Unraveling Prostaglandin and NLRP3 Inflammasomemediated Pathways of Primary Dysmenorrhea and the Role of Mefenamic Acid and Its Combinations

Painful menstrual cramps during or around the time of the monthly cycle are known as dysmenorrhea. The estimated global prevalence in women of reproductive age ranges from 45% to 95%. It has a significant negative impact on regular activities and productivity at work. However, despite the severe consequences on quality of life, primary dysmenorrhea (PD) is underdiagnosed. Dysmenorrhea has complex pathogenesis. It involves the release of prostaglandins and activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and also includes the involvement of other mediators such as bradykinin, histamine and acetylcholine. Even though nonsteroidal anti-inflammatory drugs (NSAIDs) remain the most common type of pain medication, the question of which one should be the most preferred is still open to debate. The current review examines the existing evidence for the pathogenesis of PD and makes evidence based and clinical experience based recommendations for the use of mefenamic acid and its combination in the treatment of dysmenorrhea. Mefenamic acid alleviates PD by inhibiting endometrial prostaglandin formation, restoring normal uterine activity, and reducing the inflammatory response by inhibiting the NLRP3 inflammasome and reducing the release of cytokines such as interleukin (IL)-1?. It is also known to have bradykinin antagonist activity. Dicyclomine has a dual action of blocking the muscarinic action of acetylcholine in postganglionic parasympathetic effect or regions and acting directly on uterine smooth muscle by blocking bradykinin and histamine receptors to relieve spasms. According to the experts, mefenamic acid and dicyclomine act synergistically by acting on the different pathways of dysmenorrhea by blocking multifactorial agents attributed to the cause of dysmenorrhea. Hence, the combination of mefenamic acid and dicyclomine should be the preferred treatment option for dysmenorrhea.

Novel epitope based peptides for vaccine against SARS-CoV-2 virus: immunoinformatics with docking approach

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative viral strain for the contagious pandemic respiratory illness in humans which is a public health emergency of international concern. There is a desperate need for vaccines and antiviral strategies to combat the rapid spread of SARS-CoV-2 infection.Methods: The present study based on computational methods has identified novel conserved cytotoxic T-lymphocyte epitopes as well as linear and discontinuous B-cell epitopes on the SARS-CoV-2 spike (S) protein. The predicted MHC class I and class II binding peptides were further checked for their antigenic scores, allergenicity, toxicity, digesting enzymes and mutation.Results: A total of fourteen linear B-cell epitopes where GQSKRVDFC displayed the highest antigenicity-score and sixteen highly antigenic 100% conserved T-cell epitopes including the most potential vaccine candidates MHC class-I peptide KIADYNYKL and MHC class-II peptide VVFLHVTYV were identified. Furthermore, the potential peptide QGFSALEPL with high antigenicity score attached to larger number of human leukocyte antigen alleles. Docking analyses of the allele HLA-B*5201 predicted to be immunogenic to several of the selected epitopes revealed that the peptides engaged in strong binding with the HLA-B*5201 allele.Conclusions: Collectively, this research provides novel candidates for epitope-based peptide vaccine design against SARS-CoV-2 infection.

Does Knee Arthroscopy for Treatment of Meniscal Damage with Osteoarthritis Delay Knee Replacement Compared to Physical Therapy Alone?

Background@#To determine patient factors that lead to treatment of meniscal tears with osteoarthritis (OA) with knee arthroscopy (KA) or physical therapy only (PT-only); and to assess differences in clinical outcomes including the time to knee arthroplasty. @*Methods@#Patients aged ≥ 45 years with OA at meniscal tear diagnosis were followed up from the date of surgery (KA) or first PT visit (PT-only) until partial/total knee replacement surgery, death, disenrollment, or end of study. Demographic and clinical characteristics were compared and used to derive propensity scores. A Cox proportional hazards model was used to estimate the risk of knee replacement surgery and greater healthcare utilization associated with KA vs. PT-only. @*Results@#Among 7,026 patients (KA, 69%; PT-only, 31%), 27% had partial or total knee replacement surgery during follow-up.PT-only patients were older and more likely to be women and had more comorbidities. After accounting for differences between groups, the cumulative incidence of knee replacement was modestly but significantly higher for those who received KA than those who underwent PT-only (hazard ratio, 1.30; 95% confidence interval, 1.17–1.44; p < 0.001), although there was no significant difference in health service utilization, narcotic medication dispenses, or knee injections after initiating treatment. @*Conclusions@#For patients with meniscal damage complicated by OA, those who underwent KA were 30% more likely to have partial or total knee replacement surgery at any given time than those who had PT alone.

Revelação diagnóstica em demência: dos desafios da decisão à busca de benefícios / Diagnostic disclosure in dementia: challenges decision to seeking benefits / Revelación del diagnóstico en demencia: desde los desafíos en la decisión a la búsqueda de beneficios

INTRODUÇÃO: A literatura aponta vantagens e desvantagens da revelação do diagnóstico de demência aos pacientes. Prejuízos envolvem riscos de impactos emocionais negativos e dificuldade de compreensão devido aos prejuízos cognitivos. Benefícios apontam maior colaboração nos tratamentos, melhor adaptação ao cotidiano com favorecimento de manejo de sintomas. OBJETIVO: Promover reflexão sobre revelação diagnóstica em demência buscando compreender os desafios de enfrentamento e benefícios da revelação. MÉTODO: Quali-quanti - 104 familiares cuidadores responderam questionário fechado e 5 participaram de entrevista para compreensão sobre vantagens da revelação. RESULTADOS E DISCUSSÃO: Há uma tendência a não reflexão ou planejamento sobre revelação. Visão protecionista, passividade, medo dos profissionais e familiares de causarem reações emocionais negativas no paciente favorecem decisão por omissão. O impacto emocional inicial do paciente perante o diagnóstico se alterou ao longo do tempo. O sofrimento pode favorecer elaboração e se a revelação diagnóstica for considerada como um processo contínuo, seus benefícios, como auxílio no manejo dos sintomas e maior adesão ao tratamento, podem ser alcançados. CONSIDERAÇÕES FINAIS: Campanhas que divulguem benefícios de tratamento e que reduzam visão derrotista da doença, bem como profissionais que abordem tema podem contribuir para que decisões familiares sejam mais planejadas e benefícios da revelação sejam atingidos.

INTRODUCTION: Literature presents the advantages and disadvantages of disclosing the dementia diagnosis to patients. Adverse consequences involve the risks of negative emotional impact and difficulty in understanding due to cognitive impairments. Also indicated is the greater compliance to treatment and better adaptation to daily life fostering the management of symptoms. OBJECTIVE: Promote reflection on diagnosis disclosure in dementia, seeking to understand the challenges of coping and the benefits of disclosure. METHODS: Qualitative and quantitative - 104 family caregivers answered a closed questionnaire and 5 of them were interviewed for understanding benefits of the disclosure. RESULTS AND DISCUSSION: There is a tendency to not think or plan out diagnosis disclosure. Protectiveness, passivity, and the fear that professionals and family might cause negative emotional reactions on the patient, favor omission. Patient's initial emotional impact when faced with diagnosis changed over time. Emotional distress may favor coping and if diagnosis disclosure is considered a continuous process, its benefits can be achieved. Examples are aid in managing symptoms and greater adherence to treatment. CONCLUSION: Campaigns to disseminate benefits of treatment and reduce the defeatist view of the disease, as well as professionals addressing this issue may favor family decisions to be more planned and also to achieve the benefits of disclosure.

INTRODUCCIÓN: La literatura evidencia ventajas y desventajas sobre la revelación del diagnóstico de demencia a los pacientes. Las consecuencias adversas implican riesgos de impacto emocional negativo y dificultad en la comprensión debido a deterioros cognitivos. No obstante, los beneficios implicarían una mayor colaboración en el tratamiento y mejor adaptación a la vida diaria con favorecimiento en el manejo de los síntomas. OBJETIVO: Promover la reflexión acerca de la revelación del diagnóstico de demencia, comprender los desafíos de afrontamiento y beneficios de la revelación. MÉTODO: Cualitativos y cuantitativos - 104 familias cuidadoras respondieron a un cuestionario cerrado y 5 fueron entrevistados para entender las ventajas de revelar el diagnóstico. RESULTADOS Y DISCUSIÓN: Existe una tendencia a no pensar o planear la revelación del diagnóstico. La visión proteccionista, la pasividad, miedo de los profesionales y familiares de provocar reacciones emocionales negativas al paciente, favorecen la omisión. El sufrimiento puede favorecer el afrontamiento y, si la divulgación diagnóstica se considera un proceso continuo, sus beneficios, como mejor manejo de los síntomas y mayor adherencia al tratamiento, pueden ser alcanzados. CONCLUSIÓN: Las campañas para difundir los beneficios del tratamiento y reducir la visión derrotista de la enfermedad, así como el abordaje de los profesionales pueden contribuir para que decisiones familiares sean más planificadas y los beneficios de revelar el diagnóstico sean alcanzados.

Avaliação do impacto da capacitação de manipuladores de alimentos no âmbito domiciliar / Evaluation the impact of training of food handlers in the home

O ambiente familiar tem sido apontado como importante local na cadeia de transmissão de toxinfecções alimentares. Este estudo teve como objetivo avaliar o impacto da capacitação de manipuladores de alimentos, do ponto de vista da higiene, no âmbito domiciliar. Para tanto foi realizada em 40 residências uma análise in loco, constante de dois momentos: uma análise anterior e uma posterior à capacitação do manipulador de alimentos. Na primeira análise, foram constatadas várias inadequações na manipulação dos alimentos, indicando riscos de contaminação dos mesmos. Com os dados obtidos na segunda análise, observou-se diferença significativa, após a capacitação desenvolvida, quanto aos aspectos da armazenagem dos produtos perecíveis e não perecíveis, bem como às condições gerais da cozinha. Comprovou-se, portanto, um bom aproveitamento da capacitação e boa aquisição do conhecimento sobre a higiene dos alimentos.

Efeitos antidiabéticos de plantas medicinais / Antidiabetic effects of the medicinal plants

Diabetes mellitus (DM) é uma doença metabólica crônica caracterizada por hipeglicemia que tem impacto significante em seus pacientes. Sua incidência está crescendo rapidamente conduzindo para aumento no custo dos cuidados da doença e de suas complicações. O tratamento envolve, além de controle dietético e atividade física, o uso de fármacos que ocasionam efeitos colaterais para atingir ações farmacológicas desejadas. Entretanto, produtos de plantas são, freqüentemente, considerados menos tóxicos e com menos efeitos colaterais que drogas sintéticas e amplamente utilizadas pela população. Nesse trabalho várias espécies de plantas utilizadas experimentalmente ou na medicina popular, agindo de diferentes formas de modo a controlar glicemia e/ou inibir sintomas e complicações características da diabetes serão revisadas para avaliação de seus supostos efeitos terapêuticos.

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemy that has a significant impact for their patients. Its incidence is raising leading to an increase in the cost of the cares of the disease and of its complications. The treatment involves, besides dietary control and physical activity, the use of drugs that cause side effects to reach wanted pharmacological actions. However, products of plants are, frequently, considered less poisonous and with fewer side effects than synthetic drugs and widely used by the population. In this paper, several species of plants, used experimentally or in the popular medicine, acting by different ways to control glycemia and/or to inhibit symptoms and characteristic complications of the diabetes, they will be reviewed for evaluation of their supposed therapeutic effects.

Diversidad mitooondrial en el nor-occidente de enezuela. implicaciones para prrobables rutas migratorias prehispániass / Mitochondrial diversity in Northwest Venezuela. Implications for probable prehispanic migratory routes.

La utilidad del ADN mitocondrial (ADNmt) para determinar afinidad genética entre grupos indígenas contemporáneos e inferir sobre migraciones, ha sido demostrada; pero la imposibilidad de estudiar grupos prehispánicos extintos, limita las inferencias sobre migraciones en esa época. El mestizaje en poblaciones neoamericanas ha sido caracterizado por uniones entre hombres europeos y mujeres indígenas, permitiendo detectar en la población contemporánea haplogrupos mitocondriales amerindios que informan sobre poblaciones extintas. Para conocer los linajes femeninos en el occidente de Venezuela, se estudiaron los haplogrupos del ADNmt a partir de RFLP, en una muestra de 193 individuos con antepasados procedentes del occidente de Venezuela, 81 del Estado Lara (Barquisimeto) y 112 de tres pueblos del Estado Falcón (Macu-quita=25, Macanillas=29 y Churuguara=58). Se comparó la distribución de haplogrupos entre las poblaciones y se estimó el mestizaje por línea femenina en ellas. Se comparó la distribución de cuatro haplogrupos indígenas con otras regiones de América. Se observa que en las cuatro poblaciones predominan haplogrupos amerindios, seguidos de los africanos. Al comparar la fracción indígena con el resto de América encontramos que Macanillas, Lara y Churuguara se asemejan a grupos de Amazonas y Suramérica, mientras que Macuquita a Aruba. Esto sugiere una diversidad genética importante en esa zona como probable ruta de paso hacia el sur y el Caribe; además refleja vínculos genéticos importantes entre grupos prehispánicos de Aruba y los de la Península de Paraguaná. Evidencias arqueológicas soportan estos postulados. Se recomienda aumentar la muestra y realizar análisis de secuencias para un nivel mayor de precisión.

Mitocondrial DNA (mtDNA) has been widely used to study genetic relationships between contemporary Amerindian groups and to infer ancestral migration movements; however inferences about migration routes of prehispanic extinct groups are difficult. Admixture of Neoamerican groups has been characterized by unions between European males and Amerindian females. This allows the identification in present populations of Amerindian mitocondrial haplogroups which give information on ancestral groups. In order to investigate female lineages present in western Venezuela, RFLP haplogroups from mtDNA were obtained from 193 individuals with grandparents from this region, 81 from the State of Lara (Barquisimeto) and 112 from 3 towns of the State of Falcon (Macuquita=25; Macanilla=29 and Churuguara=58). Comparison of haplogroup distributions between groups was performed, and admixture estimates based on female lineages were obtained. The distribution of four Amerindian haplogroups was compared with those of other populations from the American Continent. In our four samples Amerindian haplogroups predominate, followed by those of African origin. In the comparison of the mtDNA Amerindian fraction with other populations we find that Macanillas, Lara and Churuguara are similar to South American and Amazonian groups whilst Macuquita is similar to groups from Aruba. Our findings suggest an important genetic diversity in this region, explained by migration routes to and from the south and the Caribean. They also suggest genetic relationship between prehispanic groups from Aruba and those from the Paraguaná peninsula, which have been inferred by archeological evidences. An increase in sample size and analysis of sequences for more precision is recommended.