On the legacy of normalization

In 1998 Howard Parker, Judith Aldridge & Fiona Measham published Illegal Leisure, a ground‐breaking study of profound changes in British youth cultures in the 1990s, and the place of drugs and drug use in these upheavals. This work introduced the ‘normalization thesis’ to the social sciences, offering a novel vocabulary for re‐imagining the normative character of young people's attitudes towards and experiences of illicit drug use. Arriving at the dawn of the new century, the book offered a thoroughgoing re‐thinking of the character of youth cultures at a time of great social, cultural, economic and technological disruption. In so doing, the book deftly anticipated many of the most interesting currents of critical drug studies that followed.     

Bone Microarchitecture Phenotypes Identified in Older Adults Are Associated With Different Levels of Osteoporotic Fracture Risk

Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a “one-size-fits-all” approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured. In this study, we propose that there are common combinations of bone properties, referred to as phenotypes, that are predisposed to different levels of fracture risk. Using HR-pQCT data from a multinational cohort (n = 5873, 71% female) between 40 and 96 years of age, we employed fuzzy c-means clustering, an unsupervised machine-learning method, to identify phenotypes of bone microarchitecture. Three clusters were identified, and using partial correlation analysis of HR-pQCT parameters, we characterized the clusters as low density, low volume, and healthy bone phenotypes. Most males were associated with the healthy bone phenotype, whereas females were more often associated with the low volume or low density bone phenotypes. Each phenotype had a significantly different cumulative hazard of major osteoporotic fracture (MOF) and of any incident osteoporotic fracture (p < 0.05). After adjustment for covariates (cohort, sex, and age), the low density followed by the low volume phenotype had the highest association with MOF (hazard ratio = 2.96 and 2.35, respectively), and significant associations were maintained when additionally adjusted for femoral neck aBMD (hazard ratio = 1.69 and 1.90, respectively). Further, within each phenotype, different imaging biomarkers of fracture were identified. These findings suggest that osteoporotic fracture risk is associated with bone phenotypes that capture key features of bone deterioration that are not distinguishable by aBMD. © 2021 American Society for Bone and Mineral Research (ASBMR).     

The Neurosteroid Allopregnanolone Is Reduced in Prefrontal Cortex in Alzheimer’s Disease

BACKGROUND: Few data are currently available investigating neurosteroids (NS) in Alzheimer's disease (AD). The NS allopregnanolone may be decreased in serum and plasma in patients with AD, but it is unclear if allopregnanolone is also reduced in brain. Because a number of NS exhibit neuroprotective effects and impact cognitive performance in rodent models, these molecules may be relevant to the pathophysiology of neurodegenerative disorders. We therefore investigated prefrontal cortex (PFC) NS levels in AD. METHODS: Neurosteroid levels (allopregnanolone, pregnenolone, dehydroepiandrosterone [DHEA]) were determined in postmortem PFC in 14 male subjects with AD and 15 cognitively intact male control subjects by gas chromatography/mass spectrometry preceded by high-performance liquid chromatography purification. RESULTS: Subjects with AD exhibit significant reductions in allopregnanolone compared with cognitively intact control subjects (median levels = 2.50 ng/g vs. 5.59 ng/g, respectively; p = .02). Allopregnanolone levels are inversely correlated with neuropathological disease stage (Braak), r = -.49, p = .007. Median DHEA levels are elevated in subjects with AD (p = .01). CONCLUSIONS: Subjects with AD demonstrate significant reductions in PFC allopregnanolone levels, a finding that may be relevant to neuropathological disease stage severity. Neurosteroids may have utility as candidate biomarkers in AD.     

Differences in SLE disease activity between patients of Caucasian and South‐East Asian/Chinese background in an Australian hospital

Aim: We performed a semiprospective and retrospective review of all admissions to a single institution of systemic lupus erythematosus (SLE) patients, admitted due to active disease. The aim was to describe differences in disease activity as a cause of hospital admissions between patients originating from South‐East Asia/China (SAC) and Caucasians. Method: There were 210 patients admitted for active disease, with a total of 567 admissions for active SLE over a 16‐year period. Allowing for patients who had left our database, there was a total of 3415 patient years of observation. Results: Patients from SAC with a flare requiring admission presented earlier in their disease course and with more active disease than did Caucasians (median SLE Disease Activity Index 13 vs. 8, P= 0.002). They had longer inpatient stays (7 vs. 5 days P = 0.03). There was a trend to higher rates of re‐presentation to hospital for flare (59% in SAC patients vs. 41% in Caucasians, P = 0.09) with more subsequent admissions (3 vs. 2 P = 0.06) despite a shorter period of observation. Conclusions: South‐East Asian/Chinese were more likely to be diagnosed with class III/IV glomerulonephritis and require cyclophosphamide both at presentation and subsequent admissions. More patients from SAC were readmitted to hospital for severe central nervous system disease after their first hospital admission. In this population, lupus patients had more severe flares and more frequently required admission for these than Caucasians.     

The effect of placental removal method on the incidence of postcesarean infections

OBJECTIVE: Our purpose was to determine whether the incidence of postoperative endometritis and wound infection is associated with the method of placental removal at the time of cesarean section.STUDY DESIGN: Parturients undergoing cesarean delivery were prospectively randomized to have the placenta removed manually or spontaneously. Patients were excluded from participation if they had received intrapartum prophylactic antibiotics or had been determined to have chorioamnionitis. After delivery of the infant women in the manual group had the placenta extracted by the primary surgeon, whereas women in the spontaneous group had the placenta delivered by gentle traction on the umbilical cord. All study subjects received perioperative prophylactic antibiotics. The primary outcome variable was a postcesarean infection, defined as postcesarean endometritis or wound cellulitis requiring drainage and antibiotic therapy.RESULTS: A total of 333 women were enrolled in the investigation, with 165 assigned to the manual removal group and 168 allocated to have spontaneous removal. There were no statistically significant differences in mean gestational age, frequency or duration of ruptured membranes, frequency or duration of labor, or mean number of vaginal examinations between the two study groups. Postoperative infections occurred in 25 of 168 (15%) women in the spontaneous delivery group compared with 44 of 165 (27%) women in which the placenta was manually extracted (relative risk 0.6, 95% confidence interval 0.4 to 0.9, p = 0.01). Subset analysis of patients delivered with ruptured membranes similarly demonstrated a statistically significant reduction in the incidence of postoperative infections with spontaneous placental removal compared with manual extraction (20% vs. 38%, relative risk 0.5, 95% confidence interval 0.3 to 0.9, p = 0.02). There was a similar trend toward a reduction in postdelivery infections associated with spontaneous placental removal in women with intact membranes; however, this difference did not attain statistical significance.CONCLUSIONS: Spontaneous delivery of the placenta after cesarean delivery is associated with a decrease in the incidence of postcesarean infections. (Am J Obstet Gynecol 1997;176:1250-4.)     

A glutamatergic mechanism for aluminum toxicity in astrocytes

The effect of aluminum on the metabolism of glutamate and glutamine in astrocytes was studied to provide information about a possible biochemical mechanism for aluminum neurotoxicity and its potential contribution to neurodegenerative disease. Exposure of cultured rat brain astrocytes for 3–4 d to 5–7.5 mM aluminum lactate increased glutamine synthetase activity by 100–300% and diminished glutaminase activity by 50–85%. Increased glutamine synthetase enzyme activity was accompanied by an elevated level of glutamine synthetase mRNA. Alterations in glutaminase and glutamine synthetase following aluminum exposure caused increased intracellular glutamine levels, decreased intracellular glutamate levels, and increased conversion of glutamate to glutamine and the release of the latter into the extracellular space. The results of these changes may alter the availability of neurotransmitter glutamate in vivo and may be a mechanism for the aluminum neurotoxicity observed in individuals exposed to the metal during dialysis procedures and other situations.     

Immunological outcomes of exercise in older adults

Aging is associated with a dysregulation of the immune system known as immunosenescence. Immunosenescence involves cellular and molecular alterations that impact both innate and adaptive immunity, leading to increased incidences of infectious disease morbidity and mortality as well as heightened rates of other immune disorders such as autoimmunity, cancer, and inflammatory conditions. While current data suggests physical activity may be an effective and logistically easy strategy for counteracting immunosenescence, it is currently underutilized in clinical settings. Long-term, moderate physical activity interventions in geriatric populations appear to be associated with several benefits including reduction in infectious disease risk, increased rates of vaccine efficacy, and improvements in both physical and psychosocial aspects of daily living. Exercise may also represent a viable therapy in patients for whom pharmacological treatment is unavailable, ineffective, or inappropriate. The effects of exercise impact multiple aspects of immune response including T cell phenotype and proliferation, antibody response to vaccination, and cytokine production. However, an underlying mechanism by which exercise affects numerous cell types and responses remains to be identified. Given this evidence, an increase in the use of physical activity programs by the healthcare community may result in improved health of geriatric populations.