Occurrence of Clostridium perfringens in Wild Mammals in the Amazon Biome.

The objective of this study was to evaluate the occurrence of Clostridium perfringens in stool samples and swabs collected from wild mammals in the Amazon biome. Sixty-five faecal and swab samples were collected in situ and ex situ from 16 species and three genera of wild mammals, some of which were in good health and some of which had diarrhoea. After pre-enrichment, the samples were plated on selective agar for C. perfringens. Characteristic colonies were subjected to multiplex PCR for the detection of genes encoding the main C. perfringens toxins (alpha, beta, epsilon, and iota toxin and enterotoxin). Among the 65 samples, 40 (61.5%) were positive for the gene encoding the alpha toxin and were classified as type A, 36 of which were asymptomatic animals and four were diarrheal. No other toxinotypes were found. The findings of this study suggest that C. perfringens type A is commonly found in mammal species of the Amazon biome. This seems to be the first study to identify C. perfringens type A in species such as B. variegatus (common ground sloth), C. didactylus (two-toed sloth), P. flavus (Jupará), T. tetradactyla (anteater), S. collinsi (squirrel monkey), S. niger (black marmoset), and S. apella (Guyana capuchin) and in the genus Didelphis sp. (opossum).

Fecal Shedding of Clostridioides difficile in Calves in Sao Paulo State, Brazil.

OBJECTIVE: This study aimed to evaluate the fecal shedding of C. difficile in calves on farms in Sao Paulo State, Brazil. MATERIALS AND METHODS: Fecal samples (n=300) were collected from diarrheic (n=78) and nondiarrheic (n=222) calves less than 60 days of age from 20 farms. Fecal samples were inoculated into enrichment broth supplemented with taurocholate and cultured under anaerobic conditions. Colonies suspected to be C. difficile were harvested for DNA extraction and then multiplex PCR for the detection of genes encoding toxins A and B and binary toxins. All toxigenic isolates were ribotyped and tested for antimicrobial susceptibility, and five selected strains were subjected to whole-genome sequencing to determine their sequence type. RESULTS AND DISCUSSION: C. difficile was isolated from 29.3% (88/300) of the samples. All toxigenic isolates (17/88, 19.3%) were classified as ribotypes RT046 (13/17 -79.47%, A+B+ CDT-) and RT126 (4/17=20.53%, A+B+ CDT+). The sequenced strains from RT046 were classified as ST35 (Clade 1), while those from RT126 were classified as ST11 (Clade 5). No associations between the epidemiological factors in any of the groups and C. difficile isolation were observed. Most of the toxigenic isolates (16/17=94.41%) were classified as multidrug-resistant. Calves can be an important source of toxigenic C. difficile strains, including multidrug-resistant isolates from ribotypes commonly observed in humans.

External validation of a nomogram for outcome prediction in management of medium-sized (1-2 cm) kidney stones.

BACKGROUND: Stone nomogram by Micali et al., able topredict treatment failure of shock-wave lithotripsy (SWL), retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PNL) in the management of single 1-2 cm renal stones, was developed on 2605 patients and showed a high predictive accuracy, with an area under ROC curve of 0.793 at internal validation. The aim of the present study is to externally validate the model to assess whether it displayed a satisfactory predictive performance if applied to different populations. METHODS: External validation was retrospectively performed on 3025 patients who underwent an active stone treatment from December 2010 to June 2021 in 26 centers from four countries (Italy, USA, Spain, Argentina). Collected variables included: age, gender, previous renal surgery, preoperative urine culture, hydronephrosis, stone side, site, density, skin-to-stone distance. Treatment failure was the defined outcome (residual fragments >4 mm at three months CT-scan). RESULTS: Model discrimination in external validation datasets showed an area under ROC curve of 0.66 (95% 0.59-0.68) with adequate calibration. The retrospective fashion of the study and the lack of generalizability of the tool towards populations from Asia, Africa or Oceania represent limitations of the current analysis. CONCLUSIONS: According to the current findings, Micali's nomogram can be used for treatment prediction after SWL, RIRS and PNL; however, a lower discrimination performance than the one at internal validation should be acknowledged, reflecting geographical, temporal and domain limitation of external validation studies. Further prospective evaluation is required to refine and improve the nomogram findings and to validate its clinical value.

Environmental Homeopathy: Homeopathic Potencies Regulate the Toxicity and Growth of Raphidiopsis raciborskii (cyanobacteria) and can be Tracked Physico-Chemically. Part 1: Biological Results.

INTRODUCTION: Cyanobacteria are microorganisms found in many parts of the world and several genera, such as Raphidiopsis raciborskii, are producers of cyanotoxins. Homeopathic potencies have been found to modulate toxicity in different biological models, and the present study endeavors to discover whether this might also be the case with cyanobacteria. OBJECTIVES: Our objective was to investigate the possible effects of homeopathic potencies on the resilience of Artemia franciscana (brine shrimp) embryos to saxitoxin (STX; cyanotoxin) and on controlling the growth of R. raciborskii in vitro. METHOD: A. franciscana cysts were cultivated in seawater in 96-well plates to evaluate the hatching rate and vitality, plus the gene expression of heat shock proteins (HSPs), after being challenged with R. raciborskii extract containing 2.5 µg/L of STX and treated with different homeopathic potencies. Untreated wells were used as controls ("base-line"). Potencies were chosen from a screening process based on seven selected homeopathic preparations according to the similitude of STX symptoms (Sulphur, Zincum metallicum, Nitric acidum, Plumbum metallicum, Mercurius solubilis, Phosphoric acidum, Isotherapic from R. raciborskii extract; all at 6cH, 30cH and 200cH). Cultures of R. raciborskii maintained in an artificial seawater medium were equally treated with screened homeopathic potencies selected from the same list but specifically for their growth control as a function of time. RESULTS: A 15% lower rate of hatching of A. franciscana cysts was observed after treatment with Nitric acidum 6cH in comparison with baseline (p = 0.05). A complete toxicity reversal was seen after treatment with Isotherapic 200cH, with a 23-fold increase of Hsp 26 gene expression (p = 0.023) and a 24-fold increase of p26 gene expression (p ≤ 0.001) in relation to baseline. Nitric acidum 200cH and Mercurius solubilis 30cH limited the exponential growth of cyanobacteria up to 95% and 85% respectively (p ≤ 0.003) in relation to baseline. Succussed water presented only a transitory 50% inhibition effect. CONCLUSION: Isotherapic 200cH improved A. franciscana bioresilience to STX; Nitric acidum 200cH and Mercurius solubilis 30cH showed the optimal performance on limiting R. raciborskii growth. The results point to the potential of homeopathic potencies to mitigate environmental problems related to water quality.

Environmental Homeopathy: Homeopathic Potencies Regulate the Growth and Toxicity of Raphidiopsis raciborskii (cyanobacteria) and Can be Tracked Physico-Chemically. Part 2: Physico-chemical Results.

INTRODUCTION: The control of cyanobacterial toxicity and growth by homeopathic potencies was described in Part 1 of this two-part report. Here, a parallel approach characterized the physico-chemical features of the potencies used and the liquid media treated with them, correlating these results with their respective biological effects. OBJECTIVES: Our objective was to establish if physico-chemical parameters can track homeopathic potencies in seawater or artificial seawater medium (ASM)-1 and to discover whether these parameters correlate with previously described biological effects. METHOD: Artemia franciscana (brine shrimp) cysts were cultivated in seawater challenged with Raphidiopsis raciborskii extract and treated with different homeopathic potencies chosen from a screening process. Cultures of R. raciborskii maintained in ASM-1 were also treated with previously screened homeopathic potencies, and their growth was monitored as a function of time. The physico-chemical properties of the treated media (seawater or ASM-1) were evaluated by their interaction with solvatochromic dyes and changes in pH, conductivity and temperature. RESULTS: Coumarin 7 was found to be a marker for Nitric acidum 6cH and Isotherapic (R. raciborskii extract) 200cH in seawater (analysis of variance [ANOVA], p = 0.0015). Nile red was found to be a marker for Nitric acidum 200cH and Mercurius solubilis 30cH in ASM-1 (ANOVA, p ≤ 0.001). An increase in pH of ASM-1 and endothermic effects were observed after these treatments (two-way ANOVA, p = 0.0001). Seawater and ASM-1 to which potencies had been added were also subjected to a constant unidirectional 2,400 Gauss static magnetic field and found to have enhanced effects on the solvatochromic dyes tested. CONCLUSION: Homeopathic potencies were specifically traceable in aqueous media using solvatochromic dyes, especially when the samples were subjected to a magnetic field. Results from monitoring other physical parameters, such as pH and temperature, were less specific in relation to potency tracking. However, potency-induced endothermic effects might provide valuable thermodynamic data relating to the nature of potencies.

Assessment of multispecies biofilm growth on root canal dentin under different radiation therapy regimens.

OBJECTIVES: To assess the growth of a multispecies biofilm on root canal dentin under different radiotherapy regimens. MATERIALS AND METHODS: Sixty-three human root dentin cylinders were distributed into six groups. In three groups, no biofilm was formed (n = 3): NoRT) non-irradiated dentin; RT55) 55 Gy; and RT70) 70 Gy. In the other three groups (n = 18), a 21-day multispecies biofilm (Enterococcus faecalis, Streptococcus mutans, and Candida albicans) was formed in the canal: NoRT + Bio) non-irradiated + biofilm; RT55 + Bio) 55 Gy + biofilm; and RT70 + Bio) 70 Gy + biofilm. The biofilm was quantified (CFUs/mL). Biofilm microstructure was assessed under SEM. Microbial penetration into dentinal tubules was assessed under CLSM. For the biofilm biomass and dentin microhardness pre- and after biofilm growth assessments, 45 bovine dentin specimens were distributed into three groups (n = 15): NoRT) non-irradiated + biofilm; RT55 + Bio) 55 Gy + biofilm; and RT70 + Bio) 70 Gy + biofilm. RESULTS: Irradiated specimens (70 Gy) had higher quantity of microorganisms than non-irradiated (p = .010). There was gradual increase in biofilm biomass from non-irradiated to 55 Gy and 70 Gy (p < .001). Irradiated specimens had greater reduction in microhardness after biofilm growth. Irradiated dentin led to the growth of a more complex and irregular biofilm. There was microbial penetration into the dentinal tubules, regardless of the radiation regimen. CONCLUSION: Radiotherapy increased the number of microorganisms and biofilm biomass and reduced dentin microhardness. Microbial penetration into dentinal tubules was noticeable. CLINICAL RELEVANCE: Cumulative and potentially irreversible side effects of radiotherapy affect biofilm growth on root dentin. These changes could compromise the success of endodontic treatment in oncological patients undergoing head and neck radiotherapy.

Seroepidemiological survey to cell culture rabies vaccines (CCRV) in Brazil.

Rabies is a contagious viral disease that can be easily transmitted by the saliva and brain/nervous system tissues of the infected animals, causing severe and fatal encephalitis in both animals and humans. Vaccination campaigns are crucial to combat and prevent rabies's spread in dogs and humans. The Modified Fuenzalida & Palicios vaccines have been widely used since the 70s and have proven effective in producing a solid serological response. Since 2008, the Brazilian Ministry of Health has introduced a Cell Culture Rabies Vaccine (CCRV) for all dog mass vaccination campaigns in Brazil. However, to date, there is limited evidence on the immunologic response of dogs to this type of vaccine in field conditions. The present study evaluated the serological response in dogs vaccinated with CCRV from blood samples of 724 dogs using the Simplified Fluorescence Inhibition Microtest - SFIMT. Dogs with a titer equal to 0.5 IU/mL or above were considered seropositive. The results revealed that 59.12% (428/724) of all dogs tested and 48.49% (32/66) of primo-vaccinated animals were seropositive. The percentage of seronegative animals was higher than seropositive for animals that received a single dose during their life (p < 0.05). The opposite was observed in animals with five or more doses. The results of this study demonstrated that the CCRV vaccines elicit a satisfactory immunological response in field conditions and can constitute an essential population-level preventive strategy as part of annual canine rabies vaccination campaigns. Although its effectiveness has been studied, there is limited evidence of its immunological response in dogs under field conditions. This paper evaluates the serological response to CCRV in dogs vaccinated during mass vaccination campaigns from 2012 to 2017.

BMP7-induced osteoblast differentiation requires hedgehog signaling and involves nuclear mechanisms of gene expression control.

During the morphological changes occurring in osteoblast differentiation, Sonic hedgehog (Shh) plays a crucial role. While some progress has been made in understanding this process, the epigenetic mechanisms governing the expression of Hh signaling members in response to bone morphogenetic protein 7 (BMP7) signaling in osteoblasts remain poorly understood. To delve deeper into this issue, we treated pre-osteoblasts (pObs) with 100 ng/mL of BMP7 for up to 21 days. Initially, we validated the osteogenic phenotype by confirming elevated expression of well-defined gene biomarkers, including Runx2, Osterix, Alkaline Phosphatase (Alp), and bone sialoprotein (Bsp). Simultaneously, Hh signaling-related members Sonic (Shh), Indian (Ihh), and Desert (Dhh) Hedgehog (Hh) exhibited nuanced modulation over the 21 days in vitro period. Subsequently, we evaluated epigenetic markers, and our data revealed a notable change in the CpG methylation profile, considering the methylation/hydroxymethylation ratio. CpG methylation is a reversible process regulated by DNA methyltransferases and demethylases, including Ten-eleven translocation (Tets), which also exhibited changes during the acquisition of the osteogenic phenotype. Specifically, we measured the methylation pattern of Shh-related genes and demonstrated a positive Pearson correlation for GLI Family Zinc Finger 1 (Gli1) and Patched (Ptch1). This data underscores the significance of the epigenetic machinery in modulating the BMP7-induced osteogenic phenotype by influencing the activity of Shh-related genes. In conclusion, this study highlights the positive impact of epigenetic control on the expression of genes related to hedgehog signaling during the morphogenetic changes induced by BMP7 signaling in osteoblasts.

Characterization of the fragmentation mechanisms in electrospray ionization tandem mass spectrometry of chloroquinoline derivatives with larvicidal activity against Aedes aegypti.

RATIONALE: 4,7-Dichloroquinoline (DCQ) represents a group of synthetic molecules inspired by natural products with important roles in biological and biomedical areas. This work aimed to characterize DCQ and its derivatives by high-resolution electrospray ionization (ESI) mass spectrometry and tandem mass spectrometry (ESI-MS/MS), supported by theoretical calculations. Biological assays were carried out with DCQ and its derivatives to determine LC50 values against Aedes aegypti larvae. METHODS: Five DCQ derivatives were synthesized by using previously described protocols. ESI-MS/MS analyses were carried out with a quadrupole/time-of-flight and ion-trap instrument. The proposed gas-phase protonation sites and fragmentation were supported by density functional theory calculations. The larvicidal tests were performed with the Ae. aegypti Rockefeller strain, and the LC50 values were determined by employing five test concentrations. Larval mortality was determined after treatment for 48 h. RESULTS: DCQ bromides or aldehydes (C-3 or C-8 positions), as well as the trimethylsilyl derivative (C-3 position), were prepared. Detailed ESI-MS/MS data revealed heteroatom elimination through an exception to the even-electron rule, to originate open-shell species. Computational studies were used to define the protonation sites and fragmentation pathways. High activity of DCQ and its derivatives against Ae. aegypti larvae was demonstrated. CONCLUSION: Our results provided a well-founded characterization of the fragmentation reactions of DCQ and its derivatives, which can be useful for complementary studies of the development of a larvicidal product against Ae. aegypti.

Hemophagocytic lymphohistiocytosis and macrophage activation syndrome: two rare sides of the same devastating coin.

Hemophagocytic lymphohistiocytosis (HLH) is a rare genetic hyperinflammatory syndrome that occurs early in life. Macrophage activation syndrome (MAS) usually refers to a secondary form of HLH associated with autoimmunity, although there are other causes of secondary HLH, such as infections and malignancy. In this article, we reviewed the concepts, epidemiology, clinical and laboratory features, diagnosis, differential diagnosis, prognosis, and treatment of HLH and MAS. We also reviewed the presence of MAS in the most common autoimmune diseases that affect children. Both are severe diseases that require prompt diagnosis and treatment to avoid morbidity and mortality.

Modulation of sHLA-G, PD-1, and PD-L1 Expression in Cervical Lesions Following Imiquimod Treatment and Its Association with Treatment Success.

(1) Background: Cervical intraepithelial neoplasia (CIN) is a precancerous condition linked to human papillomavirus (HPV) infection, often necessitating surgical interventions carrying the risk of subsequent preterm births. This study explores the potential of imiquimod (IMQ), as a non-invasive alternative treatment. The focus is on understanding IMQ impact on immune checkpoint molecules, particularly PD-1, PD-L1, and sHLA-G, which play pivotal roles in shaping immune responses and cancer progression. (2) Methods: Forty-three patients diagnosed with a high-risk squamous intraepithelial lesion (HSIL, p16-positive) self-applied 5% IMQ encapsulated in sachets containing 250 g of cream into the vaginal cavity three times a week for 16 weeks. The impact of IMQ therapy on cervical lesion regression was assessed through immunohistochemistry (IHC), examining changes in sHLA-G, PD-L1, and PD-1 levels. The antiviral activity of IMQ was evaluated through HPV-E7 immunofluorescence. Ethical considerations were adhered to, and the research methods were based on a previously approved clinical trial (clinicaltrials.gov Identifier: NCT04859361). (3) Results: IMQ treatment demonstrated efficacy, leading to lesion regression. sHLA-G levels in CIN before starting IMQ application were associated with unsuccessful treatment (p = 0.0036). IMQ did not significantly alter the expression of PD-1. We observed a decrease in PD-L1 levels in those who were successfully treated (p = 0.0509) and a reduction in HPV burden. (4) Conclusions: IMQ exhibits promise as a non-invasive treatment for CIN, emphasising its potential to modulate the immune microenvironment. Baseline sHLA-G levels emerge as potential predictors of treatment response. Understanding the nuanced dynamics of immune checkpoints sheds light on IMQ mechanism of action. Further exploration is warranted to decipher the intricate mechanisms underlying IMQ treatment in the context of cervical lesions.

Therapeutic exercises in the clinical practice of Brazilian physical therapists in the management of rotator cuff tendinopathy: An online survey.

The objective of this study was to investigate how Brazilian physical therapists (PTs) use therapeutic exercises in the rehabilitation of individuals with rotator cuff (RC) tendinopathy. The study used an online survey with a mix of 62 open- and closed-ended questions divided into three sections: participant demographics, professional experience, and clinical practice in the rehabilitation of patients with RC tendinopathy. One hundred and fifty-nine Brazilian physical therapists completed the survey. Most of our sample recommended isometric exercises (69.9%) in the initial phase of rehabilitation and eccentric exercises (47.4%) in the advanced phase. However, there was a wide variability in determining the volume of exercises, particularly with isometric exercises. Most of our sample considered patient comfort and pain levels when adjusting exercise intensity, regardless of exercise type. The majority (48.40%) recommended weekly reassessment and modification of exercises. Additionally, despite pain being a key factor for discharge and the primary adverse effect of exercise, most of our sample would not discontinue exercises in case of pain during the early and late phases of rehabilitation. Despite the lack of consensus on some aspects, the clinical practice of our sample is in line with the current literature and practice in other countries. However, further research and implementation are crucial to enhance future rehabilitation outcomes, including exploring the exercise training volume, the safety and effectiveness of exercising with pain and identifying the optimal pain level for best results.

Thermodynamic Study of Alkylsilane and Alkylsiloxane-Based Ionic Liquids.

The thermodynamic properties of ionic liquids (ILs) bearing alkylsilane and alkylsiloxane chains, as well as their carbon-based analogs, were investigated. Effects such as the replacement of carbon atoms by silicon atoms, the introduction of a siloxane linkage, and the length of the alkylsilane chain were explored. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to study the thermal and phase behavior (glass transition temperature, melting point, enthalpy and entropy of fusion, and thermal stability). Heat capacity was obtained by high-precision drop calorimetry and differential scanning microcalorimetry. The volatility and cohesive energy of these ILs were investigated via the Knudsen effusion method coupled with a quartz crystal microbalance (KEQCM). Gas phase energetics and structure were also studied to obtain the gas phase heat capacity as well as the energy profile associated with the rotation of the IL side chain. The computational study suggested the existence of an intramolecular interaction in the alkylsiloxane-based IL. The obtained glass transition temperatures seem to follow the trend of chain flexibility. An increase of the alkylsilane chain leads to a seemingly linear increase in molar heat capacity. A regular increment of 30 J·K-1·mol-1 in the molar heat capacity was found for the replacement of carbon by silicon in the IL alkyl chain. The alkylsilane series was revealed to be slightly more volatile than its carbon-based analogs. A further increase in volatility was found for the alkylsiloxane-based IL, which is likely related to the decrease of the cohesive energy due to the existence of an intramolecular interaction between the siloxane linkage and the imidazolium headgroup. The use of Si in the IL structure is a suitable way to significantly reduce the IL's viscosity while preserving its large liquid range (low melting point and high thermal stability) and low volatilities.

Acute ST-Elevation Myocardial Infarction in a Young Adult: Rare Presentation of Giant Atrial Myxoma. / Infarto com Supra-ST em Adulto Jovem: Rara Apresentação de Mixoma Atrial Gigante.

Cardiac tumors are rare entities, among which atrial myxoma (AM) stands as the most frequent, accounting for approximately half of all reported cases. The incidence of AM is estimated to range from 0.001% to 0.3% within the general population, yet only about 0.06% of these cases present with coronary embolic events. We report on a 33-year-old male smoker who experienced acute, severe precordial pain radiating to the left upper limb, lasting for one hour. The electrocardiographic evaluation demonstrated ST-segment elevation in leads D2, D3, and aVF, alongside significantly elevated serum troponin levels, confirming a diagnosis of ST-segment elevation myocardial infarction (STEMI). Subsequent coronary angiography revealed proximal occlusion of the right coronary artery due to thrombus. An initial attempt of thrombus aspiration was unsuccessful, followed by primary angioplasty with balloon inflation without stent placement. Further diagnostic exploration through transthoracic echocardiography identified a homogenous, smooth-surfaced mass measuring 5.2 cm x 2.3 cm attached to the interatrial septum. This mass, characterized by lobulations, prolapsed into the mitral valve and left ventricle during diastole, consistent with AM. Surgical resection of the mass was successfully performed, with the patient being discharged asymptomatic. In the reported case, the patient's profile, notably his age, and gender, diverges from the typical epidemiological characteristics associated with AM. This case adds to the limited number of reports where the inferior wall is affected by the right coronary artery being occluded. This report emphasizes the significance of differential diagnoses in younger patients presenting with STEMI.

Neoplasias cardíacas são raras, tendo como principal representante o mixoma atrial (MA), que corresponde a cerca de metade de todos os casos. O MA tem incidência estimada entre 0.001% e 0.3% na população em geral, no entanto apenas aproximadamente 0,06% desses cursam com eventos embólicos coronarianos. Homem de 33 anos, tabagista, admitido com quadro de precordialgia intensa e irradiação para membro superior esquerdo com duração de uma hora. O eletrocardiograma evidenciou elevação de segmento ST nas derivações D2, D3 e aVF troponina sérica elevada, confirmando infarto com supra desnivelamento do segmento ST (IAMCSST). Foi realizada cineangiocoronariografia, a qual revelou oclusão em terço proximal de artéria coronária direita por trombo. Realizada tentativa de aspiração do trombo, sem sucesso, seguido por angioplastia primária com balão sem colocação de stent. Durante a investigação do quadro, paciente realizou ecocardiograma transtorácico o qual demonstrou massa homogênea de superfície regular, de 5.2 cm x 2.3 cm, aderida ao septo interatrial, com lobulações de características emboligênicas prolapsando para valva mitral e ventrículo esquerdo na diástole, compatível com MA. Foi realizada ressecção cirúrgica com paciente evoluindo assintomático, recebendo alta para seguimento ambulatorial. O caso relatado difere em idade e sexo do perfil epidemiológico típico sendo um dos poucos descritos com acometimento da parede inferior apresentando a artéria coronária direita como culpada. Este relato ratifica a importância do diagnóstico diferencial frente às apresentações de IAMCSST em jovens.

Analysis of modified ilib therapy in patients submitted to plastic surgery.

The sample comprised 44 volunteers who had undergone some surgical procedure and were equally divided into four groups. G1 started the therapy 24 h after the surgical procedure with the device off. G2 followed the same time pattern, 24 h, but with the device turned on. G3 and G4 started therapy three days after the surgical procedure; in G3, the device was turned off, and in G4, the device remained on during therapy; each session lasted 30 min, using 660 nm (red), energy 180 J. For all groups, the therapy started with daily use for seven days and followed the interval use of three times a week until completed 21 days. The revaluation was performed after 7 and 21 days. The results found show changes in HR at rest, systolic and diastolic BP, and in peripheral oxygen saturation, which showed a significant difference in the groups that used on-therapy (p < 0.05). In the MCGILL Scale evaluation, the mean total score showed a more accentuated drop in the groups that used ILIB, (p < 0.05). ILIB may have prevented a more significant evolution of firosis levels; however, no changes were observed in the evaluation of sleep and anxiety. The application of the ILIB in patients undergoing plastic surgery was supported in terms of hemodynamics and pain; in addition, starting the ILIB application 24 h after the procedure proved to be more advantageous.

Intestinal microbiota diversity from broilers with runting and stunting syndrome performed by metagenomics.

Runting and stunting syndrome (RSS) is an enteric viral disease in commercial poultry that directly affects gut health; however, its influence on gut microbiota remains unknown. This study aimed to investigate the compositional changes in the bacterial community of the ileum of 7-day-old broiler chicks naturally affected and not affected by RSS, using next-generation sequencing (NGS) technology. Twenty-one samples were obtained from the ileal contents and mucosa of 11 chicks with RSS and 10 healthy chicks, raised in a dark house system located on a farm in the state of Minas Gerais, Brazil. The results revealed overall changes in the gut microbiota of the chicks with RSS, including a decrease in microbial richness and diversity. In particular, there was a decrease in Lactobacillus and an increase in Candidatus Arthromitus and Clostridium sensu stricto 1. These results indicate a relationship between viral infection and the gut microbial composition, which can cause gut dysbiosis and may influence inflammation in this organ.RESEARCH HIGHLIGHTSRSS causes dysbiosis of the gut microbiota of the ilea of chicks.A difference was found in gut microbiota between chicks with and without RSS.Candidatus Arthromitus was predominant in chicks with RSS.Clostridium sensu stricto 1 was strictly associated with chicks with RSS.

Effect of prednisolone in a kindling model of epileptic seizures in rats on cytokine and intestinal microbiota diversity.

Epilepsy is a neurological disease characterized by spontaneous and recurrent seizures. Epileptic seizures can be initiated and facilitated by inflammatory mechanisms. As the dysregulation of the immune system would be involved in epileptogenesis, it is suggested that anti-inflammatory medications could impact epileptic seizures. These medications could potentially have a side effect by altering the structure and composition of the intestinal microbiota. These changes can disrupt microbial homeostasis, leading to dysbiosis and potentially exacerbating intestinal inflammation. We hypothesize that prednisolone may affect the development of epileptic seizures, potentially influencing the diversity of the intestinal microbiota and the regulation of pro-inflammatory cytokines in intestinal tissue. This study aimed to evaluate the effects of prednisolone treatment on epileptic seizures and investigate the effect of this drug on the bacterial diversity of the intestinal microbiota and markers of inflammatory processes in intestinal tissue. We used Male Wistar rat littermates (n = 31, 90-day-old) divided into four groups: positive control treated with 2 mg/kg of diazepam (n = 6), negative control treated with 0.9 g% sodium chloride (n = 6), and the remaining two groups were subjected to treatment with prednisolone, with one receiving 1 mg/kg (n = 9) and the other 5 mg/kg (n = 10). All administrations were performed intraperitoneally (i.p.) over 14 days. To induce the chronic model of epileptic seizures, we administered pentylenetetrazole (PTZ) 25 mg/kg i.p. on alternate days. Seizure latency (n = 6 - 10) and TNF-α and IL-1ß concentrations from intestinal samples were measured by ELISA (n = 6 per group), and intestinal microbiota was evaluated with intergenic ribosomal RNA (rRNA) spacer (RISA) analysis (n = 6 per group). The prednisolone treatment demonstrated an increase in the latency time of epileptic seizures and TNF-α and IL-1ß concentrations compared to controls. There was no statistically significant difference in intestinal microbiota diversity between the different treatments. However, there was a strong positive correlation between microbial diversity and TNF-α and IL-1ß concentrations. The administration of prednisolone yields comparable results to diazepam on increasing latency between seizures, exhibiting promise for its use in clinical studies. Although there were no changes in intestinal microbial diversity, the increase in the TNF-α and IL-1ß cytokines in intestinal tissue may be linked to immune system signaling pathways involving the intestinal microbiota. Additional research is necessary to unravel the intricacies of these pathways and to understand their implications for clinical practice.

Monitoring bar velocity to quantify fatigue in resistance training.

We analyzed the effects of load magnitude and bar velocity variables on sensitivity to fatigue. Seventeen resistance-trained men (age=25.7±4.9 years; height=177.0±7.2 cm; body mass=77.7±12.3 kg; back-squat 1RM=145.0±33.9 kg; 1RM/body mass=1.86) participated in the study. Pre- and post-exercise changes in the mean propulsive velocity (MPV) and peak velocity (PV) in the back-squat at different intensities were compared with variations in the countermovement jump (CMJ). CMJ height decreased significantly from pre- to post-exercise (∆%=-7.5 to -10.4; p<0.01; ES=0.37 to 0.60). Bar velocity (MPV and PV) decreased across all loads (∆%=-4.0 to -12.5; p<0.01; ES=0.32 to 0.66). The decrease in performance was similar between the CMJ, MPV (40% and 80% 1RM; p=1.00), and PV (80% 1RM; p=1.00). The magnitude of reduction in CMJ performance was greater than MPV (60% 1RM; p=0.05) and PV (40% and 60% 1RM; p<0.01) at the post-exercise moment. Low systematic bias and acceptable levels of agreement were only found between CMJ and MPV at 40% and 80% 1RM (bias=0.35 to 1.59; ICC=0.51 to 0.71; CV=5.1% to 8.5%). These findings suggest that the back-squat at 40% or 80% 1RM using MPV provides optimal sensitivity to monitor fatigue through changes in bar velocity.

A comprehensive characterization of the spectrum of MUTYH germline pathogenic variants in Latin America.

MUTYH-Associated Polyposis (MAP) is caused by biallelic pathogenic germline variants in the MUTYH gene. However, individuals harboring monoallelic MUTYH pathogenic variants in the presence of a positive family history have been reported to have a twofold increased risk of colorectal cancer (CRC) and extra colonic cancers. Our aim was to characterize the spectrum of monoallelic and biallelic germline MUTYH pathogenic variants in Latin American patients and to describe their clinical and genetic characteristics. Patients were identified from eight high-risk genetic cancer centers of five Latin American countries. Statistical analysis was performed using the two-sided P test using the Vassarstats statistical tools. Statistical significance was set at a p value ≤ 0.05. Of the 105 unrelated patients with cancer or colorectal polyposis, 84.8% and 15.2% carried pathogenic monoallelic and biallelic MUTYH variants, respectively. The most common pathogenic variants were p.Gly396Asp and p.Tyr179Cys (55% and 23%, respectively). The mean age at first diagnosis was 48.29 years (range 31-71) and 49.90 years (range 27-87) in biallelic and monoallelic MUTYH patients, respectively. CRC was the only cancer diagnosed in patients with biallelic MUTYH pathogenic variants (75%), while breast cancer (46.1%) was more common than CRC (24.7%) in individuals with monoallelic MUTYH pathogenic variants. We reported a high frequency of European founder variants in our diverse population. Some phenotypic differences from current studies were identified, such as a higher breast cancer burden in monoallelic carriers and a complete absence of extra-colon tumors in biallelic patients.

Insights into nucleoside hydrolase from Leishmania donovani inhibition: A new bioaffinity chromatography-based screening assay and docking studies.

Leishmaniasis, a group of neglected infectious diseases, encompasses a serious health concern, particularly with visceral leishmaniasis exhibiting potentially fatal outcomes. Nucleoside hydrolase (NH) has a fundamental role in the purine salvage pathway, crucial for Leishmania donovani survival, and presents a promising target for developing new drugs for visceral leishmaniasis treatment. In this study, LdNH was immobilized into fused silica capillaries, resulting in immobilized enzyme reactors (IMERs). The LdNH-IMER activity was monitored on-flow in a multidimensional liquid chromatography system, with the IMER in the first dimension. A C18 analytical column in the second dimension furnished the rapid separation of the substrate (inosine) and product (hypoxanthine), enabling direct enzyme activity monitoring through product quantification. LdNH-IMER exhibited high stability and was characterized by determining the Michaelis-Menten constant. A known inhibitor (1-(ß-d-Ribofuranosyl)-4-quinolone derivative) was used as a model to validate the established method in inhibitor recognition. Screening of three additional derivatives of 1-(ß-d-Ribofuranosyl)-4-quinolone led to the discovery of novel inhibitors, with compound 2a exhibiting superior inhibitory activity (Ki = 23.37 ± 3.64 µmol/L) compared to the employed model inhibitor. Docking and Molecular Dynamics studies provided crucial insights into inhibitor interactions at the enzyme active site, offering valuable information for developing new LdNH inhibitors. Therefore, this study presents a novel screening assay and contributes to the development of potent LdNH inhibitors.