Early Effects of Abaloparatide on Bone Formation and Resorption Indices in Postmenopausal Women With Osteoporosis

Anabolic osteoporosis drugs improve bone mineral density by increasing bone formation. The objective of this study was to evaluate the early effects of abaloparatide on indices of bone formation and to assess the effect of abaloparatide on modeling-based formation (MBF), remodeling-based formation (RBF), and overflow MBF (oMBF) in transiliac bone biopsies. In this open-label, single-arm study, 23 postmenopausal women with osteoporosis were treated with 80 μg abaloparatide daily. Subjects received double fluorochrome labels before treatment and before biopsy collection at 3 months. Change in dynamic histomorphometry indices in four bone envelopes were assessed. Median mineralizing surface per unit of bone surface (MS/BS) increased to 24.7%, 48.7%, 21.4%, and 16.3% of total surface after 3 months of abaloparatide treatment, representing 5.5-, 5.2-, 2.8-, and 12.9-fold changes, on cancellous, endocortical, intracortical, and periosteal surfaces (p < .001 versus baseline for all). Mineral apposition rate (MAR) was significantly increased only on intracortical surfaces. Bone formation rate (BFR/BS) was significantly increased on all four bone envelopes. Significant increases versus baseline were observed in MBF on cancellous, endocortical, and periosteal surfaces, for oMBF on cancellous and endocortical surfaces, and for RBF on cancellous, endocortical, and intracortical surfaces. Overall, modeling-based formation (MBF + oMBF) accounted for 37% and 23% of the increase in bone-forming surface on the endocortical and cancellous surfaces, respectively. Changes from baseline in serum biomarkers of bone turnover at either month 1 or month 3 were generally good surrogates for changes in histomorphometric endpoints. In conclusion, treatment with abaloparatide for 3 months stimulated bone formation on cancellous, endocortical, intracortical, and periosteal envelopes in transiliac bone biopsies obtained from postmenopausal women with osteoporosis. These increases reflected stimulation of both remodeling- and modeling-based bone formation, further elucidating the mechanisms by which abaloparatide improves bone mass and lowers fracture risk. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Effect of postbariatric maternal weight loss and surgery to conception interval on perinatal outcomes of nulliparous women

BackgroundBariatric surgery is associated with an increased risk of delivering a small neonate. The role of maternal weight loss and surgery to conception interval is unclear.ObjectivesTo investigate the effect of maternal weight loss, as a result of bariatric surgery, and surgery to conception interval on fetal growth and birthweight (BW).SettingInner London Teaching HospitalMethodsWe studied prospectively nulliparous women with previous bariatric surgery. Information on type, time, and presurgery weight was obtained. Surgery-to-conception interval was calculated as the time between surgery and conception, defined as the fourteenth day of the pregnancy dated by first trimester ultrasound scan. In the first trimester, maternal weight was measured. Assessment of maternal weight change between presurgery and first trimester of pregnancy was defined as total weight loss (TWL) (%). Fetal ultrasound scans were performed twice; 30–32 and 35–37 weeks’ gestation and estimated fetal weight (EFW) was calculated. Fetal growth rate was calculated as the ratio of EFW increase (in grams) between 30–32 and 35–37 weeks divided by the time interval (in days) between the 2 examinations. BW was recorded.ResultsThe study included 54 pregnant women, 26 with a restrictive procedure (gastric band or vertical sleeve gastrectomy) and 28 with a gastric bypass. Surgery to conception interval was not a significant predictor of the offspring’s growth. Maternal TWL was a significant predictor of fetal growth rate (P = .04) and predictor of BW (P = .005), even after adjustment for confounders.ConclusionsMaternal weight loss, as a result of bariatric surgery, has an inverse correlation with fetal growth rate and BW.     

Psychosocial Adjustment to Illness Scale in family caregivers of patients with Parkinson’s Disease: Spanish validation study

Psychosocial adjustment to a complex and disabling long-term condition like Parkinson´s disease is a complex, dynamic, cyclical and interactive process. Family caregivers, face multiple challenges that require a significant effort in terms of psychosocial adjustment, which must be considered by healthcare professionals in order to provide a holistic care. The patients’ self-report version of the Psychosocial Adjustment to Illness Scale (PAIS-SR), which has been validated in Spain for use in Parkinson's disease, is designed to evaluate the psychosocial adjustment of patients. Our purpose was to validate the Spanish PAIS-SR version for caregivers of patients with Parkinson's disease. An open, national cross-sectional study with one point-in-time evaluation and retest was carried out in 450 family caregivers of patients with Parkinson's disease. Data were collected in Spain from April 2016 to September 2017. The psychometric analysis performed showed that the Spanish version of the PAIS-SR for caregivers presents adequate indicators of reliability, internal and external validity, and is structured according to the seven-domain model proposed by the author of the instrument.     

The Effect of Basic Fibroblast Growth Factor on the Reversion of Omental Adipocytes from Lean and Obese Patients

Background: this study was designed to characterize some of the biochemical and molecular genetic changes during reversion of human fat cells. Methods: mature adipocytes were isolated from greater omental fat tissue of eight lean and 14 massively obese persons by established methodology. Results: at day 7 of adherence to Leighton tubes, there was appreciable depletion of triacylglycerol, as well as assumption of an elongated contour. Relatedly, there was an increase in the expression of β-actin mRNA and a significant decrease in the specific activity of cytosolic glycerophosphate dehydrogenase. The decrement in the specific activity of glycerophosphate dehydrogenase, after 7 days in culture, was significant at p < 0.001. Basic fibroblast growth factor at 10 ngml^-1 accelerated significantly (p < 0.03) the decrease in the specific activity of glycerophosphate dehydrogenase in adipose cells from lean subjects. In contrast, basic fibroblast growth factor had no significant influence on cells from massively obese persons. Conclusion: such resistance may contribute to the intractability of massive obesity.     

[18F] FDG PET in Gastric Non-Hodgkin's Lymphoma

The possibility of using [¹⁸F] FDG PET for assessment of tumor extension in primary gastric non-Hodgkin's lymphoma (NHL) was studied in 8 patients (6 high-grade and 2 Iow-grade, one of the MALT type) and in a control group of 7 patients (5 patients with NHL without clinical signs of gastric involvement, 1 patient with NHL and benign gastric ulcer and 1 patient with adenocarcinoma of the stomach). All patients with gastric NHL and the two with benign gastric ulcer and adenocarcinoma, respectively, underwent endoscopy including multiple biopsies for histopathological diagnosis. All patients with high-grade and one of the two with low-grade NHL and the patient with adenocarcinoma displayed high gastric uptake of [¹⁸F] FDG corresponding to the pathological findings at endoscopy and/or CT. No pathological tracer uptake was seen in the patient with low-grade gastric NHL of the MALT type. In 6/8 patients with gastric NHL, [¹⁸F] FDG PET demonstrated larger tumor extension in the stomach than was found at endoscopy, and there was high tracer uptake in the stomach in two patients who were evaluated as normal on CT. [¹⁸F] FDG PET correctly excluded gastric NHL in the patient with a benign gastric ulcer and in the patients with NHL without clinical signs of gastric involvement. Although the experience is as yet limited, [¹⁸F] FDG PET affords a novel possibility for evaluation of gastric NHL and would seem valuable as a complement to endoscopy and CT in selected patients, where the technique can yield additional information decisive for the choice of therapy.     

Spectacle use and reduced unaided vision in third grade students: a comparative study in different educational settings

Background: The development of myopia is influenced by hereditary factors, environmental factors and geneenvironment interaction. Reading and near‐work activity are associated with myopia and myopic progression. This study sought to determine and compare the prevalence of reduced unaided vision and spectacle use among third grade Israeli students from three different educational settings. Method: A sample of 917 students (mean age 8.5 years, range seven to 10 years) was drawn from the three Israeli educational streams: secular, Orthodox and ultra‐Orthodox. Children in the ultra‐Orthodox education pathway begin studying at the age of three years and their daily reading involves sustained near work with increased accommodative effort accompanied by head‐rocking movements. Reduced distance vision was used to indicate the likely development of or an increase in the amount of myopia. Spectacle lenses were measured to determine the prevalence of myopia. Results: Of the 917 students studied, 103 (11.2 per cent) wore spectacles (14.2 per cent of the males and eight per cent of the females); 82.5 per cent of those who wore spectacles were myopic. Males from ultra‐Orthodox schools had the highest rate of reduced unaided vision (72.5 per cent) compared with males from secular schools (27.3 per cent), males from Orthodox schools (59.3 per cent) or with females from all three groups (average of 34.8 per cent, p < 0.0001, chi squared). Males had a higher rate of reduced unaided vision, especially in the Orthodox and ultra‐Orthodox schools. Conclusions: Our study suggests that Jewish ultra‐Orthodox males have a higher prevalence and degree of myopia. The study habits of young children, including exposure to prolonged near tasks, high accommodative demands and possibly optical defocus induced by body sway, may contribute to the development of myopia.     

Less anticipatory guidance is associated with more subsequent injury visits among infants.

OBJECTIVE: To describe clinician delivery of injury prevention anticipatory guidance and injury visits in a birth cohort, and to describe the association of injury prevention anticipatory guidance with subsequent injury visits. METHODS: We performed a prospective cohort study of 2610 infants born from July 1, 1998 to June 30, 1999, at an urban safety-net hospital and seen subsequently for well child care (WCC, visits = 10558) and/or injury by 16 months of age. Injury guidance was defined as the proportion of recommended injury prevention anticipatory guidance items delivered to those expected, given the WCC visits the child attended. The outcome was a first injury visit to a clinic, emergency department, or hospital. RESULTS: The injury prevention items most discussed were car seats (84%-95% of all WCC visits) and rolling over at the 2-month WCC visit (80%). Other items were addressed at 36%-69% of visits. A total of 1931 (74%) of children received > or = 50% expected injury guidance. A total of 277 children (11%) had an injury visit, primarily for minor injuries. In unadjusted analysis, children receiving < 25% expected injury guidance were more likely to have a subsequent injury visit (unadjusted odds ratio 6.2; 95% confidence interval [95% CI] 3.2-9.7). In adjusted analysis, children who received < 25% and 25%-49% expected injury guidance were more likely to have a subsequent injury visits (adjusted odds ratio [AOR] 6.6; 95% CI 3.8-11.2; and AOR 2.9, 95% CI 2.0-4.3, respectively). CONCLUSIONS: Disadvantaged children whose families received less injury guidance than other children in their cohort were more likely to have a subsequent injury visit. Further studies are needed to determine whether increased injury prevention counseling reduces injury visits.     

Interactions of chronic lead exposure and intermittent stress: consequences for brain catecholamine systems and associated behaviors and HPA axis function.

Elevated lead (Pb) burden and high stress levels are co-occurring risk factors in low socioeconomic status (SES) children. Our previous work demonstrated that maternal Pb exposure can permanently alter hypothalamic-pituitary-adrenal (HPA) axis function and responsivity to stress challenges in offspring. The current study sought to determine the consequences of chronic Pb exposures initiated later in development combined with variable intermittent stress challenges. Male rats were exposed chronically from weaning to 0, 50, or 150 ppm Pb acetate drinking solutions (producing blood Pb levels of <5, 9-15, and 23-27 mug/dl, respectively). Pb itself decreased basal plasma corticosterone, with greater effects at 50 than 150 ppm; 150 ppm reduced both cytosolic and nuclear glucocorticoid receptor binding. Responsivity to stress challenges including novelty, cold, and restraint, was measured as changes in Fixed Interval (FI) schedule-controlled behavior in a subset of rats within each group. FI performance was modified by novelty stress only in Pb-treated rats, whereas cold and restraint stress effects were comparable across groups. Novelty elevated corticosterone equivalently across groups, but cold stress markedly increased corticosterone only in Pb-treated groups. The pattern of Pb-induced changes in serotonin (5-HT) or its metabolite 5-HIAA in frontal cortex, nucleus accumbens, striatum, and hypothalamus resembled that observed for basal corticosterone levels indicating a relationship between these variables. In addition to suggesting the potential for HPA axis-mediated effects of Pb on the central nervous system, these findings also raise questions about whether single chemicals studied in isolation from other relevant risk factors can adequately identify neurotoxic hazards.