypothesis that treatment of symptomatic, partial-thickness rotator cuff tear (sPTRCT) with fresh, uncultured, unmodified, autologous adipose derived regenerative cells (UA-ADRCs) isolated from lipoaspirate at the point of care is safe and more effective than corticosteroid injection. Methods: Subjects aged between 30 and 75 years with sPTRCT who did not respond to physical therapy treatments for at least six weeks were randomly assigned to receive a single injection of an average 11.4×10⁶ UA-ADRCs (in 5 mL liquid; mean cell viability: 88%) (n=11; modified intention-to-treat (mITT) population) or a single injection of 80 mg of methylprednisolone (40 mg/ml; 2 mL) plus 3 mL of 0.25% bupivacaine (n=5; mITT population), respectively. Safety and efficacy were assessed using the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), RAND Short Form-36 Health Survey and pain visual analogue scale (VAS) at baseline (BL) as well as three weeks (W3), W6, W9, W12, W24, W32, W40 and W52 post treatment. Fat-saturated T2 weighted magnetic resonance imaging of the shoulder was performed at BL as well as at W24 and W52 post treatment. Results: No severe adverse events related to the injection of UA-ADRCs were observed in the 12 months post treatment. The risks connected with treatment of sPTRCT with UA-ADRCs were not greater than those connected with treatment of sPTRCT with corticosteroid injection. However, one subject in the corticosteroid group developed a full rotator cuff tear during the course of this pilot study. Despite the small number of subjects in this pilot study, those in the UA-ADRCs group showed statistically significantly higher mean ASES total scores at W24 and W52 post treatment than those in the corticosteroid group (p < 0.05). Discussion: This pilot study suggests that the use of UA-ADRCs in subjects with sPTRCT is safe and leads to improved shoulder function without adverse effects. To verify the results of this initial safety and feasibility pilot study in a larger patient population, a randomized controlled trial on 246 patients suffering from sPTRCT is currently ongoing.

Antimicrobial stewardship efforts are an emphasis among many institutions around the world to combat inappropriate antimicrobial utilization, rising healthcare costs and emerging antimicrobial resistance. Implementation of new innovative strategies may be challenging for many institutions with limited or constrained resources. Using proven effective methods as evidenced by other institutions in the peer-reviewed literature may offer an opportunity to evaluate institution-specific practices, which may be implemented locally. A structured examination and survey of the peer-reviewed, stewardship literature by an expert group of clinicians, scholars and educators determined the most influential publications from 2016. Herein, the top thirteen manuscripts are reviewed to aid clinicians identify potential stewardship opportunities and serve as an educational tool for trainees and others.

Paclitaxel is a natural, highly lipophilic anti proliferative drug widely used in medicine. We have studied the release of tritium-labeled paclitaxel (³H-PTX) from matrices destined for the coating of vascular stents and produced by the electrospinning method from the solutions of polycaprolactone (PCL) with paclitaxel (PTX) in hexafluoisoropropanol (HFIP) and/or solutions of PCL with PTX and human serum albumin (HSA) in HFIP or HIFP-dimethyl sulphoxide (DMSO) blend. The release of PTX has been shown to depend on the solvent and the composition of electrospinning solution, as well as the composition of the surrounding medium, particularly the concentration of free PTX and PTX-binding biomolecules present in human serum. It was shown that 3D matrices can completely release PTX without weight loss. Two-phase PTX release from optimized 3D matrices was obtained: ~27% of PTX was released in the first day, another 8% were released over the next 26 days. Wherein ~2.8%, ~2.3%, and ~0.25% of PTX was released on day 3, 9, and 27, respectively. Considering PTX toxicity, the rate of its diffusion through the arterial wall, and the data obtained the minimum cytostatic dose of the drug in the arterial wall will be maintained for at least three months.

Background. The course of the COVID-19 epidemic process depends on population immunity which prevents pathogen spread among the population. Aim: to study the evolution of SARS-CoV-2 humoral immunity in the Belarusian population relative to COVID-19 pandemic dynamics. Materials and methods. The work was carried out according to a methodology for assessing population immunity developed by Rospotrebnadzor (Russia) and the Belarusian Ministry of Health with the participation of the St. Petersburg Pasteur Institute (SPPI), taking into account WHO recommendations. The study was approved by the Bioethics Committee of Belarus and the SPPI Bioethics Committee. Participant selection was carried out by questionnaire using a cloud (internet server) service. To monitor population immunity, a cohort of 4,661 people (participating in all stages of seromonitoring) was formed from the overall volunteer group. Volunteers were randomized by age group (1-17, 18-29, 30-39, 40-49, 50-59, 60-69, 70+ years), region, and professional group. For the detection of antibodies (Abs) to nucleocapsid (Nc) and S glycoprotein receptor-binding domain (RBD), corresponding assay systems were used following manufacturer instructions. The study was conducted in 4 stages according to a single scheme. Results. In the 1st stage (pandemic month 15), collective immunity was due mainly to Nc+RBD+ Ab status alone. By the 2nd stage (carried out after 4 months), their share decreased 1.2-fold, while the share of volunteers who had only RBD Abs increased 1.7-fold. In the 3rd and 4th stages (carried out after 9 and 19 months), the share of persons with RBD+Nc‒ compared to the 2nd stage decreased by 3.5%; the proportion of persons with Nc+RBD‒ Abs increased by 1.5-fold. The most important factor in population immunity was vaccination of the population, the coverage of which reached 70% by the 4th stage. Among vaccines, the Sputnik V and Sputnik Light vector designs were used most often. The whole-virion, inactivated BIBP-CorV vaccine was used less often. Conclusion. The evolution of collective SARS-CoV-2 humoral immunity included a set of changes in circulating Ab levels (Nc, RBD). The hybrid immunity formed helped to reduce the incidence to nearly zero.

Celtis iguanaea is popularly used in the treatment of diabetes mellitus. However, thorough chemical and pharmacological investigations regarding its activity are lacking. In this study, we investigated the effects of the hydroalcoholic extract from C. iguanaea (CI) on markers of cardiovascular diseases and the glucose metabolism in cholesterol-fed rats. Therefore, hypercholesterolemic rats (1% cholesterol) were orally treated with CI (150, 300, or 600 mg/kg) or simvastatin (4 mg/kg) (n = 6) once a day for 30 days along with a hypercholesterolemic diet. A control group (C) was given saline solution. CI showed significant decreases in serum levels of total cholesterol, LDL-cholesterol, HMG-CoA-reductase, IL-1, IL-6, TNF-α, and IFN-γ when compared to group C (p ˂ 0.05). Hypoglycemic effects were observed along with a decrease of the activity of sucrase (CI 600), maltase (CI 150, CI 300), and an increase in muscle glycogen levels (CI 300). Antioxidant effects were observed in plasma, and the histopathological analysis showed a significant decrease in the liver fat area for CI compared to group C (p < 0.001). Our results suggest that the biological effects of CI could be related to the presence of flavonoids that possibly exert antioxidant, enzymatic inhibitory, and insulin-mimetic effects.

The cucumber mosaic virus (CMV) 2b protein is a suppressor of plant defenses and a pathogenicity determinant. Amongst the 2b protein’s host targets is the RNA silencing factor Argonaute 1 (AGO1), which it binds to and inhibits. In Arabidopsis thaliana, if 2b-induced inhibition of AGO1 is too efficient it induces reinforcement of antiviral silencing by AGO2, and triggers increased resistance against aphids, CMV’s insect vectors. These effects would be deleterious to CMV replication and transmission, respectively, but are moderated by the CMV 1a protein by sequestering sufficient 2b protein molecules into P-bodies to prevent excessive inhibition of AGO1. Mutant 2b protein variants were generated and red and green fluorescent protein fusions used to investigate subcellular colocalization with AGO1 and the 1a protein, and the effects of mutations on complex formation with the 1a protein and AGO1 were investigated using bimolecular fluorescence complementation and co-immunoprecipitation assays. Although we found that residues 56-60 influenced the 2b protein’s interactions with the 1a protein and AGO1, it appears unlikely that any single residue or sequence domain is solely responsible. In silico predictions of intrinsic disorder within the 2b protein secondary structure were supported by circular dichroism (CD) but not by nuclear magnetic resonance (NMR) spectroscopy. Intrinsic disorder provides a plausible model to explain the 2b protein’s ability to interact with AGO1, the 1a protein and other factors. However, the reasons for the conflicting conclusions provided by CD and NMR must first be resolved.

In this paper, we present an experimental procedure to enhance the dimensional accuracy of fabrication via Stereolithography (SLA) of features at the micro-scale. Using a custom benchmark part, deviations in feature dimensions (micro-pores diameters and depths) were detected and measured by confocal microscopy. Samples characterization and experimental observations allowed the identification of inaccuracy sources, mainly due to the laser beam scanning strategy and to the incomplete removal of uncured liquid resin in post-processing (i.e., IPA washing). As a technology baseline, the measured dimensional errors on pores diameters were up to -46%. A compensation method of the nominal laser spot diameter (85m) was defined and implemented resulting in relevant improvements in dimensional accuracy of 9.8% and 11.3% on full-open pores diameter and depth, respectively. Further investigation was performed on a customized test part to adjust the calibration procedure. The measurements revealed that the estimate of the laser beam spot size is 968m. Measurements on micro-pores having different sizes revealed that a constant compensation parameter (i.e., C=85, 96, 120m) is not fully effective at the micro-scale, where average errors still remain at -24%, -18.8%, and -16% for compensations equals to 85, 96 and 120m, respectively. A further experimental campaign allowed the identification of an effective nonlinear compensation law where the compensation parameter depends on the micro-feature size C= f (D). Results show a sharp improvement in dimensional accuracy on micro-pore fabrication, with errors consistently below +8.2%. The proposed compensation method can be extended for the fabrication of any micro-features without restrictions on the specific technology implementation. Concerning the inaccuracy introduced by the laser path, experimentation with a customized part allowed the optimization of the part orientation to reduce the errors and their differences along the X and Y machine axes.

The recent introduction of foot-and-mouth disease virus serotype O (O/EA-2 topotype) in Southern Africa region has changed virus dynamics and the FMD vaccine requirements. This study describes an assessment of the heterologous antibody responses induced by O Manisa vaccine (three PD50/dose) against a representative O/EA-2 virus collected from an FMD outbreak in Zambia. Commercial and subsistence cattle herds were monitored following vaccination, where the benefits of employing a double vaccination schedule were compared to single-dose vaccination. Testing using virus neutralisation showed cattle that received two vaccine doses had a mean reciprocal log virus neutralisation titre of 2.02 (standard error [SE] = 0.16, n = 9) for commercial herds and 1.65 (SE = 0.17, n = 5) for subsistence herds , 56 days after first vaccination (dpv). Significantly lower mean titres were observed for single-dosed commercial herds (0.90, SE = 0.08, n = 9) and subsistence herds (1.15, SE = 0.18, n = 3), 56 dpv. Comparison of these results and those generated by solid-phase competitive ELISA by cohen’s kappa coefficient observed a statistically significant (ρ = 0.598 for 1:10 dilution, and ρ = 0.562 for 1:30 dilution of SPCE % inhibition results, p &lt; 0.001 for both dilutions) positive correlation.

Reactions of picolinamides with 1,3-propanesultone in methanol followed by the treatment with ketones led to a series of previously unknown chemical transformations, yielding first pyridinium salts (2a-f) with a protonated endocyclic nitrogen atom and then heterocyclic salts (3a-j) containing a 4-imidazoline ring. The structures of intermediate and final products were determined by IR and 1H, 13C NMR spectroscopy and X-ray study. The effects of the ketone and alcohol structures on the product yield were studied by quantum-chemical calculations. The stability of salts 3a-j towards hydrolysis and alcoholysis makes them excellent candidates for the search of new types of biologically active compounds.

Background: Although electronic health records (EHR) provide useful insights into disease patterns and patient treatment optimisation, their reliance on unstructured data presents a difficulty. Because of their narrative structure, echocardiography reports, which provide extensive pathology information for cardiovascular patients, are particularly challenging to extract and analyse. Although natural language processing (NLP) has been utilised successfully in a variety of medical fields, it is not commonly used in echocardiography analysis. Objectives: To develop an NLP-based approach for extracting and categorizing data from echocardiography reports by accurately converting continuous (e.g. LVOT VTI, AV VTI, and TR Vmax) and discrete (e.g. Regurgitation severity) outcomes in semi-structured narrative format into structured and categorized format, allowing for future research or clinical use. Methods: 135,062 Trans-Thoracic Echocardiogram (TTE) reports were derived from 146967 baseline Echocardiogram reports and split into three cohorts: Training and Validation (n = 1075), Test Dataset (n = 98) and Application Dataset (n = 133,889). The NLP system was developed and iteratively refined using medical expert knowledge. The system was used to curate a moderate-fidelity database from extractions of 133,889 reports. A hold-out validation set of 98 reports was blindly annotated and extracted by two clinicians for comparison with the NLP extraction. Agreement, discrimination, accuracy and calibration of outcome measure extractions were evaluated. Results: Continuous outcomes including LVOT VTI, AV VTI, and TR Vmax exhibited perfect inter-rater reliability using intra-class correlation scores (ICC=1.00, P< 0.05) alongside high R2 values, demonstrating an ideal alignment between the NLP system and clinicians. Good level (ICC =0.75-0.9, P<0.05) of inter-rater reliability were observed for outcomes such as LVOT Diam, Lateral MAPSE, Peak E Velocity, Lateral E' Velocity, PV Vmax, Sinuses of Valsalva, and Ascending Aorta diameters. Furthermore, the accuracy rate for discrete outcome measures was 91.38% in the confusion matrix analysis, indicating effective performance. Conclusions: The NLP-based technique yielded good results when it came to extracting and categorising data from echocardiography reports. The system demonstrated a high degree of agreement and concordance with clinician extractions. This study contributes to the effective use of semi-structured data by providing a useful tool for converting semi-structured text to structured echo report that can be used for data management. Additional validation and implementation in healthcare settings can improve data availability and support research and clinical decision-making.

Left ventricular (LV) remodeling is a dynamic process which is characterized by abnormal LV wall thickness and altered myocardial geometry, and it is considered as a negative prognostic factor in both heart failure with reduced eject fraction (HFrEF) and heart failure with preserved eject fraction (HFpEF). Hypertension, type 2 diabetes (T2D) and obesity are strongly correlated with the development and the progression of LV remodeling, LV hypertrophy and LV systolic and/or diastolic dysfunction. Indeed, the beneficial impact of exercise training on primary and secondary prevention of cardiovascular disease (CVD) has been well-established. Recent studies highlight that exercise training enhances functional capacity, muscle strength and endurance, cardiac function and cardiac-related biomarkers, among patients with established coronary artery disease (CAD) or HF, thus improving substantially their cardiovascular prognosis, survival rates and needs for rehospitalization. Therefore, in this review article, we discuss the evidence of LV remodeling in patients with cardiometabolic risk factors, such as hypertension, T2D, obesity, and also highlight the current studies evaluating the effect of exercise training on LV remodeling in these patients.

In the current study, we assessed the effects of conventional and Ultra High Dose Rate (UHDR) irradiation on behavioral and cognitive performance one month following exposure and assessed whether these effects were associated with alterations in the number of immune cells in the hippocampus using flow cytometry. Conventional- and UHDR-irradiated mice showed impaired novel object recognition. During fear learning, conventional- and UHDR-irradiated mice moved less during the inter-stimulus-interval (ISI) and UHDR-irradiated mice also moved less during the baseline period (prior to the first tone). In irradiated mice, reduced activity levels were also seen in the home cage; conventional- and UHDR-irradiated mice moved less during the light period and UHDR-irradiated mice moved less during the dark period. Following behavioral and cognitive testing, infiltrating immune cells in the hippocampus were analyzed by flow cytometry. The percent Ly6G+ CD45+ cells in the hippocampus was lower in conventional- and UHDR-irradiated than sham-irradiated mice, suggesting that neutrophils might be particularly sensitive to radiation. The percent of Ly6G+ CD45+ cells in the hippocampus was positively correlated with the time spent exploring the novel object in the object recognition test, suggesting that the reduced percent Ly6G+ CD45+ cells in the hippocampus might mediate some of the detrimental radiation-induced cognitive effects.

Red mud (RM) is composed of a waste alkaline solution (pH = 13.3) obtained from the production of alumina. It contains high concentrations of soluble hematite (Fe2O3), goetite (FeOOH), gibisite [Al(OH)3], a boemite (AlOOH), anatase (Tetragonal - TiO2), rutile (Ditetragonal dipyramidal - TiO2), hydrogarnets [Ca3Al2(SiO4)3−x(OH)4x], and perovskite (CaTiO3). It was shown to be an excellent catalytic mixture for biodiesel production. To demonstrate the value of RM, an environmentally friendly process of transesterification in aqueous medium using waste cooking oil (WCO), MeOH and waste alkaline solution (WAS) obtained from aluminum production was proposed. Triglycerides of WCO reacted with MeOH at 60 oC to yield mixtures of fatty acid methyl esters (FAMEs) in the presence of 0.019% (w/w) WAS/WCO using the WAS (0.204 mol L-1, predetermined by potentiometric titration) from aluminum production by the Bayer process. The use of the new catalyst (WAS) resulted in a high yield of the products (greater than 99% yield).

Cryptococcus neoformans is a human multidrug-resistant yeast with high mortality rates in immunocompromised patients. Recently, the synthetic peptide Mo-CBP3-PepII emerged as a potent anticryptococcal molecule with an MIC50 at low concentration. Here, the mechanisms of action of Mo-CBP3-PepII were deeply analyzed to provide new information about how it led C. neoformans cells to death. Light and fluorescence microscopies, analysis of enzymatic activities, and proteomic analysis were employed to understand the effect of Mo-CBP3-PepII on C. neoformans cells. Light and fluorescence microscopies revealed Mo-CBP3-PepII induced the accumulation of anion superoxide and hydrogen peroxide in C. neoformans cells. In addition to a reduction in the activity of superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT) in the cells treated with Mo-CBP3-PepII. In the presence of Ascorbic acid (AsA), no ROS were detected and Mo-CBP3-PepII lost the inhibitory activity against C. neoformans. Yet, Mo-CBP3-PepII inhibited the activity of lactate dehydrogenase (LDH), ergosterol biosynthesis, and induced the decoupling of cytochrome c from the mitochondrial membrane. Proteomic analysis revealed a reduction in the abundance of proteins related to energetic metabolism, DNA and RNA metabolism, pathogenicity, protein metabolism, cytoskeleton, and cell wall organization and division. Our findings indicated that Mo-CBP3-PepII might have multiple mechanisms of action against C. neoformans cells, mitigating the development of resistance and thus being a potent molecule to be employed in the production of new drugs against C. neoformans infections.

Introduction: Body size is correlated with many aspects of an animal species' natural history, such as life span, abundance, dispersal capacity and diet breadth. However, contrasting trends have been reported for the relationship between body size and these ecological traits. Methods: Butterfly species from fruit-feeding guilds were used to investigate whether body size correlates with species abundances, dispersal, permanence, and diet breadth in a Neotropical savanna in Brazil (Cerrado). We used Blomberg’s K and Phylogenetic Generalized Least Squares models (PGLS) to measure phylogenetic signal strength in species traits, and to estimate size-dispersal-diet breadth associations while taking shared ancestry into account. Results: 539 individuals from 27 species were captured, and 190 individuals were recaptured, representing a 35% recapture rate. We found that body size negatively influenced butterfly abundance. In contrast, body size was positively associated with dispersal levels, distance traveled, number of traps visited, individual permanence, and diet breadth. These results indicate that larger butterflies have a greater proportion of dispersing individuals over longer distances, as they permanence were detected over longer periods than their smaller relatives. Moreover, larger butterflies are more generalized, based on the number of host plant families and genera they consume. Smaller butterflies demand fewer resources, which is reflected in their higher survival in small patches, and may explain their lower dispersal ability, and higher diet specialization. Nevertheless, lower dispersal ability, if not compensated by large population sizes, may threaten small-bodied species inhabiting environments with intense deforestation rates, such as the Cerrado. Conclusions: Body size positively influences dispersal and diet breadth in the fruit-feeding butterflies collected in this study.

A novel cytoplasmic dye decolorizing peroxidase from Dictyostelium discoideum was investigated that oxidizes anthraquinone dyes, lignin model compounds and general peroxidase substrates like ABTS efficiently. Unlike related enzymes, an aspartate residue replaces the first glycine of the conserved GXXDG motif in Dictyostelium DyPA. In solution, Dictyostelium DyPA exists as a stable dimer with the side chain of Asp146 contributing to the stabilization of the dimer interface by extending the hydrogen bond network connecting two monomers. To gain mechanistic insights, we solved the Dictyostelium DyPA structures in the absence of substrate as well as in the presence of potassium cyanide and veratryl alcohol to 1.7, 1.85, and 1.6 Å resolution, respectively. The active site of Dictyostelium DyPA has a hexa-coordinated heme iron with a histidine residue at the proximal axial position and either an activated oxygen or CN^- molecule at the distal axial position. Asp149 is in an optimal conformation to accept a proton from H₂O₂ during the formation of compound I. Two potential distal solvent channels and a conserved shallow pocket leading to the heme molecule were found in Dictyostelium DyPA. Further, we identified two substrate-binding pockets per monomer in Dictyostelium DyPA at the dimer interface. Long-range electron transfer pathways associated with a hydrogen-bonding network that connects the substrate-binding sites with the heme moiety are described.

Guided by the Conceptual Model of Implementation Research, we explored the acceptability, appropriateness, and feasibility of: 1) automated screening approaches utilizing existing health data to identify those who require subsequent diagnostic evaluation for familial hypercholesterolemia (FH) and 2) family communication methods including chatbots and direct contact to communicate information about inherited risk for FH. Focus groups were conducted with 22 individuals with FH (2 groups) and 20 clinicians (3 groups). These were recorded, transcribed, and analyzed using deductive (coded to implementation outcomes) and inductive (themes based on focus group discussions) methods. All stakeholders described these initiatives as: 1) acceptable and appropriate to identify individuals with FH and communicate risk with at-risk relatives; and 2) feasible to implement in current practice. Stakeholders cited current initiatives, outside of FH (e.g., pneumonia protocols, colon cancer and breast cancer screenings), that gave them confidence for successful implementation. Stakeholders described perceived obstacles, such as nonfamiliarity with FH, that could hinder implementation and potential solutions to improve systematic uptake of these initiatives. Automated health data screening, chatbots, and direct contact approaches may be useful for patients and clinicians to improve FH diagnosis and cascade screening.

The coffee leaf miner (CLM) Leucoptera coffeella moth is a major threat to coffee production. Insect damage is related to the feeding behavior of the larvae on the leaf. During the immature life stages, the insect feeds in the mesophyll, triggering necrosis and causing loss of photosynthetic capacity, defoliation, and significant yield loss to coffee crops. Chemical control is mandatory to sustain the coffee production chain, though market requirements move towards conscious consumption, claiming for more sustainable methods. In this overview, we discuss aspects about the CLM concerning biology, history, geographical distribution, economic impacts, and the most relevant control strategies in progress. Insights to develop an integrate approach for a safer and eco-friendly control of the CLM are discussed, including bio-extracts, nanotechnology, pheromones, and tolerant cultivars.

Kluyveromyces marxianus (K. marxianus) is a newly emerging industrially relevant yeast. It is known to possess a highly efficient Non-Homologous End Joining (NHEJ) pathway that promotes random integration of non-homologous DNA fragments into its genome. The nature of the integration events was traditionally analyzed by Southern blot hybridization. However, the precise DNA sequence at the insertion sites were not fully explored. We transformed a PCR product of the Saccharomyces cerevisiae URA3 gene (ScURA3) into an uracil auxotroph K. marxianus wildtype strain and picked 24 stable Ura+ transformants for sequencing analysis. We took advantage of rapid advances in DNA sequencing technologies and developed a method using a combination of Illumina MiSeq and Oxford Nanopore sequencing. This approach enables us to uncover the Gross Chromosomal Rearrangements (GCRs) that are associated with the ScURA3 random integration. Moreover, it will shine a light on understanding DNA repair mechanisms in Eukaryotes, which could potentially provide insights for cancer research.

Social distancing policies put in place during COVID-19 epidemic in addition to helping to limit the spread of the disease also contributed to improving urban air quality. Here we show a decrease in air pollutant concentration as a consequence of mobility reduction in São Paulo during the containment measure which began on 22^nd March 2020. When comparing to foregoing weeks to equivalent periods of 2019, the concentration of most air pollutants sharply decreased in the first days of mobility restriction, to then increase again after government officials downplayed the threat of the disease. This trend is also followed by a decrease in hospital admissions by SARS-influenza. Therefore, despite the great economic and social unrest caused by the pandemic, this unique situation shows that large-scale mobility reduction policy had a significant impact on air quality, benefiting, directly and indirectly, the public health system.

Opioids are highly addictive substances with a relapse rate of over 90%. While preclinical models of chronic opioid exposure exist for studying opioid dependence, none recapitulate the relapses observed in human opioid addiction. The mechanisms associated with opioid dependence, the accompanying withdrawal symptoms and the relapses that are often observed months or years after opioid dependence are poorly understood. Therefore, we developed a novel model of chronic opioid exposure whereby the level of administration is self-directed with periods of behavior acquisition, maintenance and then extinction alternating with reinstatement. This profile arguably mirrors that seen in humans, with initial opioid use followed by alternating periods of abstinence and relapse. Recent evidence suggests that dietary interventions that reduce inflammation, including omega-3 fatty acids such as docosahexaenoic acid (DHA), may reduce substance misuse liability. Using the self-directed intake model, we characterize the observed profile of opioid use and demonstrate that a diet enriched in polyunsaturated fat acids (PUFAs) ameliorates oxycodone-seeking behaviors in the absence of drug availability and reduces anxiety. Guided by the major role gut microbiota have on brain function, neuropathology, and anxiety, we profile the microbiome composition and the effects of chronic opioid exposure and DHA supplementation. We demonstrate that withdrawal of opioids led to a significant depletion in specific microbiota genera whereas DHA supplementation increased microbial richness, phylogenetic diversity, and evenness. Lastly, we examined the activation state of microglia in the striatum and found that DHA supplementation reduced the basal activation state of microglia. These preclinical data suggest that a diet enriched in PUFAs could be used as a treatment to alleviate anxiety induced opioid-seeking behavior and relapse in human opioid addiction.

Despite needs for new therapies and improvements in existing approaches in cardiovascular, pulmonary, endocrine, and renal disease, investment in these areas is lagging relative to other specialties. This article summarizes a meeting of key stakeholders of U.S. Food and Drug Administration (FDA) officials, representatives from academia, national organizations, and patients and caregivers. The purpose was to identify and discuss high-priority issues, establish areas of common interest, and explore opportunities for collaboration. During the meeting (September 2016), the construct of a “multimorbidity continuum” emerged, in which chronic diseases are understood as their effects on the whole rather than individual organ systems. Cross-disciplinary priorities included: 1) the need to generate greater high-quality evidence at lower cost; 2) the imperative to develop and implement patient-centered approaches to clinical investigations; 3) the importance of trial participation in under-represented populations, particularly with comorbid conditions, and 4) the need for progress in tobacco regulation. Representatives from each therapeutic area reported on their consensus priorities, and FDA representatives discussed the agency’s role in facilitating broader approaches to therapeutic development and evaluation of disease as linked across organ systems rather than in isolation, and emphasized the importance of patient engagement, collaboration and communication across stakeholders.

The article adds new policy insights to the way in which formal teaching methods of environmental stewardship education areas are evaluated in Tuvalu. We aimed to answer three questions: 1. What are the formal policies shaping environmental stewardship education in Tuvalu? 2. Are national educational and environmental policies mutually consistent? and 3. Are these national policies consistent with regional and global policies? These questions were addressed using a study of Tuvaluan online-available documentary assessments of national policies, frameworks, and curricula in conjunction with those obtained from the Education Department. Our findings revealed limitations and weaknesses regarding the provisions of environmental stewardship education at the national scale, including misaligned curricula, policy documents, and formal educational provisions with Tuvalu’s national environmental policy. We also found inconsistencies with regional and global policies such as the Pacific Islands Framework for Nature Conservation, the Framework for Resilient Development in the Pacific, and international strategic plans for biodiversity and climate change. These cross-scalar policy weaknesses and limitations highlight the need for the Tuvaluan government to align educational and environmental policies at different scales. We recommend a multi-pronged strategy where modes of informal environmental education can support and complement formal government policymaking on education and the environment.

Unquestionably the rapidly changing climate and, therefore, alterations in the associated bioclimate, constitute an alarming reality with implications in daily practice and natural capital management. In this research the present and projected bioclimate evolution over the phytogeographical regions of Greece is displayed. For this purpose, ultrahigh-resolution computation results on the spatial distribution of the Emberger index’s Q2 classes of bioclimatic characterisation are analysed and illustrated for the first time. The assessments are performed over the reference period (1970–2000) and two future time frames (2021–2040; 2041–2060) under the RCP4.5 and RCP8.5 emission scenarios. By 2060 and under the extreme RCP8.5, intense xerothermic trends are demonstrated owing to the resulting significant spatial evolution mainly of the Arid-Hot, Semi-Arid-Very Hot, Semi-Arid-Hot and Semi-Arid-Temperate Q2 classes, respectively, over the phytogeographical regions of Kiklades (up to 29% occupation), Kriti and Karpathos (up to 30%), West Aegean Islands (up to 26%), North East (up to 56%)–North Central (up to 31%). The RCP8.5 long-term period exhibits the strongest impacts over approximately the right half of the Greek territory the bioclimate of which appears as more dry-thermal in the future.

Splenic rupture and hematoma are significant complications that can arise in patients with non-Hodgkin lymphoma (NHL). Understanding these associations is essential for optimal patient management and patients' enhancing outcomes. Histopathological and immunohistochemistry analyses are crucial in diagnosing NHL and assessing splenic involvement. A judicial autopsy was requested by the Prosecutor's Office for a malpractice claim due to a fall in the hospital. In the Emergency Department, a 72-year-old man fell from the gurney, reporting a wound to his forehead. No other symptoms were reported. A face and brain CT scan showed no abnormalities. Nine days after discharge, the patient presented with abdominal pain. Abdominal CT revealed splenic rupture and hemoperitoneum. The patient underwent open splenectomy, but the patient showed signs of hemodynamic shock and subsequently died. The evidence emerging from the autopsy allowed us to diagnose a Mantle Cell non-Hodgkin lymphoma with spleen involvement, previously unknown. Histopathological and immunohistochemical analyses were performed to assess splenic rupture's diagnosis and time estimation. The findings strongly suggest that the splenic rupture was associated with the patient's fall and the pre-existing malignancy. This case highlights the importance of considering underlying hematological malignancies when investigating delayed splenic rupture. Immunohistochemical study of spleen samples allowed the assessment of the timing of splenic hematoma and rupture, leading to establishing a causal relationship with trauma.

CRISPR/Cas9 has emerged as the predominant method for genome editing due to its cost-effectiveness and broad applicability, playing a crucial role in advancing sustainable practices across various sectors. This systematic review leverages the PRISMA methodology to explore CRISPR/Cas9's impact on environmental protection, thereby supporting the Sustainable Development Goals (SDGs). Analyzing data from the Web of Science, the review found significant growth in related publications, with a 30% increase since 2014, predominantly from the US, China, Germany, and the UK. The study categorizes the scientific developments into three trends: advancements in agriculture, gene editing techniques, and biofuel production. Key discussions include the use of CRISPR/Cas9 in developing fourth-generation biofuels and environmental biosensors, as well as its applications in enhancing genetic resilience and controlling invasive species. These innovations highlight CRISPR/Cas9's potential in promoting sustainable resource management and energy generation, marking a pivotal contribution to ecological conservation and sustainability efforts.

Microalgae are highly attractive to various industrial sectors and can serve as indicators of aquatic environmental health. An essential step for cultivating microalgae is assessing the cell density, which is traditionally performed through viable cell counting by optical microscopy (OM). However, this method has some limitations, such as the time involved in the process of counting, and the need for specialized training of laboratory personnel. Spectrophotometry is an affordable alternative, especially when applied to culture growth and toxicological tests. We chose the wavelength of 680 nm to detect the optical density (OD) of the green freshwater microalga Desmodesmus subspicatus and green the marine microalga Tetraselmis sp. The correlation between the number of cells and OD was suitable for both microalgae and accuracy was comparable to traditional OM counting. In toxicological tests, the OD technique allowed the monitoring of microalgal growth in the presence of the chemicals potassium dichromate, potassium chloride and sodium dodecyl sulfate (SDS), with results very close to those reported in the scientific literature. This study sheds light on this well-known technique, which is an important contribution since few articles have explored its potentialities and fragilities, showing the successful application to monitoring green microalgal cultures and toxicological assays.

Articular cartilage healing and repair is one of the biggest clinical challenges in trauma and orthopaedic medicine, leading to high economic loss due to athletic impairment in sport horses. Multipotent Mesenchymal stem/stromal cells are part of novel therapeutic arsenal aimed at tissue regeneration and restoring organ function. These cells release biomolecules and factors in the culture media, producing the so called conditioned medium, which have a pro-regenerative effect through paracrine mechanisms. Considering this, a therapeutic product combining equine synovial membrane derived Mesenchymal stem/stromal cells and equine umbilical cord stroma-derived Mesenchymal stem/stromal cells conditioned medium was employed. In this work the treatment of two articular defects, in the first phalanx and third metacarpus of the left front limb of a five-year-old horse, is described. Following surgical debridement of the lesions, the treatment comprised two intra-articular administrations of the above-mentioned therapeutic combination, 15 days apart. This was followed by a thorough rehabilitation program. A second-round treatment was performed 6 months later. Diagnostic imaging demonstrated significant improvement of the articular defects. The clinical outcome allowed a full return to the athletic performance demonstrating the safety and potential advantages of this approach when compared with other therapeutic options.

Repeated single-point measurements of thoracic bioimpedance at single (low)-frequency are strongly related to fluid changes during hemodialysis. Extension to semi-continuous measurements may provide longitudinal details in the time pattern of the bioimpedance signal, and multifrequency measurements may add in-depth information on the distribution between intra- and extracellular fluid. This study aims to investigate the feasibility of semi-continuous multifrequency thoracic bioimpedance measurements by a wearable device in hemodialysis patients. Therefore, thoracic bioimpedance was recorded semi-continuously (i.e. every ten minutes) at nine frequencies (8 – 160 kHz) in 68 patients during two consecutive hemodialysis sessions, complemented by a single-point measurement at home in-between both sessions. On average, the resistance signals increased during both hemodialysis sessions and decreased during the interdialytic interval. The increase during dialysis was larger at 8 kHz (∆ 32.6 Ω during session 1 and ∆ 10 Ω during session 2) compared to 160 kHz (∆ 29.5 Ω during session 1 and ∆ 5.1 Ω during session 2). Whereas the resistance at 8 kHz showed a linear time pattern, the evolution of the resistance at 160 kHz was significantly different [p < 0.0001]. Measuring bioimpedance semi-continuously and with a multifrequency current is a major step forward in the understanding of fluid dynamics in hemodialysis patients. This study paves the road towards remote fluid monitoring.

A change in biological properties of the SARS-CoV-2 virus can enhance its transmissibility and virulence, complicate the disease course, and reduce the effectiveness of anti-viral therapy and vaccination. We have studied 16 genetic lineages of the Omicron variant. The viral reproduction course was analyzed based on plaque morphology in the agar layer and the maximum titer in Vero E6 cells. BALB/c mice and Syrian hamsters were used as animal models. Viral load and infectious SARS-CoV-2 titer were determined in the nasal tissue and lungs. The severity of infectious process was assessed using histological methods. An increased plug size was observed in CH.1.1 and BQ.1.2.1 strains after six passages. This was due to substitutions D614G, H655Y, and N764K in the coronavirus S protein. The same changes in gene variants Gamma and BA.1 were caused by the substitution R682W, which is not present in lineages CH.1.1 and BQ.1.2.1. A similar substitution, namely R682P, was observed in the BA.5.1 strain. We characterized BA.1 (as a reference), BA.5.2, and XBB.3 strains in vivo as representatives of the main circulating genetic lineages. For the BA.1 strain, ID50 was 1.3 and 14 TCD50 in Syrian hamsters and BALB/c mice, respectively. An insignificant increase in the BA.5.2 virulence compared to that of BA.1 was noted (ID50 was 07. and 10 TCD50, respectively). The XBB.3 pathogenicity in laboratory animals is similar to that of BA.1 (ID50 was 1.8 and 15 TCD50, respectively). Experiments showed a consistent decrease in the virulence of Omicron strains compared to previously circulating SARS-CoV-2 variants. A co-evolutionary change in amino acid sequences, affecting the conformation of the coronavirus S protein and its surface epitopes in representatives of different genetic lineages, was noted. The emergence of potential proteolysis sites and alterations of the furin cleavage site have been observed in numerous Omicron coronavirus variants.

(1) Background If placenta percreta (PP) is suspected, one should take into account ultrasound and MRI data, which allow one to assess not only the depth of invasion of the placenta into the myometrium, but also the degree of involvement of the blood vessels of the uteroplacental region and the pelvis, the formation of adhesions and collaterals between organs as well; (2) Methods: The patient with suspected PP was examined by ultrasound and Magnetic Resonance Imaging (MRI) examination. Histological study was performed on paraffin sections (hematoxylin &amp; eosin, Mallory staining); cytotrophoblast was detected with antibodies to cytokeratin-8; (3) Results MRI and ultrasound examinations showed placental invasion extending beyond the serous lining of the uterus involving the posterior wall of the bladder. Elective abdominal delivery was performed at 37 weeks. Surgical excision of the uterine wall with invaded villi and involved fibrous bladder wall were performed. Histological study revealed invasive cytotrophoblast cells in the uterine wall located up to adventitia of the uterine subserosal vessels only. Thinning of the uterine wall up to the serous membrane was detected; (4) Conclusions: Placental villi and trophoblast extended beyond the uterus is not histology equivalent to placenta percreta. To diagnose PP instrumental visualization methods should be used.

Colletotrichum lini is a flax fungal pathogen, comprising differently virulent strains. In this work, we sequenced the genomes of three C. lini strains of different virulence: high virulent #390-1, medium virulent #757, and low virulent #771. We obtained more than 100× genome coverage with Oxford Nanopore Technologies reads and more than 50× genome coverage with Illumina data. To construct high-quality genomes, several assembly strategies were tested. The final assemblies were obtained using the Canu – Racon ×2 – Medaka – Polca scheme and were 54.0-55.3 Mb in length, contained 26-32 contigs, had an N50 > 5 Mb and the BUSCO completeness > 96%. Comparative analysis of the constructed genomes showed high similarity between mitochondrial and nuclear genomes. However, a rearrangement event and the loss of a 0.9 Mb contig were revealed. The candidate effectors were predicted in sets of proteins received after genome annotation. The obtained genome sequences of C. lini strains extend the knowledge on the genetic diversity of Colletotrichum species and are the basis for establishing molecular mechanisms of pathogenicity of the flax pathogen and effective control of flax anthracnose.

The creation of mitochondria-targeted vector systems is a new tool for the treatment of socially significant diseases. Phosphonium groups provide targeted delivery of drugs through biological barriers to organelles. For this purpose, a new class of alkyl(diethylamino)(phenyl) phosphonium iodides (bromides) 1 containing one, two, or three diethylamino groups were obtained by the reaction of alkyl iodides (bromides) with (diethylamino)(phenyl)phosphines under mild conditions and high yields. The structure of compounds 1 was established by NMR and XRD. In vitro a high cytotoxicity against the lines M-Hela, HuTu 80, PC3, DU-145, PANC-1 and MCF-7 was found. Selectivity index are in the range of 0.06-4.0 M (SI 17-277) for the most active compounds. ROS production, mitochondrial localization and the process of cellular apoptosis were investigated. Decorated by 1 of lipid systems (liposomes and solid lipid nanoparticles) improve the cytotoxicity and a decrease in toxicity against normal cell lines. Compounds 1 induce apoptosis proceeding along the mitochondrial pathway. Aminophosphonium salts 1 also exhibit a high selective activity against the Gram-positive bacteria strains S. aureus 209P, B. segeus 8035, including methicillin-resistant strains of S. aureus (MRSA-1, MRSA-2), comparable to the activity of the fluoroquinolone antibiotic norfloxacin. A moderate in vivo toxicity in CD-1 mice was established for the lead compounds.

The autosomal recessive disorder Ataxia-Telangiectasia is caused by dysfunction of the stress response protein ATM. In the nucleus of proliferating cells, ATM senses DNA double-strand breaks and coordinates their repair. This role explains T-cell dysfunction and tumor risk. However, it remains unclear whether this function is relevant for postmitotic neurons and underlies the cerebellar atrophy, since ATM is cytoplasmic in postmitotic neurons. Here, we used ATM-null mice that survived early immune deficits by bone-marrow transplantation, and reached initial neurodegeneration stages at 12 months of age. Global cerebellar transcriptomics demonstrated ATM depletion to trigger upregulations in most neurotransmission and neuropeptide systems. Downregulated transcripts were found for the ATM interactome component Usp2, many non-coding RNAs, ataxia genes Itpr1, Grid2, immediate early genes and immunity factors. Allelic splice changes affected prominently neuropeptide machinery, e.g. Oprm1. Validation experiments with stressors were performed in human neuroblastoma cells, where ATM localized only to cytoplasm, similar to brain. Effect confirmation in SH-SY5Y cells occurred after ATM depletion and osmotic stress better than nutrient / oxidative stress, not after ATM kinase inhibition or DNA stressor bleomycin. Overall, we provide pioneer observations from a faithful A-T mouse model, which suggest general changes in synaptic and dense-core vesicle stress adaptation.

Background: Accurate estimation of dietary intake is challenging. But whilst some progress has been made in high-income countries, low- and middle-income countries (LMICs) remain behind, contributing to critical nutritional data gaps. This study aimed to validate an objective, passive image-based dietary intake assessment method against weighed food records in London, UK for onward deployment to LMICs. Methods: Wearable camera devices were used to capture food intake of eating occasions in 18 adults and 17 children of Ghanaian and Kenyan origin living in London. Participants were provided pre-weighed meals of Ghanaian and Kenyan cuisine and camera devices to automatically capture images of the eating occasions. Food images were assessed for portion size, energy, and nutrient intake, and relative validity of the method compared to the weighed food records. Results: Pearson and Intra-class correlation coefficient of estimates of intakes of food, energy and 19 nutrients ranged from 0.60 to 0.95 and 0.67 to 0.90, respectively. Bland-Altman analysis showed good agreement between the image-based method and weighed food record. Under-estimation of dietary intake by the image-based method ranged from 4 to 23%. Conclusions: Passive food image capture and analysis provides an objective assessment of dietary intake comparable to weighed food records.

Bladder cancer (BLCA) is the sixth most common type of cancer and has a dismal prognosis if diagnosed late. To identify treatment options for BLCA, we systematically evaluated data from the Broad Institute DepMap project. We found that urothelial BLCA cell lines are among the most sensitive to microtubule assembly inhibition by paclitaxel treatment. Strikingly, we unveiled that the top dependencies in BLCA cell lines include genes encoding proteins involved in microtubule assembly, thus highlighting the importance of microtubule network dynamics as a major vulnerability in human BLCA. In cancers, such as ovarian and breast, where paclitaxel is the golden standard of care, resistance to paclitaxel treatment has been linked to p53-inactivating mutations. To study the response of BLCA to microtubule assembly inhibition and its mechanistic link with the mutational status of p53 protein, we treated a collection of BLCA cell lines with a dose range of paclitaxel and performed a detailed characterization of the response. We herein discovered that BLCA cell lines are significantly sensitive to low concentrations of paclitaxel, independently of their p53 status. Paclitaxel induced a G2/M cell cycle arrest and growth inhibition, followed by robust activation of apoptosis. Most importantly, we revealed that paclitaxel triggered a robust DNA-damage response and apoptosis program without activating the p53 pathway. Integration of transcriptomics, epigenetic and dependency data demonstrated that the response of BLCA to paclitaxel is independent of p53 mutational signatures, but strongly depends on the expression of DNA-repair genes. Our work highlights urothelial BLCA as an exceptional candidate for paclitaxel treatment and paves the way for the rational use of a combination of paclitaxel and DNA-repair inhibitors as an effective, novel therapeutic strategy.

Graphene quality for use in biosensors was assessed in fabricated chips by a set of methods that includes atomic force microscopy (AFM), Raman spectroscopy, and low-frequency noise. It is shown that local areas of residues on the graphene surface, which arisen due to the interaction of graphene with a photoresist at the initial stage of chips development, leads to a spread of chips resistance (R) within 1-10 kΩ and to an increase in the root mean square (RMS) roughness up to 10 times that can significantly impair reproducibility of graphene parameters in biosensors chips. It was observed that the control of the photoresist residues after photolithography (PLG) by AFM and subsequent additional cleaning allow reducing the spread of R values in chips to 1–1.6 kΩ and obtaining RMS roughness similar to the roughness in pristine graphene before PLG. Monitoring of the spectral density of low-frequency voltage fluctuation (SU), which provides integral information about the defect system and quality of the material, makes it possible to identify chips with low graphene quality and with inhomogeneously distributed compressive stresses areas by the type of frequency dependence SU (f).

It is believed that fetal hemoglobin (HbF) expression in adults is largely genetically regulated. The increased expression of HbF in pregnancy has been reported in a small number of articles. Different mechanisms have been proposed, but the description of HbF expression during pregnancy remains unclear. The objectives of this study were to document HbF expression during peri and postpartum periods, confirm its maternal origin, and assess clinical and biochemical parameters potentially associated with HbF modulation. In this observational prospective study, 345 pregnant women were followed. At baseline, 169 had HbF expression (≥1% of total hemoglobin) and 176 did not have HbF expression. Women were followed at the obstetric clinic during their pregnancy. Clinical and biochemical parameters were measured at each visit. Analyses were made to determine which parameters had a significant correlation to HbF expression. Results show that HbF expression of ≥ 1% during peri and postpartum periods in pregnant women without influencing comorbidities is at its highest peak during the first trimester. In all women, it was proven that HbF was of maternal origin. A significant positive correlation between HbF expression, β-HCG, and HbA1C was present. A significant negative association between HbF expression and total hemoglobin was found. HbF expression induction during pregnancy is probably associated with increase in β-HCG and HbA1C, and decrease of total hemoglobin, which could temporarily reactivate the fetal erythropoietic system.

A key component of efforts to identify the biological and drug-specific aspects that contribute to therapeutic failure or unexpected exposure-associated toxicity is the study of drug-intestinal barrier interactions. While methods supporting such assessments are widely described for human therapeutics, there is relatively little information available for similar evaluation in support of veterinary pharmaceuticals. There is, therefore, a critical need to develop novel approaches for evaluating drug-gut interactions in veterinary medicine. Three-dimensional (3D) organoids can address these difficulties in a reasonably affordable system that circumvents the need for more invasive in vivo assays in live animals. However, a first step in the development of such systems is understanding organoid interactions in a 2D monolayer. Given the importance of orally administered medications for meeting the therapeutic need of companion animals, we demonstrate growth conditions under which canine colonoid-derived intestinal epithelial cells survive, mature, and differentiate into confluent cell systems with high monolayer integrity. We further examine the applicability of this canine colonoid-derived 2D model to assess the permeability of three structurally diverse, passively absorbed β-blockers (e.g., propranolol, metoprolol, and atenolol). Both absorptive and secretive apparent permeability (Papp) of these drugs at two different pH conditions were evaluated in canine colonoid-derived monolayers and were compared with that of Caco-2 cells. This proof-of-concept study provides promising preliminary results with regard to the utility of canine-derived organoid monolayers for species-specific assessments of therapeutic drug passive permeability.

The aim of study was to investigate epidemiology aspects of magnetic resonance imaging (MRI) during COVID-19 pandemic. The study comprised depersonalized residents of Tomsk and Tomsk Region (n = 1714). Invitations to take online survey were sent to 50,000 residents by target SMS with response rate of 1.2% (n = 727, Cohort 1). Cohort 2 comprised retrospective patients (n = 987) who underwent contrast-enhanced cardiac MRI (CMR) in 2019-2022. Referrals, clinical characteristics, diagnosis, gender, age, past COVID-19, MRI study protocols, and MRI data were analyzed. 29% of respondents in cohort 1 received MRI examination within past two years; 26% of respondents considered MRI the most informative imaging modality for detecting COVID-19 pneumonia; 12% of respondents reported MRI unavailable. Proportion of CMR among MRI studies increased during COVID-19 pandemic, and maximum incidence of cardiac diseases detected by MRI was in 2021. Incidence of myocardial fibrosis increased from ~67% in 2019 to ~84% in 2022. The rate of outpatient MRI studies significantly increased in 2020, but returned to pre-pandemic level in 2021. COVID-19 pandemic increased the need for MRI and CMR. Patients with history of COVID-19 had persistent and newly occurring symptoms of myocardial damage suggesting chronic cardiac involvement requiring continuous follow-up.

Congenital Disorders of Glycosylation (CDG) are a heterogenous group of primarily autosomal recessive mendelian diseases caused by disruptions in the synthesis of lipid linked oligosaccha-rides and their transfer to proteins. CDGs affect multiple organ systems and vary in presentation, even within families. Here we describe a chemically induced mouse mutant, tvrm76, with early onset photoreceptor degeneration. The recessive mutation was mapped to Chromosome 9 and as-sociated with a missense mutation in the Dpagt1 gene encoding UDP-N-acetyl-D-glucosamine:dolichyl-phosphate N-acetyl-D-glucosaminephosphotransferase (EC 2.7.8.15). The mutation is predicted to cause a substitution of aspartic acid with glycine at residue 166 of DPAGT1. Increased expression of Ddit3, and elevated levels of HSPA5 (BiP) sug-gest the presence of early-onset endoplasmic reticulum (ER) stress. These changes were associated with induction of photoreceptor apoptosis in tvrm76 retinas. Mutations in human DPAGT1 cause Myasthenic Syndrome 13 and severe forms of Congenital Disorder of Glycosylation Type Ij. In contrast, Dpagt1tvrm76 homozygous mice present with congenital photoreceptor degeneration without overt muscle or muscular junction involvement. Our results suggest the possibility of DPAGT1 mutations in human patients that present primarily with retinitis pigmentosa with little or no muscle disease. Variants in DPAGT1 should be considered when evaluating cases of non-syndromic retinal degeneration.

Hybrid organic-inorganic (dendritic polymer-silica) xerogels containing silver nanoparticles (Ag-Nps) were developed as antibacterial leather coatings. The preparation method is environmentally friendly, based on two biomimetic reactions. Silica gelation and spontaneous (Ag-Np) formation were both mediated by hyperbranched poly (ethylene imine) (PEI) scaffolds of variable Mw (2000-750000). The formation of precursor hydrogels was monitored by dynamic light scattering (DLS). The chemical composition of the xerogels was assessed by Infra-Red Spectroscopy (IR) and Energy-dispersive X-ray spectroscopy (EDS) while the uniformity of the coatings was established by scanning electron microscopy (SEM). Release properties of coated leather samples and overall behaviour in water in comparison to untreated analogs were investigated by UV-Vis spectroscopy. Antibacterial activity was tested towards Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, and antibiofilm properties against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Acinetobacter baumannii, Enterococcus faecalis while SARS-Cov-2 clinical isolate was employed for the first estimation of their antiviral potential. Toxicity was evaluated using the Jurkat E6.1-cell line. Finally, water contact angle measurements were implemented to determine the enhancement of the leather surface hydrophilicity caused by these composite layers. The final advanced products are intended for use in medical applications.

External stressors strongly increase cardiovascular activity and induce metabolic changes that ensure the availability of glucose and oxygen as part of a co-ordinated stress response. Exposure to stress during early life appears to have an exaggerated long-term effect on this response, leading to an increased risk or cardiometabolic disorders. Here we demonstrate that acute stress induced glucose release is impacted by the early life environment in rodent maternal deprivation and early-life infection models and this was validated in our EpiPath human early-life adversity cohort. In all three models differences in baseline blood glucose levels after ELA exposure were sex dependent. The human ELA model showed higher levels of basal glucose in females, similar to the mouse infection and rat maternal deprivation models. We anticipated that the stress induced glucose rise would be a GC dependent process. However, the kinetics of stress-induced glucose release, peaking 15-28 minutes before cortisol suggest that it is a GC-independent process. We confirmed this by administering an escalating dose of cortisol to a health human cohort, and the inability of an intravenous GC bolus induce a glucose rise in man confirms that it is a rapid, GC independent, process.In conclusion, we provide a novel perspective on the mechanisms behind stress related metabolic changes and highlights the importance of collecting early life data as a measure to understand an individual’s metabolic status in a better light.

Mixture of abramis brama (freshwater bream), carassius carassius (crucian carp), and sander lucioperca (pike perch) scales was used for the preparation of fish scale powder containing about 26.5 wt. % of removed when heating components preferably of organic nature, and 63.5 wt. % of mineral components. Fish scale powder enriched with inorganic components was prepared from washed, dried, and ground fish scale mixture using vibration sieving. Inorganic powders consisting of hydroxyapatite and magnesium whitlockite were obtained via heat treatment of this fish scale powder at 800-1000 oC. Particles of these inorganic powders consisted of sintered grains with dimensions less than 100 nm after heat treatment at 800 oC, less than 200 nm after heat treatment at 900 oC, and 100-500 nm after heat treatment at 1000 oC. Fish scale powder enriched with inorganic components as well as heat-treated inorganic powders consisting of hydroxyapatite and magnesium whitlockite can be recommended for the production of different materials such as ceramics or composites.

Cell secretome has been explored as a cell-free technique with high scientific and medical interest for Regenerative Medicine. In this work, the secretome produced and collected from Olfactory Mucosa Mesenchymal Stem Cells and Olfactory Ensheating Cells was analyzed and therapeutically applied to promote peripheral nerve regeneration. The analysis of the conditioned medium revealed the production and secretion of several factors with immunomodulatory functions, capable of intervening beneficially in the phases of nerve regeneration. Subsequently, the conditioned medium was applied to sciatic nerves of rats after neurotmesis, using Reaxon^® as tube-guides. Over 20 weeks, the animals were subjected to periodic functional assessments, and after this period, the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed to confirm the beneficial effects resulting from the application of this therapeutic combination. The administration of conditioned medium from Olfactory Mucosal Mesenchymal Stem Cells led to the best results in motor performance, sensory recovery, and gait patterns. Stereological and histomorphometric evaluation also revealed the ability of this therapeutic combination to promote nervous and muscular histologic reorganization during the regenerative process. The therapeutic combination discussed in this work shows promising results and should be further explored to clarify irregularities found in the outcomes and to allow establishing the use of cell secretome as a new therapeutic field applied in the treatment of peripheral nerves after injury.

Background Reliable and field-applicable diagnosis of schistosome infections in non-human animals is important for surveillance, control, and verification of interruption of human schistosomiasis transmission. This study aimed to summarize uses of available diagnostic techniques through a systematic review and meta-analysis. Methods and principal findings We systematically searched the literature and reports comparing two or more diagnostic tests in non-human animals for schistosome infection. Out of 4,909 articles and reports screened, 18 met our inclusion criteria, four of which were considered in the meta-analysis. A total of 14 techniques (parasitologic, immunologic, and molecular) and nine types of non-human animals were involved in the studies. Notably, four studies compared parasitologic tests (miracidium hatching test (MHT), Kato-Katz (KK), the Danish Bilharziasis Laboratory technique (DBL), and formalin-ethyl acetate sedimentation-digestion (FED-SD)) with quantitative polymerase chain reaction (qPCR), and sensitivity estimates (using qPCR as the reference) were extracted and included in the meta-analyses, showing significant heterogeneity across studies and animals hosts. The pooled estimate of sensitivity was 0.21 (95% confidence interval (CI): 0.03 – 0.48) with FED-SD showing highest sensitivity (0.89, 95% CI: 0.65 – 1.00). Conclusions and significance Our findings suggest that the parasitologic technique FEA-SD and the molecular technique, qPCR, are the most promising field-applicable techniques for schistosome diagnosis in non-human animal hosts. Future studies are needed for validation and standardization of the techniques for real-world field applications.

Objectives: This study aimed to determine the relationship between objective chewing ability and nutritional status of Japanese community-dwelling elders. Design: Cross sectional study. Participants: In total, 509 community-dwelling elders living in the Tokyo metropolitan area participated in a comprehensive survey occurring in October 2013. Measurements: Basic characteristics referred to sex, age, and body mass index. Undernutrition was examined through serum albumin levels. Chewing ability was examined through a color-changeable xylitol gum. By evaluating color changes in the chewing gum. Nutritional intake was examined through the semi-quantitative Food Frequency Questionnaire. Results: In the poor chewing ability group, all nutrient intake levels were significantly low, except for carbohydrates and all food groups intake levels were significantly low, except for cereals, confectionery, sugars, seasonings, and spices. Additionally, after adjusting for covariates, chewing ability showed a significant association with undernutrition. Conclusion: We concluded that chewing ability was closely associated with nutrient and different food groups intake as well as undernutrition among Japanese community-dwelling elders. Thus, in order to ensure a comprehensive nutritional management, nutritionists and dentists should collaborate when treating the same patients.

Despite the publication in 2009 of a paper on ‘terms and definitions of immune thrombocytopenia’, (ITP) some unresolved issues remain and are reflected by the disagreement in the treatment suggested for primary ITP in adults. Considering that these disagreements could be ascribed to non-shared goals, a ‘consensus’ to classify the different lines of treatment for primary ITP in adults according to their indications and goals was proposed in October 2018 to the XIX annual meeting of the Italian Gruppo di Studio delle Piastrine (GSP), a non-profit platelet study group of scientists and physicians. Having approved the project, 60 potential co-authors and experts in the world were invited to take part to a consensus through e-Delphy method and nine of the 12 who initially accepted the invitation completed the work. Agreement was reached on a classification of four lines of treatment for primary ITP in adults based on their indications and goals. The consensus obtained regarded also the criteria, ‘timing’ included, to consider practicable elective splenectomy in these patients. In our opinion, the classification of the lines of treatment for primary ITP in adults here proposed could facilitate the realization of better shared evidence-based guidelines for the treatment of the disease.

Shiga toxin (Stx) produced by Escherichia coli is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L) which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types. The aim of this work was to determine if the interaction between the oxidative response and platelet-derived sCD40L participates in the pathogenic mechanism during HUS. Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets to adhere to them. Although platelet adhesion did not contribute to endothelial damage, high levels of sCD40L were released to the medium. The release of sCD40L by activated platelets was inhibited by antioxidant treatment. Furthermore, we found increased levels of sCD40L in plasma from HUS patients, which were also able to trigger the respiratory burst in monocytes, in a sCD40L-dependent manner. Thus, we concluded that platelet-derived sCD40L and the oxidative response are reciprocally stimulated during Stx2-associated HUS. This process may contribute to the evolution of glomerular occlusion and the microangiopathic lesions.

Vancomycin is one of the ‘last-line’ classes of antibiotics used in the treatment of life-threatening infections caused by Gram-positive bacteria. Even though vancomycin was discovered in 1950s it was widely used after 1980s for the treatment of infections caused by methicillin-resistant Staphylococci as prevalence of such strains were increased. However, currently it is evident that vancomycin resistant Staphylococcusaureusandvancomycin-resistant Enterococci have been developed as a result of various reasons including use of avaparcin, which is an analog of vancomycin, as feed additive in livestock. In present day context, more attention should be paid on prevention of emergence of resistance for the antibiotics in order to keep antibiotics effective. In order to prevent emergence of resistance, proper guidance for the responsible use of antimicrobials is indispensable. Therefore, almost all stakeholders who use antibiotics should have in depth understanding on the antibiotic they use. As such, it is imperative to be aware of the important aspects of vancomycin. In the present review, efforts have been made to discussthe pharmacokinetics and pharmacodynamics, indications, emergence of resistance, control of resistance, adverse effects and alternative therapy for vancomycin.

Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles derivatives as potent FGFR inhibitors. Compound 10a was first identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that compound 13a is the most potent FGFR1 inhibitor in this series with the enzyme inhibitory activity about 30.2 nM of IC50 value.

Microalgae cultivation for biotechnological purposes is an expanding field. Their cultivation is usually performed on a liquid culture medium and require the presence of an energy source. Culture media are water-salt solutions containing nitrogen, sulfur, phosphate sources, with trace of transition metals. Light source supplies energy through photosynthesis process, resulting in metabolic reactions and cell growth. Thanks to the huge number of existing species and their diversity, it is possible to exploit alternative water sources with chemical and physical properties far from the commonly used freshwater media. Among these, oilfield or formation waters (AFW) are saline wastewater produced during oil drilling. They represent over 95 % of the total fluids collected from gas and oil wells during fuel extraction. This study exploits the adaptation capability of a Galdieria sulphuraria strain in different salinity conditions to build up a more feasible microalgae-based platform. Batch cultivation of G. sulphuraria was evaluated in a range from 0 to 20 g/L NaCl in terms of growth rate, metabolite content, photophysiology, and intracellular redox state. Moreover, the same strain has been tested for artificial formation water growth in semicontinuous cultivation mode. In these condition, NaCl preadaptation effect has been assessed too. Results clearly demonstrate that biomass composition is influenced from medium salinity. Strains preadapted in 0 to 20 g/L range of NaCl salinity show almost same cell growth profile and a slightly different ratio between lipids, carbohydrates, and proteins. Pigments content and photophysiology point out that variations of osmotic pressure and ionic strength in medium affect Photosystem II (PSII). Regulation of light harvesting is necessary to trigger metabolism shift toward synthesis of metabolites required in the adaptation process.

Hybrid forecasting methods have emerged as a solution surpassing the limitations of both statistical and deep learning approaches. While the first emphasize the significance of variables, they often produce worse forecasting results when compared to newer techniques. In contrast, deep learning models remain enigmatic "black boxes" in terms of interpretability, although achieving better results in forecasting. This article introduces the Comprehensive Cross-Correlation and Lagged Linear Regression Deep Learning (CCLR-DL) framework, designed to harness the best of both approaches, enhancing forecasting accuracy while retaining model interpretability through a feature selection process. CCLR-DL blens cross-correlation analysis, lagged multiple linear regression and granger's causality procedures with deep learning architectures based on LSTM. In a practical demonstration, CCLR-DL was applied to a real database of clinical visits associated to diagnoses in Catalonia, Spain (tracking a population of 6.3 million patients during 10 years). Predicting visits enables the healthcare managers to be ready for future demand shifts. Results demonstrate a consistent and substantial improvement over standalone statistical and deep learning methods when predicting healthcare demand. This hybrid approach not only showcases its efficacy but also offers a promising solution to the challenge of balancing predictive accuracy with model explicability. In this context, this work aims to design and validate a method for feature selection and forecasting of multivariate high dimensional time series datasets not only to improve prediction accuracy but also to model transparency by identifying a subset of variables that improve predictions and G-cause the target variable.

The development of new target stations for radioisotope production based on a dedicated 70~MeV commercial cyclotron is described. Currently known as the South African Isotope Facility (SAIF), this initiative will free the existing separated-sector cyclotron (SSC) at iThemba LABS (near Cape Town) to mainly pursue research activities in nuclear physics and radiobiology. It is foreseen that the completed SAIF facility will realize a three-fold increase in radioisotope production capacity compared to the current programme based on the SSC.

Modular nanotransporters (MNTs) are drug delivery systems for targeted cancer treatment. Being composed of several modules, they offer the advantage of high specificity and biocompatibility in delivering drugs to the target compartment of cancer cells. The large carrier module brings together functioning MNT modules and serves as a platform for drug attachment. The development of smaller-sized MNTs via truncation of the carrier module looks advantageous in facilitating tissue penetration. In this study, two new MNTs with a truncated carrier module containing either an N-terminal (MNTN) or a C-terminal (MNTC) part were developed by genetic engineering. Both new MNTs demonstrated high affinity for target receptors, as revealed by fluorescently labeled ligand-competitive binding. The liposome leakage assay proved the endosomolytic activity of MNTs. Binding to the importin heterodimer of each truncated MNT was revealed by a thermophoresis assay, while only MNTN possessed binding to Keap1. Finally, the photodynamic efficacy of the photosensitizer attached to MNTN was significantly higher than when attached to either MNTC or the original MNT. Thus, this work reveals that MNT’s carrier module can be truncated without losing MNT functionality, favoring the N-terminal part of the carrier module due to its ability to bind Keap1.

In the ongoing shift towards electric vehicles (EVs) primarily utilizing lithium-ion battery technology, a significant population of hybrid electric vehicles (HEVs) remains operational, reliant on established NiMH battery systems. Over the last twenty years, these HEVs have generated a substantial quantity of NiMH batteries that are either inoperable, experiencing performance degradation, or approaching the end of their service life. This results in a twofold challenge: a growing volume of environmentally hazardous waste due to the difficulty of NiMH battery reclamation, and escalating maintenance costs for HEV owners necessitated by replacement battery purchases. Patent WO2015092107A1, published in 2015, proposed a "Method for regenerating NiMh batteries." This method claims the ability to restore NiMH batteries to their original functionality. However, a comprehensive review of relevant scientific literature fails to identify any empirical evidence supporting the efficacy of the regeneration technique detailed in the patent. Within this context, this paper presents a detailed analysis and evaluation of the feasibility of the aforementioned patented method. To achieve this objective, the authors propose a prototype constructed utilizing NiMH battery cells sourced from a Toyota Prius. The experimental results obtained from this prototype demonstrate the potential for battery regeneration using the proposed method. These findings offer a promising solution for mitigating the challenges associated with NiMH battery disposal and maintenance within the HEV domain.

It has been argued that the historical nature of evolution makes it a highly path-dependent process. Under this view, the outcome of evolutionary dynamics could have resulted in organisms with different forms and functions. At the same time, there is ample evidence that convergence and constraints strongly limit the domain of the potential design principles that evolution can achieve. Are these limitations relevant in shaping the fabric of the possible? Here, we argue that fundamental constraints are associated with the logic of living matter. We illustrate this idea by considering the thermodynamic properties of living systems, the linear nature of molecular information, the cellular nature of the building blocks of life, multicellularity and development, the threshold nature of computations in cognitive systems, and the discrete nature of the architecture of ecosystems. In all these examples, we present available evidence and suggest potential avenues towards a well-defined theoretical formulation.

Introduction: A plethora of biological molecules regulate chondrogenesis in the epiphyseal growth plate. Disruptions of quantity and function of these molecules can manifest clinically as stature abnormalities of various etiologies. Traditionally, the growth hormone/insulin-like growth factor 1 (IGF1) axis represents the etiological center of final stature attainment. Of note, little is known about the molecular events that dominate the growth of the craniofacial complex and its correlation with somatic stature. Aim: Given the paucity of the relevant data, this review discusses available information regarding potential applications of lateral cephalometric radiography as a potential clinical indicator of genetic short stature in children. Materials and Methods: A literature search was conducted in the PubMed electronic database using the key words: cephalometric analysis and short stature; cephalometric analysis and achondroplasia; cephalometric analysis and hypochondroplasia; cephalometric analysis and skeletal abnormalities; cephalometr* and SHOX; cephalometr* and CNP; cephalometr* and ACAN; cephalometr* and CNVs; cephalometr* and IHH; cephalometr* and FGFR3; cephalometr* and Noonan syndrome; cephalometr* and “Turner syndrome”; cephalometr* and achondroplasia. Results: In individuals with genetic syndromes causing short stature, linear growth of the craniofacial complex is confined, following the pattern of somatic short stature regardless of its etiology. The angular cephalometric measurements differ from the average height normal individuals and are suggestive of a posterior placement of the jaws and a vertical growth pattern of the face. Conclusion: The greater part of the existing literature regarding cephalometric measurements in short statured children with genetic syndromes provides qualitative data. Furthermore, cephalometric data for individuals affected with specific rare genetic conditions causing short stature, should be the focus of future studies. These quantitative data are required to potentially establish cut-off values to refer for genetic testing based on craniofacial phenotypes.

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment ele-vation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued. Out-of-hospital car-diac arrest and cardiogenic shock remain a major cause of high in-hospital mortality, whilst the growing burden of heart failure in long-term STEMI survivors presents a growing problem. Many elements aiming to optimize STEMI treatment are still subject to debate or lack sufficient evidence. This review provides an overview of the most contentious current issues in pPCI in STEMI patients, with an emphasis on unresolved questions and persistent challenges.

With an increase in proportion of elderly patients, the global burden of spinal disease is on the rise. Likewise, there has been an increasing trend in the number of spine surgeries being performed worldwide. As we know, rehabilitation following spine surgery is critical for optimal recovery. However, current literature lacks consensus regarding the appropriate post operative rehabilitation protocol. The goals of rehabilitation after lumbar spine surgery are to improve physical and psychosocial function and may include multiple modalities such as physical therapy, cognitive behavioral therapy, specialized instruments, and instruction to be followed during activities of daily living. In recent years, not only are a greater number of spine surgeries being performed, various different techniques of lumbar spine surgery and spinal fusion have emerged. Physical therapy programs need to be curated after assessing the functional status of the patient by using various patient reported outcome measures and taking into consideration the technique of spinal fusion used and the muscle groups involved in these surgeries. By doing so it is possible to assess the level of functional impairment and then specifically target strengthening of those muscle groups affected by surgery whilst also improving impaired balance and allowing return to activities of daily living. We reviewed available literature pertaining to the history of spinal rehabilitation, the popular patient reported outcome measures used and different rehabilitation methods with the purpose of summarizing the current guidelines for postoperative rehabilitation after spine surgery and to introduce the rehabilitation after lumbar surgeries that we provide at our hospital.

Human activities (e.g., exploitation, utilization, and conservation) exert substantial impact on forest ecological functions (FEF). The human influence on FEF significantly varies across developmental stages, which are attributed to the temporal and spatial in nature. This study evaluates some notable FEF indices (FEFI) in the 448 counties within the Yellow River basin (YRB) using panel data from the Seventh to Ninth National Forest Inventory. Data analysis involves employing the residual trends, geographical and temporal weighted regression. Results indicate that, firstly, the overall forest ecological function in the YRB is moderate to inferior, with superior FEF in counties endowed with more natural forest resources. Afforestation demonstrates a short-term improvement, but its effectiveness diminishes over time. Secondly, the positive spatial correlation is stronger among counties, characterized by both high-high and low-low agglomeration effects. Scattered planting, simple stand structure, and concentrated harvesting of forests at the identical stand ages hinder the formation of complex and large-scale FEF agglomerations. Thirdly, significant spatial-temporal differences exist in the impact of human activities on FEF. In the upper reaches of the basin, increased vegetation coverage through agricultural and forestry production benefited FEF, however, some over-exploitation of forests and grasslands is observed there. In the middle reaches, the economic development, expanding population and the greening activities help to improve FEF effectively, but excessive water using in agricultural production brought more difficulties to FEF improvement. In the lower reaches of the basin, improved wastelands and forest protection positively influence FEF. This study recommends that county governments should prioritize forest management with multi-species and multi-layered complex forests. Each county should define its position in regional development and ecological protection, considering the potential impacts on neighboring regions. This holistic approach promotes more effective integrated regional management.

This study aimed at testing the effectiveness of novel combinations of chemical and physical methods to control Prosopis juliflora, an invasive weed in the Moshi and Simanjiro districts of Nothern Tan-zania. Six different treatments including manual uprooting, glyphosate, bark chop with chemical application, two separate chemical mixtures and control were tested in a total of 32 plots, which represented two land use types (grazing land and farmland) found in the two districts. Each plot covered 20m×30m plot area. Two response variables (stem count and tree volume) were recorded to compare weed population density before and after treatment six months later. An analysis of the untreated control plots, showed that the inherent growth potential of P. juliflora was higher in Moshi than in Simanjiro district. The number of stems increased during the experiment for all six treatments showing that the P. juliflora population had not yet reached the local carrying capacity. For the manual control treatment, the increase was reduced compared to the untreated control. For all other treatments, the increase in stem count was on par with that in the untreated control or even higher. Thus, we conclude that only manual uprooting had a controlling effect but not to the extent that it eradicated P. juliflora. Thus, it is for P. juliflora as for weed control in general: weed control must be an ongoing effort.

This study investigates the historical variability in annual average precipitation in the northwest region of Mexico, aiming to evaluate the cumulative impact of precipitation on soil degradation and associated risks posed by rainfall. Despite being known as "The Agricultural Heart of Mexico," the region's soil has experienced significant damage to its granulometric structure due to unpredictable rainfall patterns attributed to climate change. Sixteen historical series of average annual rainfall were analyzed as stationary stochastic processes for spectral analysis. The results revealed exponential decay curves in each radial spectrum, indicating a linear relationship between frequency and amplitude. These curves identified initial impulses correlated with moments of severity for structural damages caused by rainfall-induced degradation. The degradation process, exacerbated by water stress, accelerates, as evidenced by maps illustrating approximately 75% soil damage. In the context of climate change and the uncertainty surrounding soil responses to extreme meteorological events, understanding this phenomenon becomes crucial. Recognizing the dynamic nature of soil responses to environmental stressors is essential for effective soil management. Emphasizing the need to employ numerical processes tailored to new environmental considerations related to observed soil damages is crucial for sustainable soil management practices in any region.

Using pumps operating as turbines (PATs) offers the possibility of increasing the sustainability of water and energy systems by recovering the excess of energy that would be otherwise lost in pressure reducing valves or head loss chambers. In on-grid applications, there are many research works and implementations of PATs. However, there is still limited research for the optimization of efficiency and stability of PATs operating in off-grid systems. This work contributes to the development of stable direct current (DC) off-grid electric systems based on PATs, by optimizing and analysing the energy efficiency and stability for a wide range of operation. A self-excited induction generator (SEIG) coupled to the PAT is provided to cover the conventional type of electric ma-chines typically coupled to the hydraulic pumps. In this context, a methodology is proposed, based on the hydraulic, mechanical and electric subsystems, to define the PAT-SEIG operational area, to maximize energy conversion and the system efficiency. This will guarantee stable electric output quantities when operating in a DC off-grid system. In addition, an analytical model is proposed to estimate the PAT-SEIG operation under specific conditions. With this, water managers are suitable to design and optimize an off-grid PAT-SEIG system and to define the best hydraulic machines, electronic equipment, and all different control elements to maximize energy conversion within the target of operational limits. To develop and verify this new methodology, two micro PAT-SEIG setups were implemented in the hydraulic laboratory of IST/CERIS under typical operating conditions. The proposed solution proved to be resilient under a variable load regime. The system's maximum efficiency can be adapted using different capacitor values for the excitation of the SEIG, and the operational range is limited to the electric components. Considering the nominal efficiencies of the system’s components, the maximum p.u. efficiency obtained for each PAT-SEIG system were between 0.7 and 0.8 p.u.

The cassava whitefly, Bemisia tabaci, causes direct damage to cassava in the tropics by feeding on the phloem of leaves, inducing leaf chlorosis and abscission which can result in considerable yield loss of up to about 50% on susceptible varieties. The pest is also known to impart its indirect damage through sooty mold formation. Most of the improved cassava varieties in Uganda were developed for CMD resistance and CBSD tolerance and little is known about their reaction to whitefly infestation. A study was conducted to evaluate the reaction of 24 improved cassava varieties which were sourced from 5 different countries in the region (Uganda, Kenya, Tanzania, Malawi, and Mozambique) to whitefly infestation. These varieties were evaluated in three agro-ecological zones of Uganda, namely; North-Western Savannah Grassland, Lake Victoria Crescent and the Kyoga Plains in the second rains of 2016. Monthly data were taken on adult and nymph counts, whitefly and sooty mold damage, CMD and CBSD severities from 2 up-to 9 Months after planting (MAP). Results show that the whitefly population was highly significantly (P

Schinus terebinthifolius Raddi is a plant native to Brazil. The objective of this work was to analyze the chemical composition, antioxidant and antibacterial potential of essential oils (EOs) from the leaves, fruits and twigs of S. terebinthifolius aiming for their application in food safety. EOs were obtained by hydrodistillation and the chemical composition was determined by gas chromatog-raphy coupled to mass spectrometry. Phenolic compounds were quantified and antioxidant ac-tivity was evaluated using three different methods. The antibacterial activity was determined by the broth microdilution method against foodborne bacteria. In the chemical analysis, 22 com-pounds were identified in the leaves, 13 compounds in the fruits and 37 compounds in the twigs, revealing the presence of the main compounds germacrene D, caryophyllene, α-pinene, β-pinene and γ-gurjunene. EOs showed better antioxidant potential using the β-carotene/linoleic acid method with 40.74, 61.52 and 63.65% oxidation inhibition for leaves, fruits and twigs, respectively. The EO from the leaves showed greater antibacterial potential against Escherichia coli and Staphy-lococcus aureus with a minimum inhibitory concentration (MIC) of 0.62 mg mL-1, values lower than the MIC of sodium nitrite (5.00 mg mL-1), antimicrobial standard synthetic. The activities of pink pepper EOs suggest their potential as a biopreservative in foods.

This study aimed to identify microRNAs associated with histological grade using comprehensive microRNA analysis data obtained by next-generation sequencing in early-stage invasive breast cancer. RNA-seq data from normal breast and breast cancer samples were compared to identify candidate microRNAs with different expressions using bioinformatics. A total of 108 microRNAs were significantly differentially expressed between normal breast and breast cancer tissues. Using clinicopathological information and microRNA sequencing data of 430 patients with breast cancer from The Cancer Genome Atlas (TCGA), the differences in candidate microRNAs between low- and high-grade cases were compared. Comparing the expression of the 108 microRNAs between low- and high-grade cases, 25 and 18 microRNAs were significantly upregulated and downregulated, respectively, in high-grade cases. Clustering analysis of the TCGA cohort using these 43 microRNAs identified two groups strongly predictive of histological grade. miR-3677 is a microRNA upregulated in high-grade breast cancer. The outcome analysis revealed that patients with high miR-3677 expression had a significantly worse prognosis than those with low miR-3677 expression. This study showed that microRNAs were associated with histological grade in early-stage invasive breast cancer. These findings contribute to the elucidation of a new mechanism of breast cancer growth regulated by specific microRNAs.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic myelopoietic growth factor and proinflammatory cytokine, clinically used for multiple indications and serving as a promising target for treatment of many disorders, including cancer, multiple sclerosis, rheumatoid arthritis, psoriasis, asthma, COVID-19. We have previously shown that dimeric Ca2+-bound forms of S100A6 and S100P proteins, members of the multifunctional S100 protein family, are specific to GM-CSF. To probe selectivity of these interactions, the affinity of recombinant human GM-CSF to dimeric Ca2+-loaded forms of 18 recombinant human S100 proteins was studied by surface plasmon resonance spectroscopy. Of them, only S100A4 protein specifically binds to GM-CSF with equilibrium dissociation constant, Kd, values of 0.3-2 μM, as confirmed by intrinsic fluorescence and chemical crosslinking data. Calcium removal prevents S100A4 binding to GM-CSF, whereas monomerization of S100A4/A6/P proteins disrupts S100A4/A6 interaction with GM-CSF and induces a slight decrease in S100P affinity for GM-CSF. Structural modelling indicates the presence in the GM-CSF molecule of a conserved S100A4/A6/P-binding site, consisting of the residues from its termini, helices I and III, some of which are involved in the interaction with GM-CSF receptors. The predicted involvement of the ‘hinge’ region and F89 residue of S100P in GM-CSF recognition was confirmed by mutagenesis. Examination of S100A4/A6/P ability to affect GM-CSF signaling showed that S100A4/A6 inhibit GM-CSF/S100-induced suppression of viability of monocytic THP-1 cells. The ability of the S100 proteins to modulate GM-CSF activity is relevant to progression of various neoplasms and other diseases, according to bioinformatics analysis. The direct regulation of GM-CSF signaling by extracellular forms of the S100 proteins should be taken into account in the clinical use of GM-CSF and development of the therapeutic interventions targeting GM-CSF or its receptors.

This study investigates the therapeutic potential of new compound, potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (Compound I), in depression. Willner's chronic unpredictable mild stress model of depression in 48 male Wistar rats was used a depression model. The rats were randomized into four groups, including an intact group, a Compound I group, a Fluoxetine group, and a control group receiving saline. Behavioral tests, such as the Porsolt forced swim test, hole-board test, elevated plus maze test, and light-dark box, were used to assess the animals' conditions. Our results demonstrated that Compound I effectively reduced the immobilization time of rats in the forced swim test, increased orientation and exploratory behavior, and decreased the latency period of going into the dark compartment compared to the control group. Hippocampal and striatal serotonin concentrations were increased in the Compound I group, and the compound also reduced the level of corticosterone in the blood plasma of rats compared to intact animals. These results suggest that Compound I has a reliable antidepressant activity, comparable to that of the reference antidepressant Fluoxetine.

This study presents a novel polyurethane-activated carbon composite (PACC) as an effective and sustainable adsorbent for treating lead-ion-contaminated waters. The PACC was characterized using SEM-EDX, FTIR, BET, XRD, and TGA to evaluate its physicochemical and thermal properties. Furthermore, the PACC was employed in an experimental column adsorption setup to investigate its adsorption performance and to develop a dynamic method suitable for industrial implementation. Parameters such as bed height (50, 100, 150 mm), flow rate (4, 6, 8 mL min-1), pH (2, 4, 6), and initial metal ion concentrations (10, 50, 100 mg L-1) were examined. The experimental data exhibited strong agreement with the Thomas and Yoon-Nelson models (R2 ≥ 0.96), indicating efficient adsorption mechanisms. Remarkably, the depleted adsorbent has the potential for facile regeneration without substantial loss in capacity. The PACC demonstrated excellent adsorption performance for lead ions in aqueous solutions in a fixed-bed column system. Thus, the novel PACC material holds potential for scalable application in industrial settings to address water pollution challenges, especially in regions with uncontrolled effluent discharge.

Indoor residual spray (IRS), mainly employing pyrethroid insecticides, is the most common intervention to prevent malaria transmission in many regions of Latin America; the use of long-lasting insecticidal nets (LLINs) has been more limited. Knockdown resistance (kdr) is a well-characterized target-site resistance mechanism associated with pyrethroid and DDT resistance. Most mutations detected in acetylcholinesterase-1 (Ace-1) and voltage-gated sodium channel (VGSC) genes are non-synonymous, resulting in a change of amino acid leading to non-binding of the insecticide. In the present study, we analyzed target-site resistance in Nyssorhynchus darlingi, the primary malaria vector in the Amazon, in multiple malaria endemic localities. We screened 988 wild-caught specimens of Ny. darlingi from three localities in Amazonian Peru and four in Amazonian Brazil. Collections were conducted between 2014-2021. Criteria were Amazonian localities with a recent history as malaria hotspots, primary transmission by Ny. darlingi and the use of both IRS and LLINs as interventions. Fragments of Ace-1 (456 bp) and VGSC (228 bp) were amplified, sequenced and aligned with Ny. darlingi sequences available in GenBank. We detected only synonymous mutations in the frequently reported Ace-1 codon 280 known to confer resistance to organophosphates and carbamates, but detected three non-synonymous mutations in other regions of the gene. Similarly, no mutations linked to insecticide resistance were detected in the frequently reported codon (995) at the S6 segment of domain II of VGSC. The lack of genotypic detection of IR mutations by sequencing the Ace-1 and VGSC genes from multiple Ny. darlingi populations in Brazil and Peru could be associated with low-intensity resistance, or possibly the main resistance mechanism is metabolic.

Histoplasmosis is one of the most underdiagnosed and underreported endemic mycoses in the United States. Histoplasma capsulatum is the causative agent of this disease. To date, molecular epidemiologic studies detailing the phylogeographic structure of H. capsulatum in the United States have been limited. We conducted genomic sequencing using isolates from histoplasmosis cases reported in the United States. We identified North American Clade 2 (NAm2) as the most prevalent clade in the country. Despite high intra-clade diversity, isolates from Minnesota and Michigan cases predominately clustered by state. Future work incorporating environmental sampling and veterinary surveillance may further elucidate the molecular epidemiology of H. capsulatum in the United States and how genomic sequencing can be applied for surveillance and outbreak investigation of histoplasmosis.

The study aimed to identify clinical pharmacology patterns of prescribed and taken medications in older cardiovascular patients using electronic health records (EHRs) (n = 704) (2019–2022). Medscape Drug Interaction Checker was used to identify pairwise drug-drug interactions (DDIs). Prevalence rates of DDIs were 73.5% and 68.5% among taken and prescribed drugs, respectively. However, total number of DDIs was significantly higher among prescribed medications compared with the list of taken drugs (p < 0.05). Serious DDIs comprised 16% and 7% of all DDIs among prescribed and taken medications, correspondingly (p < 0.05). Median DDI numbers between prescribed versus taken medications were Me = 2, IQR 0-7 and Me = 3, IQR 0-7 per record, respectively. Prevalence of polypharmacy was significantly higher among prescribed medications compared with taken medications (p < 0.05). Women were taking significantly more drugs and had higher rates of polypharmacy and DDIs (p < 0.05). No sex-related differences were observed in the list of prescribed medications. ICD code U07.1 (COVID-19, virus identified) was associated with the highest median DDI number per record. Further research is warranted to improve EHR structure, patient engagement in reporting adverse drug reactions, and genetic profiling of patients to avoid potentially serious DDIs.

Radiomics involves the extraction of information from medical images not visible to the human eye. There is evidence these features can be used for treatment stratification and outcome prediction. However, there is much discussion about the reproducibility of results between different studies. This paper studies the reproducibility of CT texture features used in radiomics, comparing two feature extraction implementations namely Matlab toolkit and Pyradiomics when applied on independent datasets of CT scans of patients i) the open access RIDER dataset containing a set of repeat CT scans taken 15 minutes apart for 31 patients (RIDER Scan 1 and Scan 2 respectively) treated for lung cancer and ii) the open access HN1 dataset containing 137 patients treated for head and neck cancer. Gross tumor volume (GTV) manually outlined by an experienced observer available on both datasets was used. 43 common radiomics features available on Matlab and Pyradiomics were calculated using 2 intensity-level quantization methods with and without an intensity threshold. Cases were ranked for each feature for all combinations of quantization parameters and the Spearman’s rank coefficient, rs, calculated. Reproducibility was defined when a highly correlated feature in the RIDER dataset also correlated highly in the HN1 dataset and vice versa. 29 out of 43 reported stable features were found to be highly reproducible between Matlab and Pyradiomics implementations, having consistently high correlation in rank ordering for RIDER Scan 1 and RIDER Scan 2 (rs &gt; 0.8). 18/43 reported features were common in RIDER and HN1 datasets, suggesting they may be agnostic to disease site. Useful radiomics features should be selected based on reproducibility. This study identified a set of features that meet this requirement and validated the methodology for evaluating reproducibility between datasets.

Multiresistant pathogens pose a serious threat to human health. The genus candida is one class of human pathogenic yeasts responsible for infections affecting healthy and immunocompromised patients. In this context, plant essential oils emerged as a future natural alternative to control the diseases caused by these pathogens. Here, it highlighted antimicrobial activity and the mechanisms of action of the essential oil extracted from Croton pluriglandulosus Carn.-Torres & Riina (CpEO) leaves on human pathogenic microorganisms in planktonic and biofilm lifestyles. In addition, for the first time, the oil composition was revealed by GC-MS analysis and the toxicity to human red blood cells (HRBC). Twenty-six chemical compounds were identified in EOCp, Elemicin, Bicyclogermacrene, caryophyllene, brevifolin and 2,4,6-trimethoxy-styrene. Through hemolytic assay, it was shown that CpEO has no toxicity to human RBCs. At the concentration of 50 μg mL-1, CpEO did not show great antibacterial potential. However, promising data were found for C. krusei and C. parapsilosis inhibiting by 89.3% and 80.7% of planktonic cell growth and 83.5% and 77.9% the biofilm formation, respectively. Furthermore, the mechanisms of action CpEO were elucidated by fluorescence. Scanning electron microscopy revealed damage to the cell membrane and pore formation, ROS overproduction, and Induction of apoptosis in candida cells. Our results reinforce the potential of CpEO as an effective alternative molecule of pharmaceutical interest.

The presence of copper in distilled sugar cane spirits, especially cachaça produced in alembics, has impeded the marketing of this product. Red mud (RM) is a residue obtained from alumina production. It contains a high concentration of metal oxides and is very alkaline. The RM was dried at 100 oC and sifted through a 150-micron sieve. The sample was characterized by B.E.T. nitrogen adsorption, scanning electron microscopy-energy-dispersive X-ray (SEM-EDX) and Atomic Absorption Spectrometry (A.A.S.). The textural parameters indicate that the total surface area (S.T.) was 21.9 m2g-1, and the total volume pore (V.T.) was 0.09 cm3g-1. The RM (1 g) was stirred for two hours with a 1.0 L cachaça sample containing 9.39 mg of copper L-1 and filtered under atmospheric pressure. The concentration of copper ions detected in the filtrate was 0.00 mg L-1. No copper ions were retained when the cachaça was filtered through the RM under high pressure without stirring prior to filtration.

Background: Sleep deficiency can adversely affect the performance of resident physicians resulting in greater medical errors. However, the impact of sleep deficiency on surgical outcomes, particularly among attending surgeons is less clear. Methods: Sixty attending surgeons from academic and community departments of surgery or obstetrics and gynecology were studied prospectively using direct observation and self-report to explore the effect of sleep deprivation on patient safety, operating room communication, medical errors, and adverse events while operating under two conditions, Post-Call (defined as >2 hours of nighttime clinical duties) and Non-Post-Call. Results: Each surgeon contributed up to five surgical procedures post-call and non-post-call yielding 362 cases total (150 Post-Call and 210 Non-Post-Call). Most common were caesarian section and herniorrhaphy. Hours of sleep on the night before the operative procedure were significantly less Post-Call (4.98 ± 1.41) vs. Non-Post-Call (6.68 ± 0.88, p<0.01). Errors were infrequent and not related to hours of sleep or post-call status. However, Non-Technical Skills for Surgeons (NOTSS) ratings demonstrated poorer performance while Post-Call for Situational Awareness, Decision Making and Communication/Teamwork. Fewer hours of sleep also was related to lower ratings for Situational Awareness and Decision Making. Decreased self-reported alertness was observed to be associated with increased procedure time. Conclusions: Sleep deficiency in attending surgeons was not associated with greater errors during procedures performed during the next day. However, procedure time was increased suggesting that surgeons were able to compensate for sleep loss by working more slowly. Ratings on non-technical surgical skills were adversely affected by sleep deficiency.

As renewed interest in human space-exploration intensifies, a coherent and modernized strategy for mission-design and planning has become increasingly crucial. Biotechnology has emerged as a promising approach to increase mission resilience, flexibility, and efficiency by virtue of its ability to efficiently utilize in situ resources and reclaim resources from waste streams. Since its infancy during the Apollo years, biotechnology, and specifically biomanufacturing, have witnessed significant expansions of scope and scale. Here we outline four primary mission classes, on Luna and Mars, that drive a staged and accretive biomanufacturing strategy. Each class requires a unique approach to integrate biomanufacturing into the existing mission architecture and so faces unique challenges in technology development.These challenges stem directly from the resources available in a given mission class – the degree to which feedstocks are derived from cargo and in situ resources – and the degree to which loop-closure is necessary. We see that as mission duration and distance from Earth increase, the benefits of specialized sustainable biomanufacturing processes increases. Here we present a strategic approach, guided by technoeconomics, to development, testing, and deployment of these technologies serves to nucleate the larger effort of supporting a sustained human presence in space. The processes needed for each scenario spans the technical breadth of synthetic biology to design engineering, from sophisticated genetic tailoring of chassis-organisms to building scalable, automated, easily operable bioreactors and processing systems. As space-related technology development often does, these advancements are likely to have profound implications for the creation of a stable, resilient bioeconomy on Earth.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized mainly by the gradual decay in neuronal function as a consequence of diverse degenerating events primarily including mitochondria dysfunction and cascades of neuro-immune reactions. Besides the acquired harmful reactive oxygen species (ROS), neurotoxins, and amyloid-beta (Aβ) and TAU pathologies in neurons, accumulating evidence with time underlined the roles of cytokines and growth factors in the AD pathogenesis. It may help us in evaluating the propensities and specific mechanism(s) of cytokines and factors impacting neuron upon apoptotic decline. Proinflammatory cytokines often induce inflammation in AD and AD-like pathogenesis in response to the apoptotic scenarios where some growth factors are involved in cytokinetic reactions to activate microglia and causing inflammation in AD. In this report, we comprehensively reviewed role of cytokines and chemokines in immune response to AD and neuropsychiatry. We provided insights into the neuroinflammation and the role of diverse factors including the pro-/anti-inflammatory cytokines, APP, TAU phosphorylation, glycation end products, complement system, and the role of glial cells. Also, we discussed the pathogenic and protective role of macrophage migration inhibitory factors, choroid plexus-, neurotrophic- and hematopoietic -related growth factors in AD. We further shed light on the availability and accessibility of the cytokines across the blood-brain barrier in AD pathophysiology. Taken together, the emerging role of these factors in AD pathology emphasized the importance of building novel strategies for an effective therapeutic/neuropsychiatric management of AD in clinics.

A technique for fabrication of bacterial cellulose-based films with CeO₂ nanofiller has been developed. The structural and morphological characteristics of the materials have been studied, their thermal and mechanical properties in dry and swollen states having been determined. The preparation methodology makes it possible to obtain composites with a uniform distribution of nanoparticles. The catalytic effect of ceria regarding the thermal oxidative destruction of cellulose has been confirmed by TGA and DTA methods. An increase in CeO₂ content led to an increase in the elastic modulus (a 1.27-fold increase caused by the introduction of 5 wt.% of the nanofiller into the polymer) and strength of the films. This effect is explained by the formation of additional links between polymer macro-chains via the nanoparticles’ surface. The materials fabricated were characterised by a limited ability to swell in water. Swelling caused a 20- to 30-fold reduction in the stiffness of the material, the mechanical properties of the films in a swollen state remaining germane to their practical use. The application of the composite films in cell engineering as substrates for the stem cells’ proliferation has been studied. The increase in CeO₂ content in the films enhanced the proliferative activity of embryonic mouse stem cells. The cells cultured on the scaffold containing 5 wt.% of ceria demonstrated increased cell survival and migration activity. An analysis of gene expression confirmed improved cultivation conditions on CeO₂-containing scaffolds.

To gain new insights into the potential of mother-to-child transmission of Zika virus (ZIKV) through breast milk or breastfeeding practices, we systematically searched regional and international databases and screened 1,658 non-duplicate records describing women with suspected or confirmed ZIKV infection, intending to breastfeed or give breast milk to an infant. Fourteen studies met our inclusion criteria and inform this analysis. These studies reported on 97 mother-children pairs who provided breast milk for ZIKV assessment. Seventeen breast milk samples from different women were found positive for ZIKV via RT-PCR, and ZIKV replication was found in cell cultures from five out of seven breast milk samples from different women. Only three out of six infants who had ZIKV infection were breastfed, no evidence of clinical complications were found to be associated with ZIKV RNA in breast milk. This review updates our previous report by synthesizing the evidence from 12 new articles and we find no evidence of mother-to-child transmission through breast milk intake or breastfeeding. As the certainty of the present evidence is low, additional studies are still warranted to completely understand any potential of transmission of ZIKV through breastfeeding.

Background: Extraintestinal pathogenic Escherichia coli (ExPEC) is the most common cause of urinary tract infections (UTIs). They are often multidrug-resistant (MDR), making them challenging to treat. Additionally, virulence mechanisms as biofilm formation are associated with persistent UTIs. Aims: To reveal a possible association between patients’ risk factors and UTIs caused by MDR or biofilm-forming ExPECs and characterize ExPECs causing asymptomatic bacteriuria, community- (CA), or hospital-acquired (HA) UTIs in hospitalized patients in Brazil. Methods: Bacterial DNA was extracted from the urine of 63 hospitalized patients and sequenced using short-read sequencing. Antibiotic susceptibility was evaluated using VITEK-2, and the biofilm-forming, adhesion, and invasion abilities were quantitatively assessed. Results: Antibiotic resistance rates were high, and the majority of UTIs were complicated CA-UTIs. Most MDR- and ESBL-producing E. coli isolates belonged to high-risk lineages and were associated with UTIs in patients with comorbidities and over 60 years of age. The mortality rate of patients infected with MDR-isolates was higher than of those infected with non-MDR isolates. Most isolates were biofilm-forming, but no association with patients’ risk factors was found. Conclusions: Complicated UTIs caused by MDR- and biofilm-forming bacteria are frequently found in hospitalized patients in Brazil suffering from a UTI and are associated with high-risk lineages.

Introduction: Clinicians have been struggling with the optimal diagnostic approach of patients with suspected COVID-19. We evaluated the added value of chest CT over RT-PCR alone. Methods: Consecutive adult patients with suspected COVID-19 presenting to the emergency department (Academic Medical Center, Amsterdam University Medical Centers, the Netherlands) from March 16^th to April 16^th were retrospectively included if they required hospital admission and underwent chest CT and RT-PCR testing for SARS-CoV-2 infection. The CO-RADS classification was used to assess the radiological probability of COVID-19, where a score of 1-2 was considered as negative, 3 as indeterminate, and 4-5 as positive. CT results were stratified by initial RT-PCR results. For patients with a negative RT-PCR but a positive CT, serology or multidisciplinary discussion after clinical follow-up constituted the final diagnosis. Results: 258 patients with suspected COVID-19 were admitted, of which 239 were included because they had both CT and RT-PCR testing upon admission. Overall, 112 patients (46.9%) had a positive initial RT-PCR, and 14 (5.9%) had a positive repeat RT-PCR. Of 127 patients with a negative or indeterminate initial RT-PCR, 38 (29.9% [95%CI 21.3-39.3%]) had a positive CT. Of these, 13 had a positive RT-PCR upon repeat testing, and 5 had positive serology. The remaining 20 patients were assessed in a multidisciplinary consensus meeting, and for 13 it was concluded that COVID-19 was ‘very likely’. Of 112 patients with a positive initial RT-PCR result, CT was positive in 104 (92.9% [95%CI 89.3-97.5%]). Conclusion: In a high-prevalence emergency department setting, chest CT showed high probability of COVID-19 (CO-RADS 4-5) in 29.9% of patients with a negative or indeterminate initial RT-PCR result. As the majority of these patients had proven or ‘very likely’ COVID-19 after follow-up, we believe that CT helps in the identification of patients who should be admitted in isolation.

Importance: The rapidly expanding 2019 novel coronavirus pandemic (COVID-19, caused by the SARS-CoV-2 virus) has challenged the medical community to an unprecedented degree. Physicians and healthcare workers are at added risk of exposure and infection during the course of the patient care. Due to the rapid spread of this disease through respiratory droplets, healthcare providers such as otolaryngologists-head & neck surgeons who come in close contact with the upper aerodigestive tract during diagnostic and therapeutic procedures are particularly at risk. Here we present a set of safety recommendations based on our review of literature and communications with physicians with first-hand knowledge of safety procedures during the 2019 COVID-19 pandemic.Observations: A high number of healthcare providers were infected during the first phase of the pandemic in Wuhan province. Subsequently, by adopting strict safety precautions, other regions were able to achieve high levels of safety for healthcare providers without jeopardizing the care of patients. We reviewed the most common procedures related to the examination and treatment of upper aerodigestive tract diseases. Each category was reviewed based on the potential risk imposed to healthcare workers. Specific recommendations were made, based on the literature, when available, or consensus best practices. Specific safety recommendations were made for performing tracheostomy in COVID-19 patients. Conclusions and Relevance: Preserving highly skilled healthcare work force is a top priority for any community and healthcare system. Based on the experience of healthcare systems in Asia and Europe, by following strict safety guidelines, the risk of exposure and infection of healthcare providers could be significantly reduced, while providing high levels of care. The provided recommendations could be used as broad guidance for all healthcare workers who are involved with the care of COVID-19 patients.

In most industrialized countries, screening programs for cervical cancer have shifted from cytology (Pap smear or ThinPrep) alone on clinician-obtained samples to the addition of screening for human papillomavirus (HPV), its main causative agent. For HPV testing, self-sampling instead of clinician-sampling has proven to be equally accurate, in particular for assays that use nucleic acid amplification techniques. In addition, HPV testing of self-collected samples in combination with a follow-up Pap smear in case of a positive result is more effective in detecting precancerous lesions than a Pap smear alone. Self-sampling for HPV testing has already been adopted by some countries, while others have started trials to evaluate its incorporation into national cervical cancer screening programs. Self-sampling may result in more individuals willing to participate in cervical cancer screening, because it removes many of the barriers that prevent women, especially those in low socioeconomic and minority populations, from participating in regular screening programs. Several studies have shown that the majority of women who have been underscreened but who tested HPV-positive in a self-obtained sample, will visit a clinic for follow-up diagnosis and management. Additionally, a self-collected sample can also be used for vaginal microbiome analysis, which can provide additional information about HPV infection persistence as well as vaginal health in general.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.