Higher hemoglobin levels are an independent risk factor for adverse metabolism and higher mortality in a 20-year follow-up

The aim of this study was to cross-sectionally and longitudinally examine whether higher hemoglobin (Hb) levels within the normal variation associate with key components of metabolic syndrome and total and cardiovascular mortality. The study included 967 Finnish subjects (age 40–59 years) followed for ≥ 20 years. The focus was on Hb levels, cardiovascular diseases (CVDs) and mortality rates. Higher Hb levels associated positively with key anthropometric and metabolic parameters at baseline. At the follow-up similar associations were seen in men. The highest Hb quartile showed higher leptin levels and lower adiponectin levels at baseline and follow-up (p < 0.05) and lower plasma ghrelin levels at baseline (p < 0.05). Higher baseline Hb levels associated independently with prevalence of type 2 diabetes at follow-up (p < 0.01). The highest Hb quartile associated with higher serum alanine aminotransferase levels (p < 0.001) and independently with increased risk for liver fat accumulation (OR 1.63 [1.03; 2.57]) at baseline. The highest Hb quartile showed increased risk for total (HR = 1.48 [1.01; 2.16]) and CVD-related mortality (HR = 2.08 [1.01; 4.29]). Higher Hb levels associated with an adverse metabolic profile, increased prevalence of key components of metabolic syndrome and higher risk for CVD-related and total mortality.

Loss and Expense

This chapter identifies standard forms and bespoke forms of contract that provide a mechanism whereby the employer can order changes to the work to be done. It discusses the power to order varied work that is used frequently by employers who have often not had all their requirements sorted out at the time of the letting of the contract. It also distinguishes limitations upon the employer’s right to vary the work pursuant to a normal variation clause, such as the limitation in which the change ordered cannot alter the essential characteristic of the contract itself. This chapter covers the limitation in which the employer may not order the omission of work simply in order to instruct another contractor to do the same or almost the same work. It describes claims for sums due under the contract that are dealt with non-contentiously.

Timing of Pubertal Onset in Girls and Boys with Constitutional Delay

Context The decision whether to treat a child with delayed puberty with sex steroids is primarily based on patient, family, and provider preference. Knowing when children with constitutional delay eventually enter puberty would inform this decision. Objective, Design, Setting, Participants, and Outcome Measures To estimate and compare rates of pubertal entry, we conducted a retrospective cohort study by reviewing medical records of children evaluated for delayed puberty at a large academic medical center between 2000 and 2015, extracting data on pubertal status for all clinical visits, then conducting time-to-event analyses. Results Of 392 girls and 683 boys with delayed puberty, constitutional delay was the most common cause, found in 32% of girls and 70% of boys. In a subcohort of 97 girls and 243 boys who were prepubertal at one or more visits, we observed a broad age range for pubertal entry, up to &gt;16 years for girls and &gt;17 years for boys. The probability of entering puberty within the next year for 12- to 15.5-year-old girls and 13.5- to 16.5-year-old boys with delayed puberty ranged between 38% and 74%. No differences in the rates of pubertal entry were seen between girls and boys after data harmonization. Conclusion The broad range of ages at pubertal entry for children with constitutional delay challenges the concept that constitutional delay is merely an extreme of normal variation. Discussions with patients and families about management should consider the possibility that some children may need to wait years after presentation until puberty starts.

Engaging the complexity of diet and healthy aging in humans

Little is known about how normal variation in dietary patterns in humans affects the aging process, largely because both nutrition and the physiology of aging are highly complex and multidimensional. Here, we apply the nutritional geometry framework to data from 1560 older adults followed over four years to assess how nutrient intake patterns affect the aging process. Aging was quantified via blood biomarkers integrated to measure loss of homeostasis. Additionally, we extend nutritional geometry to 19 micronutrients. Salient results include benefits of intermediate protein and vitamin E intake. Broadly, we show that there are few simple answers of "good" or "bad" nutrients – optimal levels are generally intermediate, but dependent on other nutrients. Simpler linear/univariate analytical approaches are insufficient to capture such associations. We present an interactive tool to explore the results, and our approach presents a roadmap for future studies to explore the full complexity of the nutrition-aging landscape.

Determinants of adolescent lung function in Indians: race, nutrition and systemic inflammation

RationaleWhile determining normal variation of spirometric volumes, the geo-political construct of ‘Indian’ inadequately captures the diverse racial structure and varied lifestyles that exist for 1 in 5 people globally. It is necessary to determine the degree of racial heterogeneity and other underlying factors to know whether lower spirometric volumes of ‘Indians’ is normal or abnormal.ObjectivesTo investigate the differences in spirometric volumes and their associations with overall health parameters, for adolescent children and young adults, across geo-ethnic regions within India.MethodsData was analyzed for 2338 healthy subjects aged 9-19 years with acceptable spirometry from SOLID cohort. Associations between lung function and potential determinants (Race, anthropometry, nutrition, family/life history, airway oscillometric parameters and systemic inflammation) were examined by using multiple regression. Latent profile analysis (LPA) was performed for 903 subjects to uncover hidden sub-phenotypes.ResultsFEV1 and FVC varied significantly between Indian genetic ancestries, being highest in Tibeto-Burmans and lowest in Dravidians. After statistical adjustments, FEV1 and FVC were positively correlated with waist-height-ratio, shoulder-height-ratio, normalized BMI, and blood hemoglobin. Lower FVC was associated with lower expiratory flows (PEF and FEF25-75), higher lung reactance (X5), higher airway resistance (R10 and R15), gastro-intestinal symptoms, and higher inflammation (IL-8 and IL-17). A sub-phenotype of thinness, higher inflammation (IFN-gamma, IL-17, TNF-alpha, IL-8) and lower FVC was identified on LPA for 35% of the sample.ConclusionsSpirometric volumes in Indians are different between major racial subgroups but may also be abnormally low due to prevalent nutritional or environmental adversity. Care must be taken while establishing normative standards.