All Papers

Sathish Subramanian, Sayeeda Huq, Tanya Yatsunenko, Rashidul Haque et al.

Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM), but incomplete restoration of healthy growth remains a major problem. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S ribosomal RNA data sets generated from monthly faecal samples obtained from birth onwards in a cohort of children living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a ‘relative microbiota maturity index’ and ‘microbiota-for-age Z-score’ that compare postnatal assembly (defined here as maturation) of a child’s faecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors, including diarrhoea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.

Md Mahbub Hossain, Samia Tasnim, Abida Sultana, Farah Faizah et al.

The novel coronavirus disease 2019 (COVID-19) has become a pandemic affecting health and wellbeing globally. In addition to the physical health, economic, and social implications, the psychological impacts of this pandemic are increasingly being reported in the scientific literature. This narrative review reflected on scholarly articles on the epidemiology of mental health problems in COVID-19. The current literature suggests that people affected by COVID-19 may have a high burden of mental health problems, including depression, anxiety disorders, stress, panic attack, irrational anger, impulsivity, somatization disorder, sleep disorders, emotional disturbance, posttraumatic stress symptoms, and suicidal behavior. Moreover, several factors associated with mental health problems in COVID-19 are found, which include age, gender, marital status, education, occupation, income, place of living, close contact with people with COVID-19, comorbid physical and mental health problems, exposure to COVID-19 related news and social media, coping styles, stigma, psychosocial support, health communication, confidence in health services, personal protective measures, risk of contracting COVID-19, and perceived likelihood of survival. Furthermore, the epidemiological distribution of mental health problems and associated factors were heterogeneous among the general public, COVID-19 patients, and healthcare providers. The current evidence suggests that a psychiatric epidemic is cooccurring with the COVID-19 pandemic, which necessitates the attention of the global health community. Future epidemiological studies should emphasize on psychopathological variations and temporality of mental health problems in different populations. Nonetheless, multipronged interventions should be developed and adopted to address the existing psychosocial challenges and promote mental health amid the COVID-19 pandemic.

Samuel A.J. Trammell, Mark S. Schmidt, Benjamin J. Weidemann, Philip Redpath et al.

Abstract Nicotinamide riboside (NR) is in wide use as an NAD + precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD + metabolism in humans. We report that human blood NAD + can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral NR elevates mouse hepatic NAD + with distinct and superior pharmacokinetics to those of nicotinic acid and nicotinamide. We further show that single doses of 100, 300 and 1,000 mg of NR produce dose-dependent increases in the blood NAD + metabolome in the first clinical trial of NR pharmacokinetics in humans. We also report that nicotinic acid adenine dinucleotide (NAAD), which was not thought to be en route for the conversion of NR to NAD + , is formed from NR and discover that the rise in NAAD is a highly sensitive biomarker of effective NAD + repletion.

Nurshad Ali

The outbreak of COVID-19 has created a global public health crisis. Little is known about the protective factors of this infection. Therefore, preventive health measures that can reduce the risk of infection, progression and severity are desperately needed. This review discussed the possible roles of vitamin D in reducing the risk of COVID-19 and other acute respiratory tract infections and severity. Moreover, this study determined the correlation of vitamin D levels with COVID-19 cases and deaths in 20 European countries as of 20 May 2020. A significant negative correlation (p=0.033) has been observed between mean vitamin D levels and COVID-19 cases per one million population in European countries. However, the correlation of vitamin D with COVID-19 deaths of these countries was not significant. Some retrospective studies demonstrated a correlation between vitamin D status and COVID-19 severity and mortality, while other studies did not find the correlation when confounding variables are adjusted. Several studies demonstrated the role of vitamin D in reducing the risk of acute viral respiratory tract infections and pneumonia. These include direct inhibition with viral replication or with anti-inflammatory or immunomodulatory ways. In the meta-analysis, vitamin D supplementation has been shown as safe and effective against acute respiratory tract infections. Thus, people who are at higher risk of vitamin D deficiency during this global pandemic should consider taking vitamin D supplements to maintain the circulating 25(OH)D in the optimal levels (75-125nmol/L). In conclusion, there is not enough evidence on the association between vitamin D levels and COVID-19 severity and mortality. Therefore, randomized control trials and cohort studies are necessary to test this hypothesis.

Andrew Mente, Martin O’Donnell, Sumathy Rangarajan, Gilles R. Dagenais et al.

BACKGROUND Several studies reported a U-shaped association between urinary sodium excretion and cardiovascular disease events and mortality. Whether these associations vary between those individuals with and without hypertension is uncertain. We aimed to explore whether the association between sodium intake and cardiovascular disease events and all-cause mortality is modified by hypertension status. METHODS In this pooled analysis, we studied 133,118 individuals (63,559 with hypertension and 69,559 without hypertension), median age of 55 years (IQR 45-63), from 49 countries in four large prospective studies and estimated 24-h urinary sodium excretion (as group-level measure of intake). We related this to the composite outcome of death and major cardiovascular disease events over a median of 4.2 years (IQR 3.0-5.0) and blood pressure. FINDINGS Increased sodium intake was associated with greater increases in systolic blood pressure in individuals with hypertension (2.08 mm Hg change per g sodium increase) compared with individuals without hypertension (1.22 mm Hg change per g; pinteraction<0.0001). In those individuals with hypertension (6835 events), sodium excretion of 7 g/day or more (7060 [11%] of population with hypertension: hazard ratio [HR] 1.23 [95% CI 1.11-1.37]; p<0.0001) and less than 3 g/day (7006 [11%] of population with hypertension: 1.34 [1.23-1.47]; p<0.0001) were both associated with increased risk compared with sodium excretion of 4-5 g/day (reference 25% of the population with hypertension). In those individuals without hypertension (3021 events), compared with 4-5 g/day (18,508 [27%] of the population without hypertension), higher sodium excretion was not associated with risk of the primary composite outcome (≥ 7 g/day in 6271 [9%] of the population without hypertension; HR 0.90 [95% CI 0.76-1.08]; p=0.2547), whereas an excretion of less than 3 g/day was associated with a significantly increased risk (7547 [11%] of the population without hypertension; HR 1.26 [95% CI 1.10-1.45]; p=0.0009). INTERPRETATION Compared with moderate sodium intake, high sodium intake is associated with an increased risk of cardiovascular events and death in hypertensive populations (no association in normotensive population), while the association of low sodium intake with increased risk of cardiovascular events and death is observed in those with or without hypertension. These data suggest that lowering sodium intake is best targeted at populations with hypertension who consume high sodium diets. FUNDING Full funding sources listed at end of paper (see Acknowledgments).

Ian Gilron

Neuropathic pain, caused by various central and peripheral nerve disorders, is especially problematic because of its severity, chronicity and resistance to simple analgesics. The condition affects 2%-3% of the population, is costly to the health care system and is personally devastating to the people who experience it. The diagnosis of neuropathic pain is based primarily on history (e.g., underlying disorder and distinct pain qualities) and the findings on physical examination (e.g., pattern of sensory disturbance); however, several tests may sometimes be helpful. Important pathophysiologic mechanisms include sodium-and calcium-channel upregulation, spinal hyperexcitability, descending facilitation and aberrant sympathetic-somatic nervous system interactions. Treatments are generally palliative and include conservative nonpharmacologic therapies, drugs and more invasive interventions (e.g., spinal cord stimulation). Individualizing treatment requires consideration of the functional impact of the neuropathic pain (e.g., depression, disability) as well as ongoing evaluation, patient education, reassurance and specialty referral. We propose a primary care algorithm for treatments with the most favourable risk-benefit profile, including topical lidocaine, gabapentin, pregabalin, tricyclic antidepressants, mixed serotonin-norepinephrine reuptake inhibitors, tramadol and opioids. The field of neuropathic pain research and treatment is in the early stages of development, with many unmet goals. In coming years, several advances are expected in the basic and clinical sciences of neuropathic pain, which will provide new and improved therapies for patients who continue to experience this disabling condition.

David F. Choy, Kevin M. Hart, Lee A. Borthwick, Aarti Shikotra et al.

Increasing evidence suggests that asthma is a heterogeneous disorder regulated by distinct molecular mechanisms. In a cross-sectional study of asthmatics of varying severity (n = 51), endobronchial tissue gene expression analysis revealed three major patient clusters: TH2-high, TH17-high, and TH2/17-low. TH2-high and TH17-high patterns were mutually exclusive in individual patient samples, and their gene signatures were inversely correlated and differentially regulated by interleukin-13 (IL-13) and IL-17A. To understand this dichotomous pattern of T helper 2 (TH2) and TH17 signatures, we investigated the potential of type 2 cytokine suppression in promoting TH17 responses in a preclinical model of allergen-induced asthma. Neutralization of IL-4 and/or IL-13 resulted in increased TH17 cells and neutrophilic inflammation in the lung. However, neutralization of IL-13 and IL-17 protected mice from eosinophilia, mucus hyperplasia, and airway hyperreactivity and abolished the neutrophilic inflammation, suggesting that combination therapies targeting both pathways may maximize therapeutic efficacy across a patient population comprising both TH2 and TH17 endotypes.

Willian A. da Silveira, Hossein Fazelinia, Sara Brin Rosenthal, Evagelia C. Laiakis et al.

Spaceflight is known to impose changes on human physiology with unknown molecular etiologies. To reveal these causes, we used a multi-omics, systems biology analytical approach using biomedical profiles from fifty-nine astronauts and data from NASA’s GeneLab derived from hundreds of samples flown in space, to determine transcriptomic, proteomic, metabolomic, and epigenetic responses to spaceflight. Overall pathway analyses on the multi-omic datasets showed significant enrichment for mitochondrial processes, as well as innate immunity, chronic inflammation, cell cycle, circadian rhythm, and olfactory functions. Importantly, NASA’s Twin Study provided a platform to confirm several of our principal findings. Evidence of altered mitochondrial function and DNA damage was also found in the urine and blood metabolic data compiled from the astronaut cohort and NASA Twin Study data, indicating mitochondrial stress as a consistent phenotype of spaceflight.

Md Shahjahan, Khanam Taslima, Mohammad Shadiqur Rahman, Md Al-Emran et al.

The pollution by heavy metals poses a serious threat to the aquatic environment and to the organisms if the concentration of heavy metals in the environment exceeds the safe limits. Due to their non-biodegradable and long persistence nature in the environment, heavy metals cause toxicity in fish by producing oxygen reactive species through oxidizing radical production. In this review, we investigated the effects of heavy metals on fish physiology with special emphasis on hemato-biochemical properties, immunological parameters especially hormones and enzymes, histopathology of different major organs and underlying molecular mechanisms. All those parameters are significantly affected by heavy metal exposure and are found to be important bio-monitoring tools to assess heavy metal toxicity. Hematological and biochemical alterations have been documented including cellular and nuclear abnormalities in different fish species exposed to different concentrations of heavy metals. Major fish organs (gills, liver, kidneys) including intestine, muscles showed different types of pathology specific to organs in acute and chronic exposure to different heavy metals. This study also revealed the expression of different genes involved in oxidative stress and detoxification of heavy metals. In a nutshell, this article shades light on the manipulation of fish physiology by the heavy metals and sought attention in the prevention and maintenance of aquatic environments particularly from heavy metals contaminations.

Sabine Ring, Sascha W. Weyer, Susanne B. Kilian, Elaine Waldron et al.

It is well established that the proteolytic processing of the beta-amyloid precursor protein (APP) generates beta-amyloid (Abeta), which plays a central role in the pathogenesis of Alzheimer's disease (AD). In contrast, the physiological role of APP and of its numerous proteolytic fragments and the question of whether a loss of these functions contributes to AD are still unknown. To address this question, we replaced the endogenous APP locus by gene-targeted alleles and generated two lines of knock-in mice that exclusively express APP deletion variants corresponding either to the secreted APP ectodomain (APPs alpha) or to a C-terminal (CT) truncation lacking the YENPTY interaction motif (APPdeltaCT15). Interestingly, the deltaCT15 deletion resulted in reduced turnover of holoAPP, increased cell surface expression, and strongly reduced Abeta levels in brain, likely because of reduced processing in the endocytic pathway. Most importantly, we demonstrate that in both APP knock-in lines the expression of APP N-terminal domains either grossly attenuated or completely rescued the prominent deficits of APP knock-out mice, such as reductions in brain and body weight, grip strength deficits, alterations in circadian locomotor activity, exploratory activity, and the impairment in spatial learning and long-term potentiation. Together, our data suggest that the APP C terminus is dispensable and that APPs alpha is sufficient to mediate the physiological functions of APP assessed by these tests.

Nurshad Ali, Jenny Katsouli, Emma L. Marczylo, Timothy W. Gant et al.

Humans are exposed to micro-and-nano plastics (MNPs) through various routes, but the adverse health effects of MNPs on different organ systems are not yet fully understood. This review aims to provide an overview of the potential impacts of MNPs on various organ systems and identify knowledge gaps in current research. The summarized results suggest that exposure to MNPs can lead to health effects through oxidative stress, inflammation, immune dysfunction, altered biochemical and energy metabolism, impaired cell proliferation, disrupted microbial metabolic pathways, abnormal organ development, and carcinogenicity. There is limited human data on the health effects of MNPs, despite evidence from animal and cellular studies. Most of the published research has focused on specific types of MNPs to assess their toxicity, while other types of plastic particles commonly found in the environment remain unstudied. Future studies should investigate MNPs exposure by considering realistic concentrations, dose-dependent effects, individual susceptibility, and confounding factors.

Ana Navas‐Acién, Ellen K. Silbergeld, Robin A. Streeter, Jeanne M. Clark et al.

Chronic arsenic exposure has been suggested to contribute to diabetes development. We performed a systematic review of the experimental and epidemiologic evidence on the association of arsenic and type 2 diabetes. We identified 19 in vitro studies of arsenic and glucose metabolism. Five studies reported that arsenic interfered with transcription factors involved in insulin-related gene expression: upstream factor 1 in pancreatic beta-cells and peroxisome proliferative-activated receptor gamma in preadipocytes. Other in vitro studies assessed the effect of arsenic on glucose uptake, typically using very high concentrations of arsenite or arsenate. These studies provide limited insight on potential mechanisms. We identified 10 in vivo studies in animals. These studies showed inconsistent effects of arsenic on glucose metabolism. Finally, we identified 19 epidemiologic studies (6 in high-arsenic areas in Taiwan and Bangladesh, 9 in occupational populations, and 4 in other populations). In studies from Taiwan and Bangladesh, the pooled relative risk estimate for diabetes comparing extreme arsenic exposure categories was 2.52 (95% confidence interval, 1.69-3.75), although methodologic problems limit the interpretation of the association. The evidence from occupational studies and from general populations other than Taiwan or Bangladesh was inconsistent. In summary, the current available evidence is inadequate to establish a causal role of arsenic in diabetes. Because arsenic exposure is widespread and diabetes prevalence is reaching epidemic proportions, experimental studies using arsenic concentrations relevant to human exposure and prospective epidemiologic studies measuring arsenic biomarkers and appropriately assessing diabetes should be a research priority.

Martin Tondel, Mizanur Rahman, Anders Magnuson, I. Chowdhury et al.

To determine the relationship of arsenic-associated skin lesions and degree of arsenic exposure, a cross-sectional study was conducted in Bangladesh, where a large part of the population is exposed through drinking water. Four villages in Bangladesh were identified as mainly dependent on wells contaminated with arsenic. We interviewed and examined 1,481 subjects [Greater/equal to] 30 years of age in these villages. A total of 430 subjects had skin lesions (keratosis, hyperpigmentation, or hypopigmentation). Individual exposure assessment could only be estimated by present levels and in terms of a dose index, i.e., arsenic levels divided by individual body weight. Arsenic water concentrations ranged from 10 to 2,040 microg/L, and the crude overall prevalence rate for skin lesions was 29/100. After age adjustment to the world population the prevalence rate was 30. 1/100 and 26.5/100 for males and females, respectively. There was a significant trend for the prevalence rate both in relation to exposure levels and to dose index (p < 0.05), regardless of sex. This study shows a higher prevalence rate of arsenic skin lesions in males than females, with clear dose-response relationship. The overall high prevalence rate in the studied villages is an alarming sign of arsenic exposure and requires an urgent remedy.

Mahfuzar Rahman, Martin Tondel, Sk Akhtar Ahmad, Ireen Akhter Chowdhury et al.

-A prevalence comparison of hypertension among subjects with and those without arsenic exposure through drinking water was conducted in Bangladesh to confirm or refute an earlier observation of a relation in this respect. Wells with and without present arsenic contamination were identified, and we interviewed and examined 1595 subjects who were depending on drinking water from these wells for living, all >/=30 years of age. The interview was based on a questionnaire, and arsenic exposure was estimated from the history of well-water consumption and current arsenic levels. Of the 1595 subjects studied, 1481 had a history of arsenic-contaminated drinking water, whereas 114 had not. Time-weighted mean arsenic levels (in milligrams per liter) and milligram-years per liter of arsenic exposure were estimated for each subject. Exposure categories were assessed as <0.5 mg/L, 0.5 to 1.0 mg/L, and >1.0 mg/L and alternatively as <1.0 mg-y/L, 1.0 to 5.0 mg-y/L, >5.0 but </=10.0 mg-y/L, and >10.0 mg-y/L, respectively. Hypertension was defined as a systolic blood pressure of >/=140 mm Hg in combination with a diastolic blood pressure of >/=90 mm Hg. Corresponding to the exposure categories, and using "unexposed" as the reference, the prevalence ratios for hypertension adjusted for age, sex, and body mass index were 1.2, 2.2, 2.5 and 0.8, 1.5, 2.2, 3.0, in relation to arsenic exposure in milligrams per liter and milligram-years per liter, respectively. The indicated dose-response relationships were significant (P<<0.001) for both series of risk estimates. These results suggest that arsenic exposure may induce hypertension in humans.

Edwin Dale, Detlef H. Gerlach, AVA L. WILHITE

The problem of menstrual dysfunction in women who engage in endurance training for participation in distance running events has been studied. Through survey, selected aspects of the personal, training, menstrual, and contraceptive histories of 168 women who were defined as runners, joggers, or controls were evaluated. In addition, defined subsets of the study subjects were evaluated for serum levels of pituitary and ovarian hormones and determination of percentage body fat. The data show significant differences among the 3 groups. It is concluded that menstrual dysfunction in distance runners is a real phenomenon. Presumably this is related to decreased percentage of body fat and/or minimal ovarian function secondary to diminished hypothalamic or pituitary hormone secretion.

Yu Chen, Faruque Parvez, Mary V. Gamble, Tariqul Islam et al.

The contamination of groundwater by arsenic in Bangladesh is a major public health concern affecting 35-75 million people. Although it is evident that high levels (>300 microg/L) of arsenic exposure from drinking water are related to adverse health outcomes, health effects of arsenic exposure at low-to-moderate levels (10-300 microg/L) are not well understood. We established the Health Effects of Arsenic Longitudinal Study (HEALS) with more than 20,000 men and women in Araihazar, Bangladesh, to prospectively investigate the health effects of arsenic predominantly at low-to-moderate levels (0.1 to 864 microg/L, mean 99 microg/L) of arsenic exposure. Findings to date suggest adverse effects of low-to-moderate levels of arsenic exposure on the risk of pre-malignant skin lesions, high blood pressure, neurological dysfunctions, and all-cause and chronic disease mortality. In addition, the data also indicate that the risk of skin lesion due to arsenic exposure is modifiable by nutritional factors, such as folate and selenium status, lifestyle factors, including cigarette smoking and body mass index, and genetic polymorphisms in genes related to arsenic metabolism. The analyses of biomarkers for respiratory and cardiovascular functions support that there may be adverse effects of arsenic on these outcomes and call for confirmation in large studies. A unique strength of the HEALS is the availability of outcome data collected prospectively and data on detailed individual-level arsenic exposure estimated using water, blood and repeated urine samples. Future prospective analyses of clinical endpoints and related host susceptibility will enhance our knowledge on the health effects of low-to-moderate levels of arsenic exposure, elucidate disease mechanisms, and give directions for prevention.

Habibul Ahsan, Yu Chen, Faruque Parvez, Lydia B. Zablotska et al.

Millions of persons around the world are exposed to low doses of arsenic through drinking water. However, estimates of health effects associated with low-dose arsenic exposure have been extrapolated from high-dose studies. In Bangladesh, many persons have been exposed to a wide range of doses of arsenic from drinking water over a significant period of time. The authors evaluated dose-response relations between arsenic exposure from drinking water and premalignant skin lesions by using baseline data on 11,746 participants recruited in 2000-2002 for the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh. Several measures of arsenic exposure were estimated for each participant based on well-water arsenic concentration and usage pattern of the wells and on urinary arsenic concentration. In different regression models, consistent dose-response effects were observed for all arsenic exposure measures. Compared with drinking water containing <8.1 microg/liter of arsenic, drinking water containing 8.1-40.0, 40.1-91.0, 91.1-175.0, and 175.1-864.0 microg/liter of arsenic was associated with adjusted prevalence odds ratios of skin lesions of 1.91 (95% confidence interval (CI): 1.26, 2.89), 3.03 (95% CI: 2.05, 4.50), 3.71 (95% CI: 2.53, 5.44), and 5.39 (95% CI: 3.69, 7.86), respectively. The effect seemed to be influenced by gender, age, and body mass index. These findings provide information that should be considered in future research and policy decisions.

Aneesa Ansari, Md. Shahedur Rahman, Subbroto Kumar Saha, Forhad Karim Saikot et al.

In mammals, seven members of the sirtuin protein family known as class III histone deacetylase have been identified for their characteristic features. These distinguished characteristics include the tissues where they are distributed or located, enzymatic activities, molecular functions, and involvement in diseases. Among the sirtuin members, SIRT3 has received much attention for its role in cancer genetics, aging, neurodegenerative disease, and stress resistance. SIRT3 controls energy demand during stress conditions such as fasting and exercise as well as metabolism through the deacetylation and acetylation of mitochondrial enzymes. SIRT3 is well known for its ability to eliminate reactive oxygen species and to prevent the development of cancerous cells or apoptosis. This review article provides a comprehensive review on numerous (noteworthy) molecular functions of SIRT3 and its effect on cancer cells and various diseases including Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease.

Darryl P. Leong, Koon Teo, Sumathy Rangarajan, V. Raman Kutty et al.

Abstract Background The measurement of handgrip strength (HGS) has prognostic value with respect to all‐cause mortality, cardiovascular mortality and cardiovascular disease, and is an important part of the evaluation of frailty. Published reference ranges for HGS are mostly derived from Caucasian populations in high‐income countries. There is a paucity of information on normative HGS values in non‐Caucasian populations from low‐ or middle‐income countries. The objective of this study was to develop reference HGS ranges for healthy adults from a broad range of ethnicities and socioeconomically diverse geographic regions. Methods HGS was measured using a Jamar dynamometer in 125,462 healthy adults aged 35‐70 years from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Results HGS values differed among individuals from different geographic regions. HGS values were highest among those from Europe/North America, lowest among those from South Asia, South East Asia and Africa, and intermediate among those from China, South America, and the Middle East. Reference ranges stratified by geographic region, age, and sex are presented. These ranges varied from a median (25 th –75 th percentile) 50 kg (43–56 kg) in men &lt;40 years from Europe/North America to 18 kg (14–20 kg) in women &gt;60 years from South East Asia. Reference ranges by ethnicity and body‐mass index are also reported. Conclusions Individual HGS measurements should be interpreted using region/ethnic‐specific reference ranges.