Development of electrophysiological properties of fusiform neurons from the dorsal cochlear nucleus of mice before and after hearing onset.

The dorsal cochlear nucleus (DCN) in the auditory brainstem integrates auditory and somatosensory information. Mature DCN fusiform neurons fall into two qualitatively distinct types: quiet, with no spontaneous regular action potential firing, or active, with regular spontaneous action potential firing. However, how these firing states and other electrophysiological properties of fusiform neurons develop during early postnatal days to adulthood is not known. Thus, we recorded fusiform neurons from mice from P4 to P21 and analyzed their electrophysiological properties. In the prehearing phase (P4-P13), we found that most fusiform neurons are quiet, with active neurons emerging after hearing onset at P14. Subthreshold properties underwent significant changes before hearing onset, whereas changes to the action potential waveform occurred mainly after P14, with the depolarization and repolarization phases becoming markedly faster and half-width significantly decreased. The activity threshold in posthearing neurons was more negative than in prehearing cells. Persistent sodium current (INaP) was increased after P14, coinciding with the emergence of spontaneous firing. Thus, we suggest that posthearing expression of INaP leads to hyperpolarization of the activity threshold and the active state of the fusiform neuron. At the same time, other changes refine the passive membrane properties and increase the speed of action potential firing of fusiform neurons.NEW & NOTEWORTHY Auditory brainstem neurons express unique electrophysiological properties adapted for their complex physiological functions that develop before hearing onset. Fusiform neurons of the DCN present two firing states, quiet and active, but the origin of these states is not known. Here, we showed that the quiet and active states develop after hearing onset at P14, along with changes in action potentials, suggesting an influence of auditory input on the refining of fusiform neuron's excitability.

Congenital diaphragmatic hernia increases the sensitivity of pulmonary arteries to nitric oxide.

Left congenital diaphragmatic hernia (CDH) can lead to pulmonary arteries abnormalities in the contralateral and ipsilateral sides of the diaphragm. Nitric oxide (NO) is the main therapy used to attenuate the vascular effects of CDH, but it is not always effective. We hypothesized that the left and right pulmonary arteries do not respond similarly to NO donors during CDH. Therefore, vasorelaxant responses of the left and right pulmonary arteries to sodium nitroprusside (SNP, a NO donor) were determined in a rabbit experimental model of left CDH. CDH was surgically induced in the fetuses of rabbits on the 25th day of pregnancy. On the 30th day of pregnancy, a midline laparotomy was performed to access the fetuses. The fetuses' left and right pulmonary arteries were isolated and mounted in myograph chambers. Vasodilation was evaluated by cumulative concentration-effect curves to SNP. Protein expression of guanylate cyclase isoforms (GCα, GCß) and the α isoform of cGMP-dependent protein kinase 1 (PKG1α), and the concentration of NO and cGMP were determined in the pulmonary arteries. The left and right pulmonary arteries of newborns with CDH exhibited increased vasorelaxant responses to SNP (i.e. the potency of SNP was increased) compared to the control group. GCα, GCß, and PKG1α expression were decreased, while NO and cGMP concentrations were increased in the pulmonary arteries of newborns with CDH compared to the control group. The increased cGMP mobilization may be responsible for the increased vasorelaxant responses to the SNP in the pulmonary arteries during left CDH.

Quercetin-1,2,3-Triazole Hybrids as Multifunctional Anti-Alzheimer's Agents.

The number of patients with Alzheimer's disease (AD) continues to rise and, despite the efforts of researchers, there are still no effective treatments for this multifaceted disease. The main objective of this work was the search for multifunctional and more effective anti-Alzheimer agents. Herein, we report the evaluation of a library of quercetin-1,2,3-triazole hybrids (I-IV) in antioxidant, hydrogen peroxide-induced oxidative stress protection, and cholinesterases (AChE and BuChE) inhibitory activities. Hybrids IIf and IVa-d showed potent in vitro inhibitory activity on eqBuChE (IC50 values between 11.2 and 65.7 µM). Hybrid IIf, the best inhibitor, was stronger than galantamine, displaying an IC50 value of 11.2 µM for eqBuChE, and is also a competitive inhibitor. Moreover, toxicity evaluation for the most promising hybrids was performed using the Artemia salina toxicity assay, showing low toxicity. Hybrids IIf, IVb, and IVd did not affect viability at 12.5 µM and also displayed a protective effect against oxidative stress induced by hydrogen peroxide in cell damage in MCF-7 cells. Hybrids IIf, IVb, and IVd act as multifunctional ligands in AD pathologies.

Feasibility Study of Transanal Irrigation Using a Colostomy Irrigation System in Patients With Low Anterior Resection Syndrome.

BACKGROUND: Low anterior resection syndrome has a negative impact on quality of life. Intestinal irrigation is a method of lavage consisting of a scheduled evacuation. OBJECTIVE: This study aims to evaluate functional and quality-of-life outcomes in patients with low anterior resection syndrome after transanal irrigation using a colostomy irrigation system. DESIGN: This was a prospective case series. SETTINGS: This study presents a single-center experience at a tertiary oncological center in an upper-middle-income country. PATIENTS: Patients classified as having minor or major low anterior resection syndrome 12 months after their operation were selected. INTERVENTIONS: Transanal irrigation was performed using an ostomy irrigation kit. Questionnaires assessing patients' bowel function (low anterior resection syndrome and Wexner score) and quality of life (Short Form-36 questionnaire) were applied before and after treatment. MAIN OUTCOME MEASURES: The primary outcomes were low anterior resection syndrome score and quality-of-life improvement after a 12-month treatment. RESULTS: Of the 22 patients included, 20 had major and 2 had minor low anterior resection syndrome, with a median score of 39, especially high rates of incontinence for liquid stool (21; 95.5%), clustering (21; 95.5%), and urgency (17; 77.3%). All patients successfully completed the 3-day training, and there were no complications during the treatment. After the 12-month period, the median score was 8, with 90% of the patients classified as having "no syndrome" and great improvement in all domains of this score. The most improved quality-of-life sections were patient vitality (p = 0.025) and physical (p = 0.002), social (p = 0.001), and emotional aspects (p = 0.001). LIMITATIONS: The study was limited by its small sample size and the limited follow-up period. CONCLUSIONS: This study presents a safe implementation protocol of an ostomy irrigation device for transanal irrigation. It also adds to the literature that transanal irrigation is a safe, effective, and easily implemented procedure for patients with low anterior resection syndrome with a significant improvement in quality of life. See Video Abstract at http://links.lww.com/DCR/B563.ESTUDIO DE FACTIBILIDAD DE LA IRRIGACIÓN TRANSANAL UTILIZANDO EL SISTEMA DE IRRIGACIÓN PARA COLOSTOMÍA EN PACIENTES CON SÍNDROME DE RESECCIÓN ANTERIOR BAJAANTECEDENTES:El síndrome de resección anterior baja tiene un impacto negativo en la calidad de vida de los pacientes. La irrigación intestinal es un método de lavado que consiste en evacuaciones programadas.OBJETIVOS:Evaluar los resultados de la funcionalidad e impacto en la calidad de vida de los pacientes con síndrome de resección anterior y baja posterior a la irrigación transanal utilizando un sistema de irrigación de colostomía.DISEÑO:Es estudio prospectivo de una serie de casos.ESCENARIO:En este estudio se muestra la experiencia de un centro oncológico de tercer nivel en un país en vías de desarrollo.PACIENTES:Aquellos clasificados como síndrome con afección en menor o mayor grado doce meses después de la cirugía.METODO:Se efectuó irrigación transanal utilizando un equipo de irrigación de estomas. Se aplicaron cuestionarios para valorar la función intestinal de los pacientes (síndrome de resección anterior baja y la escala de Wexner) y para calidad de vida (Cuestionario Corto-36) antes y después del tratamiento.EVALUACION DE LOS RESULTADOS PRINCIPALES:Los principales resultados se obtuvieron de la escala del síndrome de resección baja y la mejoría en la calidad vida doce meses después de tratamiento.RESULTADOS:De los veintidós pacientes incluidos, veinte presentaron manifestaciones mayores del síndrome de resección baja y dos, manifestaciones menores. Con una media de treinta y nueve, se encontraron, especialmente, altos índices de incontinencia a líquidos (21; 95'5%) hiperdefecación "clustering" (21; 95'5%) y urgencia (17; 77'3%). Todos los pacientes completaron en forma satisfactoria el entrenamiento de tres días sin presentarse complicaciones durante el tratamiento. Al término del mes doce la media fue de ocho, con el 90% de los pacientes clasificados como "sin síndrome" y se observó una mejoría substancial en todos los puntos de la evaluación. Las secciones de calidad de vida que mostraron una mejoría significativa fueron: la vitalidad del paciente (p = 0'025), física (p = 0'002), social (p = 0'001) y emocional (p = 0'001).LIMITACIONES:El tamaño de la muestra es pequeño y el tiempo de seguimiento corto.CONCLUSIONES:Este estudio muestra la implementación de un protocolo seguro para la irrigación de estomas mediante un dispositivo transanal. Además contribuye con el concepto en la literatura de que la seguridad de la irrigación transanal es seguro, efectivo y facilmente reproducible para pacientes con síndrome de resección anterior baja con una mejoría significativa en la calidad de vida. Consulte Video Resumen en http://links.lww.com/DCR/B563. (Traducción-Dr. Miguel Esquivel-Herrera).

MicroRNA-186-5p controls GluA2 surface expression and synaptic scaling in hippocampal neurons.

Homeostatic synaptic scaling is a negative feedback response to fluctuations in synaptic strength induced by developmental or learning-related processes, which maintains neuronal activity stable. Although several components of the synaptic scaling apparatus have been characterized, the intrinsic regulatory mechanisms promoting scaling remain largely unknown. MicroRNAs may contribute to posttranscriptional control of mRNAs implicated in different stages of synaptic scaling, but their role in these mechanisms is still undervalued. Here, we report that chronic blockade of glutamate receptors of the AMPA and NMDA types in hippocampal neurons in culture induces changes in the neuronal mRNA and miRNA transcriptomes, leading to synaptic upscaling. Specifically, we show that synaptic activity blockade persistently down-regulates miR-186-5p. Moreover, we describe a conserved miR-186-5p-binding site within the 3'UTR of the mRNA encoding the AMPA receptor GluA2 subunit, and demonstrate that GluA2 is a direct target of miR-186-5p. Overexpression of miR-186 decreased GluA2 surface levels, increased synaptic expression of GluA2-lacking AMPA receptors, and blocked synaptic scaling, whereas inhibition of miR-186-5p increased GluA2 surface levels and the amplitude and frequency of AMPA receptor-mediated currents, and mimicked excitatory synaptic scaling induced by synaptic inactivity. Our findings elucidate an activity-dependent miRNA-mediated mechanism for regulation of AMPA receptor expression.

Branching patterns of the superficial fibular nerve: an anatomical study with meta-analysis.

PURPOSE: To review variations regarding the branching patterns of the superficial fibular nerve (SFN) concerning the deep fascia of leg and to the ankle joint level. METHODS: Searches were conducted in PubMed, Scopus, Lilacs, and Web of Science databases on October 14th, 2021. We followed the PRISMA guidelines to report this review. Articles with data on SFN variations prevalence were included. The data were extracted and pooled into a meta-analysis. We also dissected 60 formalin-fixed Brazilian fetuses (n = 120 lower limbs). RESULTS: Twenty-five studies (n = 1272 lower limbs) comprised this review. Concerning the SFN branching at the deep fascia, Type 1 variation (in which the SFN pierces the fascia as a single nerve trunk) had a pooled prevalence of 86.4% (95% CI 84.5-88.2), while Type 2 had a pooled prevalence of 13.6% (95% CI 11.8-15.5). At the ankle joint level, Type 2 variation (in which the SFN branches off below the joint level) was the most common anatomical pattern, with a pooled prevalence of 78.7% (95% CI 74.5-82.7). CONCLUSION: Typically, the SFN branches off between its exit from the deep fascia and the ankle joint level. The SFN variations have great importance for surgeries, such as arthroscopies and fascia release surgeries, regional anesthesia, and clinical evaluation of SFN entrapment syndrome.

Variations in the compartmental location of the superficial fibular nerve: a cadaveric study with meta-analysis.

PURPOSE: To investigate variations in the course of the superficial fibular nerve (SFN) and its branches-the medial dorsal cutaneous nerve (MDCN) and intermediate dorsal cutaneous nerve (IDCN)-concerning the leg compartments by means of a meta-analysis supplemented with an original anatomical study. MATERIALS AND METHODS: A literature survey was conducted in the PubMed, Scopus, Web of Science, and Lilacs databases on October 14th, 2021, to obtain anatomical data, and the PRISMA statement was adopted as a methodological guideline. We used MetaXL software for data analysis. We classified the anatomical data into three location patterns: in Type 1, the SFN courses through the lateral compartment; in Type 2, the SFN courses through the anterior compartment; in Type 3, the MDCN courses through the anterior compartment and the IDCN courses in the lateral compartment. RESULTS: Twelve studies (n = 837 lower limbs) comprised the current review. The SFN location was normal (Type 1 variation) in 77% (95% CI 72.9-78.9) of the cases, while Type 2 had a pooled prevalence of 14.3% (95% CI 11.1-15.9). Type 3 was the less common course, with a prevalence of 8.7% (95% CI 5.9-9.7). We found differences among the geographical subgroups analyzed. CONCLUSIONS: The SFN courses through the lateral compartment of the leg most times, and the prevalence of this pattern varies significantly between the different geographical subgroups evaluated. These results are of great clinical and surgical relevance.

Mefloquine synergism with anti-tuberculosis drugs and correlation to membrane effects: Biologic, spectroscopic and molecular dynamics simulations studies.

Studies displaying the combination of mefloquine (MFL) with anti-tuberculosis (TB) substances are limited in the literature. In this work, the effect of MFL-association with two first-line anti-TB drugs and six fluoroquinolones was evaluated against Mycobacterium tuberculosis drug resistant strains. MFL showed synergistic interaction with isoniazid, pyrazinamide, and several fluoroquinolones, reaching fractional inhibitory concentration indexes (FICIs) ranging from 0.03 to 0.5. In order to better understand the observed results, two approaches have been explored: (i) spectroscopic responses attributed to the effect of MFL on physicochemical properties related to a liposomal membrane model composed by soybean asolectin; (ii) molecular dynamics (MD) simulation data regarding MFL interaction with a membrane model based on PIM2, a lipid constituent of the mycobacterial cell wall. FTIR and NMR data showed that MFL affects expressively the region between the phosphate and the first methylene groups of soybean asolectin membranes, disordering these regions. MD simulations results detected high MFL density in the glycolipid interface and showed that the drug increases the membrane lateral diffusion, enhancing its permeability. The obtained results suggest that synergistic activities related to MFL are attributed to its effect of lipid disorder and membrane permeability enhancement.

An Evaluation of Human Induced Pluripotent Stem Cells to Test for Cardiac Developmental Toxicity.

To prevent congenital defects arising from maternal exposure, safety regulations require pre-market developmental toxicity screens for industrial chemicals and pharmaceuticals. Traditional embryotoxicity approaches depend heavily on the use of low-throughput animal models which may not adequately predict human risk. The validated embryonic stem cell test (EST) developed in murine embryonic stem cells addressed the former problem over 15 years ago. Here, we present a proof-of-concept study to address the latter challenge by updating all three endpoints of the classic mouse EST with endpoints derived from human induced pluripotent stem cells (hiPSCs) and human fibroblasts. Exposure of hiPSCs to selected test chemicals inhibited differentiation at lower concentrations than observed in the mouse EST. The hiPSC-EST also discerned adverse developmental outcomes driven by novel environmental toxicants. Evaluation of the early cardiac gene TBX5 yielded similar toxicity patterns as the full-length hiPSC-EST. Together, these findings support the further development of hiPSCs and early molecular endpoints as a biologically relevant embryotoxicity screening approach for individual chemicals and mixtures.

Preliminary assessment of anti-α-Gal IgG and IgM levels in patients with patent Plasmodium vivax infection.

Anti-α-Gal responses may exert a protective effect in falciparum malaria. However, the biological role of such antibodies is still unknown during Plasmodium vivax infections. We investigated IgG and IgM responses to α-Gal in individuals with vivax malaria. Anti-α-Gal IgG and IgM levels were higher in these patients than in controls, but no significant correlation was found between parasitaemia and anti-α-Gal response, nor between this response and ABO blood group status. This is the first study to investigate anti-α-Gal antibodies in P. vivax-infected patients; a larger survey is necessary to achieve a better understanding of host immune response during vivax malaria.

Association between pelvic floor dysfunction, and clinical and ultrasonographic evaluation in primiparous women: a cross-sectional study.

PURPOSE: Disorders related to pelvic floor include urinary incontinence (UI), anal incontinence, pelvic organ prolapse, sexual dysfunction and pelvic pain. Because pelvic floor dysfunctions (PFD) can be diagnosed clinically, imaging techniques serve as auxiliary tools for establishing an accurate diagnosis. The objective is to evaluate the PFD in primiparous women after vaginal delivery and the association between clinical examination and three-dimensional ultrasonography (3DUS). METHODS: A cross-sectional study was conducted in a in tertiary maternity. All primiparous women with vaginal deliveries that occurred between January 2013 and December 2015 were invited. Women who attended the invitation underwent detailed anamnesis, questionnaire application, physical examination and endovaginal and endoanal 3DUS. Crude and adjusted predictor factors for PFD were analyzed. RESULTS: Fifty women were evaluated. Sexual dysfunction was the most prevalent PFD (64.6%). When associated with clinical features and PFD, oxytocin use increased by approximately four times the odds of UI (crude OR 4.182, 95% CI 1.149-15.219). During the multivariate analysis, the odds of UI were increased in forceps use by approximately 11 times (adjusted OR 11.552, 95% CI 11.155-115.577). When the clinical and obstetrical predictors for PFD were associated with 3DUS, forceps increased the odds of lesion of the pubovisceral muscle and anal sphincter diagnosed by 3DUS by sixfold (crude OR 6.000, 95% CI 1.172-30.725), and in multivariate analysis forceps again increased the odds of injury by approximately 7 times (adjusted OR 7.778, 95% CI 1.380-43.846). CONCLUSION: Sexual dysfunction was the most frequent PFD. The use of forceps in primiparous women was associated with a greater chance of UI and pelvic floor muscle damage diagnosed by 3DUS.

Acute cholangitis in an old patient with Crigler-Najjar syndrome type II - a case report.

BACKGROUND: Crigler-Najjar syndrome (CN) is a very rare genetic disorder characterized by an inability to conjugate bilirubin. Contrary to CN type I, patients with CN II exhibit residual capacity to conjugate bilirubin and may present a normal life expectancy. CASE PRESENTATION: We report an unusual late diagnosis of CN type II in an 80-year-old female admitted with severe acute cholangitis. While the patient present typical clinical and radiologic signs of bile duct obstruction and cholangitis, her blood analysis showed severe unconjugated hyperbilirubinemia. Endoscopic retrograde cholangiopancreatography confirmed the diagnosis and allowed therapeutic intervention. The anatomopathologic examination of her gallbladder following cholecystectomy showed signs of chronic cholecystitis. CONCLUSION: The risk of gallstone disease may be increased in patients with CN syndrome. While unusual, we alert to this curious and potential life-threatening presentation.

Suspension culture of pluripotent stem cells: effect of shear on stem cell fate.

Despite significant promise, the routine usage of suspension cell culture to manufacture stem cell-derived differentiated cells has progressed slowly. Suspension culture is an innovative way of either expanding or differentiating cells and sometimes both are combined into a single bioprocess. Its advantages over static 2D culturing include a homogeneous and controllable culture environment and producing a large quantity of cells in a fraction of time. This feature makes suspension cell culture ideal for use in stem cell research and eventually ideal in the large-scale production of differentiated cells for regenerative medicine. Because of their tremendous differentiation capacities and unlimited growth properties, pluripotent stem cells (PSCs) in particular are considered potential sources for future cell-replacement therapies. Currently, expansion of PSCs is accomplished in 2D, which only permits a limited amount of cell growth per culture flask before cells need to be passaged. However, before stem cells can be applied clinically, several aspects of their expansion, such as directed growth, but also differentiation, need to be better controlled. This review will summarize recent advantages in suspension culture of PSCs, while at the same time highlighting current challenges.

Leiomyoma and the importance of genetic variation on genes related to the vasculature system - CßS, MTHFR, NOS3, CYBA, and ACE1.

OBJECTIVE: The link between the systemic vasculature system and tumor biology is here investigated by studying the contribution of CßS (844ins68), MTHFR (677C > T), NOS3 (4a/4b), CYBA (C242T), and ACE1 (I/D) genes to leiomyoma onset, uterus and leiomyoma volumes. METHODS: DNA samples from 130 women with leiomyomas and 527 from healthy women were genotyped by PCR or PCR-RFLP. Qui-square (χ2) or Fisher's exact test were used to test associations. All the mentioned tests were performed in IBM® SPSS® Statistics Version 28. Statistical significance was defined as a p-value < 0.05. RESULTS: Results revealed that CßS (in the codominant and allelic models, p = 0.044 and, p = 0.015, OR = 1.791 [1.114-2.879], respectively), MTHFR (in the codominant, allelic and dominant models, p = 0.009, p = 0.002, OR = 0.585 [0.416-0.824] and p = 0.003, OR = 0.527 [0.346-0.802], respectively) and ACE1 (dominant model, p = 0.045, OR = 0.639 [0.411-0.992]) genes are associated with leiomyoma onset. NOS3 4a4a genotype is associated with a lower uterus volume (p = 0.004). This study also uncovers intriguing epistatic interactions among some genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the CC genotype (MTHFR) and (+/+) (CßS; p = 0.003), 4b4b (NOS3; p = 0.006, OR = 2.050 [1.223-3.439]) or DD (ACE1; p < 0.001, OR = 2.362 [1.438-3.880]) were shown to be associated with the disease, while 4a presence (NOS3) in epistasis with I presence (ACE1), increased the effect protection having just the I allele presence (p = 0.029, OR = 0.446 [0.214-0.930]). CONCLUSIONS: We conclude that variation in genes related to the systemic vascular system can play a role in the onset and development of leiomyoma.

Antiviral, anti-inflammatory and antioxidant effects of curcumin and curcuminoids in SH-SY5Y cells infected by SARS-CoV-2.

COVID-19, caused by SARS-CoV-2, affects neuronal cells, causing several symptoms such as memory loss, anosmia and brain inflammation. Curcuminoids (Me08 e Me23) and curcumin (CUR) are derived from Curcuma Longa extract (EXT). Many therapeutic actions have been linked to these compounds, including antiviral action. Given the severe implications of COVID-19, especially within the central nervous system, our study aims to shed light on the therapeutic potential of curcuminoids against SARS-CoV-2 infection, particularly in neuronal cells. Here, we investigated the effects of CUR, EXT, Me08 and Me23 in human neuroblastoma SH-SY5Y. We observed that Me23 significantly decreased the expression of plasma membrane-associated transmembrane protease serine 2 (TMPRSS2) and TMPRSS11D, consequently mitigating the elevated ROS levels induced by SARS-CoV-2. Furthermore, Me23 exhibited antioxidative properties by increasing NRF2 gene expression and restoring NQO1 activity following SARS-CoV-2 infection. Both Me08 and Me23 effectively reduced SARS-CoV-2 replication in SH-SY5Y cells overexpressing ACE2 (SH-ACE2). Additionally, all of these compounds demonstrated the ability to decrease proinflammatory cytokines such as IL-6, TNF-α, and IL-17, while Me08 specifically reduced INF-γ levels. Our findings suggest that curcuminoid Me23 could serve as a potential agent for mitigating the impact of COVID-19, particularly within the context of central nervous system involvement.

Photobiomodulation Therapy to Treat Snakebites Caused by Bothrops atrox: A Randomized Clinical Trial.

Importance: Bothrops venom acts almost immediately at the bite site and causes tissue damage. Objective: To investigate the feasibility and explore the safety and efficacy of low-level laser therapy (LLLT) in reducing the local manifestations of B atrox envenomations. Design, Setting, and Participants: This was a double-blind randomized clinical trial conducted at Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, in Manaus, Brazil. A total of 60 adult participants were included from November 2020 to March 2022, with 30 in each group. Baseline characteristics on admission were similarly distributed between groups. Data analysis was performed from August to December 2022. Intervention: The intervention group received LLLT combined with regular antivenom treatment. The laser used was a gallium arsenide laser with 4 infrared laser emitters and 4 red laser emitters, 4 J/cm2 for 40 seconds at each application point. Main Outcomes and Measures: Feasibility was assessed by eligibility, recruitment, and retention rates; protocol fidelity; and patients' acceptability. The primary efficacy outcome of this study was myolysis estimated by the value of creatine kinase (U/L) on the third day of follow-up. Secondary efficacy outcomes were (1) pain intensity, (2) circumference measurement ratio, (3) extent of edema, (4) difference between the bite site temperature and that of the contralateral limb, (5) need for the use of analgesics, (6) frequency of secondary infections, and (7) necrosis. These outcomes were measured 48 hours after admission. Disability assessment was carried out from 4 to 6 months after patients' discharge. P values for outcomes were adjusted with Bonferroni correction. Results: A total of 60 patients (mean [SD] age, 43.2 [15.3] years; 8 female individuals [13%] and 52 male individuals [87%]) were included. The study was feasible, and patient retention and acceptability were high. Creatine kinase was significantly lower in the LLLT group (mean [SD], 163.7 [160.0] U/L) 48 hours after admission in relation to the comparator (412.4 [441.3] U/L) (P = .03). Mean (SD) pain intensity (2.9 [2.7] vs 5.0 [2.4]; P = .004), circumference measurement ratio (6.6% [6.6%] vs 17.1% [11.6%]; P < .001), and edema extent (25.8 [15.0] vs 40.1 [22.7] cm; P = .002) were significantly lower in the LLLT group in relation to the comparator. No difference was observed between the groups regarding the mean difference between the bite site temperature and the contralateral limb. Secondary infections, necrosis, disability outcomes, and the frequency of need for analgesics were similar in both groups. No adverse event was observed. Conclusions and Relevance: The data from this randomized clinical trial suggest that the use of LLLT was feasible and safe in a hospital setting and effective in reducing muscle damage and the local inflammatory process caused by B atrox envenomations. Trial Registration: Brazilian Registry of Clinical Trials Identifier: RBR-4qw4vf.

Validation of low anterior resection syndrome score in Brazil with Portuguese.

PURPOSE: This study was performed to investigate the convergent validity, discriminative validity, and reliability of the Brazilian version of the low anterior resection syndrome (LARS) score in a population with low educational and socioeconomic levels. METHODS: The LARS score was translated into the Portuguese language by forward- and back-translation procedures. In total, 127 patients from a public hospital in Brazil completed the questionnaires. The convergent validity was tested by comparing the LARS score with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core Module 30 (QLQ-C30) and with patients' self-reported quality of life. For the discriminative validity, we tested the ability of the score to differentiate among subgroups of patients regarding neoadjuvant radiotherapy, type of surgery, and tumor distance from the anal verge. The test-retest reliability was investigated in a subgroup of 36 patients who responded to the survey twice in 2 weeks. RESULTS: The LARS score demonstrated a strong correlation with 5 of 6 items from the EORTC QLQ-C30 (P<0.05) and good concordance with patients' self-reported quality of life (95.3%), confirming the convergent validity. The score was able to discriminate between subgroups of patients with different clinical characteristics related to LARS (P<0.001). The agreement between the test and retest showed that 86.1% of the patients remained in the same LARS category, and there was no significant difference between the LARS score numerical values (P=0.80), indicating good reliability overall. CONCLUSION: The Brazilian version of the LARS score is a valid and reliable instrument to assess postoperative bowel function in a population with low educational and socioeconomic levels.

Genetic Modulation of HPV Infection and Cervical Lesions: Role of Oxidative Stress-Related Genes.

Human papillomavirus (HPV) infection is a necessary but not sufficient factor for the development of invasive cervical cancer (ICC) and high-grade intraepithelial lesion (HSIL). Oxidative stress is known to play a crucial role in HPV infection and carcinogenesis. In this study, we comprehensively investigate the modulation of HPV infection, HSIL and ICC, and ICC through an exploration of oxidative stress-related genes: CßS, MTHFR, NOS3, ACE1, CYBA, HAP, ACP1, GSTT1, GSTM1, and CYP1A1. Notably, the ACE1 gene emerges as a prominent factor with the presence of the I allele offering protection against HPV infection. The association of NOS3 with HPV infection is perceived with the 4a allele showing a protective effect. The presence of the GSTT1 null mutant correlates with increased susceptibility to HPV infection, HSIL and ICC, and ICC. This study also uncovers intriguing epistatic interactions among some of the genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the BB genotype (ACP1) and DD genotype (ECA1) were shown to increase the risk of HPV infection, and the interaction between BB (ACP1) and 0.0 (GSTT1) was associated with HPV infection and cervical lesions. These findings underscore the pivotal role of four oxidative stress-related genes in HPV-associated cervical lesions and cancer development, enriching our clinical understanding of the genetic influences on disease manifestation. The awareness of these genetic variations holds potential clinical implications.

Staphylococcus argenteus Infections, Brazil.

In 2015, two new species related to the Staphylococcus aureus were proposed. We describe five isolates of the new species Staphylococcus argenteus cultured from human cases of bacteremia and skin and soft tissue infections. This is the first report of S. argenteus, from South America, causing community-acquired and nosocomial infections.

A surveillance program for long-term central venous access-associated infections in outpatient chemotherapy services.

OBJECTIVE: In this study, we described the first results of a surveillance system for infections associated with long-term central venous catheters (LT-CVC) in patients under outpatient chemotherapy. DESIGN: This was a multicentric, prospective study. SETTING: Outpatient chemotherapy services. PARTICIPANTS: The study included 8 referral cancer centers in the State of São Paulo. INTERVENTION: These services were invited to participate in a newly created surveillance program for patients under chemotherapy. Several meetings were convened to share previous experiences on LT-CVC infection surveillance and to define the surveillance method. Once the program was implemented, all bloodstream infection (LT-CVC BSIs), tunnel infection, and exit-site infections associated with LT-CVC were reported. Data from January to May 2021 were analyzed. The median monthly number of chemotherapy sessions per clinic was 925 (IQR, 270-5,855). We used Poisson regression to analyze the association of rates with the characteristics of the services. RESULTS: In total, 107 LT-CVC infections were reported, of which 95% were BSIs, mostly associated with totally implantable devices (76%). Infections occurred a median of 4 days after the last catheter manipulation and 116 after the LT-CVC insertion. Also, 102 microorganisms were isolated from LT-CVC BSIs; the most common pathogen was Staphylococcus epidermidis, at 22%. Moreover, 44 infections (44%) fulfilled the criteria for CVC-related LT-CVC BSI and 27 infections (27%) met the criteria for mucosal barrier injury. The 1-year cumulative LT-CVC BSI rate was 1.94 per 1,000 CVC days of use. The rates were higher in public hospitals (IRR, 6.00; P < .001) and in hospitals that already had in place surveillance for LT-CVC infections (IRR, 2.01; P < .01). CONCLUSION: Our study describes an applicable surveillance method for infections in cancer outpatients using LT-CVC.