Impact of preconception and antenatal supplementation with myo-inositol, probiotics, and micronutrients on offspring BMI and weight gain over the first 2 years.

BACKGROUND: Nutritional intervention preconception and throughout pregnancy has been proposed as an approach to promoting healthy postnatal weight gain in the offspring but few randomised trials have examined this. METHODS: Measurements of weight and length were obtained at multiple time points from birth to 2 years among 576 offspring of women randomised to receive preconception and antenatally either a supplement containing myo-inositol, probiotics, and additional micronutrients (intervention) or a standard micronutrient supplement (control). We examined the influence on age- and sex-standardised BMI at 2 years (WHO standards, adjusting for study site, sex, maternal parity, smoking and pre-pregnancy BMI, and gestational age), together with the change in weight, length, BMI from birth, and weight gain trajectories using latent class growth analysis. RESULTS: At 2 years, there was a trend towards lower mean BMI among intervention offspring (adjusted mean difference [aMD] - 0.14 SD [95% CI 0.30, 0.02], p = 0.09), and fewer had a BMI > 95th percentile (i.e. > 1.65 SD, 9.2% vs 18.0%, adjusted risk ratio [aRR] 0.51 [95% CI 0.31, 0.82], p = 0.006). Longitudinal data revealed that intervention offspring had a 24% reduced risk of experiencing rapid weight gain > 0.67 SD in the first year of life (21.9% vs 31.1%, aRR 0.76 [95% CI 0.58, 1.00], p = 0.047). The risk was likewise decreased for sustained weight gain > 1.34 SD in the first 2 years of life (7.7% vs 17.1%, aRR 0.55 [95% CI 0.34, 0.88], p = 0.014). From five weight gain trajectories identified, there were more intervention offspring in the "normal" weight gain trajectory characterised by stable weight SDS around 0 SD from birth to 2 years (38.8% vs 30.1%, RR 1.29 [95% CI 1.03, 1.62], p = 0.029). CONCLUSIONS: Supplementation with myo-inositol, probiotics, and additional micronutrients preconception and in pregnancy reduced the incidence of rapid weight gain and obesity at 2 years among offspring. Previous reports suggest these effects will likely translate to health benefits, but longer-term follow-up is needed to evaluate this. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02509988 (Universal Trial Number U1111-1171-8056). Registered on 16 July 2015.

Higher early pregnancy plasma myo-inositol associates with increased postprandial glycaemia later in pregnancy: Secondary analyses of the NiPPeR randomized controlled trial.

AIM: Myo-inositol supplementation from ~13 weeks' gestation reportedly improves glycaemia regulation in metabolically at-risk women, with speculation that earlier supplementation might bring further improvement. However, the NiPPeR trial of a myo-inositol-containing supplement starting preconception did not lower gestational glycaemia in generally healthy women. We postulated that the earlier timing of supplementation influences the maternal metabolic adaptation for gestational glycaemia regulation. METHODS: In total, 585 women were recruited from Singapore, UK and New Zealand for the NiPPeR study. We examined associations of plasma myo-inositol concentrations at 7 and 28 weeks' gestation with 28 weeks plasma glucose (PG; fasting, and 1 h and 2 h in 75 g oral glucose tolerance test) and insulin indices using linear regression adjusting for covariates. RESULTS: Higher 7-week myo-inositol, but not 28-week myo-inositol, associated with higher 1 h PG [ßadj (95% confidence intervals) 0.05 (0.01, 0.09) loge mmol/L per loge µmol/L, p = .022] and 2 h PG [0.08 (0.03, 0.12), p = .001]; equivalent to 0.39 mmol/L increase in 2 h PG for an average 7-week myo-inositol increase of 23.4 µmol/L with myo-inositol supplementation. Higher 7-week myo-inositol associated with a lower 28-week Stumvoll index (first phase), an approximation of insulin secretion [-0.08 (-0.15, -0.01), p = .020] but not with 28-week Matsuda insulin sensitivity index. However, the clinical significance of a 7-week myo-inositol-related increase in glycaemia was limited as there was no association with gestational diabetes risk, birthweight and cord C-peptide levels. In-silico modelling found higher 28-week myo-inositol was associated with lower gestational glycaemia in White, but not Asian, women after controlling for 7-week myo-inositol effects. CONCLUSION: To our knowledge, our study provides the first evidence that increasing first trimester plasma myo-inositol may slightly exacerbate later pregnancy post-challenge glycaemia, indicating that the optimal timing for starting prenatal myo-inositol supplementation needs further investigation.

Teriparatide and pelvic fracture healing: a phase 2 randomized controlled trial.

Pelvic fracture patients were randomized to blinded daily subcutaneous teriparatide (TPTD) or placebo to assess healing and functional outcomes over 3 months. With TPTD, there was no evidence of improved healing by CT or pain reduction; however, physical performance improved with TPTD but not placebo (group difference p < 0.03). INTRODUCTION: To determine if teriparatide (20 µg/day; TPTD) results in improved radiologic healing, reduced pain, and improved functional outcome vs placebo over 3 months in pelvic fracture patients. METHODS: This randomized, placebo-controlled study enrolled 35 patients (women and men >50 years old) within 4 weeks of pelvic fracture and evaluated the effect of blinded TPTD vs placebo over 3 months on fracture healing. Fracture healing from CT images at 0 and 3 months was assessed as cortical bridging using a 5-point scale. The numeric rating scale (NRS) for pain was administered monthly. Physical performance was assessed monthly by Continuous Summary Physical Performance Score (based on 4 m walk speed, timed repeated chair stands, and balance) and the Timed Up and Go (TUG) test. RESULTS: The mean age was 82, and >80% were female. The intention to treat analysis showed no group difference in cortical bridging score, and 50% of fractures in TPTD-treated and 53% of fractures in placebo-treated patients were healed at 3 months, unchanged after adjustment for age, sacral fracture, and fracture displacement. Median pain score dropped significantly in both groups with no group differences. Both CSPPS and TUG improved in the teriparatide group, whereas there was no improvement in the placebo group (group difference p < 0.03 for CSPPS at 2 and 3 months). CONCLUSION: In this small randomized, blinded study, there was no improvement in radiographic healing (CT at 3 months) or pain with TPTD vs placebo; however, there was improved physical performance in TPTD-treated subjects that was not evident in the placebo group.

Vertebral fracture assessment (VFA) for osteoporosis screening in US postmenopausal women: is it cost-effective?

Vertebral fracture assessment (VFA) is cost-effective when it was incorporated in the routine screening for osteoporosis in community-dwelling women aged ≥ 65 years, which support guidelines, such as the National Osteoporosis Foundation (NOF) for the diagnostic use of VFA as an important addition to fracture risk assessment. INTRODUCTION: To evaluate the cost-effectiveness of VFA as a screening tool to reduce future fracture risk in US community-dwelling women aged ≥ 65 years. METHODS: An individual-level state-transition cost-effectiveness model from a healthcare perspective was constructed using derived data from published literature. The time horizon was lifetime. Five screening strategies were compared, including no screening at all, central dual-energy X-ray absorptiometry (DXA) only, VFA only, central DXA followed by VFA if the femoral neck T-score (FN-T) ≤ - 1.5, or if the FN-T ≤ - 1.0. Various initiation ages and rescreening intervals were evaluated. Oral bisphosphonate treatment for 5-year periods was assumed. Incremental cost-effectiveness ratios (2017 US dollars per quality-adjusted life-year (QALY) gained) were used as the outcome measure. RESULTS: The incorporation of VFA slightly increased life expectancy by 0.1 years and reduced the number of subsequent osteoporotic fractures by 3.7% and 7.7% compared with using DXA alone and no screening, respectively, leading to approximately 30 billion dollars saved. Regardless of initiation ages and rescreening intervals, central DXA followed by VFA if the FN-T ≤ - 1.0 was most cost-effective ($40,792 per QALY when the screening is initiated at age 65 years and with rescreening every 5 years). Results were robust to change in VF incidence and medication costs. CONCLUSION: In women aged ≥ 65 years, VFA is cost-effective when it was incorporated in routine screening for osteoporosis. Our findings support the National Osteoporosis Foundation (NOF) guidelines for the diagnostic use of VFA as an important addition to fracture risk assessment.

Factors associated with the contemplative stage of readiness to initiate osteoporosis treatment.

We investigated the factors associated with readiness for initiating osteoporosis treatment in women at high risk of fracture. We found that women in the contemplative stage were more likely to report previously being told having osteoporosis or osteopenia, acknowledge concern about osteoporosis, and disclose prior osteoporosis treatment. INTRODUCTION: Understanding factors associated with reaching the contemplative stage of readiness to initiate osteoporosis treatment may inform the design of behavioral interventions to improve osteoporosis treatment uptake in women at high risk for fracture. METHODS: We measured readiness to initiate osteoporosis treatment using a modified form of the Weinstein Precaution Adoption Process Model (PAPM) among 2684 women at high risk of fracture from the Activating Patients at Risk for OsteoPOroSis (APROPOS) clinical trial. Pre-contemplative participants were those who self-classified in the unaware and unengaged stages of PAPM (stages 1 and 2). Contemplative participants were those in the undecided, decided not to act, or decided to act stages of PAPM (stages 3, 4, and 5). Using multivariable logistic regression, we evaluated participant characteristics associated with levels of readiness to initiate osteoporosis treatment. RESULTS: Overall, 24% (N = 412) self-classified in the contemplative stage of readiness to initiate osteoporosis treatment. After adjusting for age, race, education, health literacy, and major osteoporotic fracture in the past 12 months, contemplative women were more likely to report previously being told they had osteoporosis or osteopenia (adjusted odds ratio [aOR] (95% CI) 11.8 (7.8-17.9) and 3.8 (2.5-5.6), respectively), acknowledge concern about osteoporosis (aOR 3.5 (2.5-4.9)), and disclose prior osteoporosis treatment (aOR 4.5 (3.3-6.3)) than women who self-classified as pre-contemplative. CONCLUSIONS: For women at high risk for future fractures, ensuring women's recognition of their diagnosis of osteoporosis/osteopenia and addressing their concerns about osteoporosis are critical components to consider when attempting to influence stage of behavior transitions in osteoporosis treatment.

The effects of myo-inositol and probiotic supplementation in a high-fat-fed preclinical model of glucose intolerance in pregnancy.

Glucose intolerance during pregnancy - a major driver of gestational diabetes mellitus (GDM) - has significant short- and long-term health consequences for both the mother and child. As GDM prevalence continues to escalate, there is growing need for preventative strategies. There is limited but suggestive evidence that myo-inositol (MI) and probiotics (PB) could improve glucose tolerance during pregnancy. The present study tested the hypothesis that MI and/or PB supplementation would reduce the risk of glucose intolerance during pregnancy. Female C57BL/6 mice were randomised to receive either no treatment, MI, PB (Lactobacillus rhamnosus and Bifidobacterium lactis) or both (MIPB) for 5 weeks. They were then provided with a high-fat diet for 1 week before mating commenced and throughout mating/gestation, while remaining on their respective treatments. An oral glucose tolerance test occurred at gestational day (GD) 16·5 and tissue collection at GD 18·5. Neither MI nor PB, separately or combined, improved glucose tolerance. However, MI and PB both independently increased adipose tissue expression of Ir, Irs1, Akt2 and Pck1, and PB also increased Pparγ. MI was associated with reduced gestational weight gain, whilst PB was associated with increased maternal fasting glucose, total cholesterol and pancreas weight. These results suggest that MI and PB may improve insulin intracellular signalling in adipose tissue but this did not translate to meaningful differences in glucose tolerance. The absence of fasting hyperglycaemia or insulin resistance suggests this is a very mild model of GDM, which may have affected our ability to assess the impact of these nutrients.

Computing the relevant colors that describe the color palette of paintings.

In this paper, we introduce an innovative parameter that allows us to evaluate the so-called "relevant colors" in a painting; in other words, the number of colors that would stand out for an observer when just glancing at a painting. These relevant colors allow us to characterize the color palette of a scene and, on this basis, those discernible colors that are colorimetrically different within the scene. We tried to carry out this characterization of the chromatic range of paints according to authors and styles. We used a collection of 4,266 paintings by 91 painters, from which we extracted various parameters that are exclusively colorimetric to characterize the range of colors. After this refinement of the set of selected colors, our algorithm obtained an average number of 18 relevant colors, which partially agreed with the total 11-15 basic color names usually found in other categorical color studies.

Self-perception of fracture risk: what can it tell us?

In this study, we report that self-perception of fracture risk captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is associated with improved medication uptake. It suggests that adequate appreciation of fracture risk may be beneficial and lead to greater healthcare engagement and treatment. INTRODUCTION: This study aimed to assess how well self-perception of fracture risk, and fracture risk as estimated by the fracture prediction tool FRAX, related to fracture incidence and uptake and persistence of anti-osteoporosis medication among women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW). METHODS: GLOW is an international cohort study involving 723 physician practices across 10 countries in Europe, North America and Australia. Aged ≥ 55 years, 60,393 women completed baseline questionnaires detailing medical history, including co-morbidities, fractures and self-perceived fracture risk (SPR). Annual follow-up included self-reported incident fractures and anti-osteoporosis medication (AOM) use. We calculated FRAX risk without bone mineral density measurement. RESULTS: Of the 39,241 women with at least 1 year of follow-up data, 2132 (5.4%) sustained an incident major osteoporotic fracture over 5 years of follow-up. Within each SPR category, risk of fracture increased as the FRAX categorisation of risk increased. In GLOW, only 11% of women with a lower baseline SPR were taking AOM at baseline, compared with 46% of women with a higher SPR. AOM use tended to increase in the years after a reported fracture. However, women with a lower SPR who were fractured still reported lower AOM rates than women with or without a fracture but had a higher SPR. CONCLUSIONS: These results suggest that SPR captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is also associated with improved medication uptake.

Novel Water-Soluble Mucoadhesive Carbosilane Dendrimers for Ocular Administration.

The purpose of this research was to determine the potential use of water-soluble anionic and cationic carbosilane dendrimers (generations 1-3) as mucoadhesive polymers in eyedrop formulations. Cationic carbosilane dendrimers decorated with ammonium -NH3(+) groups were prepared by hydrosylilation of Boc-protected allylamine and followed by deprotection with HCl. Anionic carbosilane dendrimers with terminal carboxylate groups were also employed in this study. In vitro and in vivo tolerance studies were performed in human ocular epithelial cell lines and rabbit eyes respectively. The interaction of dendrimers with transmembrane ocular mucins was evaluated with a surface biosensor. As proof of concept, the hypotensive effect of a carbosilane dendrimer eyedrop formulation containing acetazolamide (ACZ), a poorly water-soluble drug with limited ocular penetration, was tested after instillation in normotensive rabbits. The methodology used to synthesize cationic dendrimers avoids the difficulty of obtaining neutral -NH2 dendrimers that require harsher reaction conditions and also present high aggregation tendency. Tolerance studies demonstrated that both prototypes of water-soluble anionic and cationic carbosilane dendrimers were well tolerated in a range of concentrations between 5 and 10 µM. Permanent interactions between cationic carbosilane dendrimers and ocular mucins were observed using biosensor assays, predominantly for the generation-three (G3) dendrimer. An eyedrop formulation containing G3 cationic carbosilane dendrimers (5 µM) and ACZ (0.07%) (289.4 mOsm; 5.6 pH; 41.7 mN/m) induced a rapid (onset time 1 h) and extended (up to 7 h) hypotensive effect, and led to a significant increment in the efficacy determined by AUC0(8h) and maximal intraocular pressure reduction. This work takes advantage of the high-affinity interaction between cationic carbosilane dendrimers and ocular transmembrane mucins, as well as the tensioactive behavior observed for these polymers. Our results indicate that low amounts of cationic carbosilane dendrimers are well tolerated and able to improve the hypotensive effect of an acetazolamide solution. Our results suggest that carbosilane dendrimers can be used in a safe range of concentrations to enhance the bioavailability of drugs topically administered in the eye.

Disease-specific perception of fracture risk and incident fracture rates: GLOW cohort study.

UNLABELLED: Accurate patient risk perception of adverse health events promotes greater autonomy over, and motivation towards, health-related lifestyles. INTRODUCTION: We compared self-perceived fracture risk and 3-year incident fracture rates in postmenopausal women with a range of morbidities in the Global Longitudinal study of Osteoporosis in Women (GLOW). METHODS: GLOW is an international cohort study involving 723 physician practices across ten countries (Europe, North America, Australasia); 60,393 women aged ≥55 years completed baseline questionnaires detailing medical history and self-perceived fracture risk. Annual follow-up determined self-reported incident fractures. RESULTS: In total 2,945/43,832 (6.8%) sustained an incident fracture over 3 years. All morbidities were associated with increased fracture rates, particularly Parkinson's disease (hazard ratio [HR]; 95% confidence interval [CI], 3.89; 2.78-5.44), multiple sclerosis (2.70; 1.90-3.83), cerebrovascular events (2.02; 1.67-2.46), and rheumatoid arthritis (2.15; 1.53-3.04) (all p < 0.001). Most individuals perceived their fracture risk as similar to (46%) or lower than (36%) women of the same age. While increased self-perceived fracture risk was strongly associated with incident fracture rates, only 29% experiencing a fracture perceived their risk as increased. Under-appreciation of fracture risk occurred for all morbidities, including neurological disease, where women with low self-perceived fracture risk had a fracture HR 2.39 (CI 1.74-3.29) compared with women without morbidities. CONCLUSIONS: Postmenopausal women with morbidities tend to under-appreciate their risk, including in the context of neurological diseases, where fracture rates were highest in this cohort. This has important implications for health education, particularly among women with Parkinson's disease, multiple sclerosis, or cerebrovascular disease.

The Role of the Army Medical Corps (MC) in the Caribbean Campaign of the Spanish American War.

The 5th Army Medical Corps Caribbean campaigns provided valuable lessons on the noncombat hazards to troops and the challenges to the provision of care in a tropical theater of operations. The Army quickly adapted the lessons learnt for the invasion in Puerto Rico and future overseas expeditions.

Higher Plasma Myo-Inositol in Pregnancy Associated with Reduced Postpartum Blood Loss: Secondary Analyses of the NiPPeR Trial.

We previously reported that a combined myo-inositol, probiotics, and enriched micronutrient supplement (intervention) taken preconception and in pregnancy reduced postpartum blood loss (PBL) and major postpartum hemorrhage compared with a standard micronutrient supplement (control), as secondary outcomes of the NiPPeR trial. This study aimed to identify the intervention components that may contribute to this effect. Associations of plasma concentrations of myo-inositol and vitamins B2, B6, B12, and D at preconception (before and after supplementation), early (~7-weeks), and late pregnancy (~28-weeks) with PBL were assessed by multiple linear regression, adjusting for site, ethnicity, preconception BMI, parity, and previous cesarean section. Amongst 583 women, a higher concentration of myo-inositol in early pregnancy was associated with a PBL reduction [ßadj -1.26 (95%CI -2.23, -0.29) mL per µmol/L myo-inositol increase, p = 0.011]. Applying this co-efficient to the increase in mean 7-week-myo-inositol concentration of 23.4 µmol/L with the intervention equated to a PBL reduction of 29.5 mL (~8.4% of mean PBL of 350 mL among controls), accounting for 84.3% of the previously reported intervention effect of 35 mL. None of the examined vitamins were associated with PBL. Therefore, myo-inositol may be a key intervention component mediating the PBL reduction. Further work is required to determine the mechanisms involved.

Skeletal effects of nutrients and nutraceuticals, beyond calcium and vitamin D.

There is a need to understand the role of nutrition, beyond calcium and vitamin D, in the treatment and prevention of osteoporosis in adults. Results regarding soy compounds on bone density and bone turnover are inconclusive perhaps due to differences in dose and composition or in study population characteristics. The skeletal benefit of black cohosh and red clover are unknown. Dehydroepiandrosterone (DHEA) use may benefit elderly individuals with low serum dehydroepiandrosterone-sulfate levels, but even in this group, there are inconsistent benefits to bone density (BMD). Higher fruit and vegetable intakes may relate to higher BMD. The skeletal benefit of flavonoids, carotenoids, omega-3-fatty acids, and vitamins A, C, E and K are limited to observational data or a few clinical trials, in some cases investigating pharmacologic doses. Given limited data, it would be better to get these nutrients from fruits and vegetables. Potassium bicarbonate may improve calcium homeostasis but with little impact on bone loss. High homocysteine may relate to fracture risk, but the skeletal benefit of each B vitamin is unclear. Magnesium supplementation is likely only required in persons with low magnesium levels. Data are very limited for the role of nutritional levels of boron, strontium, silicon and phosphorus in bone health. A nutrient rich diet with adequate fruits and vegetables will generally meet skeletal needs in healthy individuals. For most healthy adults, supplementation with nutrients other than calcium and vitamin D may not be required, except in those with chronic disease and the frail elderly.

Prediction of fat-free mass in young children using bioelectrical impedance spectroscopy.

BACKGROUND: Bioimpedance devices are practical for measuring body composition in preschool children, but their application is limited by the lack of validated equations. OBJECTIVES: To develop and validate fat-free mass (FFM) bioimpedance prediction equations among New Zealand 3.5-year olds, with dual-energy X-ray absorptiometry (DXA) as the reference method. METHODS: Bioelectrical impedance spectroscopy (SFB7, ImpediMed) and DXA (iDXA, GE Lunar) measurements were conducted on 65 children. An equation incorporating weight, sex, ethnicity, and impedance was developed and validated. Performance was compared with published equations and mixture theory prediction. RESULTS: The equation developed in ~70% (n = 45) of the population (FFM [kg] = 1.39 + 0.30 weight [kg] + 0.39 length2/resistance at 50 kHz [cm2/Ω] + 0.30 sex [M = 1/F = 0] + 0.28 ethnicity [1 = Asian/0 = non-Asian]) explained 88% of the variance in FFM and predicted FFM with a root mean squared error of 0.39 kg (3.4% of mean FFM). When internally validated (n = 20), bias was small (40 g, 0.3% of mean FFM), with limits of agreement (LOA) ±7.6% of mean FFM (95% LOA: -0.82, 0.90 kg). Published equations evaluated had similar LOA, but with marked bias (>12.5% of mean FFM) when validated in our cohort, likely due to DXA differences. Of mixture theory methods assessed, the SFB7 inbuilt equation with personalized body geometry values performed best. However, bias and LOA were larger than with the empirical equations (-0.43 kg [95% LOA: -1.65, 0.79], p < 0.001). CONCLUSIONS: We developed and validated a bioimpedance equation that can accurately predict FFM. Further external validation of the equation is required.

The effect of a preconception and antenatal nutritional supplement on children's BMI and weight gain over the first 2 years of life: findings from the NiPPeR randomised controlled trial.

BACKGROUND: Nutritional intervention before and throughout pregnancy might promote healthy infant weight gain; however, clinical evidence is scarce. Therefore, we examined whether preconception and antenatal supplementation would affect the body size and growth of children in the first 2 years of life. METHODS: Women were recruited from the community before conception in the UK, Singapore, and New Zealand, and randomly allocated to either the intervention (myo-inositol, probiotics, and additional micronutrients) or control group (standard micronutrient supplement) with stratification by site and ethnicity. Measurements of weight and length were obtained from 576 children at multiple timepoints in the first 2 years of life. Differences in age and sex standardised BMI at age 2 years (WHO standards) and the change in weight from birth were examined. Written informed consent was obtained from the mothers, and ethics approval was granted by local committees. The NiPPeR trial was registered with ClinicalTrials.gov (NCT02509988) on July 16, 2015 (Universal Trial Number U1111-1171-8056). FINDINGS: 1729 women were recruited between Aug 3, 2015, and May 31, 2017. Of the women randomised, 586 had births at 24 weeks or more of gestation between April, 2016, and January, 2019. At age 2 years, adjusting for study site, infant sex, parity, maternal smoking, maternal prepregnancy BMI, and gestational age, fewer children of mothers who received the intervention had a BMI of more than the 95th percentile (22 [9%] of 239 vs 44 [18%] of 245, adjusted risk ratio 0·51, 95% CI 0·31-0·82, p=0·006). Longitudinal data revealed that the children of mothers who received the intervention had a 24% reduced risk of experiencing rapid weight gain of more than 0·67 SD in the first year of life (58 [21·9%] of 265 vs 80 [31·1%] of 257, adjusted risk ratio 0·76, 95% CI 0·58-1·00, p=0·047). Risk was likewise decreased for sustained weight gain of more than 1·34 SD in the first 2 years (19 [7·7%] of 246 vs 43 [17·1%] of 251, adjusted risk ratio 0·55, 95% CI 0·34-0·88, p=0·014). INTERPRETATION: Rapid weight gain in infancy is associated with future adverse metabolic health. The intervention supplement taken before and throughout pregnancy was associated with lower risk of rapid weight gain and high BMI at age 2 years among children. Long-term follow-up is required to assess the longevity of these benefits. FUNDING: National Institute for Health Research; New Zealand Ministry of Business, Innovation and Employment; Société Des Produits Nestlé; UK Medical Research Council; Singapore National Research Foundation; National University of Singapore and the Agency of Science, Technology and Research; and Gravida.

Skeletal effects of vitamin D supplementation in postmenopausal black women.

Black women have lower serum 25-hydroxyvitamin D (25[OH]D) levels and higher parathyroid hormone (PTH) levels than white peers but lower bone turnover, suggesting skeletal resistance to PTH. Our objective was to determine if vitamin D supplementation (1,000 IU/day) would prevent bone loss and whether vitamin D receptor (VDR) polymorphisms modify the response. We performed a 2-year randomized, controlled, double-blind study of 1,000 IU vitamin D(3) vs. placebo in postmenopausal black women with serum 25(OH)D levels <20 ng/mL (n = 103). Measurements of 25(OH)D, PTH, and bone turnover were evaluated at baseline and 3, 6, 12, 18, and 24 months. DNA was extracted from peripheral blood leukocytes, and genotyping was conducted using standard techniques. Spine and hip bone mineral density (BMD) was measured at baseline and every 6 months. Serum 25(OH)D increased 11 ng/mL with vitamin D supplementation (p < 0.001), with no change in the placebo group. Vitamin D supplementation produced a significant decline in PTH at 3 months only, with no differences in bone turnover between placebo and vitamin D at any time point. Two-year changes in BMD were not significantly different between placebo- and vitamin D-treated black women at any skeletal site. Despite similar elevations in 25(OH)D, femoral neck BMD was only responsive to vitamin D supplementation in FF subjects (n = 47), not Ff/ff subjects (n = 31). Vitamin D supplementation does not appear to influence bone loss in black women. However, in the FF polymorphism of the VDR gene group, vitamin D supplementation may retard the higher rate of bone loss.

Casualties of the Spanish Army in Cuba During the "Long War" of 1868-1878.

Spanish continental soldiers were ill prepared for the environmental conditions they encountered in the first of three wars for Cuban independence. The disease fatality rate was over 80% with yellow fever the most prevalent disease. Another 7% of these soldiers died in battle or from their combat wounds.

Use of Nicergoline as Adjunctive Treatment of Neurotrophic Keratitis in Routine Clinical Practice: A Case Series.

PURPOSE: To describe the effectiveness and safety of nicergoline in patients with epithelial corneal defect or corneal ulcer due to neurotrophic keratitis (NK). METHODS: A prospective case series review was performed in 14 patients with NK who started treatment with nicergoline as an off-label prescription from January to November 2020. Patients with a epithelial defect or corneal ulcer due to NK were treated with oral nicergoline. RESULTS/SERIAL CASES: Complete corneal healing was observed in 10 (71.4%) of the 14 patients after 25.6 ± 26.60 days (range 7-90) with nicergoline. In three (21.5%) patients wound healing was not achieved, and one patient (7.1%) was lost to follow-up. The mean time between diagnosis and the starting of nicergoline was 10.92 ± 8.85 days (0-28). No adverse effects of nicergoline were observed. CONCLUSION: Nicergoline as an adjunctive treatment for NK showed a potential use in the healing of epithelial defect in real-life clinical practice.

Fragility fractures of the hip and femur: incidence and patient characteristics.

SUMMARY: Using national discharge and medical claims data, we studied the epidemiology of femoral fractures from 1996 to 2006. The annual hip fracture incidence declined from 600/100,000 to 400/100,000, without decline in the more rare femur fractures. Incidence rates for subtrochanteric and femoral shaft fractures were each below 20 per 100,000. INTRODUCTION: This study's purpose is to describe the site-specific epidemiology of femur fractures among people aged 50 and older. METHODS: Using the National Hospital Discharge Survey from 1996 to 2006 and a large medical claims database (MarketScan), we studied epidemiology of all femur fractures. Hip fractures were grouped together; subtrochanteric, shaft, and distal femur fractures were kept separate. RESULTS: In females, the overall hospital discharge rates of hip fracture decreased from about 600/100,00 to 400/100,000 person-years from 1996 to 2006. Subtrochanteric, femoral shaft, and lower femur rates remained stable, each approximately 20 per 100,000 person-years. Similar trends but lower rates existed in males. No significant trends were found in any of these fractures during the more recent years of 2002-2006 (MarketScan data). Using MarketScan, the overall incidence of hip fracture was <300/100,000 person-years; incidence of subtrochanteric and femoral shaft fractures combined was <25/100,000 person-years and distal femur fracture incidence was <18/100,000 person-years in females; rates were lower in males. The incidence of hip and other femur fractures increased exponentially with age. CONCLUSIONS: We found no evidence of an increasing incidence of any femoral fracture. Hip fracture incidence is declining but the incidence of each of the more rare femur fractures (distal to the lesser trochanter) is stable over time.