Voice Disorder, Job Stress, and COVID-19 in Teachers: Impacts in Times of Pandemic

Introduction: The conditions of teachers' work during the COVID-19 pandemic affected teachers' lives regarding voice disorder and stress, even in emergency remote classroom situation. Objective: To analyze the relationship between the presence of voice disorder, job stress, and COVID-19 in teachers when in emergency remote classroom teaching situation at the time of the pandemic. Method: This is a primary, exploratory, observational cross-sectional study with the use of survey forwarded online during the period of emergency classes after the arrival of COVID-19 pandemic in Brazil. The teachers answered the sociodemographic questions about the presence of COVID-19 and the following instruments: Condition of Vocal Production-Teacher [Condição de Produção Vocal - Professor (CPV-P)], Screening Index for Voice Disorder (SIVD), and Job Stress Scale (JSS). Results: Of the 118 teachers analyzed, 94.1% were female; the average age was 44 years. The SIVD recorded the presence of voice disorder in 66.9% of the participants. Regarding the JSS, which are the findings related to stress at work in the demand domain, the teachers showed high levels, a fact which presupposes the existence of pressure of psychological nature to perform their work. Conclusion: The teachers self-reported the presence of voice disorder even in remote class situation, on the occasion of COVID-19, which were more common in older teachers. When comparing the presence of voice disorders, coronavirus symptoms, and stress domains in relation to demand, control, and social support, there was no significance. It is hoped that this study will help to reflect on the need to improve teachers' working conditions, strengthening work-related voice disorder actions and guiding actions for vocal care and well-being.

Introducción: Las condiciones de trabajo de los profesores durante la pandemia de COVID-19 afectaron sus vidas en lo que respecta al trastorno de la voz y el estrés, incluso en situaciones de emergencia en aulas remotas. Objetivo: Analizar la relación entre la presencia de trastorno de la voz, estrés laboral y COVID-19 en profesores cuando se encontraban en situación de emergencia de enseñanza en aulas remotas en la época de la pandemia. Método: Se trata de un estudio primario, exploratorio, observacional de tipo transversal, con el uso de encuesta remitida online durante el periodo de clases de emergencia tras la llegada de la pandemia de COVID-19 en Brasil. Los profesores respondieron a las preguntas sociodemográficas sobre la presencia de COVID-19 y a los siguientes instrumentos: Condición de Producción Vocal-Profesor (CPV-P), Índice de Detección de los Trastornos de la Voz (SIVD) y Escala de Estrés Laboral (JSS). Resultados: De los 118 profesores analizados, el 94,1% eran mujeres; la mediana de edad era de 44 años. El (SIVD) registró la presencia de trastorno de la voz en el 66,9% de los participantes. En cuanto a la JSS, que son los hallazgos relacionados con el estrés laboral en el dominio de la demanda, los profesores mostraron niveles elevados, hecho que presupone la existencia de presiones de naturaleza psicológica para realizar su trabajo. Conclusión: Los profesores autoinformaron de la presencia de trastornos de la voz incluso en situación de clase a distancia, con ocasión del COVID-19, que fueron más frecuentes en los profesores de más edad. Al comparar la presencia de trastornos de la voz, los síntomas del coronavirus y los dominios de estrés en relación con la demanda, el control y el apoyo social, no hubo resultados significativos. Se espera que este estudio ayude a reflexionar sobre la necesidad de mejorar las condiciones de trabajo de los docentes, fortaleciendo las acciones de Trastorno de la voz relacionado con el trabajo (WRVD) y orientando acciones para el cuidado y bienestar vocal.

Ajuste fino de un modelo de producción vocal para estimar el estrés de impacto utilizando un método metaheurístico

Introducción: En modelos de producción vocal que emplean estructuras de resorte-masa-amortiguador, la precisión en la determinación de coeficientes de amortiguamiento que se asemejen a las características fisiológicas de las cuerdas vocales es crucial, teniendo en cuenta posibles variaciones en la representación de la viscoelasticidad. Objetivo: Este estudio tiene como objetivo realizar un ajuste paramétrico de un modelo de producción vocal basado en un sistema de resorte-masa-amortiguador que incorpora interacción con la presión subglótica, con el fin de modelar de manera precisa las fuerzas de colisión ejercidas por las cuerdas vocales durante la fonación. Método: Se utilizó un algoritmo de búsqueda metaheurística para la síntesis paramétrica. El algoritmo se aplicó a los coeficientes de elasticidad c1 y c2, así como a los coeficientes de amortiguamiento ε1 y ε2, que se correlacionan directamente con las matrices de masa del modelo. Esto facilita el ajuste de la composición de las cuerdas para lograr un comportamiento fisiológico deseado. Resultados: El comportamiento del sistema vocal para cada ciclo de simulación se comparó con un estándar predefinido en condiciones normales. El algoritmo determinó el punto final de la simulación evaluando las discrepancias entre características clave de las señales obtenidas y las deseadas. Conclusión: El ajuste paramétrico permitió la aproximación del comportamiento fisiológico de la producción vocal, proporcionando estimaciones de las fuerzas de impacto experimentadas por las cuerdas vocales durante la fonación.

Introduction: In vocal production models employing spring-mass-damper frameworks, precision in determining damping coefficients that align with physiological vocal fold characteristics is crucial, accounting for potential variations in the representation of viscosity-elasticity properties. Objective: This study aims to conduct a parametric fitting of a vocal production model based on a mass-spring-damper system incorporating subglottic pressure interaction, with the purpose of accurately modeling the collision forces exerted by vocal folds during phonation. Method: A metaheuristic search algorithm was employed for parametric synthesis. The algorithm was applied to elasticity coefficients c1 and c2, as well as damping coefficients ε1 and ε2, which directly correlate with the mass matrices of the model. This facilitates the adjustment of fold composition to achieve desired physiological behavior. Results: The vocal system's behavior for each simulation cycle was compared to a predefined standard under normal conditions. The algorithm determined the simulation endpoint by evaluating discrepancies between key features of the obtained signals and the desired ones. Conclusion: Parametric fitting enabled the approximation of physiological vocal production behavior, providing estimates of the impact forces experienced by vocal folds during phonation.

Effects of glyphosate herbicide ingestion on kidney function in rats on a balanced diet / Efeitos da ingestão do herbicida glifosato na função renal de ratos em uma dieta balanceada

Abstract Introduction: Glyphosate is the most widely used herbicide worldwide and in Brazil. There is currently increasing concern about the effects of glyphosate on human health. The Brazilian Institute for Consumer Protection showed data on the presence of glyphosate in some of Brazil's most consumed ultra-processed products. Currently, regulations on the upper limit for these residues in ultra-processed foods have yet to be established by the National Health Surveillance, and ultra-processed food consumption is independently associated with an increased risk of incident chronic kidney disease. Methods: Since an unbalanced diet can interfere with kidney function, this study aims to investigate the effect of daily intake of 5 mg/kg bw glyphosate in conjunction with a balanced diet and the possible impact on renal function in rats. Kidney function, kidney weight, markers of renal injury, and oxidative stress were evaluated. Results: There was a decrease in kidney weight. The main histopathological alterations in renal tissues were vacuolation in the initial stage and upregulation of the kidney injury marker KIM-1. Renal injury is associated with increased production of reactive oxygen species in mitochondria. Conclusion: This study showed changes in the kidney of rats exposed to a balanced diet with glyphosate, suggesting a potential risk to human kidney. Presumably, ultra-processed food that contain glyphosate can potentiate this risk. The relevance of these results lies in drawing attention to the need to regulate glyphosate concentration in ultra-processed foods in the future.

RESUMO Introdução: O glifosato é o herbicida mais utilizado no mundo e no Brasil. Atualmente, há uma preocupação crescente com os efeitos do glifosato na saúde humana. O Instituto Brasileiro de Defesa do Consumidor apresentou dados sobre a presença de glifosato em alguns dos produtos ultraprocessados mais consumidos no Brasil. Atualmente, as regulamentações sobre o limite máximo desses resíduos em alimentos ultraprocessados ainda não foram estabelecidas pela Vigilância Sanitária Nacional, e o consumo de alimentos ultraprocessados está indepen­dentemente associado a um risco maior de doença renal crônica incidente. Métodos: Como uma dieta desbalanceada pode interferir na função renal, este estudo tem como objetivo investigar o efeito da ingestão diária de 5 mg/kg pc de glifosato em conjunto com uma dieta equilibrada e o possível impacto na função renal em ratos. Foram avaliados função renal, peso dos rins, marcadores de lesão renal e estresse oxidativo. Resultados: Houve redução no peso dos rins. As principais alterações histopatológicas nos tecidos renais foram vacuolização no estágio inicial e regulação positiva do marcador de lesão renal KIM-1. A lesão renal está associada à produção aumentada de espécies reativas de oxigênio nas mitocôndrias. Conclusão: Esse estudo mostrou alterações nos rins de ratos expostos a uma dieta balanceada com glifosato, sugerindo um risco potencial ao rim humano. Presumivelmente, alimentos ultraprocessados que contenham glifosato podem potencializar esse risco. A relevância desses resultados está no fato de chamar a atenção para a necessidade de regulamentar a concentração de glifosato em alimentos ultraprocessados no futuro.

Effects of garlic (Allium sativum L) and Citrullus colocynthis (L.) Schrad individually and in combination on male reproductive damage due to diabetes: suppression of the AGEs/RAGE/Nox-4 signaling pathway.

BACKGROUND: Diabetes Mellitus is associated with disturbances in male reproductive function and fertility. Studies have shown that oxidative stress with the subsequent inflammation and apoptosis cause these complications in diabetes. Garlic (G) (Allium sativum L) and Citrullus colocynthis (L.) Schrad (C) both have antidiabetic and antioxidant properties. Recently, we demonstrated their synergistic effects in alleviating reproductive complications when administered concomitantly. However, as even medicinal plants in long term usage may lead to some unwanted side effects of their own, we examined whether with half the original doses of these two medicinal plants we could achieve the desired results. METHODS: Thirty-five male Wistar rats were divided into five groups (n = 7/group): Control, Diabetic, Diabetic + G (0.5 ml/100 g BW), Diabetic + C (5 mg/kg BW) and Diabetic + GC (0.5 ml/100 g BW of garlic and 5 mg/kg BW of C. colocynthis) groups. The experimental period was 30 days. RESULTS: Oxidative stress, advanced glycation end products (AGEs), immunoexpression of caspase-3, and expression of mRNAs for receptor for advanced glycation end products (RAGE), NADPH oxidase-4 (NOX-4) and nuclear factor kappa B increased in testis of diabetic rats. Treatment with garlic and C. colocynthis alone showed some beneficial effects, but in the combination form the effectiveness was more profound. CONCLUSIONS: We conclude that the combination therapy of diabetic rats with lower doses is still as efficient as higher doses; therefore, the way forward for reducing complications in long term consumption.

Pyrroloquinoline quinone promotes human mesenchymal stem cell-derived mitochondria to improve premature ovarian insufficiency in mice through the SIRT1/ATM/p53 pathway.

BACKGROUND: DNA damage and oxidative stress induced by chemotherapy are important factors in the onset of premature ovarian insufficiency (POI). Studies have shown that mitochondria derived from mesenchymal stem cells (MSC-Mito) are beneficial for age-related diseases, but their efficacy alone is limited. Pyrroloquinoline quinone (PQQ) is a potent antioxidant with significant antiaging and fertility enhancement effects. This study aimed to investigate the therapeutic effect of MSC-Mito in combination with PQQ on POI and the underlying mechanisms involved. METHODS: A POI animal model was established in C57BL/6J mice by cyclophosphamide and busulfan. The effects of MSC-Mito and PQQ administration on the estrous cycle, ovarian pathological damage, sex hormone secretion, and oxidative stress in mice were evaluated using methods such as vaginal smears and ELISAs. Western blotting and immunohistochemistry were used to assess the expression of SIRT1, PGC-1α, and ATM/p53 pathway proteins in ovarian tissues. A cell model was constructed using KGN cells treated with phosphoramide mustard to investigate DNA damage and apoptosis through comet assays and flow cytometry. SIRT1 siRNA was transfected into KGN cells to further explore the role of the SIRT1/ATM/p53 pathway in combination therapy with MSC-Mito and PQQ for POI. RESULTS: The combined treatment of MSC-Mito and PQQ significantly restored ovarian function and antioxidant capacity in mice with POI. This treatment also reduced the loss of follicles at various stages, improving the disrupted estrous cycle. In vitro experiments demonstrated that PQQ facilitated the proliferation of MitoTracker-labelled MSC-Mito, synergistically restoring mitochondrial function and inhibiting oxidative stress in combination with MSC-Mito. Both in vivo and in vitro, the combination of MSC-Mito and PQQ increased mitochondrial biogenesis mediated by SIRT1 and PGC-1α while inhibiting the activation of ATM and p53, consequently reducing DNA damage-mediated cell apoptosis. Furthermore, pretreatment of KGN cells with SIRT1 siRNA reversed nearly all the aforementioned changes induced by the combined treatment. CONCLUSIONS: Our research findings indicate that PQQ facilitates MSC-Mito proliferation and, in combination with MSC-Mito, ameliorates chemotherapy-induced POI through the SIRT1/ATM/p53 signaling pathway.

Targeting Fatty Acid Desaturase I Inhibits Renal Cancer Growth Via ATF3-mediated ER Stress Response.

Monounsaturated fatty acids (MUFAs) play a pivotal role in maintaining endoplasmic reticulum (ER) homeostasis, an emerging hallmark of cancer. However, the role of polyunsaturated fatty acid (PUFAs) desaturation in persistent ER stress driven by oncogenic abnormalities remains elusive. Fatty Acid Desaturase 1 (FADS1) is a rate-limiting enzyme controlling the bioproduction of long-chain PUFAs. Our previous research has demonstrated the significant role of FADS1 in cancer survival, especially in kidney cancers. We explored the underlying mechanism in this study. We found that pharmacological inhibition or knockdown of the expression of FADS1 effectively inhibits renal cancer cell proliferation and induces cell cycle arrest. The stable knockdown of FADS1 also significantly inhibits tumor formation in vivo. Mechanistically, we show that while FADS1 inhibition induces ER stress, its expression is also augmented by ER-stress inducers. Notably, FADS1-inhibition sensitized cellular response to ER stress inducers, providing evidence of FADS1's role in modulating the ER stress response in cancer cells. We show that, while FADS1 inhibition-induced ER stress leads to activation of ATF3, ATF3-knockdown rescues the FADS1 inhibition-induced ER stress and cell growth suppression. In addition, FADS1 inhibition results in the impaired biosynthesis of nucleotides and decreases the level of UPD-N-Acetylglucosamine, a critical mediator of the unfolded protein response. Our findings suggest that PUFA desaturation is crucial for rescuing cancer cells from persistent ER stress, supporting FADS1 as a new therapeutic target.

Surfactant protein-D, diabetes mellitus, oxidative stress, infections and inflammation on the crossroad: A Systematic review.

Objective: To review the association of surfactant protein-D with type 2 diabetes mellitus, infections, oxidative stress and inflammation, and the changes in oxidative stress markers in type 2 diabetes mellitus. METHODS: The systematic review was conducted from April to September 2022, and comprised search on PubMed, Web of Sciences, Scopus, Science Direct and Google Scholar databases for relevant studies published in English language between January 1, 2000, and June 30, 2022. The search was updated in September 2022. After transferring literature to Mendeley, relevant data was extracted from the included studies. Quality assessment for eligible studies was done using Joanna Briggs Institute Critical Appraisal Checklist. Quality of evidences was assessed by using Grading of Recommendations Assessment, Development and Evaluation tool. RESULTS: Of the 203 studies identified, 18(8.9%) were analysed; 16(89%) with humans and 2(11%) with animals as subjects There were 5 (31.25%) studies for SP-D, of which 4 (80%) studies reported lower surfactant protein-D in type 2 diabetes mellitus cases than controls. Its significant negative association with glycated haemoglobin was reported by 1(20%) study and 2(40%) studies with fasting blood glucose levels. Higher surfactant protein-D in type 2 diabetes mellitus cases and its positive association with glycated haemoglobin was reported by 1(20%) study. Recurrent infections were frequent in type 2 diabetes mellitus patients. Malondialdehyde level was higher and superoxide dismutase activity was lower in type 2 diabetes mellitus cases, reflecting oxidative stress. Animal studies also showed that reactive oxygen species generating from hypochlorous acid during oxidative stress promoted the formation of non-disulfide linkages in surfactant protein-D structure, resulting in its decreased functionality. Conclusion: Surfactant protein-D, oxidative stress, inflammation and infections were found to be linked to each other for pathogenesis of infections in type 2 diabetes mellitus.

Maternal Migration, Prenatal Stress and Child Autistic Traits: Insights From a Population-Based Cohort Study.

OBJECTIVE: There is emerging evidence for an increased prevalence of autism in children of mothers with a migration background. To date, the mechanisms underlying this relationship are poorly understood. We investigated whether prenatal stress exposure mediates the association between maternal migration and child autistic traits, assessing first- and second-generation migrant mothers in the Netherlands and their children. METHOD: The study was embedded in the prospective population-based Generation R cohort. Of the 4,727 participants, 1,773 mothers (38%) had a migration background. Prenatal stress was assessed using questionnaires related to stressful life events, family functioning, self-esteem, long-lasting difficulties, symptoms of psychopathology, social support, and perceived discrimination. Autistic traits were measured at age 6 years with the parent-reported Social Responsiveness Scale exclusively. Longitudinal multiple mediation analyses were performed. Analyses were stratified by migration origin (Europe and outside Europe) because of differences in migration characteristics. RESULTS: Maternal migration background was associated with more experienced stress and with higher child autistic trait scores (Europe: mean = 0.42, SD = 0.25; outside Europe: mean = 0.50, SD = 0.24) compared to no migration background (Netherlands: mean = 0.38, SD = 0.23; both p < .01). Prenatal stress, especially perceived discrimination and maternal psychopathology, accounted for up to half of the total effect of maternal migration, which remained after adjusting for sociodemographic factors (Bindirect = 0.035, 95% CI = 0.027, 0.043, Btotal = 0.074). CONCLUSION: Stress during pregnancy mediated the association between maternal migration status and child autistic traits. Future research should focus on early interventions to assess whether reducing prenatal stress exposure among women with a migration background can result in lower offspring autistic traits. DIVERSITY & INCLUSION STATEMENT: We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Prenatal maternal negative life events associated with child emotional and behavioral problems in the French EDEN cohort.

INTRODUCTION: Prenatal negative life events (NLEs) have been linked to adverse health outcomes in children. However, few studies examine this relationship during late childhood using trajectory analyses. Additionally, the impact of specific NLEs domains on child development remains unclear. This study aims to longitudinally explore the association between NLEs (cumulative score and specific NLEs domains) and child outcomes from birth to late childhood. METHODS: 1135 mother-child pairs from the French EDEN cohort were followed from 24 to 28 weeks of pregnancy up to 11 years of age. Maternal self-reports of prenatal NLEs were collected immediately after birth, then analyzed as a cumulative score and by NLEs domain. Children's emotional and behavioral symptoms were assessed at 4 timepoints through the Strengths and Difficulties Questionnaire. RESULTS: Children of mothers exposed to ≥3 NLEs were more likely to follow trajectories of high levels of peer relationship problems (aOR [95 % CI] = 5.69 [1.74-18.69]), emotional symptoms (aOR [95 % CI] = 3.05 [1.08-8.63]), and conduct problems (aOR [95 %] = 3.53 [1.20-10.42]). Among the domains of NLEs, only events related to housing, finance, and living conditions were significantly associated with high emotional and behavioral difficulties trajectories (aOR [95%CI] = 2.71[1.26-5.81]). LIMITATIONS: Potential attrition bias due to a higher dropout rate for children experiencing early indications of emotional and behavioral difficulties. CONCLUSION: Findings support the relationship between prenatal NLEs and child outcomes, underscoring the importance of assessing prenatal stressors across life domains to identify mothers who might be in need of support.

Potential role of Citrus bergamia flower essential oil against oral pathogens.

BACKGROUND: Oral bacterial infections are difficult to treat due to emergence of resistance against antibiotic therapy. Essential oils are considered emerging alternate therapy against bacterial infections and biofilms. We investigated Citrus bergemia flower essential oil against oral pathogens. METHODS: The essential oil was analsyed using Gas Chromatography(GC-MS), in silico investigations, antioxidant, antimicrobial, antibiofilm and antiquorum sensing assays. RESULTS: Gas Chromatography analysis confirmed presence of 17 compounds including 1,6-Octadien-3-ol,3,7-dimethyl, 48.17%), l-limonene (22.03%) and p-menth-1-ol, 8-ol (7.31%) as major components. In silico analysis showed compliance of all tested major components with Lipinski's rule, Bioavailability and antimicrobial activity using PASS (prediction of activity spectrum of substances). Molecular docking with transcriptional regulators 3QP5, 5OE3, 4B2O and 3Q3D revealed strong interaction of all tested compounds except 1,6-Octadien-3-ol,3,7-dimethyl. All tested compounds presented significant inhibition of DPPH (2,2-diphenyl-1-picrylhydrazyl) (IC50 0.65 mg/mL), H2O2 (hydrogen peroxide) (63.5%) and high FRAP (ferrous reducing antioxidant power) value (239.01 µg). In antimicrobial screening a significant activity (MIC 0.125 mg/mL) against Bacillus paramycoides and Bacillus chungangensis was observed. Likewise a strong antibiofilm (52.1 - 69.5%) and anti-QS (quorum sensing) (4-16 mm) activity was recorded in a dose dependent manner. CONCLUSION: It was therefore concluded that C. bergemia essential oil posess strong antioxidant, antimicrobial and antibiofilm activities against tested oral pathogens.

Stress responses in surgical trainees during simulation-based training courses in laparoscopy.

BACKGROUND: Simulation-based training courses in laparoscopy have become a fundamental part of surgical training programs. Surgical skills in laparoscopy are challenging to master, and training in these skills induces stress responses in trainees. There is limited data on trainees' stress levels, the stress responses related to training on different laparoscopic simulators, and how previous experiences influence trainees' stress response during a course. This study investigates physiologic, endocrine and self-reported stress responses during simulation-based surgical skills training in a course setting. METHODS: We conducted a prospective observational study of trainees attending basic laparoscopic skills training courses at a national training centre. During the three-day course, participants trained on different laparoscopic simulators: Two box-trainers (the D-box and P.O.P. trainer) and a virtual reality simulator (LAPMentor™). Participants' stress responses were examined through heart rate variability (HRV), saliva cortisol, and the State Trait Anxiety Inventory-6 (STAI-6). The correlation between previous laparoscopic experiences and stress response measurements was explored. RESULTS: Twenty-four surgical trainees were included in the study. Compared to resting conditions, stress measures were significantly higher during simulation-training activity (the D-box (SDNN = 58.5 ± 23.4; LF/HF-ratio = 4.58 ± 2.71; STAI-6 = 12.3 ± 3.9, P < 0.05), the P.O.P trainer (SDNN = 55.7 ± 7.4; RMSSD = 32.4 ± 17.1; STAI-6 = 12.1 ± 3.9, P < 0.05), and the LAPMentor™ (SDNN = 59.1 ± 18.5; RMSSD = 34.3 ± 19.7; LF/HF-ratio = 4.71 ± 2.64; STAI-6 = 9.9 ± 3.0, P < 0.05)). A significant difference in endocrine stress response was seen for the simulation-training activity on the D-box (saliva cortisol: 3.48 ± 1.92, P < 0.05), however, no significant differences were observed between the three simulators. A moderate correlation between surgical experience, and physiologic and endocrine stress response was observed (RMSSD: r=-0.31; SDNN: r=-0.42; SD2/SD1 ratio: r = 0.29; Saliva cortisol: r = 0.46; P < 0.05), and a negative moderate correlation to self-reported stress (r=-0.42, P < 0.05). CONCLUSION: Trainees have a significant higher stress response during simulation-training compared to resting conditions, with no difference in stress response between the simulators. Significantly higher cortisol levels were observed on the D-box, indicating that simulation tasks with time pressure stress participants the most. Trainees with more surgical experience are associated with higher physiologic stress measures, but lower self-reported stress scores, demonstrating that surgical experience influences trainees' stress response during simulation-based skills training courses.

TXNIP knockdown protects rats against bupivacaine-induced spinal neurotoxicity via the inhibition of oxidative stress and apoptosis.

Bupivacaine (BUP) is an anesthetic commonly used in clinical practice that when used for spinal anesthesia, might exert neurotoxic effects. Thioredoxin-interacting protein (TXNIP) is a member of the α-arrestin protein superfamily that binds covalently to thioredoxin (TRX) to inhibit its function, leading to increased oxidative stress and activation of apoptosis. The role of TXNIP in BUP-induced oxidative stress and apoptosis remains to be elucidated. In this context, the present study aimed to explore the effects of TXNIP knockdown on BUP-induced oxidative stress and apoptosis in the spinal cord of rats and in PC12 cells through the transfection of adeno-associated virus-TXNIP short hairpin RNA (AAV-TXNIP shRNA) and siRNA-TXNIP, respectively. In vivo, a rat model of spinal neurotoxicity was established by intrathecally injecting rats with BUP. The BUP + TXNIP shRNA and the BUP + Control shRNA groups of rats were injected with an AAV carrying the TXNIP shRNA and the Control shRNA, respectively, into the subarachnoid space four weeks prior to BUP treatment. The Basso, Beattie & Bresnahan (BBB) locomotor rating score, % MPE of TFL, H&E staining, and Nissl staining analyses were conducted. In vitro, 0.8 mM BUP was determined by CCK-8 assay to establish a cytotoxicity model in PC12 cells. Transfection with siRNA-TXNIP was carried out to suppress TXNIP expression prior to exposing PC12 cells to BUP. The results revealed that BUP effectively induced neurological behavioral dysfunction and neuronal damage and death in the spinal cord of the rats. Similarly, BUP triggered cytotoxicity and apoptosis in PC12 cells. In addition, treated with BUP both in vitro and in vivo exhibited upregulated TXNIP expression and increased oxidative stress and apoptosis. Interestingly, TXNIP knockdown in the spinal cord of rats through transfection of AAV-TXNIP shRNA exerted a protective effect against BUP-induced spinal neurotoxicity by ameliorating behavioral and histological outcomes and promoting the survival of spinal cord neurons. Similarly, transfection with siRNA-TXNIP mitigated BUP-induced cytotoxicity in PC12 cells. In addition, TXNIP knockdown mitigated the upregulation of ROS, MDA, Bax, and cleaved caspase-3 and restored the downregulation of GSH, SOD, CAT, GPX4, and Bcl2 induced upon BUP exposure. These findings suggested that TXNIP knockdown protected against BUP-induced spinal neurotoxicity by suppressing oxidative stress and apoptosis. In summary, TXNIP could be a central signaling hub that positively regulates oxidative stress and apoptosis during neuronal damage, which renders TXNIP a promising target for treatment strategies against BUP-induced spinal neurotoxicity.

Development of a stability indicating high-performance liquid chromatography method for determination of cenobamate: study of basic degradation kinetics.

This study presents a stability indicating high-performance liquid chromatography HPLC method for the determination of cenobamate (CNB) in presence of its main impurity (CNB H-impurity) and degradation products. The chromatographic separation was carried out on a Thermo BDS Hypersil-C18 column (150 × 4.6 mm; 5 µm) with a mobile phase consisting of a 50:50 (%v/v) ratio of methanol and purified water. The flow rate was maintained at 1.0 mL. min- 1. CNB was detected at 210 nm using a PDA detector. The column temperature was held at 40 °C.The retention time of the drug was found to be 3.2 min. Furthermore, the study investigates the degradation behavior of CNB under various stress conditions, including acidic, basic, oxidative, and light-induced degradation. The results indicate that CNB is particularly susceptible to basic degradation. Consequently, a comprehensive study of the basic degradation kinetics was conducted. The method was also successfully applied for the determination of CNB in its dosage form. The results also show that there is no co-elution from degradation products or excipients as indicated by the mass balance and peak purity values confirming the specificity of the proposed method and its applicability for routine analysis of CNB.

Embryo growth alteration and oxidative stress responses in germinating Cucurbita pepo seeds exposed to cadmium and copper toxicity.

This study investigated the influence of cadmium (Cd) and copper (Cu) heavy metals on germination, metabolism, and growth of zucchini seedlings (Cucurbita pepo L.). Zucchini seeds were subjected to two concentrations (100 and 200 µM) of CdCl2 and CuCl2. Germination parameters, biochemical and phytochemical attributes of embryonic axes were assessed. Results revealed that germination rate remained unaffected by heavy metals (Cd, Cu). However, seed vigor index (SVI) notably decreased under Cd and Cu exposure. Embryonic axis length and dry weight exhibited significant reductions, with variations depending on the type of metal used. Malondialdehyde and H2O2 content, as well as catalase activity, did not show a significant increase at the tested Cd and Cu concentrations. Superoxide dismutase activity decreased in embryonic axis tissues. Glutathione S-transferase activity significantly rose with 200 µM CdCl2, while glutathione content declined with increasing Cd and Cu concentrations. Total phenol content and antioxidant activity increased at 200 µM CuCl2. In conclusion, Cd and Cu heavy metals impede zucchini seed germination efficiency and trigger metabolic shifts in embryonic tissue cells. Response to metal stress is metal-specific and concentration-dependent. These findings contribute to understanding the intricate interactions between heavy metals and plant physiology, aiding strategies for mitigating their detrimental effects on plants.

Structure elucidation and antiviral activity of a cold water-extracted mannogalactofucan Ts1-1A from Trametes sanguinea against human cytomegalovirus in vitro.

In this study, we purified a partially acetylated heteropolysaccharide (Ts1-1A) from the fruit bodies of Trametes sanguinea Lloyd through cold water extraction and serial chromatographic separation. The purified polysaccharide Ts1-1A (12.8 kDa) was characterized as a branched mannogalactofucan with a backbone of alternately connected 1,3-linked α-Fucp and 1,6-linked α-Galp, which was partially substituted by non-reducing end units of ß-Manp at O-2 and O-3 positions of 1,6-linked α-Galp. Ts1-1A showed pronounced anti-human cytomegalovirus activity at the concentration of 200 and 500 µg/mL in systematical assessments including morphological changes, western blotting, qPCR, indirect immunofluorescence and tissue culture infective dose assays. Moreover, Ts1-1A exerted its antiviral activity at two distinct stages of viral proliferation manifesting as significantly inhibiting viral protein (IE1/2 and p52) expression and reducing viral gene (UL123, UL44 and UL32) replication in the HCMV-infected WI-38 cells. At viral attachment stage, Ts1-1A interacted with HCMV and prevented HCMV from attaching to its host cells. While at early phase of viral replication stage, Ts1-1A suppressed HCMV replication by downregulating NQO1 and HO-1 proteins related to oxidative stress as an antioxidant. To sum up, Ts1-1A is a promising anti-HCMV agent which could be developed for HCMV infection prevention and therapy.

Prolonged exposure treatment for post-traumatic stress disorder: Single case studies in a sample of adults with mild intellectual disabilities.

BACKGROUND: Post-traumatic stress disorder (PTSD) is common in adults with intellectual disabilities. Often there are additional disorders such as substance use, mood and anxiety disorders. The current study focuses on the feasibility and initial efficacy of prolonged exposure (PE) for PTSD in adults with mild intellectual disabilities. The secondary effect of PE on additional mood, anxiety and substance use disorders is also examined. METHODS: A single case experimental design (N = 12) with an A (baseline)-B (intervention) phase including a follow-up measurement after 3 months was conducted. Time series and single time points measurements were performed. RESULTS: Six participants dropped-out. The results showed a significant decrease in PTSD symptoms and a significant decrease in additional symptoms (social avoidance, anxiety and stress), among participants who completed treatment. CONCLUSION: PE appears to be a feasible and effective treatment for PTSD in some adults with mild intellectual disabilities. Suggestions emerge from this study to make standard PE treatment more appropriate for adults with mild intellectual disabilities. Further research is needed to reduce drop-out in trauma treatment. Some suggestions for this are made in this study. Treatment of PTSD with PE did not appear to affect comorbid mood disorders. Further research is needed.

Epidemiology of Stress Fracture in Police Trainees.

BACKGROUND: Military recruits and athletes have high occurrence of stress fractures, with very high incidence among military recruits. Symptomatic stress fractures can be disabling in some people. This study aims at identifying pattern and distribution of such fractures in Nepal Police trainee and assess the risk factors and demographics that may help to develop the local guidelines. METHODS: This study analysed 65 police trainees who presented to the orthopaedic Out Patient Department at Nepal Police and Province Police Hospital diagnosed as a case of stress fracture from 29 December, 2020 to 29 December, 2021. Ethical approval was obtained and different variables analysed were age, sex, Body Mass Index, location of fracture, duration of pain, method of treatment, time to heal the fracture and time to pain free mobilisation of patient. RESULTS: There were 65 trainees with 86 sites of fracture at different bones with 50.8% (33) of male population. The majority of fracture was located at tibia (58.1%) followed by pubic rami (33.7%) with potentially debilitating fracture neck of femur seen in 4.6% subjects. Mean duration of pain was 20.7±14.2 days with mean time for pain free mobilisation 42.2±17.7 days after presentation. 96.5% of those recovered with conservative treatment (activity restriction or cast). CONCLUSIONS: The location of stress fracture depends upon the type of training or activities. Modification of activities in early phase of training with early visit for medical care in case of trainees with increasing pain may decrease morbidities and complications requiring operative treatment.

Role of CRH in colitis and colitis-associated cancer: a combinative result of central and peripheral effects?

Corticotropin-releasing factor family peptides (CRF peptides) comprise corticotropin releasing hormone (CRH), urocortin (UCN1), UCN2 and UCN3. CRH is first isolated in the brain and later with UCNs found in many peripheral cells/tissues including the colon. CRH and UCNs function via the two types of receptors, CRF1 and CRF2, with CRH mainly acting on CRF1, UCN1 on both CRF1 &CRF2 and UCN2-3 on CRF2. Compiling evidence shows that CRH participates in inflammation and cancers via both indirect central effects related to stress response and direct peripheral influence. CRH, as a stress-response mediator, plays a significant central role in promoting the development of colitis involving colon motility, immunity and gut flora, while a few anti-colitis results of central CRH are also reported. Moreover, CRH is found to directly influence the motility and immune/inflammatory cells in the colon. Likewise, CRH is believed to be greatly related to tumorigenesis of many kinds of cancers including colon cancer via the central action during chronic stress while the peripheral effects on colitis-associated-colon cancer (CAC) are also proved. We and others observe that CRH/CRF1 plays a significant peripheral role in the development of colitis and CAC in that CRF1 deficiency dramatically suppresses the colon inflammation and CAC. However, up to date, there still exist not many relevant experimental data on this topic, and there seems to be no absolute clearcut between the central and direct peripheral effects of CRH in colitis and colon cancer. Taken together, CRH, as a critical factor in stress and immunity, may participate in colitis and CAC as a centrally active molecule; meanwhile, CRH has direct peripheral effects regulating the development of colitis and CAC, both of which will be summarized in this review.

Biological validation of faecal corticosterone metabolites as a non-invasive stress assessment in translocated California valley quail (Callipepla californica).

US quail species are vulnerable to population declines as a result of climate change, habitat loss and habitat fragmentation, all of which can result in physiological stress. Additionally, population restoration techniques (PRTs), like translocations, also induce stress. Traditional assessments of avian stress hormone levels include capturing and handling birds to extract blood, methods that are inherently stressful and can compound stress analyses. However, the stress hormone corticosterone (CORT) is metabolized from the blood and excreted in faeces as faecal corticosterone metabolites (FCMs). FCMs have been used as a non-invasive measurement of stress hormone levels in a variety of species, but must be validated for each species. The objective of this study was to biologically validate the use of FCMs as a non-invasive measurement of CORT levels in California valley quail (Callipepla californica). Reference and treatment quail were acclimated for 3 weeks in an outdoor aviary. Subsequently, treatment quail were subjected to a simulated 48-h translocation, a common and stress hormone-inducing PRT. Faecal samples were collected every 4 h and processed using an enzyme immunoassay. Mean FCM concentrations of treatment quail (41.50 ± 16.13 ng/g) were higher than reference FCM concentrations (24.07 ± 10.4 ng/g). These results biologically validate the use of FCMs as a non-invasive method to assess CORT levels in California valley quail, demonstrate diurnal variation in quail CORT levels, and confirm that quail translocations are a stress-inducing PRT. Ultimately, this research validates a new non-invasive tool for stress response measurement to advance quail research, management and conservation.

Protective effects of Embelin in Benzo[α]pyrene induced cognitive and memory impairment in experimental model of mice.

Alzheimer's disease (AD) is a neurodegenerative disease that affects the neurons in the hippocampus, resulting in cognitive and memory impairment. The most prominent clinical characteristics of AD are the production of amyloid-beta (Aß) plaques, neurofibrillary tangles, and neuroinflammation in neurons. It has been proven that embelin (Emb) possesses antioxidant, anti-inflammatory, and neuroprotective properties. Therefore, we assessed the therapeutic potential of Emb in Benzo [α]pyrene (BaP)-induced cognitive impairment in experimental mice. BaP (5 mg/kg, i. p) was given to mice daily for 28 days, and Emb (2.5, 5, and 10 mg/kg, i. p) was given from 14 to 28 days of a protocol. In addition, locomotor activity was evaluated using open-field and spatial working, and non-spatial memory was evaluated using novel object recognition tasks (NORT), Morris water maze (MWM), and Y- maze. At the end of the study, the animal tissue homogenate was used to check biochemicals, neuroinflammation, and neurotransmitter changes. BaP-treated mice showed a significant decline in locomotor activity, learning and memory deficits and augmented oxidative stress (lipid peroxidation, nitrite, and GSH). Further, BaP promoted the release of inflammatory tissue markers, decreased acetylcholine, dopamine, GABA, serotonin, and norepinephrine, and increased glutamate concentration. However, treatment with Emb at dose-dependently prevented biochemical changes, improved antioxidant levels, reduced neuroinflammation, restored neurotransmitter concentration, and inhibited the NF-κB pathway. The current study's finding suggested that Emb improved cognitive functions through antioxidant, anti-inflammatory, and neuroprotective mechanisms and inhibition of acetylcholinesterase (AChE) enzyme activities and Aß-42 accumulation.