Cognitive Aging and the Primate Basal Forebrain Revisited: Disproportionate GABAergic Vulnerability Revealed.

Basal forebrain (BF) projections to the hippocampus and cortex are anatomically positioned to influence a broad range of cognitive capacities that are known to decline in normal aging, including executive function and memory. Although a long history of research on neurocognitive aging has focused on the role of the cholinergic basal forebrain system, intermingled GABAergic cells are numerically as prominent and well positioned to regulate the activity of their cortical projection targets, including the hippocampus and prefrontal cortex. The effects of aging on noncholinergic BF neurons in primates, however, are largely unknown. In this study, we conducted quantitative morphometric analyses in brains from young adult (6 females, 2 males) and aged (11 females, 5 males) rhesus monkeys (Macaca mulatta) that displayed significant impairment on standard tests that require the prefrontal cortex and hippocampus. Cholinergic (ChAT+) and GABAergic (GAD67+) neurons were quantified through the full rostrocaudal extent of the BF. Total BF immunopositive neuron number (ChAT+ plus GAD67+) was significantly lower in aged monkeys compared with young, largely because of fewer GAD67+ cells. Additionally, GAD67+ neuron volume was greater selectively in aged monkeys without cognitive impairment compared with young monkeys. These findings indicate that the GABAergic component of the primate BF is disproportionally vulnerable to aging, implying a loss of inhibitory drive to cortical circuitry. Moreover, adaptive reorganization of the GABAergic circuitry may contribute to successful neurocognitive outcomes.SIGNIFICANCE STATEMENT A long history of research has confirmed the role of the basal forebrain in cognitive aging. The majority of that work has focused on BF cholinergic neurons that innervate the cortical mantle. Codistributed BF GABAergic populations are also well positioned to influence cognitive function, yet little is known about this prominent neuronal population in the aged brain. In this unprecedented quantitative comparison of both cholinergic and GABAergic BF neurons in young and aged rhesus macaques, we found that neuron number is significantly reduced in the aged BF compared with young, and that this reduction is disproportionately because of a loss of GABAergic neurons. Together, our findings encourage a new perspective on the functional organization of the primate BF in neurocognitive aging.

Task-shifting and family planning continuation: contraceptive trajectories of women who received their method at a community-based event in Kinshasa, DRC.

While community-based interventions are a proven high-impact strategy to increase contraceptive uptake in low-income countries, their capacity to support women's contraceptive choices (including continued use, switching and discontinuation) in the long run remains insufficiently discussed. This cohort study follows 883 women 3 and 6 months after they received a modern method during community campaigns organized in Kinshasa (D.R. Congo), to analyze their contraceptive trajectories and the factors associated with ever discontinuing contraceptive use in the first 6 months following a campaign. In the community-based distribution (CBD) model currently institutionalized in DRC, campaign clients are not provided with additional doses or support, besides baseline counseling, to (dis-)continue using the method they received, but must rely on Family Planning resources within the existing local health system. Almost a third (28.9%) of all women discontinued modern contraception during the study period, with much higher discontinuation rates for short-acting methods (38.7% for pills and up to 68.9% for DMPA-SC). Variables previously associated with high discontinuation (marital status, fertility intentions and side-effects) led to higher odds of "ever discontinuing". However, these variables became non-significant when controlling for resupply issues. Women's self-reported reasons for discontinuation confirmed the multivariate regression results. Detailed sub-analysis of resupply issues for pills, injectables and Cyclebeads pointed to the role of cost, unreliable campaign schedules and weak integration of community-based strategies into the formal health system. Extremely low rates of implants removal suggest similar access to FP services issues. The study highlights the need to identify CBD strategies best suited to support women's choices and preferences towards successful contraceptive trajectories in fragile health systems.

In countries with insufficient access to health facilities, such as the D. R. Congo, the provision of contraceptives through campaigns implemented in community settings is a commonly used strategy to increase the number of contraceptive users. However, the long-term trajectories of campaign clients are not often examined, and it is unclear whether these events can be an effective way to support women's choices and preferences when it comes to using, switching or stopping a contraceptive method. Our study looks at the contraceptive trajectories of 883 women who obtained a method during a community event to see whether they were still using that a modern contraceptive method 3 and 6 months later. Almost a third of the women discontinued at some point in that period, with much higher discontinuation rates for monthly pills and injectable contraceptives. While some individual characteristics (marital status, desired number of children, experienced side-effects) influenced discontinuation risk, the most important factor was the woman's ability to resupply her method. Implant removal was also much lower than expected and this suggested difficulties in accessing existing family planning services. Our findings indicate that campaigns are still too disconnected from existing family planning services to successfully support women's contraceptive choices in the long run.

Effect of Cardiotonic Steroid Marinobufagenin on Vascular Remodeling and Cognitive Impairment in Young Dahl-S Rats.

The hypertensive response in Dahl salt-sensitive (DSS) rats on a high-salt (HS) diet is accompanied by central arterial stiffening (CAS), a risk factor for dementia, and heightened levels of a prohypertensive and profibrotic factor, the endogenous Na/K-ATPase inhibitor marinobufagenin (MBG). We studied the effect of the in vivo administration of MBG or HS diet on blood pressure (BP), CAS, and behavioral function in young DSS rats and normotensive Sprague-Dawley rats (SD), the genetic background for DSS rats. Eight-week-old male SD and DSS rats were given an HS diet (8% NaCl, n = 18/group) or a low-salt diet (LS; 0.1% NaCl, n = 14-18/group) for 8 weeks or MBG (50 µg/kg/day, n = 15-18/group) administered via osmotic minipumps for 4 weeks in the presence of the LS diet. The MBG-treated groups received the LS diet. The systolic BP (SBP); the aortic pulse wave velocity (aPWV), a marker of CAS; MBG levels; spatial memory, measured by a water maze task; and tissue collection for the histochemical analysis were assessed at the end of the experiment. DSS-LS rats had higher SBP, higher aPWV, and poorer spatial memory than SD-LS rats. The administration of stressors HS and MBG increased aPWV, SBP, and aortic wall collagen abundance in both strains vs. their LS controls. In SD rats, HS or MBG administration did not affect heart parameters, as assessed by ECHO vs. the SD-LS control. In DSS rats, impaired whole-heart structure and function were observed after HS diet administration in DSS-HS vs. DSS-LS rats. MBG treatment did not affect the ECHO parameters in DSS-MBG vs. DSS-LS rats. The HS diet led to an increase in endogenous plasma and urine MBG levels in both SD and DSS groups. Thus, the prohypertensive and profibrotic effect of HS diet might be partially attributed to an increase in MBG. The prohypertensive and profibrotic functions of MBG were pronounced in both DSS and SD rats, although quantitative PCR revealed that different profiles of profibrotic genes in DSS and SD rats was activated after MBG or HS administration. Spatial memory was not affected by HS diet or MBG treatment in either SD or DSS rats. Impaired cognitive function was associated with higher BP, CAS, and cardiovascular remodeling in young DSS-LS rats, as compared to young SD-LS rats. MBG and HS had similar effects on the cardiovascular system and its function in DSS and SD rats, although the rate of change in SD rats was lower than in DSS rats. The absence of a cumulative effect of increased aPWV and BP on spatial memory can be explained by the cerebrovascular and brain plasticity in young rats, which help the animals to tolerate CAS elevated by HS and MBG and to counterbalance the profibrotic effect of heightened MBG.

Adapting the informed push model to the last mile of the contraceptive supply chain in South Kivu in the Democratic Republic of Congo.

In the Democratic Republic of Congo (DRC), contraceptive security is one of the largest barriers to improving access to family planning. This article presents findings from a pilot study that adapted an informed push distribution model to the last mile of the contraceptive supply chain, between the health zone pharmacy and health facilities, in the eastern region of DRC. The intervention consisted of three changes in the supply chain: organization of more efficient transportation routes, in-depth involvement of the community in supply chain management and bundling of contraceptives with other essential medications for efficient delivery. The intervention was implemented from October 2017 to October 2018 in the Katana health zone of the South Kivu province. Although there was not a statistically significant difference in availability of contraceptives during the pilot study period, there were sharp declines in the mean length of stockouts at health facilities and the monthly transportation costs of delivering contraceptives. Overall, the pilot study demonstrated it is feasible to adapt the IPM to a new location with complex geographical, political and socioeconomical influences. Future studies will be required to evaluate whether the adapted informed push model is more effective than the existing pull supply chain system for contraceptives in the DRC.

Women living with their mothers-in-law.

Background Many studies have documented the impacts mothers-in-law have on daughters-in-law living in the same household, but few have quantified the scale of this co-residence.   This study aims to estimate the proportion of married women living with their mothers-in-law across countries and time.  Methods Using household rosters from 250 Demographic and Health Surveys in 75 countries, this paper uses the "relationship to head of household" question to identify households where married women live with their mothers-in-law.  For select countries with large changes, we decompose changes in rates into changes in the age structure of married women and the rate of women living with their mothers-in-law by age. Results This paper finds large variation in family structure around the globe, from 1% of married women in Rwanda to 49% in Tajikistan living with their mother-in-law.  Many countries with high co-residence in the 1990s continue to see high and increasing numbers today, especially in Central and Southern Asia, while some North and sub-Saharan African countries experienced substantial declines.  Decomposing changes by age and rates shows that changes in the age structure of married women is not driving changes in co-residence, but rather the rates are changing across age groups.  Conclusions These findings show the large variation in women living with their mothers-in-law across the globe.  The authors provide publicly available code and future research ideas to encourage others to further our understanding of the impact of living with her mother-in-law on a woman's life.

The gap in contraceptive knowledge and use between the military and non-military populations of Kinshasa, DRC, 2016-2019.

INTRODUCTION: The objective of this study is to assess change over time in the modern contraceptive prevalence rate (MCPR) and related variables among married women of reproductive age (15-49 years) in the military population in Kinshasa, Democratic Republic of Congo, compared to women in the non-military population, based on cross-sectional surveys in 2016 and 2019. METHODS: Data among women living in military camps were collected as a special study of contraceptive knowledge, use, and exposure to FP messaging, for comparison to women in the non-military population from the annual PMA2020 survey. Both used a two-stage cluster sampling design to randomly select participants. This analysis is limited to women married or in union. Bivariate and multivariate analysis was used to compare the military and non-military populations. RESULTS: The socio-demographic profile of women in the military camps differed between 2016 and 2019, which may reflect the more mobile nature of this population. In both populations, knowledge of modern contraceptive methods increased significantly. Similarly, use of a modern contraceptive method also increased significantly in both, though by 2019 women in the military camps were less likely to use modern contraception (24.9%) than their non-military counterparts (29.7%). Multivariate analysis showed no significant difference in the amount of increase in MCPR for the two populations. Among contraceptive users in both populations, the implant was the leading method. Potential effects of FP programming were evident in the military population: exposure to FP messaging increased (in comparison to a decrease among the non-military population). Moreover, women who had lived in the camps for 4+ years had a higher MCPR than those living in the camps for less than four years. CONCLUSIONS: This study demonstrates the feasibility and importance of collecting data in military camps for better understanding contraceptive dynamics among this specialized population.