Development and Evaluation of Microencapsulated Oregano Essential Oil as an Alternative Treatment for Candida albicans Infections.

Vulvovaginal candidiasis (VVC) is characterized as a very common fungal infection that significantly affects women's health worldwide. Essential oils (EOs) are currently being evaluated as an alternative therapy. The development of efficient techniques such as micro- or nanoencapsulation for protecting and controlling release is essential to overcome the limitations of EO applications. Therefore, the aim of this study was to develop and characterize oregano EO-loaded keratin microparticles (OEO-KMPs) as a potential treatment for VVC. OEO-KMPs were produced using high-intensity ultrasonic cycles and characterized in terms of morphological and physicochemical parameters. In vitro evaluation included assessing the toxicity of the OEO-KMPs and their effect against Candida albicans using microdilution and agar diffusion, while the activity against biofilm was quantified using colony forming units (CFU). The efficacy of the OEO-KMPs in an in vivo VVC mouse model was also studied. Female BALB/c mice were intravaginally infected with C. albicans, 24 h postinfection animals were treated intravaginally with 15 µL of OEO-KMPs and 24 h later vaginal fluid was analyzed for C. albicans and Lactobacillus growth (CFU mL-1). The results showed the stability of the OEO-KMPs over time, with high encapsulation efficiency and controlled release. This nanoparticle size facilitated penetration and completely inhibited the planktonic growth of C. albicans. In addition, an in vitro application of 2.5% of the OEO-KMPs eradicated mature C. albicans biofilms while preserving Lactobacillus species. In in vivo, a single intravaginal application of OEO-KMPs induced a reduction in C. albicans growth, while maintaining Lactobacillus species. In conclusion, this therapeutic approach with OEO-KMPs is promising as a potential alternative or complementary therapy for VVC while preserving vaginal microflora.

Highly-selective optical filter for NADH fluorescence detection in multiphoton microscopy.

Colorectal cancer (CRC) is a pressing global health concern, emphasizing the need for early detection tools. In this study an optical filter for precise detection of nicotinamide adenine dinucleotide (NADH) fluorescence via two-photon excitation fluorescence (TPEF) was developed. Fabricated with silicon dioxide and titanium dioxide thin films in a Fabry-Perot structure, the filter achieved a peak transmittance of about 95% at 483 nm, with a 12 nm full-width at half maximum. TPEF measurements using a tailored setup and NADH liquid phantoms underscored the filter's significance in selectively capturing NADH fluorescence while mitigating interference from other fluorophores. This work marks a substantial stride towards integrating multiphoton microscopy into conventional colonoscopy, enabling non-invasive, objective optical biopsy for colorectal tissue analysis. Further refinements of the experimental setup are imperative to advance tissue differentiation and enhance CRC diagnosis.

Glycemic variability after mechanical thrombectomy for anterior circulation acute ischemic stroke. / Variabilidad glucémica tras trombectomía mecánica en el ictus isquémico agudo de la circulación anterior.

INTRODUCTION: Morbidity remains high among patients who undergo successful mechanical thrombectomy (MT) for anterior circulation large vessel occlusion (LVO). Stress hyperglycemia worsens the prognosis after acute ischemic stroke (AIS), but aggressively treating hyperglycemia does not improve the outcome. There is no consensus on how to best manage glycemia after AIS. Glycemic variability (GV) reflects glycemic fluctuations over time and could be the culprit. We aimed to elucidate how GV impacts outcome of AIS patients treated with MT. PATIENTS AND METHODS: This was a single-center retrospective study. We consecutively included AIS patients who received MT for anterior circulation LVO. We recorded discrete blood glucose measurements within the first 24 hours post thrombectomy, from which we calculated two measures of GV: standard deviation (SD) and coefficient of variation. Univariate and multivariate analyses were conducted to identify predictors of poor functional outcome (modified Ranking scale score 3-6) and mortality at 3-month follow-up. RESULTS: We included 657 patients. Patients with poor functional outcome (42.5%) and patients that died (14.8%) had significantly higher GV as measured by SD. In a multivariable model adjusted for confounders, higher SD was associated with mortality -adjusted odds ratio: 1.020 (95% CI 1.001-1.040)- but not with functional outcome -adjusted odds ratio for modified Ranking scale score 3-6: 1.007 (95% CI 0.990-1.025)-. CONCLUSIONS: Our results suggest that higher GV after MT for anterior circulation AIS is an independent risk factor for 3-month mortality. Future trials should evaluate the benefit of reducing GV in this setting.

TITLE: Variabilidad glucémica tras trombectomía mecánica en el ictus isquémico agudo de la circulación anterior.Introducción. La morbilidad de los pacientes con ictus isquémico agudo (IIA) sometidos a trombectomía mecánica (TM) exitosa permanece alta. La hiperglucemia empeora el pronóstico tras un IIA, pero tratarla agresivamente no mejora los resultados. No existe consenso sobre el tratamiento óptimo de la glucemia después de un IIA. La variabilidad glucémica (VG), que refleja las fluctuaciones glucémicas a lo largo del tiempo, puede ser un factor importante. Nuestro objetivo fue investigar cómo la VG afecta el resultado de pacientes con IIA tratados con TM. Pacientes y métodos. Realizamos un estudio retrospectivo unicéntrico que incluyó a pacientes con IIA que recibieron TM para la oclusión de un gran vaso de la circulación anterior. Se registraron mediciones discretas de glucemia en las primeras 24 horas postrombectomía, a partir de las cuales se calcularon dos medidas de VG: desviación estándar y coeficiente de variación. Se realizó un análisis univariado y multivariado para identificar predictores de resultado funcional desfavorable (escala de Rankin modificada: 3-6) y mortalidad a los tres meses. Resultados. Se incluyó a 657 pacientes. Los que tenían una puntuación en la escala de Rankin modificada = 3 (42,5%) y los fallecidos (14,8%) tuvieron una VG significativamente mayor medida por desviación estándar. En un modelo multivariado, una mayor desviación estándar se asoció de forma independiente con la mortalidad ­odds ratio ajustada: 1,02 (intervalo de confianza al 95%: 1,001-1,04)­ pero no con el resultado funcional ­odds ratio ajustada de la escala de Rankin modificada = 3: 1,007 (intervalo de confianza al 95%: 0,99-1,025)­. Conclusiones. Nuestros resultados sugieren que una mayor VG tras la TM para el IIA de la circulación anterior es un factor de riesgo independiente de mortalidad a los tres meses. Los futuros ensayos deben evaluar el beneficio de reducir la VG en este contexto.

The inhibitor of the redox activity of APE1/REF-1, APX2009, reduces the malignant phenotype of breast cancer cells.

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/REF-1) is a multifunctional protein acting on cellular signaling pathways, including DNA repair and redox activities. APE1/REF-1 has emerged as a target for cancer therapy, and its role in breast cancer models would reveal new strategies for cancer therapy. APX2009 is a specific APE1/REF-1 redox inhibitor whose anticancer properties have not been described in breast cancer cells. Here, we investigated the effect of the APX2009 treatment in the breast cancer cell lines MDA-MB-231 and MCF-7. Breast cancer cell lines were cultured, and WST1 and colony formation assays were performed to evaluate cell proliferation. Annexin V-FITC/7-AAD and LDH-Glo™ assays were performed to evaluate cell death. The wound healing assay and Matrigel transwell assay were performed after APX2009 treatment to evaluate the cellular migration and invasion processes, respectively. Our findings demonstrated that APX2009 treatment decreased breast cancer cell proliferative, migratory, and invasive properties. Furthermore, it induced apoptosis in both cell lines. Our study is the first to show the effects of APX2009 treatment on apoptosis in a breast cancer cell. Therefore, this study suggested that APX2009 treatment is a promising anticancer molecule for breast cancer.

Synthesis of temporomandibular disorders management intervention outcomes for development of core outcome sets: A systematic review.

INTRODUCTION: The selection of appropriate outcomes in clinical trials and systematic reviews is a crucial factor in determining the results that are useful, reliable, and relevant for both patients and healthcare professionals. Clinicians and researchers have been encouraged to develop and apply core outcome sets (COS) to minimise the discrepancy between studies. AIM: This systematic review is the first phase of the COS development project for clinical trials in temporomandibular disorders (COS-TMD). It aims to identify and synthesise the outcomes used in the randomised controlled trials (RCT) that evaluated the effectiveness of interventions used in TMD management. MATERIALS AND METHODS: An electronic search was performed in several databases: MEDLINE (via PubMed), Scopus, Web of Science, Cochrane Library and EMBASE. The eligibility criteria comprised RCT that applied any intervention to treat temporomandibular joint disorders or masticatory muscle disorders. The identified outcomes were categorised according to domains of the Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT). RESULTS: The electronic search resulted in 1606 studies. After removing duplicates and applying the eligibility criteria, 106 RCT were included. A total of 43 studies evaluated masticatory muscle disorders, 27 evaluated temporomandibular joint disorders, and 36 analysed mixed TMD. CONCLUSIONS: The evaluation showed significant variability in the types of outcomes and their measurement instruments. In addition, some domains such as physical and emotional functioning, participant ratings of global improvement and adverse events have been neglected when determining the effectiveness of treatments for TMD.

Phytochemical analysis, toxicity and evaluation of antioxidant and antimicrobial activities of leaves of Dipteryx alata Vogel.

In this study, our objective was to conduct a comprehensive phytochemical analysis, determine toxicity levels, and assess the antioxidant and antimicrobial properties of extracts derived from the leaves of Dipteryx alata Vogel, a native species of the Brazilian cerrado flora. Three distinct extracts were prepared utilizing assisted ultrasound and the Soxhlet apparatus, namely, Ultrasound Crude Extract (UCE), Soxhlet Crude Extract (SCE), and the Soxhlet Ethanol Extract (SEE). The phytochemical analysis revealed the presence of flavonoids, tannins, phytosterols, and saponins in all extracts. Additionally, alkaloids were specifically identified in the SCE and SEE extracts. In the analysis using LC-DAD, the compounds gallic acid, rutin, quercetin, luteolin and kampefrol were determined in higher concentrations in the SCE, followed by the SEE and UCE, respectively. The GC-MS analysis revealed the presence of campesterol, stigmasterol and ß-sitosterol in all extracts, with UCE and SCE showing a higher concentration of ß-sitosterol. SCE showed the highest concentration of all identified compounds. In the analysis of antioxidant activity by DPPH• and ABTS•+, SEE showed greater efficiency (IC50 = 2.98 ± 2.92 and 6.57 ± 0.89 µg/mL, respectively). In the toxicity test with Allium cepa, all extracts stimulated root growth at 50 g/mL; UCE and SEE stimulated root growth at 250 g/mL; and SEE inhibited root growth at 750 g/mL. In the Artemia salina toxicity, all extracts were non-toxic. Antibacterial activity was identified in the microorganisms S. aureus and S. mutans; however, the extracts did not show antifungal action against the strain of C. albicans. The extracts of D. alata have therapeutic potential for applicability in dentistry.

Genitourinary symptoms and sexual function in women with primary ovarian insufficiency.

OBJECTIVE: There are limited studies on urogenital symptoms in women who experience menopause before the age of 40 years due to primary ovarian insufficiency (POI) or bilateral oophorectomy (surgical POI). This study aimed to compare the urogenital symptoms, including sexuality, of women with POI to those without the condition. METHODS: This cross-sectional study conducted was in seven Latin American countries, in which postmenopausal women (with POI and non-POI) were surveyed with a general questionnaire, the Menopause Rating Scale (MRS) and the six-item Female Sexual Function Index (FSFI-6). The association of premature menopause with more urogenital symptoms and lower sexual function was evaluated with logistic regression analysis. RESULTS: Women with POI experience more urogenital symptoms (MRS urogenital score: 3.54 ± 3.16 vs. 3.15 ± 2.89, p < 0.05) and have lower sexual function (total FSFI-6 score: 13.71 ± 7.55 vs. 14.77 ± 7.57 p < 0.05) than women who experience menopause at a normal age range. There were no significant differences in symptoms when comparing women based on the type of POI (idiopathic or surgical). After adjusting for covariates, our logistic regression model determined that POI is associated with more urogenital symptoms (odds ratio [OR]: 1.38, 95% confidence interval [CI] 1.06-1.80) and lower sexual function (OR: 1.67, 95% CI 1.25-2.25). CONCLUSION: POI, whether idiopathic or secondary to bilateral oophorectomy, is associated with symptoms that affect vaginal and sexual health.

The inhibitor of the redox activity of APE1/REF-1, APX2009, reduces the malignant phenotype of breast cancer cells

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/REF-1) is a multifunctional protein acting on cellular signaling pathways, including DNA repair and redox activities. APE1/REF-1 has emerged as a target for cancer therapy, and its role in breast cancer models would reveal new strategies for cancer therapy. APX2009 is a specific APE1/REF-1 redox inhibitor whose anticancer properties have not been described in breast cancer cells. Here, we investigated the effect of the APX2009 treatment in the breast cancer cell lines MDA-MB-231 and MCF-7. Breast cancer cell lines were cultured, and WST1 and colony formation assays were performed to evaluate cell proliferation. Annexin V-FITC/7-AAD and LDH-Glo™ assays were performed to evaluate cell death. The wound healing assay and Matrigel transwell assay were performed after APX2009 treatment to evaluate the cellular migration and invasion processes, respectively. Our findings demonstrated that APX2009 treatment decreased breast cancer cell proliferative, migratory, and invasive properties. Furthermore, it induced apoptosis in both cell lines. Our study is the first to show the effects of APX2009 treatment on apoptosis in a breast cancer cell. Therefore, this study suggested that APX2009 treatment is a promising anticancer molecule for breast cancer.

Global methylation in 'Valencia' orange seedlings associated with rootstocks and Huanglongbing.

Citrus farming is one of the main activities that contributed to the Brazilian trade balance, with citrus seedling being the most important input in the formation of orchards to guarantee high productivity and fruit quality, which fundamentally depends on the chosen genetics. The present study aimed to analyze the existence of epigenetic variability in 'Valencia' orange plants on rootstocks, associated or not with HLB, through the quantification of the global methylation of its genome, in order to support works on genetic improvement and crop production. For this purpose, this work was carried out in greenhouse in a completely randomized experimental design, with 5 treatments and 6 replicates per treatment, each seedling being considered a replicate, namely: T1 = "Valencia" orange grafted onto "Rangpur" lemon, inoculated with HLB; T2 = "Valencia" orange grafted onto "Swingle" citrumelo, inoculated with HLB; T3 = "Valencia" orange grafted onto "Rangpur" lemon, without HLB inoculation ; T4 = "Valencia" orange grafted onto "Swingle" citrumelo, without HLB inoculation ; T5 = "Valencia" orange in free standing. The DNA was extracted from leaves and the ELISA test (Enzyme-Linked Immunosorbent Assay) was carried out, based on the use of receptors sensitive to 5-mC., to measure the relative quantification of global methylation between genomic orange DNAs . Since the control treatment (T5) consists of "Valencia" orange in free standing, it could be inferred that both the normal grafting technique in the seedling formation process and the inoculation of buds infected with HLB are external factors capable of changing the methylation pattern in the evaluated plants, including the DNA demethylation process, causing an adaptive response in association with the expression of genes previously silenced by genome methylation.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis recurrence temporally associated with allergen-specific immunotherapy in a female adolescent: a case report.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in pediatric patients. It is clinically characterized by fever flares lasting 3-7 days, reappearing every 2-8 weeks with a distinctive clockwork regularity. PFAPA generally begins before 5 years of age and usually ceases 3-5 years after onset. Recurrences may be observed in adolescence and adulthood in up to 20% of cases. The authors aim to describe a case of PFAPA recurrence in adolescence temporally associated with allergen-specific immunotherapy (ASIT). A 16-year-old female patient was referred to the rheumatology unit due to recurrent episodes of fever one month after initiating ASIT for allergic rhinitis. These episodes occurred every 4 weeks and lasted 3 days. During these episodes, she also presented with a sore throat, tonsillar exudates, and cervical lymphadenopathy. Abortive treatment with oral prednisolone was attempted in these episodes, with complete resolution of fever after a single dose. After reviewing her medical background, she had previously experienced febrile episodes accompanied by aphthous ulcers and tonsillar exudates occurring every 7-8 weeks from age 2-7. The etiopathogenesis of PFAPA remains uncertain. Environmental triggers, particularly those with immunomodulator effects, may interfere with the immune responses responsible for PFAPA occurrence, but the mechanisms are still unclear. The authors describe the first report of the reappearance of PFAPA flares, possibly due to ASIT. Further studies are needed to fully clarify if ASIT constitutes a true environmental trigger of PFAPA.

Diet quality, asthma and airway inflammation in school-aged children.

Summary: Background. Asthma is a major public health problem, with increasing prevalence in most countries, particularly among children. Poor dietary quality is also increasing in children, and evidence of the overall quality of children's food patterns effects on asthma is scarce. Methods. This cross-sectional analysis (660 children: 49.1% females, aged 7-12years) evaluated the association between diet quality and asthma (n = 56) and airway inflammation among school-aged children according to body mass index (BMI). Diet quality was assessed through the Healthy Eating Index (HEI)-2015, and categorized by tertiles. Higher scores represent a healthier diet. A questionnaire was used to enquire about self-reported medical diagnosis of asthma and asthma under medication. Lung function and airway reversibility were measured, and airway inflammation assessed measuring exhaled fractional nitric oxide (eNO). Two categories of BMI were considered: non-overweight/obese (p less than 85th), (n = 491), and overweight/obese (p ≥ than 85th), (n = 169). The associations between diet quality and asthma and airway inflammation were estimated using logistic regression models. Results. Non-overweight/obese children in 2nd tertile of HEI-2015 score had decreased odds of having eNO ≥ 35ppb (OR 0.43, 95%CI 0.19-0.98), medical diagnosis of asthma (OR 0.18; 95%CI 0.04-0.84), and asthma treatment (OR 0.12; 95%CI 0.01-0.95), compared to children in the 1st tertile. Conclusions. Our findings suggest that a higher diet quality associates with lower levels of airway inflammation and reduced prevalence of asthma among non-overweight/obese school-aged children.

Functionalized bioadhesion-enhanced carboxymethyl cellulose/polyvinyl alcohol hybrid hydrogels for chronic wound dressing applications.

Wounds produced by trauma, burns, and chronic diseases cause millions of patients to suffer discomfort, pain, and, in many cases, disability and death, leading to enormous health, social and financial impacts globally. Regrettably, current clinical treatments for chronic wounds remain unsatisfactory. Thus, this study reports for the first time the design, development, and synthesis of chemically biofunctionalized hybrid hydrogels made of carboxymethyl cellulose (CMC) and poly(vinyl alcohol) (PVA) crosslinked by citric acid using an entirely biocompatible and green process. They demonstrated suitable physicochemical properties, cytocompatibility, and hemocompatibility to be applied as a smart wound dressing for skin tissue engineering. These novel hybrids were biofunctionalized with l-arginine and RGD peptide through carbodiimide mediated-amide formation to promote bioadhesion of fibroblast and keratinocyte cells as a potential enhancement for wound healing and skin tissue engineering applications.

Uveitis in patients with oligoarticular juvenile idiopathic arthritis and juvenile spondyloarthritis/enthesitis related arthritis: is there any difference?

Juvenile idiopathic arthritis (JIA) is the most common systemic disease causing uveitis in childhood and adolescence.

Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial.

BACKGROUND: In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status. PATIENTS AND METHODS: Patients were randomized 2 : 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for ∼60% maturity or 3 years after the primary analysis. RESULTS: After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms. CONCLUSIONS: Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified exploratory analyses demonstrated improvement despite a high proportion of patients in the placebo arm receiving poly(ADP-ribose) polymerase inhibitors after progression, confirming the combination as one of the standards of care in this setting with the potential to enhance cure.

Combined Application of Antisense Oligomers to Control Transcription Factors of Candida albicans Biofilm Formation.

Antisense oligomers (ASOs) have been little exploited to control determinants of Candida albicans virulence. Biofilm formation is an important virulence factor of C. albicans, that is regulated by a complex network of transcription factors (such as EFG1, BRG1 and ROB1). Thus, the main goal of this work was to project ASOs, based on the 2'-OMethyl chemical modification, to target BRG1 and ROB1 mRNA and to validate its application either alone or in combination with the EFG1 mRNA target, to reduce C. albicans biofilm formation. The ability of ASOs to control gene expression was evaluate by qRT-PCR. The effect on biofilm formation was determined by the total biomass quantification, and simultaneously the carbohydrates and proteins reduction on extracellular matrix. It was verified that all the oligomers were able to reduce the levels of gene expression and the ability of C. albicans to form biofilms. Furthermore, the combined application of the cocktail of ASOs enhances the inhibition of C. albicans biofilm formation, minimizing biofilm thickness by reducing the quantity of matrix content (protein and carbohydrate). So, our work confirms that ASOs are useful tools for research and therapeutic development on the control of Candida species biofilm formation.

Treatment with 2 commercial antibiotics reduced clinical and systemic signs of pneumonia and the abundance of pathogenic bacteria in the upper respiratory tract of preweaning dairy calves.

The aim of this study was to evaluate the effect of therapeutically administered tildipirosin or florfenicol + flunixin meglumine for the treatment of bovine respiratory disease (BRD) accompanied by fever in calves before weaning compared with diseased and untreated animals. As specific objectives, we evaluated the composition of the bacterial microbiota of the upper respiratory tract (URT) and blood and health parameters of the animals. Preweaning Holstein female calves diagnosed with naturally acquired pneumonia were randomly assigned to one of the following experimental groups on the day of diagnosis (d 0): (1) TLD (n = 36): single subcutaneous injection with 4 mg/kg tildipirosin; (2) FLF (n = 33): single subcutaneous injection with an antimicrobial (40 mg/kg florfenicol) combined with a nonsteroidal anti-inflammatory drug (2.2 mg/kg flunixin meglumine); and (3) NEG (n = 35): no treatment within the first 5 d following enrollment. The NEG treatment group was closely monitored for 5 d, and calves were removed from the study following a standardized late treatment protocol, when necessary, to minimize health concerns. Healthy untreated calves (CTR; n = 31) were also selected for the study and used as controls. Blood samples used for biochemical analysis and nasopharyngeal swabs used for evaluation of URT microbiota were collected daily from d 0 until d 5 and then weekly until weaning. Next-generation sequencing of the 16S rRNA gene was used to assess the URT microbiota at the phylum and genus levels. Clinical signs associated with pneumonia and otitis media were assessed daily, as was the need for antibiotic interventions. Calves in the TLD and FLF groups had faster recovery from fever within the first 5 d after enrollment. In addition, antibiotic-treated calves reached the same serum haptoglobin levels as healthy calves on d 2 after diagnosis, whereas calves in the NEG group had higher haptoglobin levels than the CTR group until at least d 5 after BRD diagnosis. Calves in the TLD and FLF groups had a lower risk of treatment for pneumonia (FLF = 22.8%; TLD = 27.7%) from d 5 to weaning than calves in the NEG group (54.7%). Furthermore, FLF treatment had a significantly lower risk of nasal discharge, otitis media, and treatment failure compared with the NEG group, but did not differ from the TLD group. Differences in the composition of the URT microbiota were found between groups, and the genus Mycoplasma was the most abundant in samples collected from the URT of calves with and without pneumonia. Both drugs were effective in reducing the mean relative abundance (MRA) of important genera associated with pneumonia (Mannheimia and Pasteurella), although an increase in Mycoplasma MRA was observed for tildipirosin-treated calves. In conclusion, both drugs were effective in reducing the inflammatory signs of pneumonia and the need for antimicrobial treatment after enrollment compared with no treatment. In addition, both TLD and FLF were effective in reducing the MRA of important bacterial genera associated with pneumonia; however, TLD treatment was associated with increased Mycoplasma MRA compared with healthy and untreated calves.

Botulinum toxin in the treatment of residual limb hyperhidrosis: A systematic review.

The aim of the study was to analyze the current evidence regarding the effect of intradermal injections of botulinum toxin on residual limb hyperhidrosis. A comprehensive search of the MEDLINE and Scopus databases from inception until December 2021 was performed according to the PRISMA guidelines. The search terms used were "botulinum toxins", "botulinum toxins, Type A", "rimabotulinumtoxinB", "amputees", "amputation stumps", "amputation" and "residual limbs". The specific controlled vocabulary of each database was also used (e.g., MeSH). One hundred and thirty-one different studies met this search criteria and were reviewed. Two independent reviewers assessed the quality of the manuscripts. Eight studies met the inclusion criteria for this review. The results demonstrated an improvement in residual limb hyperhidrosis in all studies. Botulinum toxin A or B can be regarded as safe and effective for the treatment of residual limb hyperhidrosis, as well as improving prosthesis use and quality of life.

Effects of prenatal hypoxia-ischemia on male rat periaqueductal gray matter: Hyperalgesia, astrogliosis and nitrergic system impairment.

Prenatal hypoxic-ischemic insult (HI) may lead to a variety of neurological consequences that may persist throughout adulthood. In the most severe cases, HI is known to increase pain sensitivity which profoundly impacts quality of life. Periaqueductal gray matter (PAG) is a relevant region of the descending pain pathway and its function may be modulated by a complex network that includes nitrergic neurons and glial response, among other factors. Astrocytes, central players in pain modulation, are known to respond to HI by inducing hyperplasia, hypertrophy and increasing the number of their processes and the staining of glial fibrillary acidic protein (GFAP). In this work we investigated the effects of prenatal HI on touch and pain sensitivity, besides the distribution of the neuronal isoform of Nitric Oxide Synthase (nNOS) and GFAP in the PAG of young and adult male rats. At 18 days of gestation, rats had their uterine arteries clamped for 45 min (HI group). SHAM-operated animals were also generated (SHAM group). At post-natal day 30 (P30) or 90 (P90), the offspring was submitted to the behavioral tests of Von Frey and formalin or histological processing to perform immunohistochemistry for nNOS and GFAP. Although there was no significant difference between the groups concerning touch sensitivity, we observed an increase in pain sensitivity in HI P30 and HI P90. The number of nNOS + cells was reduced in HI adult animals in dlPAG and vlPAG. GFAP immunostaining was increased in HI P90 in dlPAG and dmPAG. Our results demonstrated for the first time an increase in pain sensitivity as a consequence of prenatal HI in an animal model. It reinforces the relevance of this model to mimic the effects of prenatal HI, as hyperalgesia.

Microvascular density and tumor budding in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most prevalent malignant head and neck tumor, excluding the nonmelanoma skin cancer. Despite recent advances in the diagnosis and treatment, the disease's mortality rate is nonetheless high. The presence of isolated neoplastic cells or small clusters of up to four cells at the tumor's invasive front, named tumor budding, is associated with a worse prognosis in OSCC. Angiogenesis has also been recognized as a determining factor in the progression of malignancies and in the development of metastases. Several studies have investigated the assessment of microvascular density (MVD) as a potential prognostic factor in OSCC. This study aimed to evaluate, in OSCC, differences in MVD between tumors with high-intensity tumor budding and tumors with low-intensity or no tumor budding. In samples with high-intensity tumor budding, differences in MVD between the budding area and the area outside the budding were also evaluated. Moreover, the study assessed differences in MVD concerning clinicopathological characteristics such as sex, age, tobacco smoking, tumor location and tumor size. MATERIAL AND METHODS: One hundred and fifty [150] samples of OSCC were subjected to immunohistochemistry to assess the intensity of tumor budding (by immunostaining for multi-cytokeratin) and MVD (by immunostaining for CD34 and CD105, independently). The data were treated using descriptive and analytical statistics. RESULTS: There were no differences in MVD, assessed by immunostaining for CD34 or CD105, concerning clinicopathological characteristics such as sex, age, tobacco smoking, tumor location and tumor size (p > 0.05). Tumors with high-intensity tumor budding did not show differences in MVD, assessed by immunostaining for CD34 or CD105, when compared to tumors with low-intensity or no tumor budding (p > 0.05). However, in samples with high-intensity tumor budding, the MVD assessed by immunostaining for CD34 was higher in the budding area than in the area outside the budding (p < 0.05). This difference was not observed when MVD was assessed by immunostaining for CD105 (p > 0.05). CONCLUSIONS: The higher MVD in the budding area may be an additional indication that this is a peculiar region of the tumor, associated with biological phenomena related to tumor progression.