Fundamental Clock of Biological Aging: Convergence of Molecular, Neurodegenerative, Cognitive and Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology

In humans, age-associated degrading changes, widely observed in molecular and cellular processes underly the time-dependent decline in spatial navigation, time perception, cognitive and psychological abilities, and memory. Cross-talk of biological, cognitive, and psychological clocks provides an integrative contribution to healthy and advanced aging. At the molecular level, genome, proteome, and lipidome instability are widely recognized as the primary causal factors in aging. We narrow attention to the roles of protein aging linked to prevalent amino acids chirality, enzymatic and spontaneous (non-enzymatic) post-translational modifications (PTMs SP), and non-equilibrium phase transitions. The homochirality of protein synthesis, resulting in the steady-state non-equilibrium condition of protein structure, makes them prone to multiple types of enzymatic and spontaneous PTMs, including racemization and isomerization. Spontaneous racemization leads to the loss of the balanced prevalent chirality. Advanced biological aging related to irreversible PTMs SP has been associated with the nontrivial interplay between somatic (molecular aging) and mental (psychological aging) health conditions. Through stress response systems (SRS), the environmental and psychological stressors contribute to the age-associated “collapse” of protein homochirality. The role of prevalent protein chirality and entropy of protein folding in biological aging is mainly overlooked. In a more generalized context, the time-dependent shift from enzymatic to the non-enzymatic transformation of biochirality might represent an important and yet underappreciated hallmark of aging. We provide the experimental arguments in support of the racemization theory of aging

Ampicillin Resistance and Outcome Differences in Acute Antepartum Pyelonephritis

Objective. To measure the incidence of ampicillin-resistant uropathogens in acute antepartum pyelonephritis and to determine if patients with resistant organisms had different clinical outcomes. Study design. This was a secondary analysis of a prospective cohort study of pregnant women admitted with pyelonephritis, diagnosed by standard clinical and laboratory criteria. All patients received ampicillin and gentamicin. Results. We identified 440 cases of acute pyelonephritis. Seventy-two percent (316 cases) had urine cultures with identification of organism and antibiotic sensitivities. Fifty-one percent of uropathogens were ampicillin resistant. The patients with ampicillin-resistant organisms were more likely to be older and multiparous. There were no significant differences in hospital course (length of stay, days of antibiotics, ECU admission, or readmission). Patients with ampicillin-resistant organisms did not have higher complication rates (anemia, renal dysfunction, respiratory insufficiency, or preterm birth). Conclusion. A majority of uropathogens were ampicillin resistant, but no differences in outcomes were observed in these patients

Mortalidade neonatal no Município de São Paulo: influência do peso ao nascer e de fatores sócio-demográficos e assistenciais Neonatal mortality: socio-economic, health services risk factors and birth weight in the City of São Paulo

INTRODUÇÃO: A mortalidade neonatal no Município de São Paulo, apesar da sua tendência decrescente, constitui em um importante problema para a saúde pública. Os principais fatores de risco podem ser agrupados em quatro categorias básicas de variáveis: características do recém-nascido, características maternas, condições socioeconômicas e características dos serviços de saúde. O peso ao nascer e a prematuridade constituem fatores dominantes, compondo complexas redes de articulação com os demais. METODOLOGIA: Este é um estudo caso-controle, com base em dados vinculados do SIM e SINASC no Município de São Paulo, no primeiro semestre de 1995. Foi utilizada análise hierárquica, considerando quatro blocos de variáveis (características socioeconômicas, do recém-nascido, maternas e serviços de saúde) para o conjunto de recém-nascidos e para três grupos de peso ao nascer: <1.500g, 1.500- 2.499g e 2.500g e mais. RESULTADOS: No modelo final para o conjunto de recém-nascidos mostraram associação com óbito neonatal, a idade materna inferior a de 20 anos, nascer em hospital vinculado ao SUS, peso ao nascer <2.500g e prematuridade. Os três grupos de peso ao nascer exibiram perfis distintos de fatores de risco. Os RN <1.500g tiveram menor mortalidade quando nasceram em hospital universitário e por cesárea. Nos RN de 1.500-2.499g a mortalidade estava associada a prematuridade, sexo masculino e mãe grande multípara. No grupo com peso acima de 2.500g, os fatores de risco para mortalidade foram a prematuridade, mãe adolescente, morar em área com qualidade de vida precária e nascer por cesárea e em hospital vinculado ao SUS. CONCLUSÃO: Esse estudo, além de apontar a enorme influência do peso ao nascer sobre a mortalidade neonatal, no MSP, demonstrou que as diferentes categorias de peso apresentam vulnerabilidades biológicas e sociais distintas, que constituem articulações complexas, e que os serviços de saúde têm um importante papel a desempenhar em cada uma delas.<br>BACKGROUND: Although neonatal mortality has been declining in the City of São Paulo, it still is an important public health problem. Four basic categories constitute risk factors: newborn characteristics, maternal characteristics, socio-economic conditions and quality of health care. Low birth weight and prematurity are the dominant factors and constitute a complex network with other factors. METHODS: A case-control study was carried out based on linked birth and death certificates of the City of São Paulo for the first semester of 1995. The study performed a hierarchical analysis, considering four blocks of variables (characteristics of the new-born; mothers, health care and socio-economic status) for all birth-weight groups together and separately for three birth-weight groups: <1,500g, 1,500-2,499g and >2,500g. RESULTS: The final model for all newborns together showed statistical significant association for mothers under 20 years of age, being born in a SUS hospital, birth weight <2,500g and prematurity. The three birth weight groups showed distinctive patterns of risk factors. Those <1,500g had lower mortality when born in a university hospital and caesarean section. The 1,500-2,499g group had increased risk for mortality with prematurity, male sex and high parity of mother. In the more than 2,500g group, risk factors for mortality were prematurity, adolescent mother, living in an area with low quality of life, being born in a SUS hospital and caesarean section. CONCLUSION: This study, while pointing out the enormous influence of low birth weight on neonatal mortality in São Paulo, demonstrated that different birth weight categories have distinct biological and social vulnerabilities with complex links, and that health services have an important role to play for each of them