The effect of microglia on embryonic dopaminergic neuronal survival in vitro: diffusible signals from neurons and glia change microglia from neurotoxic to neuroprotective

When embryonic dopaminergic neurons are transplanted into the adult brain, approximately 95% die within a few days. To assess whether microglia activated during transplantation might be responsible for this rapid death, we examined the effect of microglia on rat embryonic dopaminergic neurons in vitro. Conditioned medium from 7-day-old microglia was found to decrease the number of dopamine neurons surviving in primary culture, but activation of the microglia with N-formyl-methionyl-leucyl-phenylalanine (FMLP) or Zymosan A did not increase the toxicity of the conditioned medium. We next tested the effect of coculturing microglia and dopaminergic neurons by placing microglia in semipermeable well inserts over the neuronal cultures. The presence of microglia now increased dopaminergic neuronal survival, microglial activation again having no effect. To increase yet further the possible interactions between microglia and neurons, the mesencephalic cells and microglia were mixed together and placed as a tissue in three-dimensional culture, and here again the presence of microglia increased dopaminergic neuronal survival with no effect of activation. Contact of microglia with the mesencephalic cells therefore converted them from being toxic to dopaminergic neurons to promoting their survival. The change in microglial effect from toxic to protective was caused by soluble molecules secreted by cells in the neuronal cultures, as conditioned medium derived from microglia-neuronal cocultures also had a dopaminergic neuron survival effect, indicating that microglia in cocultures behave differently from microglia removed from neuronal and glial influence. Microglia cocultured with either neurons or astrocytes downregulated inducible nitric oxide synthase (iNOS), indicating a decrease in the production of nitric oxide and possibly other toxic molecules. These findings indicate that in their natural environment, microglia are likely to be beneficial for the survival of embryonic dopaminergic grafts.     

Efficacy of loxapine in the treatment of paranoid schizophrenia

A combined analysis of data from 11 controlled studies of loxapine versus either chlorpromazine or trifluoperazine in acute schizophrenia (5 studies) and chronic schizophrenia (6 studies) showed statistically significant superiority of loxapine on several items and factors of standardized psychiatric rating scales. Upon review of these findings, it was observed that the rating scale symptoms for which loxapine appeared superior to the reference compounds could, in the main, be considered a broad paranoid cluster. The data were then reanalyzed to detect possible differences in efficacy of loxapine versus the reference compounds in those patients with a clinical diagnosis of schizophrenia, paranoid type and in those patients of any diagnostic subtype other than paranoid. Results of these analyses demonstrated clear superiority of loxapine in paranoid schizophrenic patients; nonparanoid patients responded at least equally as well to loxapine as to the reference compounds. Findings could not be attributed to inadequate dosages of the reference compounds or inequality of treatment groups at baseline.Presented in part at the Ninth Annual Congress, Collegium Internationale Neuropsychopharmacologicum, Paris, July, 1974     

Menstrual Problems and Health Seeking in Sri Lanka

Menstruation is associated with some morbidity, although it is a normal physiological event. In this article, we draw on qualitative research conducted in Sri Lanka in 2006–2007, which included eight key informant interviews with healthcare providers, six focus group discussions with eight women in each, and five case studies. We describe and analyze women's perceptions of menstruation and menstrual problems, their help-seeking behaviors to reduce these health problems, and the consequences of them on their lives. The majority of women perceived menstruation as a physiological process and related problems to changes in hormone levels, pathological conditions of the uterus, and the side effects of contraceptive methods. Menstrual problems significantly affected their daily activities, mental well-being, social life, and sexual life, but few sought medical advice to resolve these problems. Implications of the findings included the need for health care providers and educators to provide accurate information on menstruation to girls and women to enable them to identify normal variation of menstruation and to take appropriate action regarding health care.     

Expansion of Patient Education Programming Regarding Live Donor Liver Transplantation via Virtual Group Encounters During the COVID-19 Pandemic

During the coronavirus 2019 pandemic we converted our liver transplant waitlist candidate education and support program to a virtual format and expanded it to include ongoing engagement sessions aimed to educate and empower patients to maximize opportunity for live donor liver transplantation. Over a period of 6 months from April 2020 to Sept 2020 we included 21 patients in this pilot quality improvement program. We collected data regarding patient response and potential donor referral activity. Overall, patient response was positive, and some patients saw progress toward live donor liver transplantation by fostering inquiry of potential live liver donors. Optimization of logistical aspects of the program including program flow, technology access, and utilization is required to enhance patient experience. Long-term follow-up is needed to assess impact on the outcome of transplantation rates. Future data collection and analysis should focus on assessment of any potential disparity that may result from utilization of virtual programming. Herein we provide a framework for this type of virtual program and describe our experience.     

HCMV Infection of Human Trophoblast Progenitor Cells of the Placenta Is Neutralized by a Human Monoclonal Antibody to Glycoprotein B and Not by Antibodies to the Pentamer Complex

Human cytomegalovirus (HCMV) is the major viral cause of congenital infection and birth defects. Primary maternal infection often results in virus transmission, and symptomatic babies can have permanent neurological deficiencies and deafness. Congenital infection can also lead to intrauterine growth restriction, a defect in placental transport. HCMV replicates in primary cytotrophoblasts (CTBs), the specialized cells of the placenta, and inhibits differentiation/invasion. Human trophoblast progenitor cells (TBPCs) give rise to the mature cell types of the chorionic villi, CTBs and multi-nucleated syncytiotrophoblasts (STBs). Here we report that TBPCs are fully permissive for pathogenic and attenuated HCMV strains. Studies with a mutant virus lacking a functional pentamer complex (gH/gL/pUL128-131A) showed that virion entry into TBPCs is independent of the pentamer. In addition, infection is blocked by a potent human neutralizing monoclonal antibody (mAb), TRL345, reactive with glycoprotein B (gB), but not mAbs to the pentamer proteins pUL130/pUL131A. Functional studies revealed that neutralization of infection preserved the capacity of TBPCs to differentiate and assemble into trophospheres composed of CTBs and STBs in vitro. Our results indicate that mAbs to gB protect trophoblast progenitors of the placenta and could be included in antibody treatments developed to suppress congenital infection and prevent disease.     

Maternal Identity Change as a Consequence of Antenatal Hospitalization

Despite low fertility rates in Western countries, maternity remains one of the major goals of women from various socioeconomic backgrounds. While most women will have low-risk pregnancies, common serious disorders of pregnancy, such as preeclampsia, premature rupture of the membranes, placenta previa, or fetal growth restriction, may compromise maternal and infant outcomes. The experiences of urban and rural women in Australia who have had difficulties in maintaining their pregnancies are analyzed in this article. We study the impact of individual and social factors that facilitate or impede women's adjustment to the risks associated with these disorders. The analysis of in-depth interviews with 27 women hospitalized antenatally indicates that most women were unfamiliar with the diagnoses and acted as passive “decision takers,” complying with medical advice to remain in the hospital. Admission to a tertiary hospital ward that provided care to women with pregnancy disorders promoted the formation of a new identity, that of a woman whose pregnancy did not follow the expected path. Further, hospitalization offered women the opportunity to interact with others in similar difficult situations and, hence, feel less isolated.     

Effect of nutritional counseling on low-density lipoprotein cholesterol among Thai HIV-infected adults receiving antiretroviral therapy

HIV-infected patients receiving antiretroviral therapy have increased risk of metabolic syndrome, including dyslipidemia. In this study, we determined whether individual nutritional counseling reduced dyslipidemia, particularly low-density lipoprotein (LDL) cholesterol, among HIV-infected patients with dyslipidemia not currently taking lipid-lowering medication. We conducted a randomized 24-week trial among HIV-infected patients with dyslipidemia who were on antiretroviral therapy and were eligible to initiate therapeutic lifestyle changes according to the Thai National Cholesterol Education Program. Participants were randomly assigned to an intervention group that received individual counseling with a nutritionist for seven sessions (baseline, weeks 2, 4, 8, 12, 18, and 24) and a control group that received standard verbal diet information at baseline and nutritional counseling only at week 24. A 24-h recall technique was used to assess dietary intake for both groups at baseline and week 24. Lipid profile (total cholesterol, LDL, high-density lipoprotein (HDL), and triglyceride) was measured at baseline and after 12 and 24 weeks of therapy. An intention-to-treat and linear mixed model were used. Seventy-two patients were randomly assigned, and 62 (86%) participants completed their lipid profile test. After 12 weeks of follow-up, there were significant reductions in the intervention group for total cholesterol (?14.4?±?4.6?mg/dL, P?=?.002), LDL cholesterol (?13.7?±?4.1?mg/dL, P?=?.001), and triglyceride (?30.4?±?13.8?mg/dL, P?=?.03). A significant reduction in LDL cholesterol was also observed in the control group (?7.7?±?3.8?mg/dL, P?=?.04), but there were no significant differences in change of mean lipid levels between the groups at 12 weeks of follow-up. After 24 weeks, participants assigned to the intervention group demonstrated significantly greater decreases in serum total cholesterol (?19.0?±?4.6?vs. 0.2?±?4.3?mg/dL, P?=?.003) and LDL cholesterol (?21.5?±?4.1?vs. ?6.8?±?3.8?mg/dL, P?=?.009). There were no significant changes in HDL cholesterol or triglyceride levels in either group.     

The Granny-Nanny: A Guide for Parents and Grandparents Who Share Child Care,by Lee Edwards Benning

In recent years interest has increased toward mental exercise as a way to promote healthy cognitive aging. Consistent findings have shown that declines in working memory performance are associated with aging. Sudoku is a popular puzzle game that has task demands similar to working memory processes. Younger and older adults completed a battery of tests and solved Sudoku puzzles. The results showed that Sudoku performance had a significant relationship to working memory. This suggests that Sudoku has the potential to become a new focus in the study of mental exercise and cognitive aging.     

Epidemiologic Evidence on Coffee and Cancer

Coffee consumption is a major and frequent dietary exposure in diverse cultures around the globe whose safety has been questioned. A substantial body of epidemiologic evidence, consisting of over 500 papers relating the consumption of coffee to cancer of various sites, has accumulated to date. Numerous individual, site-specific meta analyses have been undertaken at various times. However, there is no comprehensive, up-to-date overview of the entirety of the knowledge base. To address this need, this review summarized the findings of the meta analyses and recent papers on site-specific human cancers among coffee consumers. For hepatocellular and endometrial cancers, there appears to be a strong and consistent protective association; for colorectal cancer, the direction of association is borderline protective. There appears to be no association with breast, pancreatic, kidney, ovarian, prostate, or gastric cancer. Risk of bladder cancer appears to be associated with heavy coffee consumption in some populations and among men. The associations with childhood leukemia and mother's consumption of coffee were ambiguous—with some suggestion of risk at high levels of daily consumption.