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Endogenous estrogens mediate protective effects in the cardiovascular system, affecting both endothelium-dependent and endothelium-independent mechanisms. Previous studies have suggested that nonselective estrogen receptor agonists such as endogenous estrogens inhibit endothelium-dependent vasoconstriction; however, the role of estrogen receptors in this response has not yet been clarified. This study investigated whether the intracellular transmembrane G protein-coupled estrogen receptor (GPER) regulates vascular reactivity in mice. Effects of chronic deficiency (using mice lacking the GPER gene) and acute inhibition (using the GPER-selective antagonist G15) on endothelium-dependent and endothelium-independent vascular reactivity, and the effects of GPER deficiency on vascular gene expression and structure were investigated. We found that chronic GPER deficiency is associated with increased endothelial prostanoid-mediated vasoconstriction but has no effect on endothelial nitric oxide bioactivity, gene expression of endothelial nitric oxide synthase and thromboxane prostanoid (TP) receptor, or vascular structure. GPER deletion also increases TP receptor-mediated contraction. Acute GPER blockade enhances endothelium-dependent contractions and reduces endothelial nitric oxide bioactivity. Contractions in response to TP receptor activation are unaffected by G15. In conclusion, this study identifies GPER as the first estrogen receptor with inhibitory activity on endothelium-dependent contractility. These findings may be important for understanding and treating diseases associated with increased endothelial vasoconstrictor prostanoid activity such as hypertension and obesity. [ABSTRACT FROM AUTHOR]

Background: Tight control of cytoplasmic Ca 2+ concentration in endothelial cells is essential for the regulation of endothelial barrier function. Here, we investigated the role of Cavβ3, a subunit of voltage-gated Ca 2+ (Cav) channels, in modulating Ca 2+ signaling in brain microvascular endothelial cells (BMECs) and how this contributes to the integrity of the blood-brain barrier., Methods: We investigated the function of Cavβ3 in BMECs by Ca 2+ imaging and Western blot, examined the endothelial barrier function in vitro and the integrity of the blood-brain barrier in vivo, and evaluated disease course after induction of experimental autoimmune encephalomyelitis in mice using Cavβ3 -/- (Cavβ3-deficient) mice as controls., Results: We identified Cavβ3 protein in BMECs, but electrophysiological recordings did not reveal significant Cav channel activity. In vivo, blood-brain barrier integrity was reduced in the absence of Cavβ3. After induction of experimental autoimmune encephalomyelitis, Cavβ3 -/- mice showed earlier disease onset with exacerbated clinical disability and increased T-cell infiltration. In vitro, the transendothelial resistance of Cavβ3 -/- BMEC monolayers was lower than that of wild-type BMEC monolayers, and the organization of the junctional protein ZO-1 (zona occludens-1) was impaired. Thrombin stimulates inositol 1,4,5-trisphosphate-dependent Ca 2+ release, which facilitates cell contraction and enhances endothelial barrier permeability via Ca 2+ -dependent phosphorylation of MLC (myosin light chain). These effects were more pronounced in Cavβ3 -/- than in wild-type BMECs, whereas the differences were abolished in the presence of the MLCK (MLC kinase) inhibitor ML-7. Expression of Cacnb3 cDNA in Cavβ3 -/- BMECs restored the wild-type phenotype. Coimmunoprecipitation and mass spectrometry demonstrated the association of Cavβ3 with inositol 1,4,5-trisphosphate receptor proteins., Conclusions: Independent of its function as a subunit of Cav channels, Cavβ3 interacts with the inositol 1,4,5-trisphosphate receptor and is involved in the tight control of cytoplasmic Ca 2+ concentration and Ca 2+ -dependent MLC phosphorylation in BMECs, and this role of Cavβ3 in BMECs contributes to blood-brain barrier integrity and attenuates the severity of experimental autoimmune encephalomyelitis disease., Competing Interests: None.

Background: Analytical monitoring of adherence using mass spectrometry (MS) plays an important role in clinical toxicology. Unambiguous detection of drugs (of abuse) and/or their metabolites in body fluids is needed to monitor intake of medication as prescribed or to monitor abstinence as a follow-up to detoxification procedures. This study focused on the advantages and disadvantages of different sample matrices used for MS-based adherence monitoring., Methods: Relevant articles were identified through a literature search in the PubMed database. English articles published between January 01, 2017, and December 31, 2022, were selected using the keywords "adherence assess*" or "adherence monit*" or "compliance assess*" or "compliance monit*" in combination with "mass spectrom*" in the title or abstract., Results: A total of 51 articles were identified, 37 of which were within the scope of this study. MS-based monitoring was shown to improve patient adherence to prescribed drugs. However, MS analysis may not be able to assess whether treatment was rigorously followed beyond the last few days before the sampling event, except when hair is the sample matrix. For medication adherence monitoring, blood-based analyses may be preferred because reference plasma concentrations are usually available, whereas for abstinence control, urine and hair samples have the advantage of extended detection windows compared with blood. Alternative sample matrices, such as dried blood samples, oral fluid, and exhaled breath, are suitable for at-home sampling; however, little information is available regarding the pharmacokinetics and reference ranges of drug (of abuse) concentrations., Conclusions: Each sample matrix has strengths and weaknesses, and no single sample matrix can be considered the gold standard for monitoring adherence. It is important to have sufficient information regarding the pharmacokinetics of target substances to select a sample matrix in accordance with the desired purpose., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The purpose of this study is to examine the longitudinal impact of depressive symptoms on physical activity (PA) levels, sedentary behavior, and screen time among first-generation, Mexican-heritage youth. Mexican-heritage families were recruited by promotoras de salud from colonias in Hidalgo County, Texas. Participants (n = 200 youth, 116 families in final sample) completed at-home, interviewer-administered surveys once during the summer (June-July) and once during the fall (August-December). Youth PA and sedentary behaviors were assessed using a validated 7-day recall instrument. The validated Center for Epidemiology Studies-Depression Child scale was used to assess depression symptoms. Linear mixed-effects models were used to analyze the relationships of PA and sedentary behavior with depressive symptoms. Results showed that those depression symptoms were significantly associated with decreased number of self-reported minutes of sitting and screen time over time in the full sample and among male youth. Depression symptoms also significantly decreased the number of self-reported active and moderate to vigorous PA minutes over time among male youth. Researchers can build on our findings by identifying the mechanisms driving the relationships between depression and PA/sedentary behavior. Public health-programing efforts should intentionally consider the impact that depressive symptoms have on PA., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Every year, more new psychoactive substances (NPSs) emerge in the market of the drugs of abuse. NPSs belong to various chemical classes, such as synthetic cannabinoids, phenethylamines, opioids, and benzodiazepines. The detection of NPSs intake using different types of biological matrices is challenging for clinical toxicologists because of their structural diversity and the lack of information on their toxicokinetics, including their metabolic fate., Methods: PubMed-listed articles reporting mass spectrometry-based bioanalytical approaches for NPSs detection published during the past 5 years were identified and discussed. Furthermore, the pros and cons of using common biological matrices in clinical toxicology (CT) settings to screen for NPSs are highlighted in this review article., Results: Twenty-six articles presenting multianalyte screening methods for use in the field of CT were considered. The advantages and disadvantages of different biological matrices are discussed with a particular view of the different analytical tasks in CT, especially emergency toxicology. Finally, an outlook introduces the emerging trends in biosamples used in CT, such as the exhaled breath., Conclusions: Blood and urine represent the most common biological matrices used in a CT setting; however, reports concerning NPSs detection in alternative matrices are also available. Noteworthy, the selection of the biological matrix must depend on the clinician's enquiry because the individual advantages and disadvantages must be considered., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: To evaluate whether plasma biomarkers of amyloid (Aβ42/Aβ40), tau (p-tau181 and p-tau231), and neuroaxonal injury (neurofilament light chain [NfL]) detect brain amyloidosis consistently across racial groups., Methods: Individuals enrolled in studies of memory and aging who self-identified as African American (AA) were matched 1:1 to self-identified non-Hispanic White (NHW) individuals by age, APOE ε4 carrier status, and cognitive status. Each participant underwent blood and CSF collection, and amyloid PET was performed in 103 participants (68%). Plasma Aβ42/Aβ40 was measured by a high-performance immunoprecipitation-mass spectrometry assay. Plasma p-tau181, p-tau231, and NfL were measured by Simoa immunoassays. CSF Aβ42/Aβ40 and amyloid PET status were used as primary and secondary reference standards of brain amyloidosis, respectively., Results: There were 76 matched pairs of AA and NHW participants (n = 152 total). For both AA and NHW groups, the median age was 68.4 years, 42% were APOE ε4 carriers, and 91% were cognitively normal. AA were less likely than NHW participants to have brain amyloidosis by CSF Aβ42/Aβ40 (22% vs 43% positive; p = 0.003). The receiver operating characteristic area under the curve of CSF Aβ42/Aβ40 status with the plasma biomarkers was as follows: Aβ42/Aβ40, 0.86 (95% CI 0.79-0.92); p-tau181, 0.76 (0.68-0.84); p-tau231, 0.69 (0.60-0.78); and NfL, 0.64 (0.55-0.73). In models predicting CSF Aβ42/Aβ40 status with plasma Aβ42/Aβ40 that included covariates (age, sex, APOE ε4 carrier status, race, and cognitive status), race did not affect the probability of CSF Aβ42/Aβ40 positivity. In similar models based on plasma p-tau181, p-tau231, or NfL, AA participants had a lower probability of CSF Aβ42/Aβ40 positivity (odds ratio 0.31 [95% CI 0.13-0.73], 0.30 [0.13-0.71], and 0.27 [0.12-0.64], respectively). Models of amyloid PET status yielded similar findings., Discussion: Models predicting brain amyloidosis using a high-performance plasma Aβ42/Aβ40 assay may provide an accurate and consistent measure of brain amyloidosis across AA and NHW groups, but models based on plasma p-tau181, p-tau231, and NfL may perform inconsistently and could result in disproportionate misdiagnosis of AA individuals., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Physical activity (PA) is a public health priority due to holistic health benefits; however, many adults do not meet PA guidelines. Few studies have examined Mexican-heritage fathers' social networks, specifically with whom they are physically active. This study examines changes in Mexican-heritage fathers' PA networks after participation in a father-focused, family-centered health program. Families consisting of child (aged 9-11 years), mother, and father were recruited from colonias on the Texas-Mexico border for participation in a 6-week father-focused, family-centered program concentrated on healthy eating and active living. Fathers reported up to 5 people with whom they were active most in the previous month before and after the program as well as how often they were active with the person and what activities they did most often. Multilevel regression models examined changes in networks. Fathers (n = 42; mean age = 39.07 years, SD = 7.45) were significantly more likely to report more frequent PA with others after the program as compared with before. General active play and conditional support were mentioned most frequently. This study provides context to the social networks and PA behaviors of Mexican-heritage fathers and suggests that a father-focused, family-centered health program can increase the PA frequency with social network connections., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Physical activity (PA) is beneficial for child health; however, few children meet PA guidelines. Social relationships impact child PA behaviors; however, little is known about this effect in Mexican-heritage populations. This study aims to understand associations between self-reported play networks and PA among Mexican-heritage children. Mexican-heritage children from colonias along the Texas-Mexico border (n = 44; 54.5% girls; mean age = 9.89 years, SD = 0.97) reported information on up to 5 people they played with most often. Linear regression was used to analyze the relationship between composition of children's social network and minutes of moderate- to vigorous-intensity PA (MVPA) and sedentary minutes per day measured by accelerometers. Children who reported a higher percentage of friends as opposed to family members attained significantly more minutes of MVPA per day (β = .27, P = .04). Children who reported playing with individuals in their network more often (β = ‒.28, P = .03) were sedentary for fewer minutes per day. Increasing the connections between children in the neighborhood or community, as well as increasing a child's frequency of active play, may be promising approaches to increasing MVPA and decreasing sedentary behaviors among Mexican-heritage children., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The purpose of this short overview is to summarize and discuss the English-written and PubMed-listed review articles and original studies published between January 2015 and April 2019 on the use of metabolomics techniques for investigating the metabolism of new psychoactive substances (NPS). First, a brief introduction is given on the metabolism of NPS and metabolomics techniques in general. Afterward, the selected original studies are summarized and discussed. Finally, a section dedicated to the studies on NPS beyond metabolism using metabolomics techniques is provided. Thereafter, both sections are concluded and perspectives are given., Methods: PubMed was searched for English-written literature published between January 1, 2015 and April 1, 2019., Results: The present short overview found that the current use of metabolomics techniques in investigating the metabolism of NPS is rather limited, but these techniques can support and facilitate traditional metabolism studies., Conclusions: Thus, there may be a certain potential for using metabolomics techniques in the field of NPS research, but a great challenge remains to thoroughly adopt the existing metabolomics methods.

Rural residents are less physically active than their urban counterparts and disproportionately affected by chronic diseases and conditions associated with insufficient activity. While the ecological model has been successful in promoting and translating active living research in urban settings, relatively little research has been conducted in rural settings. The resulting research gap prohibits a comprehensive understanding and application of solutions for active living in rural America. Therefore, the purpose of this article was to assess the evidence base for an ecological model of active living for rural populations and outline key scientific gaps that inhibit the development and application of solutions. Specifically, we reexamined the 4 domains conceptualized by the model and suggest that there is a dearth of research specific to rural communities across all areas of the framework. Considering the limited rural-specific efforts, we propose areas that need addressing to mobilize rural active living researchers and practitioners into action.

Background: A multianalyte procedure (MAP) for the screening and quantification of drugs of different classes using ultra-high-performance liquid chromatography with tandem-mass spectrometric detection (UHPLC-MS/MS) was established. The aim was to elucidate whether this general approach could be transferred to the determination of drugs relevant for brain death diagnosis (BDD). This part of the MAP should cover alfentanil, etomidate, fentanyl, ketamine, morphine, piritramide, and sufentanil as an addition to the established gas chromatographic-mass spectrometric approach for the determination of propofol, barbiturates, and some benzodiazepines., Methods: This UHPLC-MS/MS approach based on liquid-liquid extraction was validated with respect to selectivity, recovery, matrix effects, process efficiency, ion suppression/enhancement, accuracy and precision, stabilities, and limits of quantification., Results: The approach was selective for the tested analytes. Accurate and precise quantification was achieved for all analytes with the exception of alfentanil and morphine. Validation data for fentanyl, piritramide, and sufentanil were acceptable, but the lowest calibrator concentration had to be set higher than half of the lower therapeutic range as recommended for BDD., Conclusions: Only etomidate and ketamine fulfill both validation and BDD criteria. Nevertheless, the MAP allowed the simultaneous screening and quantification of >90 other central nervous system-suppressing drugs with the same extract in the same run. For the screening and accurate and precise quantification of low concentrations of alfentanil, fentanyl, morphine, piritramide, and sufentanil, methods with alternative sample preparation and analysis techniques must be developed.

Childhood obesity has become a significant problem in the United States, especially in poor communities, and we know that children who have at least 1 obese parent have a much higher risk of being obese. Combined behavioral lifestyle interventions and family-based intervention programs to address pediatric obesity have the strongest evidence of effectiveness. In this pilot study, we delineate our collaborative model of family group medical visits at a community health center combined with healthy living workshops involving families with at least 1 child and 1 parent or guardian who are obese as a unique approach to address obesity in children.

In view of recent findings on the anatomic heterogeneity of rapid vasodilation via estrogen receptor (ER)-dependent mechanisms, it is obvious that with regard to human physiology and disease much of it is still unknown, and research in this area is urgently needed. This is also important because chronic drug therapy with estrogens in women systemically affects the circulation and may affect certain arterial beds but not others. It is conceivable that the presence of any vascular disease (as was the case for coronary and carotid atherosclerosis in many of the patients in the large randomized controlled trials HERS and WHI) is likely to affect vascular responses to estrogens as well, and that any beneficial effects may be attenuated or even completely lost. Further work is required to decipher the mechanisms of vasodilation brought about by estrogens in humans and experimental animals, whether anatomic heterogeneity exists with regard to vascular beds and individual estrogen receptors, and how vascular disease (atherosclerosis in particular) affects responsiveness. Also, pharmacologcial tools for newly identified ERs are now available. The hypothesis that disease may modify or even abrogate estrogen-dependent or ER-selective vasodilation should also be tested. Finally, given that certain clinically approved drugs such as SERM or SERDs (thought only to block or downregulate nuclear ERs) actually cause vasodilation through GPER and have been shown in recent clinical studies to provide cardiovascular protection in postmenopausal women, we may have to rethink our current understanding, concepts, and strategies of how to interfere with the increased risk of vascular disease in women with estrogen deficiency or after menopause.

The steady increase of new drugs of abuse on the illicit drug market is a great challenge for analytical toxicologists. Because most of these new drugs or drug classes are not included in established analytical methods targeting classic drugs of abuse, analytical procedures must be adapted or new procedures must be developed to cover such new compounds. This review summarizes procedures for analysis of these drugs of abuse published from January 2009 to January 2012 covering the following classes of emerging drugs of abuse as follows: β-keto-amphetamines, pyrrolidinophenones, tryptamines, and synthetic cannabinoids.

Background: To date, immunoassays are commercially available for quantification of valproic acid, salicylic acid, paracetamol, phenobarbital, phenytoin, and primidone. As they are no longer available, a fast, simple, and cost-effective quantitative gas chromatography-mass spectrometry (GC-MS) method was developed and fully validated for these drugs., Methods: After simple and fast liquid-liquid extraction, the samples were analyzed by GC-MS using the selected ion monitoring mode. The method was validated including the parameters selectivity, calibration model, precision, accuracy, and extraction efficiency., Results: The above-mentioned analytes were separated within 8.5 minutes and sensitively detected. No interfering peaks were observed in blank samples from 8 different sources. The linearity ranges were 20-200 mg/L for valproic acid, 100-1200 mg/L for salicylic acid, 10-200 mg/L for paracetamol, 10-200 mg/L for phenobarbital, 4-20 mg/L for primidone, and 2.5-30 mg/L for phenytoin. Generally accepted criteria for accuracy and precision were fulfilled for all analytes using 6-point calibration. Even 1-point calibration was applicable for all analytes. The assay was successfully applied to analysis of real plasma samples and proficiency testing material., Conclusions: The assay described allowed fast and reliable determination of analytes relevant in the diagnosis of poisonings. Furthermore, time- and cost-saving 1-point calibration was shown to be suitable for daily routine work, especially in emergency cases.

Like William T.G. Morton, Elton Romeo Smilie (1819-1889) was raised in Massachusetts, attended medical school in New England, practiced dentistry there, strove for clinical invention, and moved to Boston. In October 1846, both announced that inhaled ethereal preparations achieved reversible insensibility in surgical patients. Smilie published a report in the Boston Med Surg J 3 wk before Bigelow used that forum to broadcast Morton's Ether Day. Smilie's preparation was an ethereal tincture of opium, and, as he mistakenly believed the opium to be volatile and important, he ceded priority to Morton for ether anesthesia. The two authors collaborated on chloroform, but Smilie soon headed off in the Gold Rush to California. It is tempting to speculate that Charles T. Jackson and Morton were indebted in part to Smilie.

We found that the selective stimulation of the intracellular, transmembrane G protein-coupled estrogen receptor (GPER), also known as GPR30, acutely lowers blood pressure after infusion in normotensive rats and dilates both rodent and human arterial blood vessels. Stimulation of GPER blocks vasoconstrictor-induced changes in intracellular calcium concentrations and vascular tone, as well as serum-stimulated cell proliferation of human vascular smooth muscle cells. Deletion of the GPER gene in mice abrogates vascular effects of GPER activation and is associated with visceral obesity. These findings suggest novel roles for GPER in protecting from cardiovascular disease and obesity.

On-site tests based on immunoassay techniques are widely used for toxicologic screening analysis in patients with suspected poisoning. However, such assays usually have been validated using urine samples with known concentrations of the investigated substances. In the present investigation, on-site screening results were evaluated in a clinical setting. This was a retrospective study of patients with suspected poisoning from January to December 2003 in the emergency department of a tertiary urban hospital. Urine samples were analyzed using the Triage 8 panel and gas chromatography-mass spectrometry (GC-MS). A total of 111 patients were included (54 female, 57 male; average age 37.8 +/- 19.7 years). A total of 3.8% of the patients showed no symptoms, 45.2% minor, 24.0% moderate, and 26.9% serious symptoms. In 50 patients (45.0%), Triage 8 results corresponded well with GC-MS results. In 17 patients (15.3%), the Triage 8 results were confirmed by GC-MS, but additional substances were determined that could not be detected by the Triage 8 panel. A completely negative Triage 8 screening result was obtained in 23 patients (20.7%) who showed toxicologically relevant findings in GC-MS. In 21 patients (18.9%), Triage 8 results could not be confirmed by GC-MS. The analysis of the results in view of the patients' medical histories revealed that in 20 patients (18.0%), no relevant toxic substance could be detected. Additionally, 8 patients (7.2%) showed intoxication with alcohol, which could not be detected by the presently applied toxicologic screening investigations. On-site screening results in suspected poisoning were not very helpful in the present study because practically every second patient ingested substances that were not detectable by the Triage 8 device. In addition, every fifth result was not in line with GC-MS findings. On-site test findings should be interpreted very carefully, and in critical cases, a GC-MS screening should be performed.

Objective: To test the hypothesis that nonsteroidal anti-inflammatory drugs (NSAIDs) and histamine H2 receptor antagonists (H2RAs) are associated with a decreased risk of AD in late life., Background: Sustained use of non-aspirin NSAIDs has been repeatedly associated with a reduced occurrence of AD. Similar effects with aspirin have been weaker. One prior study showed a strong association between use of H2RAs and reduced AD prevalence., Methods: In a population study of AD in Cache County, UT, we used a sequenced plan of sampling and case ascertainment to identify 201 cases of AD and 4425 participants with no indication of cognitive impairment. Independently, an interview and medicine chest inventory assessed use of several medicines including aspirin, non-aspirin NSAIDs, H2RAs, and three classes of "control" drugs not thought to be associated with AD. Follow-up questioning probed possible indications for use of these drugs., Results: Compared with cognitively intact individuals, the AD cases had significantly less reported current use of NSAIDs, aspirin, and H2RAs. Stronger associations appeared when subjects reported use of both NSAIDs and aspirin (no H2RAs), two different NSAIDs (no H2RAs), or two different H2RAs (with neither aspirin nor NSAIDs). There was little or no such association with use of the control medicines. Adjustment for usage indication did not influence these findings, and there was no appreciable variation with number of APOE epsilon4 alleles., Conclusions: As predicted, use of NSAIDs and aspirin were specifically associated with reduced occurrence of AD. Notably, a previous observation of an inverse association of AD and use of H2RAs was also affirmed. Definitive evidence for a preventive action of these agents will require randomized prevention trials.

Objective: To examine the prevalence of Alzheimer's disease (AD) and other dementias in relation to age, education, sex, and genotype at APOE. Recent studies suggest age heterogeneity in the risk of AD associated with the APOE genotype and a possible interaction between APOE-epsilon4 and female sex as risk factors. We studied these topics in the 5,677 elderly residents of Cache County, Utah, a population known for long life expectancy and high participation rates., Methods: We screened for dementia with a brief cognitive test and structured telephone Dementia Questionnaire, then examined all individuals with apparent cognitive symptoms and a sample of others. We estimated age-specific prevalence of AD and other dementias and used multiple logistic regression models to describe relation of AD prevalence to age, sex, education, and APOE genotype., Results: We found 335 demented individuals, 230 (69%) with definite, probable, or possible AD (positive predictive value versus autopsy confirmation 85%). The adjusted prevalence estimate for AD was 6.5% and for all dementias 9.6%. After age 90, the adjusted prevalence estimate for AD was 28% and for all dementias 38%. Regression models showed strong variation in AD prevalence with age, sex, education, and number of epsilon4 alleles (effect of epsilon2 not significant). Models were improved by a term for age-squared (negative coefficient) and by separate terms for interaction of age with presence of one or two epsilon4 alleles. An association of AD with female sex was ascribable entirely to individuals with epsilon4., Conclusions: In participants with no epsilon4 alleles, the age-specific prevalence of AD reached a maximum and then declined after age 95. In epsilon4 heterozygotes a similar maximum was noted earlier at age 87, in homozygotes at age 73. Female sex was a risk factor for AD only in those with epsilon4. The epsilon4 allele accounted for 70% of the population attributable risk for AD.

A case is reported of herpesvirus infection in the newborn following maternal genital herpesvirus infection. The rationale for treating a newborn infant with signs of disseminated herpesvirus infection by exchange transfusion in addition to adenosine arabinoside is discussed. Because of the lack of data concerning therapy for a disease with a 50 to 100% mortality rate, it is important to present material such as this in order to provide information about possible new therapeutic modalities.