Antiviral Susceptibility of Swine-Origin Influenza A Viruses Isolated from Humans, United States.

Since 2013, a total of 167 human infections with swine-origin (variant) influenza A viruses of A(H1N1)v, A(H1N2)v, and A(H3N2)v subtypes have been reported in the United States. Analysis of 147 genome sequences revealed that nearly all had S31N substitution, an M2 channel blocker-resistance marker, whereas neuraminidase inhibitor-resistance markers were not found. Two viruses had a polymerase acidic substitution (I38M or E199G) associated with decreased susceptibility to baloxavir, an inhibitor of viral cap-dependent endonuclease (CEN). Using phenotypic assays, we established subtype-specific susceptibility baselines for neuraminidase and CEN inhibitors. When compared with either baseline or CEN-sequence-matched controls, only the I38M substitution decreased baloxavir susceptibility, by 27-fold. Human monoclonal antibodies FI6v3 and CR9114 targeting the hemagglutinin's stem showed variable (0.03 to >10 µg/mL) neutralizing activity toward variant viruses, even within the same clade. Methodology and interpretation of laboratory data described in this study provide information for risk assessment and decision-making on therapeutic control measures.

Current approaches and outstanding challenges of functional annotation of metabolites: a comprehensive review.

Metabolite profiling is a powerful approach for the clinical diagnosis of complex diseases, ranging from cardiometabolic diseases, cancer, and cognitive disorders to respiratory pathologies and conditions that involve dysregulated metabolism. Because of the importance of systems-level interpretation, many methods have been developed to identify biologically significant pathways using metabolomics data. In this review, we first describe a complete metabolomics workflow (sample preparation, data acquisition, pre-processing, downstream analysis, etc.). We then comprehensively review 24 approaches capable of performing functional analysis, including those that combine metabolomics data with other types of data to investigate the disease-relevant changes at multiple omics layers. We discuss their availability, implementation, capability for pre-processing and quality control, supported omics types, embedded databases, pathway analysis methodologies, and integration techniques. We also provide a rating and evaluation of each software, focusing on their key technique, software accessibility, documentation, and user-friendliness. Following our guideline, life scientists can easily choose a suitable method depending on method rating, available data, input format, and method category. More importantly, we highlight outstanding challenges and potential solutions that need to be addressed by future research. To further assist users in executing the reviewed methods, we provide wrappers of the software packages at https://github.com/tinnlab/metabolite-pathway-review-docker.

A higher dietary alpha-linolenic acid intake is associated with lower colorectal cancer risk based on MUC4 rs2246901 variant among Korean adults.

Alpha-linolenic acid (C18:3n-3 [ALA]) intake may have a beneficial effect in reducing cancer risk; however, its association with colorectal cancer (CRC) risk remains conflicted. Additionally, ALA was emphasized as being associated with mucins, an important glycoproteins family within the intestine. Thus, we hypothesized that a higher dietary ALA intake may reduce the risk of CRC and this preventive effect has an interaction with mucin 4 (MUC4) rs2246901. We conducted a case-control study at the National Cancer Center in Korea, involving 1039 cases and 1982 controls, aiming to determine the interaction of the MUC4 rs2246901 polymorphism and ALA intake in CRC risk. Dietary ALA intake was collected via semiquantitative food frequency questionnaire (SQFFQ), categorizing by 4 quartiles. We evaluated the odds ratios (ORs) and 95% confidence intervals (CIs) through unconditional logistic regression models. Higher dietary ALA intake was found to be inversely associated with CRC risk (adjusted OR = 0.58; 95% CI, 0.45-0.75, P for trend < .001). No significant association between MUC4 rs2246901 polymorphism and CRC risk was found. In a recessive model, MUC4 rs2246901 seemed to modify this association; participants with at least 1 major allele and higher ALA intake had a significantly lower CRC risk than those who had a lower intake (adjusted OR = 0.56; 95% CI, 0.43-0.72; P interaction = .047). A higher dietary ALA was proposed as a potential protective nutrient against CRC. Moreover, this association might be influenced by presence of the MUC4 rs2246901 polymorphism.

GABAergic neuron dysregulation in a human neurodevelopmental model for major psychiatric disorders.

"GABA dysfunction" is a major hypothesis for the biological basis of schizophrenia with indirect supporting evidence from human post-mortem brain and genetic studies. Patient-derived induced pluripotent stem cells (iPSCs) have emerged as a valuable platform for modeling psychiatric disorders, and previous modeling has revealed glutamatergic synapse deficits. Whether GABAergic synapse properties are affected in patient-derived human neurons and how this impacts neuronal network activity remain poorly understood. Here we optimized a protocol to differentiate iPSCs into highly enriched ganglionic eminence-like neural progenitors and GABAergic neurons. Using a collection of iPSCs derived from patients of psychiatric disorders carrying a Disrupted-in-Schizophrenia 1 ( DISC1 ) mutation and their unaffected family member, together with respective isogenic lines, we identified mutation-dependent deficits in GABAergic synapse formation and function, a phenotype similar to that of mutant glutamatergic neurons. However, mutant glutamatergic and GABAergic neurons contribute differentially to neuronal network excitability and synchrony deficits. Finally, we showed that GABAergic synaptic transmission is also defective in neurons derived from several idiopathic schizophrenia patient iPSCs. Transcriptome analysis further showed some shared gene expression dysregulation, which is more prominent in DISC1 mutant neurons. Together, our study supports a functional GABAergic synaptic deficit in major psychiatric disorders.

Estimating the force of infection of four dengue serotypes from serological studies in two regions of Vietnam.

Dengue is endemic in Vietnam with circulation of all four serotypes (DENV1-4) all year-round. It is hard to estimate the disease's true serotype-specific transmission patterns from cases due to its high asymptomatic rate, low reporting rate and complex immunity and transmission dynamics. Seroprevalence studies have been used to great effect for understanding patterns of dengue transmission. We tested 991 population serum samples (ages 1-30 years, collected 2013 to 2017), 531 from Ho Chi Minh City and 460 from Khanh Hoa in Vietnam, using a flavivirus protein microarray assay. By applying our previously developed inference framework to the antibody profiles from this assay, we can (1) determine proportions of a population that have not been infected or infected, once, or more than once, and (2) infer the infecting serotype in those infected once. With these data, we then use mathematical models to estimate the force of infection (FOI) for all four DENV serotypes in HCMC and KH over 35 years up to 2017. Models with time-varying or serotype-specific DENV FOI assumptions fit the data better than constant FOI. Annual dengue FOI ranged from 0.005 (95%CI: 0.003-0.008) to 0.201 (95%CI: 0.174-0.228). FOI varied across serotypes, higher for DENV1 (95%CI: 0.033-0.048) and DENV2 (95%CI: 0.018-0.039) than DENV3 (95%CI: 0.007-0.010) and DENV4 (95%CI: 0.010-0.016). The use of the PMA on serial age-stratified cross-sectional samples increases the amount of information on transmission and population immunity, and should be considered for future dengue serological surveys, particularly to understand population immunity given vaccines with differential efficacy against serotypes, however, there remains limits to what can be inferred even using this assay.

Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of OT-elicited reductions of body weight gain and adiposity in male diet-induced obese rats.

Recent studies indicate that central administration of oxytocin (OT) reduces body weight (BW) in high fat diet-induced obese (DIO) rodents by reducing energy intake and increasing energy expenditure (EE). Previous studies in our lab have shown that administration of OT into the fourth ventricle (4V; hindbrain) elicits weight loss and stimulates interscapular brown adipose tissue temperature (TIBAT) in DIO rats. We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of IBAT contributes to its ability to activate BAT and reduce BW in DIO rats. To test this, we determined the effect of disrupting SNS activation of IBAT on OT-elicited stimulation of TIBAT and reduction of BW in DIO rats. We first confirmed that bilateral surgical SNS denervation to IBAT was successful based on having achieved ≥ 60% reduction in IBAT norepinephrine (NE) content from DIO rats. NE content was selectively reduced in IBAT by 94.7 ± 2.7, 96.8 ± 1.8 and 85.9 ± 6.1% (P<0.05) at 1, 6 and 7-weeks post-denervation, respectively, and was unchanged in liver or inguinal white adipose tissue. We then measured the impact of bilateral surgical SNS denervation to IBAT on the ability of acute 4V OT (1, 5 µg) to stimulate TIBAT in DIO rats. We found that the high dose of 4V OT (5 µg) stimulated TIBAT similarly between sham and denervated rats (P=NS) and that the effects of 4V OT to stimulate TIBAT did not require beta-3 adrenergic receptor signaling. We subsequently measured the effect of bilateral surgical denervation of IBAT on the effect of chronic 4V OT (16 nmol/day) or vehicle infusion to reduce BW, adiposity and energy intake in DIO rats. Chronic 4V OT reduced BW gain by -7.2 ± 9.6 g and -14.1 ± 8.8 g in sham and denervated rats (P<0.05 vs vehicle treatment), respectively, and this effect was similar between groups (P=NS). These effects were associated with reductions in adiposity and energy intake (P<0.05). Collectively, these findings support the hypothesis that sympathetic innervation of IBAT is not required for central OT to increase BAT thermogenesis and reduce BW gain and adiposity in male DIO rats.

Characteristics and outcomes of lung cancer patients presenting through the emergency department: a Waikato District Health Board study.

AIM: This research examines the characteristics and survival outcomes of patients receiving a lung cancer diagnosis after attending the emergency department (ED) of Waikato hospitals in New Zealand. METHODS: This retrospective study was based on a comprehensive database of Waikato patients recorded on the Midland Lung Cancer Register from 2011 to 2021. We compared the characteristics of patients with and without emergency presentations within 14 days before their lung cancer diagnosis. The survival of patients with and without ED attendance was compared between Maori and non-Maori. This study also analysed the odds ratios (OR) of presenting via ED before diagnosis and surviving 12 months based on logistic regressions. RESULTS: In total, 2,397 patients were included, with 39.6% attending the ED prior to diagnosis. Maori were 1.27 times more likely than non-Maori to be diagnosed after attending the ED. Other characteristics of patients included being male, being diagnosed with small cell lung cancer and having more advanced-stage disease. Patients attending the ED were less likely to survive 12 months than those without ED visits (OR 0.42), and those with two or more ED visits were even less likely to survive 12 months (OR 0.33). CONCLUSION: Patients presenting through the ED have more advanced-stage disease, while those presenting through their general practitioners (GPs) have evidence of being diagnosed earlier and having better survival. Barriers to early diagnoses through attendance with a GP, particularly for Maori and for men, need to be explored.

Long-Range Ballistic Propagation of 80% Excitonic Fraction Polaritons in a Perovskite Metasurface at Room Temperature.

Exciton-polaritons, hybrid light-matter excitations arising from the strong coupling between excitons in semiconductors and photons in photonic nanostructures, are crucial for exploring the physics of quantum fluids of light and developing all-optical devices. Achieving room temperature propagation of polaritons with a large excitonic fraction is challenging but vital, e.g., for nonlinear light transport. We report on room temperature propagation of exciton-polaritons in a metasurface made from a subwavelength lattice of perovskite pillars. The large Rabi splitting, much greater than the optical phonon energy, decouples the lower polariton band from the phonon bath of the perovskite. These cooled polaritons, in combination with the high group velocity achieved through the metasurface design, enable long-range propagation, exceeding hundreds of micrometers even with an 80% excitonic component. Furthermore, the design of the metasurface introduces an original mechanism for unidirectional propagation through polarization control, suggesting a new avenue for the development of advanced polaritonic devices.

Structural analysis of noncanonical translation initiation complexes.

Translation initiation is a highly regulated, multi-step process that is critical for efficient and accurate protein synthesis. In bacteria, initiation begins when mRNA, initiation factors, and a dedicated initiator fMet-tRNAfMet bind the small (30S) ribosomal subunit. Specific binding of fMet-tRNAfMet in the peptidyl (P) site is mediated by the inspection of the fMet moiety by initiation factor IF2 and of three conserved G-C base pairs in the tRNA anticodon stem by the 30S head domain. Tandem A-minor interactions form between 16S ribosomal RNA nucleotides A1339 and G1338 and tRNA base pairs G30-C40 and G29-C41, respectively. Swapping the G30-C40 pair of tRNAfMet with C-G (called tRNAfMet M1) reduces discrimination against the noncanonical start codon CUG in vitro, suggesting crosstalk between the gripping of the anticodon stem and recognition of the start codon. Here, we solved electron cryomicroscopy structures of Escherichia coli 70S initiation complexes containing the fMet-tRNAfMet M1 variant paired to the noncanonical CUG start codon, in the presence or absence of IF2 and the non-hydrolyzable GTP analog GDPCP, alongside structures of 70S initiation complexes containing this tRNAfMet variant paired to the canonical bacterial start codons AUG, GUG, and UUG. We find that the M1 mutation weakens A-minor interactions between tRNAfMet and 16S nucleotides A1339 and G1338, with IF2 strengthening the interaction of G1338 with the tRNA minor groove. These structures suggest how even slight changes to the recognition of the fMet-tRNAfMet anticodon stem by the ribosome can impact the start codon selection.

Genomic characterization and identification of candidate genes for putative podophyllotoxin biosynthesis pathway in Penicillium herquei HGN12.1C.

Previous studies have reported the functional role, biochemical features and synthesis pathway of podophyllotoxin (PTOX) in plants. In this study, we employed combined morphological and molecular techniques to identify an endophytic fungus and extract PTOX derivatives. Based on the analysis of ITS sequences and the phylogenetic tree, the isolate was classified as Penicillium herquei HGN12.1C, with a sequence identity of 98.58%. Morphologically, the HGN12.1C strain exhibits white colonies, short-branched mycelia and densely packed hyphae. Using PacBio sequencing at an average read depth of 195×, we obtained a high-quality genome for the HGN12.1C strain, which is 34.9 Mb in size, containing eight chromosomes, one mitochondrial genome and a GC content of 46.5%. Genome analysis revealed 10 genes potentially involved in PTOX biosynthesis. These genes include VdtD, Pinoresinollariciresinol reductase (PLR), Secoisolariciresinol dehydrogenase (SDH), CYP719A23, CYP71BE54, O-methyltransferase 1 (OMT1), O-methyltransferase 3 (OMT3), 2-ODD, CYP71CU and CYP82D61. Notably, the VdtD gene in fungi shares functional similarities with the DIR gene found in plants. Additionally, we identified peltatin, a PTOX derivative, in the HGN12.1C extract. Docking analysis suggests a potential role for the 2-ODD enzyme in converting yatein to deoxypodophyllotoxin. These findings offer invaluable insights into the synthesis mechanism of PTOX in fungi, shedding light on the relationship between host plants and endophytes.

Effectiveness and implementation of decentralized, community- and primary care-based strategies in promoting hepatitis B testing uptake: a systematic review and meta-analysis.

Background: Expanding chronic hepatitis B (CHB) testing through effective implementation strategies in primary- and community-care setting is crucial for elimination. Our study aimed to determine the effectiveness of all available strategies in the literature and evaluate their specifications and implementation outcomes, thereby informing future programming and policymaking. Methods: We conducted a systematic review and meta-analysis (PROSPERO CRD42023455781), searching Scopus, Embase, PubMed, and CINAHL databases up to June 05, 2024, for randomized controlled trials investigating primary- and community-care-based implementation strategies to promote CHB testing. Studies were screened against a priori eligibility criteria, and their data were extracted using a standardized protocol if included. ROB-2 was used to assess the risk of bias. Implementation strategies' components were characterized using the Behavior Change Wheel (BCW) framework. Random-effect models were applied to pool the effectiveness estimate by strategy. Mixed-effect meta-regression was employed to investigate if effectiveness varied by the number of strategy's BCW components. Findings: 7146 unique records were identified. 25 studies were eligible for the review, contributing 130,598 participants. 19 studies were included in the meta-analysis. No studies were conducted in low-and-middle-income countries. Implementation outcomes were reported in only ten studies (40%). Community-based strategies included lay health workers-led education (Pooled Risk Difference = 27.9% [95% Confidence Interval = 3.4-52.4], I2 = 99.3%) or crowdsourced education on social media (3.1% [-2.2 to 8.4], 0.0%). Primary care-based strategies consisted of electronic alert system (8.4% [3.7-13.1], 95.0%) and healthcare providers-led education (HCPs, 62.5% [53.1-71.9], 27.5%). The number of BCW-framework-driven strategy components showed a significant dose-response relationship with effectiveness. Interpretation: HCPs-led education stands out, and more enriched multicomponent strategies had better effectiveness. Future implementation strategies should consider critical contextual factors and policies to achieve a sustainable impact towards hepatitis B elimination targets. Funding: Tran Dolch Post-Doctoral Fellowship in Hepatology, Johns Hopkins University School of Medicine, Baltimore MD, USA.

Daylight duration and time allocation of children and adolescents.

This study explores the allocation of time, particularly to sleep, among children and adolescents in response to daily daylight variation. Utilising a dataset of over 50,000 time-use diaries from two Australian cohorts spanning 16 years and employing an individual fixed effects estimator, we uncover a substantial causal impact of daily daylight duration on sleep patterns. Our findings reveal that days with longer daylight hours are associated with a decrease in total sleep duration, primarily driven by a later sleep onset time. Additionally, longer daylight hours correspond to reduced time spent on personal care and media activities, with increased dedication to school and physical activities. Furthermore, we identify socio-demographic factors moderating these effects, such as older age and weekend days exerting a stronger influence on sleep duration, while females and children of unemployed mothers exhibit a subtle impact. These insights contribute to our understanding of how environmental factors shape daily routines and offer implications for designing schedules that promote positive developmental outcomes in young individuals.

Hypothetical acceptability of minimally invasive tissue sampling and considerations for practice: A qualitative study in Vietnam.

The exact aetiology of the cause of death (COD) remains unknown for a high proportion of deaths caused by infectious diseases. Complete diagnostic autopsy (CDA) is considered the gold standard to determine COD, but it is often not used in low and middle-income countries (LMIC), including Vietnam, for a variety of reasons. One alternative is minimally invasive tissue sampling (MITS). This study was part of a larger project to explore the perceptions of MITS in Vietnam to provide recommendations for its potential implementation. We collected in-depth interviews and focus group discussions that explored MITS acceptability from 96 participants, including key informants, healthcare workers, community stakeholders, and people who had family members pass away recently. Participants highlighted the minimally invasive nature as the most considerable strength of MITS that could make it acceptable in Vietnam compared with CDA. However, participants still had concerns including the accuracy of the technique, the potential damage on the body, and the potential conflicts MITS results could have with original clinical diagnoses. Overall, the hypothetical acceptability of MITS was not clear-cut. It is imperative to consider acceptability before implementing new medical procedures into a given context, especially when it revolves around death, dying and the body.

Superficial temporal artery branching pattern in single stage auricular reconstruction: A novel classification.

INTRODUCTION: The two most severe complications of single-stage, porous polyethene microtia reconstruction are flap necrosis/framework exposure and frontal nerve paralysis. To reduce these risks, require a temporoparietal fascia (TPF) flap that includes both the parietal and frontal branches of the superficial temporal artery (STA) while sparing the nerve. We propose a classification that helps minimize said complications. MATERIAL AND METHODS: Fifty-five TPF flaps of 54 microtia patients who underwent single-stage auricular reconstruction from May 2018 to July 2021 were studied. Flaps were harvested using endoscopic techniques. The parietal and frontal branch characteristics and measurements were obtained using a microscope/endoscope. RESULTS: The frontal artery might have 1 to 4 branches. If they were close to Pitanguy's line (≤5 mm), there would be a high risk of nerve damage. Parietal (P) and frontal (F) artery diameters <0.5 mm were risk factors for partial flap necrosis. Based on this observation, we proposed 0.5 mm as the diameter threshold to determine whether an arterial branch is hypoplasia or sufficient. From this study, a new classification of STA branching pattern was proposed with five types: PF1 (23.6 %), PF2 (43.6 %), pF1 (3.6 %), pF2 (12.8 %), and Pf (16.4 %); where P/F indicates sufficient branches, p/f indicates absent or hypoplasia ones, and the number indicates single or multiple frontal artery branching. CONCLUSION: The risk of flap necrosis and frontal nerve damage is due to abnormalities of the frontal artery of the STA in the TPF flap. Understanding the anatomical classification with clear visualization during flap harvest ensures a successful outcome.

FeBr3-catalysed synthesis of 3-aroylimidazo[1,2-a]pyridine and 3,3'-(arylmethylene)bis(2-phenylimidazo[1,2-a]pyridines) derivatives from 2-arylimidazo[1,2-a]pyridines and aromatic aldehydes: an investigation about mechanistic insights.

In a new approach, a series of 3-aroylimidazo[1,2-a]pyridine derivatives were prepared in high yields. This approach revealed the direct Fe-catalyzed functionalization of imidazo[1,2-a]pyridine derivatives with aryl aldehydes via an aerobic oxidative cross-dehydrogenative coupling process. This transformation occurred in the presence of air, and FeBr3 served as a homogeneous Lewis catalyst. O2 was found to be the principal oxidant responsible for the method's success. Interestingly, when these reactions were carried out under an argon atmosphere, 3,3'-(arylmethylene)bis(2-phenylimidazo[1,2-a]pyridines) derivatives were prepared in good yields.

Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of oxytocin-elicited reductions of body weight and adiposity in male diet-induced obese mice.

Previous studies indicate that CNS administration of oxytocin (OT) reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain (fourth ventricular [4V]) administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (TIBAT, a surrogate measure of increased EE) in DIO mice. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO mice. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT administration to increase TIBAT and elicit weight loss in DIO mice. We first determined whether bilateral surgical SNS denervation to IBAT was successful as noted by ≥ 60% reduction in IBAT norepinephrine (NE) content in DIO mice. NE content was selectively reduced in IBAT at 1-, 6- and 7-weeks post-denervation by 95.9 ± 2.0, 77.4 ± 12.7 and 93.6 ± 4.6% (P<0.05), respectively and was unchanged in inguinal white adipose tissue, pancreas or liver. We subsequently measured the effects of acute 4V OT (1, 5 µg ≈ 0.99, 4.96 nmol) on TIBAT in DIO mice following sham or bilateral surgical SNS denervation to IBAT. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) elevated TIBAT similarly in sham mice as in denervated mice. We subsequently measured the effects of chronic 4V OT (16 nmol/day over 29 days) or vehicle infusions on body weight, adiposity and food intake in DIO mice following sham or bilateral surgical denervation of IBAT. Chronic 4V OT reduced body weight by 5.7 ± 2.23% and 6.6 ± 1.4% in sham and denervated mice (P<0.05), respectively, and this effect was similar between groups (P=NS). OT produced corresponding reductions in whole body fat mass (P<0.05). Together, these findings support the hypothesis that sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and reductions of body weight and adiposity in male DIO mice.

Expanding the Spectral Responsivity of Photodetectors via the Integration of CdSe/ZnS Quantum Dots and MEH-PPV Polymer Composite.

This study investigates the energy transfer mechanism between the organic polymer poly(2-methoxy-5(2'-ethyl)heroxyphenylenevinylene) (MEH-PPV) and CdSe/ZnS core-shell quantum dots (CdSe/ZnS CSQDs). Additionally, a hybrid ZnO-based photodetector (PD) is fabricated using the composite of MEH-PPV and CdSe/ZnS CSQDs, aiming to gain deeper insights. The combination of MEH-PPV and CdSe/ZnS CSQDs facilitates a broad spectral response in PDs, spanning from the ultraviolet (UV) to the visible range. In particular, PDs with QDs in the composite demonstrate notably excellent photosensitivity to both ultraviolet (UV) light (365 nm) (~5 fold) and visible light (505 nm) (~3 fold).

Whole genome sequence analysis of Bacillus amyloliquefaciens strain S2.5 as a potential probiotic for feed supplement in livestock production.

BACKGROUND: Supplementing probiotics in livestock feed is increasing due to concerns over the potential harm caused by antibiotics and other chemical growth promoters. Several Bacillus sp. have been used as probiotic supplements for livestock. In this study, Bacillus amyloliquefaciens S2.5 was isolated from freshwater and its potential probiotic characteristics were evaluated in vitro. The whole genome of strain S2.5 was sequenced, and its probiotic traits were annotated using bioinformatic tools. RESULTS: Both vegetative cells and spores of strain S2.5 remained stable throughout the 1.5 h of gastric juice and 48 h of intestine simulation. The strain S2.5 harbored the ability to produce glucoamylase, carboxymethyl cellulase, protease, and chitinase. It is also susceptible to all six tested antibiotics. The complete genome sequence shows genes related to acid-bile tolerance, environmental stress resistance, hydrolases, and adhesion to gut mucosa, confirming probiotic traits in the in vitro experiments. CONCLUSIONS: B. amyloliquefaciens S2.5 demonstrated potential probiotic characteristics and its genetic profile in the in vitro experiments. Further in vivo assessments of B. amyloliquefaciens S2.5 on livestock and poultry should be performed to assess its practical application.

Injectable chitosan hydrogel effectively controls lesion growth in a venous malformation murine model.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of intralesional injection of chitosan hydrogel (CH) combined with sodium tetradecyl sulfate (STS) to sclerose and embolize venous malformations (VMs) by comparison with 3% STS foam and placebo in a mouse model. MATERIALS AND METHODS: Subcutaneous VMs were created by injecting HUVEC_TIE2-L914F cells, mixed with matrigel, into the back of athymic mice (Day [D] 0). After VM-like lesions were established at D10, 70 lesions were randomly assigned to one of six treatment groups (untreated, saline, 3% STS-foam, CH, 1% STS-CH, 3% STS-CH). For 3% STS-foam, the standard Tessari technique was performed. VMs were regularly evaluated every 2-3 days to measure lesion size until the time of collection at D30 (primary endpoint). At D30, VM lesions including the matrigel plugs were culled and evaluated by histological analysis to assess vessel size, chitosan distribution and endothelial expression. One-way analysis of variance (ANOVA) test was performed to compare quantitative variables with normal distribution, otherwise Kruskal-Wallis test followed by pairwise comparisons by a Wilcoxon rank sum test was performed. RESULTS: All VMs were successfully punctured and injected. Six VMs injected with 3% STS-CH showed early skin ulceration with an extrusion of the matrigel plug and were excluded from final analysis. In the remaining 64 VMs, skin ulceration occurred on 26 plugs, resulting in the loss of three 3% STS-foam and one 1% STS-CH plugs. Both chitosan formulations effectively controlled growth of VMs by the end of follow-up compared to untreated or 3% STS-foam groups (P < 0.05). Vessel sizes were smaller with both CH formulations compared to untreated and saline groups (P < 0.05). Additionally, there were smaller vascular channels within the 1% STS-CH group compared to the 3% STS-foam group (P < 0.05). CONCLUSION: Chitosan's ability to control the growth of VMs suggests a promising therapeutic effect that outperforms the gold standard (STS-foam) on several variables.