Detection of Hanseniaspora opuntiae in anovaginal samples of pregnant women in Rio de Janeiro, Brazil-a case report.

In this study, we report the first isolation of Hanseniaspora opuntiae obtained from four pregnant women in Brazil. Clinical isolates were obtained from four samples taken between 35 and 37 gestational weeks, as part of the routine antenatal care for maternal colonization screening for Streptococcus agalactiae group B. The patients were immunocompetent, with two of them diagnosed with gestational diabetes mellitus. Species identification was performed by MALDI-TOF MS and rDNA sequencing. While Hanseniaspora species have not traditionally been considered a typical opportunist pathogen, our findings emphasize the importance of investigating and screening for Hanseniaspora in pregnant populations, highlighting H. opuntiae as a potential agent of human infections.

Short-term effects of Pilates-based exercise on upper limb strength and function in people with Parkinson's disease.

BACKGROUND: People with Parkinson's disease (PD) have impaired upper limb motor coordination, limiting the execution of activities of daily living. This study investigated the feasibility and safety of a short-term Pilates-based exercise program in the treatment of upper limb motor coordination for people with PD. METHODS: Fifteen patients - n (%) 4 women/11 men (27/73), median [interquartile range] age 66 [9] years - participated in this quasi-experimental (before-and-after) clinical trial. Patients underwent a 6-week (30 min/day, 3 days/week) Pilates exercise program using Reformer, Cadillac, Chair, and Barrel equipment. Feasibility was evaluated by adherence to the program and the ability to perform the exercises including progressions on difficulty. Safety was evaluated based on self-reported adverse events. Clinical and functional trends before and after the intervention were also computed regarding handgrip strength (HGS), fine motor coordination (9 Hole Peg Test; 9HPT), bradykinesia (Movement Disorder Society - Unified Parkinson's disease Rating Scale; MDS-UPDRS), and upper limb functionality (Test D'évaluation des Membres Supérieurs des Personnes Âgées, TEMPA). RESULTS: Of the 18 Pilates sessions, exercise adherence was 100%. The only adverse event observed was mild muscle pain. Pre-post differences were observed only for body bradykinesia and hypokinesia (1.0 [0.0] vs. 0.0 [1.0] s, adjusted p = 0.048). CONCLUSIONS: A short-term Pilates-based exercise program in the treatment of upper limb muscle strength, manual dexterity, bradykinesia, and functionality is feasible and safe for people with PD. Changes in upper limb bradykinesia encourage randomized clinical trials.

Enhanced hippocampal LTP but normal NMDA receptor and AMPA receptor function in a rat model of CDKL5 deficiency disorder.

BACKGROUND: Mutations in the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) cause a severe neurological disorder characterised by early-onset epileptic seizures, autism and intellectual disability (ID). Impaired hippocampal function has been implicated in other models of monogenic forms of autism spectrum disorders and ID and is often linked to epilepsy and behavioural abnormalities. Many individuals with CDKL5 deficiency disorder (CDD) have null mutations and complete loss of CDKL5 protein, therefore in the current study we used a Cdkl5-/y rat model to elucidate the impact of CDKL5 loss on cellular excitability and synaptic function of CA1 pyramidal cells (PCs). We hypothesised abnormal pre and/or post synaptic function and plasticity would be observed in the hippocampus of Cdkl5-/y rats. METHODS: To allow cross-species comparisons of phenotypes associated with the loss of CDKL5, we generated a loss of function mutation in exon 8 of the rat Cdkl5 gene and assessed the impact of the loss of CDLK5 using a combination of extracellular and whole-cell electrophysiological recordings, biochemistry, and histology. RESULTS: Our results indicate that CA1 hippocampal long-term potentiation (LTP) is enhanced in slices prepared from juvenile, but not adult, Cdkl5-/y rats. Enhanced LTP does not result from changes in NMDA receptor function or subunit expression as these remain unaltered throughout development. Furthermore, Ca2+ permeable AMPA receptor mediated currents are unchanged in Cdkl5-/y rats. We observe reduced mEPSC frequency accompanied by increased spine density in basal dendrites of CA1 PCs, however we find no evidence supporting an increase in silent synapses when assessed using a minimal stimulation protocol in slices. Additionally, we found no change in paired-pulse ratio, consistent with normal release probability at Schaffer collateral to CA1 PC synapses. CONCLUSIONS: Our data indicate a role for CDKL5 in hippocampal synaptic function and raise the possibility that altered intracellular signalling rather than synaptic deficits contribute to the altered plasticity. LIMITATIONS: This study has focussed on the electrophysiological and anatomical properties of hippocampal CA1 PCs across early postnatal development. Studies involving other brain regions, older animals and behavioural phenotypes associated with the loss of CDKL5 are needed to understand the pathophysiology of CDD.

Super-Suppression of Long-Wavelength Phonons in Constricted Nanoporous Geometries.

In a typical semiconductor material, the majority of the heat is carried by long-wavelength, long-mean-free-path phonons. Nanostructuring strategies to reduce thermal conductivity, a promising direction in the field of thermoelectrics, place scattering centers of size and spatial separation comparable to the mean free paths of the dominant phonons to selectively scatter them. The resultant thermal conductivity is in most cases well predicted using Matthiessen's rule. In general, however, long-wavelength phonons are not as effectively scattered as the rest of the phonon spectrum. In this work, using large-scale molecular-dynamics simulations, non-equilibrium Green's function simulations, and Monte Carlo simulations, we show that specific nanoporous geometries that create narrow constrictions in the passage of phonons lead to anticorrelated heat currents in the phonon spectrum. This effect results in super-suppression of long-wavelength phonons due to heat trapping and reductions in the thermal conductivity to values well below those predicted by Matthiessen's rule.

Long-Term Co-Circulation of Host-Specialist and Host-Generalist Lineages of Group B Streptococcus in Brazilian Dairy Cattle with Heterogeneous Antimicrobial Resistance Profiles.

Group B Streptococcus (GBS) is a major cause of contagious bovine mastitis (CBM) in Brazil. The GBS population is composed of host-generalist and host-specialist lineages, which may differ in antimicrobial resistance (AMR) and zoonotic potential, and the surveillance of bovine GBS is crucial to developing effective CBM control and prevention measures. Here, we investigated bovine GBS isolates (n = 156) collected in Brazil between 1987 and 2021 using phenotypic testing and whole-genome sequencing to uncover the molecular epidemiology of bovine GBS. Clonal complex (CC) 61/67 was the predominant clade in the 20th century; however, it was replaced by CC91, with which it shares a most common recent ancestor, in the 21st century, despite the higher prevalence of AMR in CC61/67 than in CC91, and high selection pressure for AMR from indiscriminate antimicrobial use in the Brazilian dairy industry. CC103 also emerged as a dominant CC in the 21st century, and a considerable proportion of herds had two or more GBS strains, suggesting poor biosecurity and within-herd evolution due to the chronic nature of CBM problems. The majority of bovine GBS belonged to serotype Ia or III, which was strongly correlated with CCs. Ninety-three isolates were resistant to tetracycline (≥8 µg/mL; tetO = 57, tetM = 34 or both = 2) and forty-four were resistant to erythromycin (2.0 to >4 µg/mL; ermA = 1, ermB = 38, mechanism unidentified n = 5). Only three isolates were non-susceptible to penicillin (≥8.0 µg/mL), providing opportunities for improved antimicrobial stewardship through the use of narrow-spectrum antimicrobials for the treatment of dairy cattle. The common bovine GBS clades detected in this study have rarely been reported in humans, suggesting limited risk of interspecies transmission of GBS in Brazil. This study provides new data to support improvements to CBM and AMR control, bovine GBS vaccine design, and the management of public health risks posed by bovine GBS in Brazil.

Benchmark Investigation of SCC-DFTB against Standard and Hybrid DFT to Model Electronic Properties in Two-Dimensional MOFs for Thermoelectric Applications.

Recent studies have shown that metal-organic frameworks (MOFs) have potential as thermoelectric materials, and the topic has received increasing attention. The main motivation for this project is to further our knowledge of thermoelectric properties in MOFs and find which available self-consistent-charge density functional tight binding (SCC-DFTB) method can best predict (at least trends in) the electronic properties of MOFs at a lower computational cost than standard density functional theory (DFT). In this work, the electronic properties of monolayer, serrated, AA-stacked, and/or AB-stacked Zn3C6O6, Cd3C6O6, Zn-NH-MOF─for which no previous calculations of thermoelectric performance exist─and Ni3(HITP)2 MOFs are modeled with DFT-PBE, DFT-HSE06, GFN1-xTB, GFN2-xTB, and DFTB-3ob/mio. The band structures, density of states, and their relative orbital contributions, as well as the electrical conductivity, Seebeck coefficient, and power factor, are compared across methods and geometries. Our results suggest that GFN-xTB is adequate to predict the MOFs' band structure shape and density of states but not band gap. Our calculations further indicate that Zn3C6O6, Cd3C6O6, and Zn-NH-MOF have higher power factor values than Ni3(HITP)2, one of the highest performing synthesized MOFs, and are therefore promising for thermoelectric applications.

Mitigating jaw osteonecrosis: bioactive glass and pericardial membrane combination in a rat model.

Objectives: Bisphosphonates (BFs) show clinical effectiveness in managing osteoporosis and bone metastases but pose risks of bisphosphonate-related jaw osteonecrosis (BRONJ). With no established gold standard for BRONJ treatment, our focus is on symptom severity reduction. We aimed to assess the preventive effects of bioactive glass and/or pericardial membrane in a preclinical BRONJ model, evaluating their potential to prevent osteonecrosis and bone loss post-tooth extractions in zoledronic acid (ZA)-treated animals. Methods: Rats, receiving ZA or saline biweekly for four weeks, underwent 1st and 2nd lower left molar extractions. Pericardial membrane alone or with F18 bioglass was applied post-extractions. Microarchitecture analysis and bone loss assessment utilized computerized microtomography (CT) and positron emission tomography (PET) with 18F-FDG and 18F-NaF tracers. Histological analysis evaluated bone injury. Results: Exclusive alveolar bone loss occurred post-extraction in the continuous ZA group, inducing osteonecrosis, osteolysis, osteomyelitis, and abscess formation. Concurrent pericardial membrane with F18 bioglass application prevented these outcomes. Baseline PET/CT scans showed no discernible uptake differences, but post-extraction 18F-FDG tracer imaging revealed heightened glucose metabolism at the extraction site in the ZA-treated group with membrane, contrasting the control group. Conclusion: These findings suggest pericardial membrane with F18 bioglass effectively prevents BRONJ in the preclinical model.

Viruses as a potential environmental trigger of type 1 diabetes mellitus (Review).

The etiopathogenesis of type 1 diabetes mellitus (T1DM) is a complex multifactorial process that involves an intricate network of genetic, epigenetic, immunological, and environmental factors. Despite the advances in recent years, some aspects of the mechanisms involved in triggering the disease are still unclear. Infections with certain viruses have been suggested as possible environmental triggers for the autoimmune process that leads to selective and progressive destruction of pancreatic ß-cells and insufficiency of insulin production, which is its hallmark. In this review, advances in knowledge and evidence that suggest the participation of certain viruses in the mechanisms of disease initiation and progression are described. It has been accepted that environmental factors, including viruses, can initiate and possibly sustain, accelerate, or slow down the autoimmune process and consequently damage insulin-producing pancreatic ß-cells. Although the role of these agents, especially human enteroviruses, has been exhaustively studied as the most likely triggers of the activation of autoimmunity that destroys pancreatic islets and leads to T1DM, certain doubts remain. Clinical epidemiological and experimental studies in humans and animals provide consistent and increasing evidence that persistent viral infections, especially with human enteroviruses and rotavirus infections, are associated with an increased risk of the disease in individuals genetically predisposed to autoimmunity.

Distinct Adverse Reactions to mRNA, Inactivated Virus, and Adenovirus Vector COVID-19 Vaccines: Insights from a Cohort Study on Atopic and Non-Atopic Subjects in Brazil.

The emergence of COVID-19 caused by SARS-CoV-2 prompted an unprecedented global response to develop vaccines at an accelerated pace. Messenger RNA (mRNA) and adenovirus vector vaccines emerged as the frontrunners in global immunization efforts, significantly reducing hospitalization, severity, and mortality, supplemented by inactivated virus-based vaccines in developing countries. However, concerns regarding adverse effects, including allergic reactions, have been raised. This study aimed to investigate the adverse effects following COVID-19 vaccination, particularly in atopic and non-atopic individuals. A cohort of 305 volunteers receiving BNT162, ChAdOx1, or CoronaVac vaccines were assessed based on a Skin Prick Test (SPT), specific IgE levels, and clinical history of asthma and rhinitis. Adverse effects were self-reported and scored across the different vaccination shots. The results indicated a notable presence of mild adverse effects following the first and third doses, regardless of vaccine type. ChAdOx1 recipients experienced more adverse effects compared to those receiving BNT162 and CoronaVac, including headaches, muscle pain, fever, chills, nausea, and flu-like symptoms. Atopic individuals receiving ChAdOx1 reported more adverse effects, such as muscle pain, fever, and chills, compared to non-atopic individuals. Conversely, headaches were more frequently reported in non-atopic individuals receiving BNT162 compared to atopic individuals. No anaphylaxis or allergic reactions were reported, indicating valuable evidence supporting the safety of COVID-19 vaccination in individuals with respiratory allergies. This study highlights the importance of understanding vaccine-related adverse effects, particularly in vulnerable populations, to inform vaccination strategies and address safety concerns in global immunization campaigns.

A Future European Scientific Dialogue Regulatory Framework: Connecting the Dots.

The regulatory framework of the European Union (EU) offers multiple and valuable options for Scientific Advice (SA). However, at a time of increasing scientific complexity and global competition, navigating the SA landscape may be challenging. Such challenges are related to the technicalities of the framework itself, as well as to fundamental changes in the development of promising therapeutics. This article provides an overview of these challenges and reflects on the ways in which the already available SA options could be consolidated and optimized for building an integrated, easy-to-navigate process. The key elements of the proposal are improved orientation and navigation support, a simplified process of managing parallel interactions with multiple bodies, competitive SA timelines, consistency and harmonization across stakeholders, a strengthened horizon scanning to increase network preparedness, and a mechanism for building an institutional memory. The article builds on ongoing dialogues driven by the European Medicines Agency and the European Medicines Regulatory Network, and contributes the viewpoint of the European Federation of Pharmaceutical Industries on the ways in which the EU SA framework needs to evolve to provide effective Scientific Dialogue throughout the medicine lifecycle. The article is timely because of the current discussion on the future Scientific Dialogue framework and may inform forthcoming legislative changes in the draft General Pharma Legislation revision and how they are practically implemented.

Anovaginal Colonization by Group B Streptococcus and Streptococcus anginosus among Pregnant Women in Brazil and Its Association with Clinical Features.

Streptococcus agalactiae (Group B Streptococcus; GBS) is a leading cause of neonatal invasive disease worldwide. GBS can colonize the human gastrointestinal and genitourinary tracts, and the anovaginal colonization of pregnant women is the main source for neonatal infection. Streptococcus anginosus, in turn, can colonize the human upper respiratory, gastrointestinal, and genitourinary tracts but has rarely been observed causing disease. However, in the last years, S. anginosus has been increasingly associated with human infections, mainly in the bloodstream and gastrointestinal and genitourinary tracts. Although anovaginal screening for GBS is common during pregnancy, data regarding the anovaginal colonization of pregnant women by S. anginosus are still scarce. Here, we show that during the assessment of anovaginal GBS colonization rates among pregnant women living in Rio de Janeiro, Brazil, S. anginosus was also commonly detected, and S. anginosus isolates presented a similar colony morphology and color pattern to GBS in chromogenic media. GBS was detected in 48 (12%) while S. anginosus was detected in 17 (4.3%) of the 399 anovaginal samples analyzed. The use of antibiotics during pregnancy and history of urinary tract infections and sexually transmitted infections were associated with the presence of S. anginosus. In turn, previous preterm birth was associated with the presence of GBS (p < 0.05). The correlation of GBS and S. anginosus with relevant clinical features of pregnant women in Rio de Janeiro, Brazil, highlights the need for the further investigation of these important bacteria in relation to this special population.

Atopic dermatitis pediatric patients show high rates of nasal and intestinal colonization by methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci.

BACKGROUND: Atopic dermatitis (AD) patients have high rates of colonization by Staphylococcus aureus, which has been associated with worsening of the disease. This study characterized Staphylococcus spp isolates recovered from nares and feces of pediatric patients with AD in relation to antimicrobial susceptibility, staphylococcal cassette chromosome mec (SCCmec) type, presence of pvl genes and clonality. Besides, gut bacterial community profiles were compared with those of children without AD. RESULTS: All 55 AD patients evaluated had colonization by Staphylococcus spp. Fifty-three (96.4%) patients had colonization in both clinical sites, whereas one patient each was not colonize in the nares or gut. Staphylococcus aureus was identified in the nostrils and feces of 45 (81.8%) and 39 (70.9%) patients, respectively. Methicillin-resistant Staphylococcus spp. isolates were found in 70.9% of the patients, and 24 (43.6%) had methicillin-resistant S. aureus (MRSA). S. aureus (55.6%) and S. epidermidis (26.5%) were the major species found. The prevalent lineages of S. aureus were USA800/SCCmecIV (47.6%) and USA1100/SCCmecIV (21.4%), and 61.9% of the evaluated patients had the same genotype in both sites. Additionally, gut bacterial profile of AD patients exhibits greater dissimilarity from the control group than it does among varying severities of AD. CONCLUSIONS: High rates of nasal and intestinal colonization by S. aureus and methicillin-resistant staphylococci isolates were found in AD patients. Besides, gut bacterial profiles of AD patients were distinctly different from those of the control group, emphasizing the importance of monitoring S. aureus colonization and gut microbiome composition in AD patients.

Computationally directed manipulation of cross-linked covalent organic frameworks for membrane applications.

Two-dimensional covalent organic frameworks (2D-COFs) exhibit characteristics ideal for membrane applications, such as high stability, tunability and porosity along with well-ordered nanopores. However, one of the many challenges with fabricating these materials into membranes is that membrane wetting can result in layer swelling. This allows molecules that would be excluded based on pore size to flow around the layers of the COF, resulting in reduced separation. Cross-linking between these layers inhibits swelling to improve the selectivity of these membranes. In this work, computational models were generated for a quinoxaline-based COF cross-linked with oxalyl chloride (OC) and hexafluoroglutaryl chloride (HFG). Enthalpy of formation and cohesive energy calculations from these models show that formation of these COFs is thermodynamically favorable and the resulting materials are stable. The cross-linked COF with HFG was synthesized and characterized with Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis with differential scanning calorimetry (TGA-DSC), and water contact angles. Additionally, these frameworks were fabricated into membranes for permeance testing. The experimental data supports the presence of cross-linking and demonstrates that varying the amount of HFG used in the reaction does not change the amount of cross-linking present. Computational models indicate that varying the cross-linking concentration has a negligible effect on stability and less cross-linking still results in stable materials. This work sheds light on the nature of the cross-linking in these 2D-COFs and their application in membrane technologies.

A Method to Freeze Skin Samples for Cryobanks: A Test of Some Cryoprotectants for an Endangered Deer.

The genetic diversity of endangered deer species, such as Mazama jucunda, can be preserved with the help of somatic cell cryopreservation. This procedure allows obtaining several cells from the individual even after its death, which is very important for applications in reproductive biotechnologies. This study's objective was to test cryopreservation protocols of skin fragments of M. jucunda, using different cryoprotectants in slow freezing. We evaluated four treatments, composed of three cryoprotectants, dimethyl sulfoxide (DMSO), polyvinylpyrrolidone (PVP), and ethylene glycol (EG), used alone and in combination. There was also a control group where the tissue did not undergo cryopreservation. Skin fragments were collected from the medial region of the pelvic limbs of three individuals. Each fragment was divided into 10 equal parts, standardized by weight, making two pieces for each treatment and control from each animal. The collected fragments were evaluated in culture, based on the speed of occupation of the free spaces of the cell culture flask. Cell viability was also evaluated using Trypan Blue dye and the mitotic index to understand the effect of toxicity and freezing on cell membrane integrity and cell division capacity, respectively. The treatments that used association with PVP proved to be more damaging to the cells, taking longer to reach confluence. EG alone showed better results than DMSO in the slow-freezing protocol. Clinical Trial Registration Number is 1390/21.

Dysregulated Immunity to Clostridioides difficile in IBD Patients Without a History of Recognized Infection.

BACKGROUND & AIMS: Clostridioides difficile is a toxin-secreting bacteria that is an urgent antimicrobial resistance threat, with approximately 25% of patients developing recurrent infections. Inflammatory bowel disease (IBD) patients are at increased risk of severe, recurrent C. difficile infection. METHODS: To investigate a role for C. difficile infection in IBD pathogenesis, we collected peripheral blood and stool from 20 each of ulcerative colitis patients, Crohn's disease patients, and healthy control subjects. We used a flow cytometric activation induced marker assay to quantify C. difficile toxin-specific CD4+ T cells and 16S ribosomal RNA sequencing to study microbiome diversity. RESULTS: We found IBD patients had significantly increased levels of C. difficile toxin B-specific CD4+ T cells, but not immunoglobulin G or immunoglobulin A, compared with healthy control subjects. Within antigen-specific CD4+ T cells, T helper type 17 cells and cells expressing the gut homing receptor integrin ß7 were reduced compared with healthy control subjects, similar to our previous study of non-IBD patients with recurrent C. difficile infection. Stool microbiome analysis revealed that gut homing, toxin-specific CD4+ T cells negatively associated with microbial diversity and, along with T helper type 17 cells, positively associated with bacteria enriched in healthy control subjects. CONCLUSIONS: These data suggest that IBD patients, potentially due to underlying intestinal dysbiosis, experience undiagnosed C. difficile infections that result in impaired toxin-specific immunity. This may contribute to the development of inflammatory T cell responses toward commensal bacteria and provide a rationale for C. difficile testing in IBD patients.

Crohn's disease and ulcerative colitis patients with no history of Clostridioides difficile infection had dysregulated T cell immunity to C. difficile toxin B. This was significantly different from healthy control subjects but similar to non­inflammatory bowel disease patients with recurrent C. difficile infection.

Metarhizium anisopliae E6 secretome reveals molecular players in host specificity and toxicity linked to cattle tick infection.

Although Metarhizium anisopliae is one of the most studied fungal biocontrol agents, its infection mechanism is far from being completely understood. Using multidimensional protein identification technology (MudPIT), we evaluated the differential secretome of M. anisopliae E6 induced by the host Rhipicephalus microplus cuticle. The proteomic result showed changes in the expression of 194 proteins after exposure to host cuticle, such as proteins involved in adhesion, penetration, stress and fungal defense. Further, we performed a comparative genomic distribution of differentially expressed proteins of the M. anisopliae secretome against another arthropod pathogen, using the Beauveria bassiana ARSEF2860 protein repertory. Among 47 analyzed protein families, thirty were overexpressed in the M. anisopliae E6 predicted genome compared to B. bassiana. An in vivo toxicity assay using a Galleria mellonella model confirmed that the M. anisopliae E6 secretome was more toxic in cattle tick infections compared to other secretomes, including B. bassiana with cattle ticks and M. anisopliae E6 with the insect Dysdereus peruvianus, which our proteomic results had also suggested. These results help explain molecular aspects associated with host infection specificity due to genetic differences and gene expression control at the protein level in arthropod-pathogenic fungi.