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.

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.

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.

Autographa californica M nucleopolyhedrovirus ProV-CATH is activated during infected cell death.

V-CATH, a cathepsin L-like cysteine protease encoded by the baculovirus Autographa californica M nucleopolyhedrovirus, has been shown to play an essential role in host liquefaction. Similar to cellular cathepsin L, V-CATH is synthesized as an inactive proenzyme and is activated by cleavage of the propeptide. Previous studies indicated that removal of the propeptide was rapid, occurring as soon as the protein could be detected by Western blot, 22 h postinfection. We found, however, that these results reflected artifactual processing of the proenzyme. When the protease inhibitor E-64 was used to prevent this aberration, we found that proV-CATH accumulated in infected cells and activation did not begin until the onset of cell death, at approximately 80 h postinfection. Western blot analysis of fractions of live and dead cells isolated by fluorescence-activated cell sorting revealed that mature V-CATH was found only in dead cells. The regulation of activation of proV-CATH, therefore, was quite different from that of cellular cathepsins. Acridine orange staining revealed that lysosome integrity was lost in dead cells, an occurrence that could lead to the activation of proV-CATH by lysosomal proteases.

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.

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.

Justification of hospital days and epidemiology of discharge delays in a department of neurology.

We have developed a protocol to identify unnecessary days of hospitalisation in the Department of Neurology of the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Seventy-four parameters (medical, social, type of investigation and treatment, degree of disability and of dependence) potentially associated with the length of stay were studied prospectively in 511 nonselected patients consecutively admitted to the Department over a period of 5 months. Each day spent on the wards was analyzed on a day-to-day basis and was classified into one of two groups: those due to a medical reason (4,700 hospital days), and those due to a nonmedical reason (1,184 days). These delays resulted chiefly from difficulties in obtaining laboratory investigations, especially in patients who were not disabled and who had been admitted for investigations (3.8% of hospital days, compared to 1.5% for patients with severe or total dependence) or from awaiting transfer to either another department or a nursing home. This second cause of delay markedly increased the length of stay of patients with severe or total dependence and with limited mobility on the first day (26.0 days, compared with 7.4 days for nondisabled patients) and, above all, on the last day spent in our Department (27.0 days, compared with 8.0 days). The ongoing analysis of these data may provide information as to which parameters could be influenced by neurologists in order to reduce the length of stay in hospital.

[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.

Changes in popliteal angle measurement in infants up to one year of age.

The purpose of this study was to determine trends in the changes of the popliteal angle in 130 normal infants between one day and 12 months of age, for use in assessing infants with possible neuromuscular pathology. Using a 360 degree goniometer, the popliteal angle was measured with the hip held at 90 degree flexion, to indicate hamstring-muscle tightness. Limitation of knee extension was also measured with the hip extended (HEKE angle) to indicate capsular tightness. Both the popliteal and HEKE angle measurements showed greatest limitation of knee extension at birth, which decreased until eight months of age, when most infants showed no limitation. A highly significant negative correlation was found between age and mean popliteal and HEKE angles.

[Cerebral distress in full-term newborns: method of early prognosis of the quality of long-term survival]. / Détresse cérébrale du nouveau-né à terme: méthode de pronostic précoce quant à la qualité de la survie à long terme.

A study on 122 full-term newborns with cerebral distress has given the basis for a mathematical model allowing to calculate the risk of poor evolution due to neurological disorders occurring in the first week of life. For each patient a score on his neurological status is established at 3 or 7 days of age. Only four essential neurological characteristics have to be considered: primary reflexes, convulsions, apathy or swallowing disorders, respiratory disorders. All possible score combinations are listed, and each of them is associated with a risk factor (in percent) for poor evolution. A long-term prognosis can therefore be obtained by simple clinical observation, making a score and consulting the list.

[Disorders of the mother-child relationship in newborn infants with low birth weight]. / Troubles de la relation mère-enfant chez les nouveau-nés de petits poids de naissance.

The influence of premature birth or intrauterine growth retardation (IUGR) on the mother-child relationship has been studied in 80 children with birth-weight below 2000 g, treated in the Neonatology Unit of the Pediatric Department of Lausanne University. 40 children with birth-weight over 2500 g and without perinatal complications born in the Obstetrical Department of the same hospital were used as controls. The 80 infants with low birth-weight presented only minor neonatal disturbances and showed later on a normal psychomotor development. The mother-child relationship was evaluated by free and structured interviews accompanied by a questionnaire and by regular contacts throughout the first 12 months. With the exception of the professional work of the mother during and after pregnancy, all the family and social factors were not significantly different in the 3 groups. The mothers of premature children showed significantly more disturbances of their family relationship than the mothers in the control group. On the other hand, a significantly higher number of attachment problems is the only difference observed in the group of mothers of IUGR-babies. There was no mathematical correlation between these problems and the characteristics of the family and social-economic environment of the mothers. The importance of subjective, i.e. psychological, factors as cause of difficulties in the mother-child relationship is stressed.

[Ethics problems in neonatal medicine]. / Problèmes d'éthique en médecine néonatale.

In view of the recent advances in reanimation of the newborn infant, parents, physicians and nursing staff have now to face the ethical dilemma of the quality of the surviving infant with severe brain damage which excludes a further normal development. The author discusses the situation of an infant with trisomy 21 and a total intestinal atresia: a surgical intervention leads to a living human being with a severe mental, and physical handicap; a non-intervention will let the newborn die even if he could be saved. The decision has to be made with the parents in agreement with the nursing staff, but without involving a policy making outside committee.