Optimum frequency of exercise for bone health: randomised controlled trial of a high-impact unilateral intervention

Introduction: Exercise can increase bone strength, but to be effective in reducing fracture risk, exercise must be feasible enough to be adopted into daily life and influence potentially vulnerable skeletal sites such as the superolateral cortex of the femoral neck, where thinning is associated with increased fracture risk. Brief, high-impact exercise increases femoral neck bone density but the optimal frequency of such exercise and the location of bone accrual is unknown. This study thus examined (1) the effectiveness of different weekly frequencies of exercise on femoral neck BMD and (2) whether BMD change differed between hip sites using a high-impact, unilateral intervention. Methods: Healthy premenopausal women were randomly assigned to exercise 0, 2, 4, or 7 days/week for 6 months. The exercise intervention incorporated 50 multidirectional hops on one randomly selected leg. BMD was measured by DXA at baseline and after 6 months of exercise. Changes in the exercise leg were compared between groups using ANCOVA, with change in the control leg and baseline BMD as covariates. RM-MANOVA was conducted to determine whether bone changes from exercise differed between hip sites. Results: 61 women (age 33.6±11.1 years) completed the intervention. Compliance amongst exercisers was 86.7±10.6%. Peak ground reaction forces during exercise increased from 2.5 to 2.8 times body weight. The change in femoral neck BMD in the exercise limb (adjusted for change in the control limb and baseline BMD) differed between groups (p=0.015), being −0.3% (−1.2 to 0.6), 0.0% (−1.0 to 1.0), 0.9% (−0.1 to 2.0) and 1.8% (0.8 to 2.8) in those exercising 0, 2, 4 and 7 days per week, respectively. When BMD changes at upper neck, lower neck and trochanter were compared using RM-MANOVA, a significant exercise effect was observed (p=0.048), but this did not differ significantly between sites (p=0.439) despite greatest mean increases at the upper femoral neck. Conclusions: Brief, daily hopping exercises increased femoral neck BMD in premenopausal women but less frequent exercise was not effective. Brief high-impact exercise may have a role in reducing hip fragility, but may need to be performed frequently for optimal response

Prevention of sexual transmission of Ebola in Liberia through a national semen testing and counselling programme for survivors: an analysis of Ebola virus RNA results and behavioural data

BACKGROUND: Ebola virus has been detected in semen of Ebola virus disease survivors after recovery. Liberia\u27s Men\u27s Health Screening Program (MHSP) offers Ebola virus disease survivors semen testing for Ebola virus. We present preliminary results and behavioural outcomes from the first national semen testing programme for Ebola virus. METHODS: The MHSP operates out of three locations in Liberia: Redemption Hospital in Montserrado County, Phebe Hospital in Bong County, and Tellewoyan Hospital in Lofa County. Men aged 15 years and older who had an Ebola treatment unit discharge certificate are eligible for inclusion. Participants\u27 semen samples were tested for Ebola virus RNA by real-time RT-PCR and participants received counselling on safe sexual practices. Participants graduated after receiving two consecutive negative semen tests. Counsellors collected information on sociodemographics and sexual behaviours using questionnaires administered at enrolment, follow up, and graduation visits. Because the programme is ongoing, data analysis was restricted to data obtained from July 7, 2015, to May 6, 2016. FINDINGS: As of May 6, 2016, 466 Ebola virus disease survivors had enrolled in the programme; real-time RT-PCR results were available from 429 participants. 38 participants (9%) produced at least one semen specimen that tested positive for Ebola virus RNA. Of these, 24 (63%) provided semen specimens that tested positive 12 months or longer after Ebola virus disease recovery. The longest interval between discharge from an Ebola treatment unit and collection of a positive semen sample was 565 days. Among participants who enrolled and provided specimens more than 90 days since their Ebola treatment unit discharge, men older than 40 years were more likely to have a semen sample test positive than were men aged 40 years or younger (p=0.0004). 84 (74%) of 113 participants who reported not using a condom at enrolment reported using condoms at their first follow-up visit (p \u3c 0.0001). 176 (46%) of 385 participants who reported being sexually active at enrolment reported abstinence at their follow-up visit (p \u3c 0.0001). INTERPRETATION: Duration of detection of Ebola virus RNA by real-time RT-PCR varies by individual and might be associated with age. By combining behavioural counselling and laboratory testing, the Men\u27s Health Screening Program helps male Ebola virus disease survivors understand their individual risk and take appropriate measures to protect their sexual partners. FUNDING: World Health Organization and the US Centers for Disease Control and Prevention

Online mindfulness stress intervention for family carers of children and adults with intellectual disabilities : feasibility randomized controlled trial

Objectives: Family carers of people with intellectual disabilities (ID) are twice as likely as other carers to experience stress and mental ill-health, but research exploring interventions is sparse. Online mindfulness may provide an accessible, cost-effective resource. The addition of guided telephone support could help to tailor an existing intervention for this population. A feasibility randomized controlled trial (RCT) was conducted to inform the development of a definitive RCT. Methods: Sixty participants were randomized to complete Be Mindful (a brief online mindfulness intervention) either with or without additional Peer Mentor support. Feasibility of recruitment, retention, intervention adherence, and acceptability of study design were examined. Preliminary analyses were undertaken on participant-reported outcomes pre- and post-intervention. Eighteen semi-structured interviews were conducted as a process evaluation. Results: Feasibility outcomes indicate that it would be possible to recruit and retain (88%) participants to a definitive RCT, and that the study design and intervention are acceptable. The addition of guided telephone support was not burdensome; indeed, it was additionally motivating. Telephone support can be delivered with high fidelity, but this is inconsistent and requires further piloting. Preliminary comparison data indicate small, but non-significant, improvements for participants receiving guided telephone support relative to those who did not over time. Conclusions: It is feasible to deliver online mindfulness with additional telephone guided support to family carers of people with ID, and this may lead to small benefits over receiving online mindfulness alone. A definitive RCT can be planned to examine the effectiveness and cost-effectiveness of this intervention

Fortification and health: challenges and opportunities.

Fortification is the process of adding nutrients or non-nutrient bioactive components to edible products (e.g., food, food constituents, or supplements). Fortification can be used to correct or prevent widespread nutrient intake shortfalls and associated deficiencies, to balance the total nutrient profile of a diet, to restore nutrients lost in processing, or to appeal to consumers looking to supplement their diet. Food fortification could be considered as a public health strategy to enhance nutrient intakes of a population. Over the past century, fortification has been effective at reducing the risk of nutrient deficiency diseases such as beriberi, goiter, pellagra, and rickets. However, the world today is very different from when fortification emerged in the 1920s. Although early fortification programs were designed to eliminate deficiency diseases, current fortification programs are based on low dietary intakes rather than a diagnosable condition. Moving forward, we must be diligent in our approach to achieving effective and responsible fortification practices and policies, including responsible marketing of fortified products. Fortification must be applied prudently, its effects monitored diligently, and the public informed effectively about its benefits through consumer education efforts. Clear lines of authority for establishing fortification guidelines should be developed and should take into account changing population demographics, changes in the food supply, and advances in technology. This article is a summary of a symposium presented at the ASN Scientific Sessions and Annual Meeting at Experimental Biology 2014 on current issues involving fortification focusing primarily on the United States and Canada and recommendations for the development of responsible fortification practices to ensure their safety and effectiveness

Quantitative Analysis of Outer Retinal Tubulation in Age-Related Macular Degeneration From Spectral-Domain Optical Coherence Tomography and Histology

Purpose: To assess outer retinal tubulation (ORT) morphology from spectral-domain optical coherence tomography (SD-OCT) volumes and donor eye histology, analyze ORT reflectivity, and estimate the number of cones surviving in ORT. Methods: In SD-OCT volumes from nine patients with advanced AMD, ORT was analyzed en face and in B-scans. The hyperreflective ORT border in cross-section was delineated and surface area calculated. Reflectivity was compared between ORT types (Closed, Open, Forming, and Branching). A flatmount retina from a donor with neovascular AMD was labeled to visualize the external limiting membrane that delimits ORT and allow measurements of cross-sectional cone area, center-to-center cone spacing, and cone density. The number of cones surviving in ORT was estimated. Results: By en face SD-OCT, ORT varies in complexity and shape. Outer retinal tubulation networks almost always contain Closed cross-sections. Spectral-domain OCT volumes containing almost exclusively Closed ORTs showed no significant direction-dependent differences in hyperreflective ORT border intensity. The surface areas of partial ORT assessed by SD-OCT volumes ranged from 0.16 to 1.76 mm2. From the flatmount retina, the average cross-sectional area of cone inner segments was 49.1 ± 7.9 μm2. The average cone spacing was 7.5 ± 0.6 μm. Outer retinal tubulation cone density was 20,351 cones/mm2. The estimated number of cones in ORT in a macula ranged from 26,399 to 186,833 cones, which is 6% to 44% of the cones present in a healthy macula. Conclusions: These first estimates for cone density and number of cones surviving in ORT suggest that ORT formation considerably distorts the photoreceptor mosaic. Results provide additional insight into the reflectivity characteristics and number of ORT cones observable in living patients by SD-OCT, as cones persist and disease progresses

A Case Study

OK Publisher Copyright: © 2023 American Academy of OphthalmologyPurpose: To investigate intraretinal neovascularization and microvascular anomalies by correlating in vivo multimodal imaging with corresponding ex vivo histology in a single patient. Design: A case study comprising clinical imaging from a community-based practice, and histologic analysis at a university-based research laboratory (clinicopathologic correlation). Participants: A White woman in her 90s treated with numerous intravitreal anti-VEGF injections for bilateral type 3 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD). Methods: Clinical imaging comprised serial infrared reflectance, eye-tracked spectral-domain OCT, OCT angiography, and fluorescein angiography. Eye tracking, applied to the 2 preserved donor eyes, enabled the correlation of clinical imaging signatures with high-resolution histology and transmission electron microscopy. Main Outcome Measures: Histologic/ultrastructural descriptions and diameters of vessels seen in clinical imaging. Results: Six vascular lesions were histologically confirmed (type 3 MNV, n = 3; deep retinal age-related microvascular anomalies [DRAMAs], n = 3). Pyramidal (n = 2) or tangled (n = 1) morphologies of type 3 MNV originated at the deep capillary plexus (DCP) and extended posteriorly to approach without penetrating persistent basal laminar deposit. They did not enter the subretinal pigment epithelium (RPE)–basal laminar space or cross the Bruch membrane. Choroidal contributions were not found. The neovascular complexes included pericytes and nonfenestrated endothelial cells, within a collagenous sheath covered by dysmorphic RPE cells. Deep retinal age-related microvascular anomaly lesions extended posteriorly from the DCP into the Henle fiber and the outer nuclear layers without evidence of atrophy, exudation, or anti-VEGF responsiveness. Two DRAMAs lacked collagenous sheaths. External and internal diameters of type 3 MNV and DRAMA vessels were larger than comparison vessels in the index eyes and in aged normal and intermediate AMD eyes. Conclusions: Type 3 MNV vessels reflect specializations of source capillaries and persist during anti-VEGF therapy. The collagenous sheath of type 3 MNV lesions may provide structural stabilization. If so, vascular characteristics may be useful in disease monitoring in addition to fluid and flow signal detection. Further investigation with longitudinal imaging before exudation onset will help determine if DRAMAs are part of the type 3 MNV progression sequence. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.publishersversionpublishe

Bone geometry according to menstrual function in female endurance athletes

Athletes have higher bone mineral density (BMD) relative to nonathletes. In amenorrheic athletes BMD may be compromised by estrogen deficiency, but it is unknown whether this is accompanied by structural differences. We compared femoral neck bone geometry and density of a-/oligomenorrheic athletes (AAs), eumenorrheic athletes (EAs), and eumenorrheic controls (ECs). We recruited 156 women: (68 endurance athletes and 88 controls). Femoral neck BMD, section modulus (Z), and width were measured using dual-energy X-ray absorptiometry. Menstrual function was assessed by questionnaire and classified as EA(C10 periods/year) or AA(B9periods/year): 24 athletes were AA and 44 EA. Femoral neck BMD was significantly higher in EA than AA (8 %, difference) and EC (11 % difference): mean [SE] 1.118 [0.015], 1.023 [0.020] and 0.999 [0.014] g cm-2, respectively; p\0.001. Z was significantly higher in EA than EC (11 % difference): EA 667 [19], AA 625 [21], and EC 592 [10] cm3; p\0.001. Femoral neck width did not differ between groups. All differences persisted after adjustment for height, age, and body mass. The higher femoral neck Z and BMD in athletes, despite similar width, may indicate that exercise-related bone gains are endosteal rather than periosteal. Athletes with amenorrhea had smaller increments in bone mass rather than structural adaptation. The maintained femoral neck width in controls may be an adaptive mechanism to conserve bone strength in bending despite inactivity-related bone decrement

Supporting Parental Decisions About Genomic Sequencing for Newborn Screening: The NC NEXUS Decision Aid

Advances in genomic sequencing technology have raised fundamental challenges to the traditional ways genomic information is communicated. These challenges will become increasingly complex and will affect a much larger population in the future if genomics is incorporated into standard newborn screening practice. Clinicians, public health officials, and other stakeholders will need to agree on the types of information that they should seek and communicate to parents. Currently, few evidence-based and validated tools are available to support parental informed decision-making. These tools will be necessary as genomics is integrated into clinical practice and public health systems. In this article we describe how the North Carolina Newborn Exome Sequencing for Universal Screening study is addressing the need to support parents in making informed decisions about the use of genomic testing in newborn screening. We outline the context for newborn screening and justify the need for parental decision support. We also describe the process of decision aid development and the data sources, processes, and best practices being used in development. By the end of the study, we will have an evidenced-based process and validated tools to support parental informed decision-making about the use of genomic sequencing in newborn screening. Data from the study will help answer important questions about which genomic information ought to be sought and communicated when testing newborns

Modeling a methylmalonic acid–derived change point for serum vitamin B-12 for adults in NHANES

Background: No consensus exists about which cutoff point should be applied for serum vitamin B-12 (SB-12) concentrations to define vitamin B-12 status in population-based research. Objective: The study’s aim was to identify whether a change point exists at which the relation between plasma methylmalonic acid (MMA) and SB-12 changes slope to differentiate between inadequate and adequate vitamin B-12 status by using various statistical models. Design:We used data on adults ($19 y; n = 12,683) from NHANES 1999–2004—a nationally representative, cross-sectional survey. We evaluated 6 piece-wise polynomial and exponential decay models that used different control levels for known covariates. Results: The MMA-defined change point for SB-12 varied depending on the statistical model used. A linear-splines model was determined to best fit the data, as determined by the approximate permutation test; 3 slopes relating SB-12 and MMA and resulting in 2 change points and 3 subgroups were shown. The first group (SB-12 ,126 pmol/L) was small and had the highest MMA concentration (median: 281 nmol/L; 95% CI: 245, 366 nmol/L; n = 157, 1.2%); many in this group could be considered at high risk of severe deficiency because combined abnormalities of MMA and homocysteine were very frequent and the concentrations themselves were significantly higher. The highest SB-12 group (SB-12 .287 pmol/ L; n = 8569, 67.6%) likely had adequate vitamin B-12 status (median MMA: 120 nmol/L; 95% CI: 119, 125 nmol/L). The vitamin B-12 status of the sizable intermediate group (n = 3957, 33%) was difficult to interpret. Conclusions: The 3 distinct slopes for the relation between SB-12 and MMA challenges the conventional use of one cutoff point for classifying vitamin B-12 status. In epidemiologic research, the use of one cutoff point would fail to separate the small, severely deficient group from the intermediate group that has neither normal nor clearly deficient vitamin B-12 concentrations (ie, unknown vitamin B-12 status). This intermediate group requires further characterization

A prophylactic vaccine for breast cancer?

Cancer vaccines are the Holy Grail for patients and clinicians alike. The possibility that we can be vaccinated against common cancers is very appealing and the socioeconomic consequences are significant. A recent paper from Vincent Tuohy's group, published in the journal Nature Medicine, suggests a new approach for the development of a prophylactic vaccine for breast cancer. Their strategy was to induce mammary gland failure in mice by immunisation with an antibody specific to a milk protein that resulted in autoimmunity during lactation. This also showed some efficacy as a therapeutic vaccine. Can we look forward to the elimination of breast cancer