Sex and gender differences in cognitive resilience to aging and Alzheimer's disease.

Sex and gender-biological and social constructs-significantly impact the prevalence of protective and risk factors, influencing the burden of Alzheimer's disease (AD; amyloid beta and tau) and other pathologies (e.g., cerebrovascular disease) which ultimately shape cognitive trajectories. Understanding the interplay of these factors is central to understanding resilience and resistance mechanisms explaining maintained cognitive function and reduced pathology accumulation in aging and AD. In this narrative review, the ADDRESS! Special Interest Group (Alzheimer's Association) adopted a multidisciplinary approach to provide the foundations and recommendations for future research into sex- and gender-specific drivers of resilience, including a sex/gender-oriented review of risk factors, genetics, AD and non-AD pathologies, brain structure and function, and animal research. We urge the field to adopt a sex/gender-aware approach to resilience to advance our understanding of the intricate interplay of biological and social determinants and consider sex/gender-specific resilience throughout disease stages. HIGHLIGHTS: Sex differences in resilience to cognitive decline vary by age and cognitive status. Initial evidence supports sex-specific distinctions in brain pathology. Findings suggest sex differences in the impact of pathology on cognition. There is a sex-specific change in resilience in the transition to clinical stages. Gender and sex factors warrant study: modifiable, immune, inflammatory, and vascular.

Global rural health disparities in Alzheimer's disease and related dementias: State of the science.

INTRODUCTION: Individuals living in rural communities are at heightened risk for Alzheimer's disease and related dementias (ADRD), which parallels other persistent place-based health disparities. Identifying multiple potentially modifiable risk factors specific to rural areas that contribute to ADRD is an essential first step in understanding the complex interplay between various barriers and facilitators. METHODS: An interdisciplinary, international group of ADRD researchers convened to address the overarching question of: "What can be done to begin minimizing the rural health disparities that contribute uniquely to ADRD?" In this state of the science appraisal, we explore what is known about the biological, behavioral, sociocultural, and environmental influences on ADRD disparities in rural settings. RESULTS: A range of individual, interpersonal, and community factors were identified, including strengths of rural residents in facilitating healthy aging lifestyle interventions. DISCUSSION: A location dynamics model and ADRD-focused future directions are offered for guiding rural practitioners, researchers, and policymakers in mitigating rural disparities. HIGHLIGHTS: Rural residents face heightened Alzheimer's disease and related dementia (ADRD) risks and burdens due to health disparities. Defining the unique rural barriers and facilitators to cognitive health yields insight. The strengths and resilience of rural residents can mitigate ADRD-related challenges. A novel "location dynamics" model guides assessment of rural-specific ADRD issues.

Extracellular and cellular Hsp72 differ as biomarkers in acute exercise/environmental stress and recovery.

Stress-inducible Hsp72 is a potential biomarker to track risk of exertional heat illness during exercise/environmental stress. Characterization of extracellular (eHsp72) vs cellular Hsp72 (iHsp72) responses is required to define the appropriate use of Hsp72 as a reliable biomarker. In each of four repeat visits, participants (n = 6 men, 4 trials; total n = 24): (a) passively dehydrated overnight, (b) exercised (2 h) with no fluid in a hot, humid environmental chamber, (c) rested and rehydrated (1 h), (d) maximally exercised for 0.5 h, and (e) returned after 24 h of at-home recovery and rehydration. We measured rectal temperature, hydration status (% body mass loss, urine markers, serum osmolality), and Hsp72 (ELISA, flow cytometry. eHsp72 (circulating) and iHsp72 (CD3+ PBMCs) correlated (P < 0.05) with markers of heat, exercise, and dehydration stresses. eHsp72 immediately post-exercise (>15% above baseline, P < 0.05) decreased back to baseline levels by 1 h post-exercise, but iHsp72 expression continued to rise and remained elevated 24 h post-exercise (~2.5-fold baseline, P < 0.05). These data suggest that in addition to the classic physiological biomarkers of exercise heat stress, using cellular Hsp72 as an indicator of lasting effects of stress into recovery may be most appropriate for determining long-term effects of stress on risk for exertional heat illness.

Standardized delivery room management for neonates with a prenatal diagnosis of congenital heart disease: A model for improving interdisciplinary delivery room care.

Precise characterization of cardiac anatomy and physiology through fetal echocardiography can predict early postnatal clinical course. Some neonates with prenatally defined critical congenital heart disease have anticipated precipitous compromise during perinatal transition for which specialized, diagnosis-specific delivery room care can be arranged to expeditiously stabilize cardiopulmonary hemodynamics. In this article, we describe our institutional approach to the delivery room care of neonates with prenatally diagnosed congenital heart disease, emphasizing our diagnosis-specific care pathways for newborns with critical disease.

Urease activity in the crystalline state.

Crystalline Klebsiella aerogenes urease was found to have less than 0.05% of the activity observed for the soluble enzyme under standard assay conditions. Li2SO4, present in the crystal storage buffer at 2 M concentration, was shown to inhibit soluble urease by a mixed inhibition mechanism (Ki's of 0.38 +/- 0.05 M for the free enzyme and 0.13 +/- 0.02 M for the enzyme-urea complex). However, the activity of crystals was less than 0.5% of the expected value, suggesting that salt inhibition does not account for the near absence of crystalline activity. Dissolution of crystals resulted in approximately 43% recovery of the soluble enzyme activity, demonstrating that protein denaturation during crystal growth does not cause the dramatic diminishment in the catalytic rate. Finally, crushed crystals exhibited only a three-fold increase in activity over that of intact crystals, indicating that the rate of substrate diffusion into the crystals does not significantly limit the enzyme activity. We conclude that urease is effectively inactive in this crystal form, possibly due to conformational restrictions associated with a lid covering the active site, and propose that the small amounts of activity observed arise from limited enzyme activity at the crystal surfaces or trace levels of enzyme dissolution into the crystal storage buffer.

Neonatal intracranial hemorrhage in premature infants.

Since the advent of modern methods of neonatal care, intracranial hemorrhage in premature infants, which is usually intraventricular, is probably not as uniformly fatal as generally admitted and the survivors are likely to develop post-hemorrhagic hydrocephalus. This paper is a retrospective study of 11 premature babies born between 1968 and 1972 and diagnosed as having hydrocephalus secondary to neonatal intracranial hemorrhage. Nine of these are still alive and two have died, one at 3 and one at 17 months of age. Eight underwent permanant surgical drainage of hydrocephalus. The perinatal history, laboratory data, clinical evolution, and neurological outcome were studied. Two groups of infants were identified; those with signs of acute neurological deterioration in the neonatal period who had the most severe neurological sequellae (in four cases, periventricular lesions in addition to hydrocephalus were seen on the air study and in one case confirmed at autopsy) and those showing no obvious neurological signs in the neonatal period. Of this latter group, two appear to be developing normally. The therapeutic implications of the findings are discussed.

Outcome of infants of very low birthweight treated in neonatal intensive care unit.

The neonatal survival rate of 500 VLBW (less than or equal to 1 500 g) treated in the neonatal unit of the Departement of Paediatrics in Lausanne (C.H.U.V.) was studied according to changing patterns of nursing and medical care occurring in four successive periods (1961 IX-1963, X-1963 - 1965, 1966-1968, IV-1971-1973). The survival rate at 28 days increased from 35.5% to 47.7% between 1961 and 1965. Earlier start of feeding, intravenous fluid therapy, better control of ambient temperature and better oxygenotherapy are the main changes during this period. Further improvement in neonatal care did not affect the 28-day survival rate. 213 VLBW out of 500 (42.6%) survived at 28 days, 13 (6.1%) out of these died within the first two years of life, 36 (16.9%) were lost for the follow-up. The remaining 164 VLBW were followed until ages between 18 months and 8 years. The improvement in neonatal care was associated with a decrease in the incidence of major neurological sequels from 21.1% to 12.2% between 1961 and 1973. Cerebral palsy and epilepsy are responsible for this decrease. The incidence of mental retardation (DQ or IQ less than 80) also decreased from 17.5% to 4.9% during the same period. However, the incidence of retrolental fibroplasia remained stable. The outlook for VLBW infants is now much more encouraging. Further improvement in perinatal care is likely to further reduce the incidence of major handicaps. but it is not clear whether they will affect the incidence of minor problems such as learning difficulties or poor school performances. More prospective studies are necessary to clarify these points and to ensure early detection of these developmental problems.

[Opening of an emergency center in the University Hospital Center of Vaud]. / Ouverture d'un centre des urgences au C.H.U.V.

Previously decentralised, non-programmed attendances, followed or not by hospitalisation (emergency admissions) at the C.H.U.V. were seen in 7 different sectors. In the context of the opening of a new hospital building for the C.H.U.V., emergencies were concentrated in a new common area known as the "Emergency Centre". The article describes the organisation of this new sector as well as its activity during the first year of its working (7 months). The centre received approximately 1800 patients per month, 51% examined and treated in the department of surgery, 28% by the department of internal medicine, the rest being under the primary responsibility of services of otorhinolaryngology, paediatrics and paediatric surgery and dermatology. Description of the sector includes some maps to demonstrate the architectural concept and its use in case of mass casualties.

Autographa californica M nucleopolyhedrovirus chiA is required for processing of V-CATH.

Infection of permissive insect hosts by the baculovirus Autographa californica M nucleopolyhedrovirus results in liquefaction, a pathogenic effect that enhances the dispersal of progeny virions. Two viral gene products-a protease, V-CATH, and a chitinase, chiA-have been shown to be required for liquefaction to occur. It has been generally accepted that the primary functions of these proteins is to degrade the proteinaceous and chitinous components of the host cadaver, respectively. We have generated suggestive evidence, however, that chiA may also serve as a molecular chaperone for proV-CATH, the precursor of V-CATH. When cells were infected with virus lacking a functional chiA gene, proV-CATH failed to undergo processing in vivo and in vitro and formed insoluble aggregates in the endoplasmic reticulum of infected cells. Thus, expression of chiA may be required for the proper folding of the nascent V-CATH polypeptide in the endoplasmic reticulum. Identical results were obtained when tunicamycin was used to block N-linked glycosylation in cells infected with wildtype virus, suggesting that the putative chiA/V-CATH interaction is mediated by N-linked oligosaccharides.