Synthesis, biological evaluation and molecular modeling studies of novel 1,2,3-triazole-linked menadione-furan derivatives as P2X7 inhibitors.

The P2X7 receptor (P2X7R) is an ion channel that promotes the passage of ions through the membrane through brief stimulation once activated by ATP, its endogenous opener. However, prolonged stimulation with ATP, which occurs in pathological processes, opens a nonselective pore in the plasma membrane, allowing the passage of large molecules and leading to cytokine release or even cell death. In this sense, the search for new inhibitors for this receptor has attracted a great deal of attention in recent years. Considering the booming of biomass upgrading reactions in recent years and the continued efforts to synthesize biologically active molecules containing the 1,2,3-triazole ring, in the present work, we aimed to investigate whether triazole-linked menadione-furan derivatives could present P2X7R inhibitory activity. The novel compounds were tested for their inhibitory activity on ATP-induced dye uptake in peritoneal macrophages. Some have shown promising results, having displayed IC50 values lower than that of the P2X7R inhibitor BBG. Molecular docking studies also indicated that the active compounds bind to an allosteric site on P2X7R, presenting potential P2X7R inhibition.

Treatment compliance and risk and protective factors for suicide ideation to completed suicide in adolescents: a systematic review

Objective: To review the literature regarding adolescent suicide risk and explore the associations between treatment compliance (expressed as a concept including measured adherence to treatment and/or mental health service utilization) and risk and protective factors for suicidal behavior (SB), as well as the association between treatment compliance and reattempts. Methods: PubMed, LILACS, and Google Scholar were searched using the following terms: (adolescent*) AND (suicide*) AND (risk factor OR protective factors) AND (treatment compliance OR treatment attrition OR treatment adherence OR treatment drop out OR treatment retention OR mental health utilization). We retrieved studies that focused on the relation of treatment compliance to risk and protective factors for SB and that had only adolescent samples. Results: Of 4,841 articles, 30 original articles were selected for review. Most studies indicated high mental health service (MHS) utilization and poor treatment adherence by SB patients. Social minority status and conduct disorder were associated with less treatment adherence, while female sex, parental perceived need for treatment, and major depression were associated with greater treatment adherence. Inpatient and intensive emergency care after SA and family interventions improved MHS utilization and treatment compliance. However, we found no substantial protective effect of treatment compliance against reattempts. Conclusion: Effective treatment planning for compliance requires considering psychopathology, treatment planning, and social, familial, and individual factors.

Multidimensional assessment of women after severe maternal morbidity: the COMMAG cohort study.

OBJECTIVES: To perform a multidimensional assessment of women who experienced severe maternal morbidity (SMM) and its short-term and medium-term impact on the lives and health of women and their children. DESIGN: A retrospective cohort study. SETTING: A tertiary maternity hospital from the southeast region of Brazil. PARTICIPANTS: The exposed population was selected from intensive care unit admissions if presenting any diagnostic criteria for SMM. Controls were randomly selected among women without SMM admitted to the same maternity and same time of childbirth. PRIMARY AND SECONDARY OUTCOME VARIABLES: Validated tools were applied, addressing post-traumatic stress disorder (PTSD) and quality of life (SF-36) by phone, and then general and reproductive health, functioning (WHO Disability Assessment Schedule), sexual function (Female Sexual Function Index (FSFI)), substance abuse (Alcohol, Smoking and Substance Involvement Screening Test 2.0) and growth/development (Denver Developmental Screening Test) of children born in the index pregnancy in a face-to-face interview. RESULTS: All instruments were applied to 638 women (315 had SMM; 323 were controls, with the assessment of 264 and 307 children, respectively). SF-36 score was significantly lower in the SMM group, while PTSD score was similar between groups. Women who had SMM became more frequently sterile, had more abnormal clinical conditions after the index pregnancy and a higher score for altered functioning, while proportions of FSFI score or any drug use were similar between groups. Furthermore, children from the SMM group were more likely to have weight (threefold) and height (1.5 fold) for age deficits and also impaired development (1.5-fold). CONCLUSION: SMM impairs some aspects of the lives of women and their children. The focus should be directed towards monitoring these women and their children after birth, ensuring accessibility to health services and reducing short-term and medium-term repercussions on physical, reproductive and psychosocial health.

Post-Traumatic Stress Disorder and severe maternal morbidity: is there an association?

OBJECTIVE: To evaluate the occurrence of Post-Traumatic Stress Disorder among women experiencing a severe maternal morbidity event and associated factors in comparison with those without maternal morbidity. METHODS: In a retrospective cohort study, 803 women with or without severe maternal morbidity were evaluated at 6 months to 5 years postpartum for the presence of Post-Traumatic Stress Disorder. Interviews were conducted by telephone and electronic data was stored. Data analysis was carried out by using χ2, Fisher's Exact test, and logistic regression analysis. RESULTS: There was no significant change in the prevalence of Post-Traumatic Stress Disorder related to a previous severe maternal morbidity experience. There were also no differences in diagnostic criteria for severe maternal morbidity (hypertensive syndromes, hemorrhage, surgical intervention or intensive care unit admission required, among other management criteria). Low parity (2.5-fold risk) and increasing age were factors associated with Post-Traumatic Stress Disorder. CONCLUSIONS: A severe maternal morbidity episode is not associated with Post-Traumatic Stress Disorder symptoms within five years of the severe maternal morbidity event and birth. However, a more advanced maternal age and primiparity increased the risk of Post-Traumatic Stress Disorder. This does not imply that women who had experienced a severe maternal morbidity event did not suffer or need differentiated care.

Neonatal Near Miss: the need for a standard definition and appropriate criteria and the rationale for a prospective surveillance system

In Latin American, there is currently a regional action with the main purposes of putting the concept of severe neonatal morbidity in practice and formulating proposals for interventions. A general overview of neonatal health conditions, including morbidity and mortality, is provided to update regional knowledge on the topic. An example of the development and implementation of the concept of maternal near miss is also provided, followed by results from a systematic review covering all previously published studies on Neonatal Near Miss. Finally, some proposals for building a common concept on the topic and for launching a prospective surveillance study are presented. A Neonatal Near Miss is a neonate who had a severe morbidity (organ dysfunction or failure) but who survived this condition within the first 27 days of life. The pragmatic criteria recommended to be used are as follows: birth weight below 1700 g, Apgar score below 7 at 5 minutes of life and gestational age below 33 weeks. As a proxy for organ dysfunction, the following management criteria are also confirmed: parenteral therapeutic antibiotics; nasal continuous positive airway pressure; any intubation during the first 27 days of life; phototherapy within the first 24 h of life; cardiopulmonary resuscitation; the use of vasoactive drugs, anticonvulsants, surfactants, blood products and steroids for refractory hypoglycemia and any surgical procedure. Although this study starts from a regional perspective, this topic is clearly globally relevant. All nations, especially low and middle-income countries, could benefit from the proposed standardization.