Associations Between Aldosterone-Renin-Ratio and Bone Parameters Derived from Peripheral Quantitative Computed Tomography and Impact Microindentation in Men.

Components of the renin-angiotensin-aldosterone system (RAAS) are present on bone cells. One measure of RAAS activity, the aldosterone-renin-ratio (ARR), is used to screen for primary aldosteronism. Associations between ARR and bone mineral density are conflicting. This study investigated associations between ARR and peripheral quantitative computed tomography (pQCT) and impact microindentation (IMI). Male participants (n = 431) were from the Geelong Osteoporosis Study. "Likely" primary aldosteronism was defined as ARR ≥ 70 pmol/mIU. Another group, "possible" primary aldosteronism, was defined as either ARR ≥ 70 pmol/mIU or taking a medication that affects the RAAS, but not a beta blocker, and renin < 15 mU/L. Using pQCT, images at 4% and 66% of radial (n = 365) and tibial (n = 356) length were obtained. Using IMI measurements, bone material strength index (BMSi; n = 332) was determined. Associations between ARR or likely/possible primary aldosteronism and IMI or pQCT-derived bone parameters were tested using median regression. ARR and aldosterone values were not associated with any of the pQCT-derived bone variables in either unadjusted or adjusted analyses. Men with likely primary aldosteronism (n = 16), had lower adjusted total bone area (radial 66% site, - 12.5%). No associations were observed for men with possible primary aldosteronism (unadjusted or adjusted). No associations with BMSi were observed (p > 0.05). There were no associations between ARR or aldosterone and pQCT-derived bone parameters. Men with likely primary aldosteronism had lower bone area, suggesting clinically high levels of ARR may have a negative impact on bone health.

Fracture Risk and Use of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers.

Medications used to treat hypertension may affect fracture risk. This study investigated fracture risk for users of angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). Participants (899 men, median age 70.3 yr (59.9-79.1), range 50.0-96.6 yr; 574 women, median age 65.5 yr (58.1-75.4), range 50.1-94.6 yr) were from the Geelong Osteoporosis Study. Medication use was self-reported and incident fractures were ascertained using radiological reports. Bone mineral density (BMD) was measured at the femoral neck. Participants were divided into four groups: (1) non-users without hypertension, (2) non-users with hypertension, (3) ACEI users and (4) ARB users. Dosage was calculated using the defined daily dose (DDD) criteria. Participants were followed from date of visit to first fracture, death or 31 December 2016, whichever occurred first. Cox proportional hazards models were used for analyses. At least one incident fracture was sustained by 156 men and 135 women over a median(IQR) of 11.5(6.2-13.2) and 10.9(6.3-11.6) years of follow-up, respectively. In unadjusted analyses, compared to non-users without hypertension, men in all three other groups had a higher risk of fracture (Hazard Ratio (HR, 95%CI) 1.54, 1.00-2.37; 1.90, 1.18-3.05; 2.15, 1.26-3.66), for non-users with hypertension, ACEI and ARB users, respectively). Following adjustment for age, prior fracture and BMD, these associations became non-significant. A dose effect for ARB use was observed; men using lower doses had a higher risk of fracture than non-users without hypertension, in both unadjusted (2.66, 1.34-5.29) and adjusted (2.03, 1.01-4.08) analyses, but this association was not observed at higher doses. For women, unadjusted analyses showed a higher risk for ACEI users compared to non-users without hypertension (1.74, 1.07-2.83). This was explained after adjustment for age, alcohol consumption, prior fracture and BMD (1.28, 0.74-2.22). No other differences were observed. In men, lower dose (0 < DDD ≤ 1) ARB use was associated with an increased risk of fracture. ACEI or ARB use was not associated with increased risk of incident fracture in women. These findings may be important for antihypertensive treatment decisions in individuals with a high risk of fracture.

The role of microglia in neuropsychiatric disorders and suicide.

This narrative review examines the possible role of microglial cells, first, in neuroinflammation and, second, in schizophrenia, depression, and suicide. Recent research on the interactions between microglia, astrocytes and neurons and their involvement in pathophysiological processes of neuropsychiatric disorders is presented. This review focuses on results from postmortem, positron emission tomography (PET) imaging studies, and animal models of schizophrenia and depression. Third, the effects of antipsychotic and antidepressant drug therapy, and of electroconvulsive therapy on microglial cells are explored and the upcoming development of therapeutic drugs targeting microglia is described. Finally, there is a discussion on the role of microglia in the evolutionary progression of human lineage. This view may contribute to a new understanding of neuropsychiatric disorders.

The role of mechanotransduction in heart failure pathobiology-a concise review.

This review evaluates the role of mechanotransduction (MT) in heart failure (HF) pathobiology. Cardiac functional and structural modifications are regulated by biomechanical forces. Exposing cardiomyocytes and the myocardial tissue to altered biomechanical stress precipitates changes in the end-diastolic wall stress (EDWS). Thereby various interconnected biomolecular pathways, essentially mediated and orchestrated by MT, are launched and jointly contribute to adapt and remodel the myocardium. This cardiac MT-mediated feedback decisively determines the primary cardiac cellular and tissue response, the sort (concentric or eccentric) of hypertrophy/remodeling, to mechanical and/or hemodynamic alterations. Moreover, the altered EDWS affects the diastolic myocardial properties independent of the systolic function, and elevated EDWS causes diastolic dysfunction. The close interconnection between MT pathways and the cell nucleus, the genetic endowment, principally allows for the wide variety of phenotypic appearances. However, demographic, environmental features, comorbidities, and also the genetic make-up may modulate the phenotypic result. Cardiac MT takes a fundamental and superordinate position in the myocardial adaptation and remodeling processes in all HF categories and phenotypes. Therefore, the effects of MT should be integrated in all our scientific, clinical, and therapeutic considerations.

Genetic load and biological changes to extant humans.

Extant humans are currently increasing their genetic load, which is informing present and future human microevolution. This has been a gradual process that has been rising over the last centuries as a consequence of improved sanitation, nutritional improvements, advancements in microbiology and medical interventions, which have relaxed natural selection. Moreover, a reduction in infant and child mortality and changing societal attitudes towards fertility have led to a decrease in total fertility rates (TFRs) since the 19th century. Generally speaking, decreases in differential fertility and mortality have meant that there is less opportunity for natural selection to eliminate deleterious mutations from the human gene pool. It has been argued that the average human may carry ~250-300 mutations that are mostly deleterious, as well as several hundred less-deleterious variants. These deleterious alleles in extant humans mean that our fitness is being constrained. While such alleles are viewed as reducing human fitness, they may also have had an adaptive function in the past, such as assisting in genetic complexity, sexual recombination and diploidy. Saying this, our current knowledge on these fitness compromising alleles is still lacking.

Recently increased prevalence of the human median artery of the forearm: A microevolutionary change.

The median artery has been considered as an embryonic structure, which normally regresses around the 8th week of gestation. However, various prevalences have been reported in adults since the 18th century. Furthermore, in a study by Henneberg and George (1995; Am J Phys Anthropol 96, 329-334), has suggested that increasing prevalence of the median artery during the 20th century was a 'possible secular trend'. The present study, conducted nearly a quarter of a century later, is a continuation of that study. A total of 26 median arteries were found in 78 upper limbs obtained from Australians aged 51 to 101 years, who died in the period 2015-2016, a prevalence rate of 33.3%. Analysis of the literature showed that the presence of the median artery has been significantly increasing (p = .001) over time, from approximately 10% in people born in the mid-1880s to approximately 30% by the end of the 20th century. The significance of the prevalence increased to a p value <.0001, when the results of the present study and other studies conducted by our research team were combined. After removal of the studies that were possibly biased, because of their specific focus on the evolutionary aspects of the median artery, the significance remained at p = .018. The present study provides an example of microevolutionary changes in the internal anatomy of the human body. Second-order polynomial regression of the median artery's prevalence on dates of birth shows that it is now present in 35% of people and predicts that people born 80 years from now will all carry a median artery if the trend continues. When the median artery prevalence reaches 50% or more, it should not be considered as a variant, but as a 'normal' human structure.

Advancing the understanding of treponemal disease in the past and present.

Syphilis was perceived to be a new disease in Europe in the late 15th century, igniting a debate about its origin that continues today in anthropological, historical, and medical circles. We move beyond this age-old debate using an interdisciplinary approach that tackles broader questions to advance the understanding of treponemal infection (syphilis, yaws, bejel, and pinta). How did the causative organism(s) and humans co-evolve? How did the related diseases caused by Treponema pallidum emerge in different parts of the world and affect people across both time and space? How are T. pallidum subspecies related to the treponeme causing pinta? The current state of scholarship in specific areas is reviewed with recommendations made to stimulate future work. Understanding treponemal biology, genetic relationships, epidemiology, and clinical manifestations is crucial for vaccine development today and for investigating the distribution of infection in both modern and past populations. Paleopathologists must improve diagnostic criteria and use a standard approach for recording skeletal lesions on archaeological human remains. Adequate contextualization of cultural and environmental conditions is necessary, including site dating and justification for any corrections made for marine or freshwater reservoir effects. Biogeochemical analyses may assess aquatic contributions to diet, physiological changes arising from treponemal disease and its treatments (e.g., mercury), or residential mobility of those affected. Shifting the focus from point of origin to investigating who is affected (e.g., by age/sex or socioeconomic status) and disease distribution (e.g., coastal/ inland, rural/urban) will advance our understanding of the treponemal disease and its impact on people through time.

Greater family size is associated with less cancer risk: an ecological analysis of 178 countries.

BACKGROUND: Greater family size measured with total fertility rate (TFR) and with household size, may offer more life satisfaction to the family members. Positive psychological well-being has been postulated to decrease cancer initiation risk. This ecological study aims to examine the worldwide correlation between family size, used as the measure of positive psychological well-being, and total cancer incidence rates. METHODS: Country specific estimates obtained from United Nations agencies on total cancer incidence rates (total, female and male rates in age range 0-49 years and all ages respectively), all ages site cancer incidence (bladder, breast, cervix uteri, colorectum, corpus uteri, lung, ovary and stomach), TFR, household size, life expectancy, urbanization, per capita GDP PPP and self-calculated Biological State Index (Ibs) were matched for data analysis. Pearson's, non-parametric Spearman's, partial correlations, independent T-test and multivariate regressions were conducted in SPSS. RESULTS: Worldwide, TFR and household size were significantly and negatively correlated to all the cancer incidence variables. These correlations remained significant in partial correlation analysis when GDP, life expectancy, Ibs and urbanization were controlled for. TFR correlated to male cancer incidence rate (all ages) significantly stronger than it did to female cancer incidence rate (all ages) in both Pearson's and partial correlations. Multivariate stepwise regression analysis indicated that TFR and household size were consistently significant predictors of all cancer incidence variables. CONCLUSIONS: Countries with greater family size have lower cancer risk in both females, and especially males. Our results seem to suggest that it may be worthwhile further examining correlations between family size and cancer risk in males and females through the cohort and case-control studies based on large samples.

Evolutionary Medicine: The Ongoing Evolution of Human Physiology and Metabolism.

The field of evolutionary medicine uses evolutionary principles to understand changes in human anatomy and physiology that have occurred over time in response to environmental changes. Through this evolutionary-based approach, we can understand disease as a consequence of anatomical and physiological "trade-offs" that develop to facilitate survival and reproduction. We demonstrate how diachronic study of human anatomy and physiology is fundamental for an increased understanding of human health and disease.

The cerebral basal arterial network: morphometry of inflow and outflow components.

The aim of this project was to study how the morphology of the incoming and outgoing arterial components of the cerebral basal arterial network influence the blood flow to the brain. The cerebral basal arterial network consists of the circulus arteriosus cerebri anteriorly and the basilar artery posteriorly. Diameters of inflow vessels (bilateral vertebral and internal carotid arteries), connecting vessels (anterior communicating, basilar and bilateral posterior communicating arteries) and outflow vessels (anterior, middle and posterior cerebral arteries) were measured and cross-sectional areas calculated in 51 cadaveric brain specimens. The individual and the average cross-sectional areas of inflow arteries (51.43 mm2 ) were significantly bigger than the major outflow arteries (37.76 mm2 ) but smaller than the combined cross-sectional areas of outflow (37.76 mm2 ) and connecting (25.33 mm2 ) arteries. The difference in the size of arterial cross-sectional area and the presence of the connecting arteries in the cerebral basal arterial network provides a mechanism for lowering peaks in pressure, and demonstrates a function of the cerebral basal arterial network.

Estimating a child's age from an image using whole body proportions.

The use and distribution of child pornography is an increasing problem. Forensic anthropologists are often asked to estimate a child's age from a photograph. Previous studies have attempted to estimate the age of children from photographs using ratios of the face. Here, we propose to include body measurement ratios into age estimates. A total of 1603 boys and 1833 girls aged 5-16 years were measured over a 10-year period. They are 'Cape Coloured' children from South Africa. Their age was regressed on ratios derived from anthropometric measurements of the head as well as the body. Multiple regression equations including four ratios for each sex (head height to shoulder and hip width, knee width, leg length and trunk length) have a standard error of 1.6-1.7 years. The error is of the same order as variation of differences between biological and chronological ages of the children. Thus, the error cannot be minimised any further as it is a direct reflection of a naturally occurring phenomenon.

Association between body height and month of birth among women of European origin in northern and southern hemispheres.

OBJECTIVES: The purpose of this study was to examine the potential association between month of birth and body height among women in northern and southern hemispheres. METHODS: Body heights of adult women of European origin born between 1935 and 1981 who lived in Poland (N = 3,933) and in Australia (N = 1,118) were examined in relation to month of birth by analysis of variance. RESULTS: No association between month of birth and body height was observed in either Polish or Australian women. For Polish women, a clear, statistically significant secular trend in body height was confirmed for the analyzed period (P < .0001). No such trend occurred among the Australian women. CONCLUSIONS: Results do not confirm a significant association between month of birth and adult body height in women. It is, however, important to see a difference in secular trends, which was large in Polish women and nonexistent in Australian females.

Rare events in earth history include the LB1 human skeleton from Flores, Indonesia, as a developmental singularity, not a unique taxon.

The original centrally defining features of "Homo floresiensis" are based on bones represented only in the single specimen LB1. Initial published values of 380-mL endocranial volume and 1.06-m stature are markedly lower than later attempts to confirm them, and facial asymmetry originally unreported, then denied, has been established by our group and later confirmed independently. Of nearly 200 syndromes in which microcephaly is one sign, more than half include asymmetry as another sign and more than one-fourth also explicitly include short stature. The original diagnosis of the putative new species noted and dismissed just three developmental abnormalities. Subsequent independent attempts at diagnosis (Laron Syndrome, Majewski osteodysplastic primordial dwarfism type II, cretinism) have been hampered a priori by selectively restricted access to specimens, and disparaged a posteriori using data previously unpublished, without acknowledging that all of the independent diagnoses corroborate the patent abnormal singularity of LB1. In this report we establish in detail that even in the absence of a particular syndromic diagnosis, the originally defining features of LB1 do not establish either the uniqueness or normality necessary to meet the formal criteria for a type specimen of a new species. In a companion paper we present a new syndromic diagnosis for LB1.

Evolved developmental homeostasis disturbed in LB1 from Flores, Indonesia, denotes Down syndrome and not diagnostic traits of the invalid species Homo floresiensis.

Human skeletons from Liang Bua Cave, Flores, Indonesia, are coeval with only Homo sapiens populations worldwide and no other previously known hominins. We report here for the first time to our knowledge the occipitofrontal circumference of specimen LB1. This datum makes it possible to link the 430-mL endocranial volume of LB1 reported by us previously, later confirmed independently by other investigators, not only with other human skeletal samples past and present but also with a large body of clinical data routinely collected on patients with developmental disorders. Our analyses show that the brain size of LB1 is in the range predicted for an individual with Down syndrome (DS) in a normal small-bodied population from the geographic region that includes Flores. Among additional diagnostic signs of DS and other skeletal dysplasiae are abnormally short femora combined with disproportionate flat feet. Liang Bua Cave femora, known only for LB1, match interlimb proportions for DS. Predictions based on corrected LB1 femur lengths show a stature normal for other H. sapiens populations in the region.

Comparing the face to the body, which is better for identification?

As early as the nineteenth century, measurements of the face and body were used for forensic identification. It was believed that no two individuals had the exact same measurements. However, this was overtaken by fingerprint analysis because it was considered more reliable in court proceedings as the probabilities of finding matching individuals could be calculated. With the standardisation of photographs, identification primarily occurs from the face. With the ability to take measurements from photographs, why not use the body? The Army Anthropometry Survey (ANSUR) database contains anthropometric measurements of 3982 individuals. Eight facial and eight body measurements were compared to investigate whether or not there is enough information on the body to use for identification. Measurements were compared by adding one measurement to the other(s) in a stepwise approach until there were no duplicate cases where two or more individuals share the same combination of measurements. Results consistently show that less body measurements are needed to find no duplicates when compared to the face. The larger the range of each of the measurements, the less chance there is of finding a duplicate. With the combination of eight body measurements, it is possible to achieve a probability of finding a duplicate to the order of 10(-20) or 1 in a quintillion. These results are comparable with fingerprint analysis. The body is more variable than the face and should be used in identification. An advantage to using the body is that larger dimensions are easier to locate on images and not affected by facial expression.

Diagnosing congenital syphilis using Hutchinson's method: Differentiating between syphilitic, mercurial, and syphilitic-mercurial dental defects.

OBJECTIVES: This study focuses on the dental abnormalities observed by Sir Jonathan Hutchinson, Henry Moon and Alfred Fournier in patients with congenital syphilis and in those treated with mercury, in order to define alterations in dental morphology attributable to each of these causes. These definitions are applied to reported paleopathological cases, exploring various etiologies behind the defects, in order to aid in the diagnosis of congenital syphilis. METHODS: Original works were examined for descriptions of dental abnormalities in congenital syphilis and in mercurial treatments. These descriptions were compared with dentitions of paleopathological cases (n = 4) demonstrating abnormalities attributed to congenital syphilis. RESULTS: Distinct morphological differences were recognized between congenital syphilitic teeth and teeth affected by mercury. Mercury produces a pronounced deficiency in enamel of incisors, canines and first permanent molars that become rugged and pitted, and of dirty grey honeycombed appearance. Mercury-induced dental changes are evident in three out of four cases studied here. In one case, only syphilitic changes were present. DISCUSSION: Dental changes in congenital syphilis range from no visible signs to those beyond the classical models of Hutchinson, Moon and Fournier. Treatment of neonates and infants with mercury produces additional changes. Signs of disease and treatment with mercury on teeth may occur together; permanent incisors, first molars and canines, are typically affected, premolars and second/third molars are usually spared. Signs of treatment with mercury might be the only evidence of the occurrence of the disease as mercury was rarely used to treat other diseases.

Body height of mummified pharaohs supports historical suggestions of sibling marriages.

Body height is an important factor in reconstructing health conditions and it serves as an indicator of socio-economic status. Researchers rely on ancient data to analyze evolutionary aspects of human health and its interrelation with environmental influences. This study presents body height estimates from all periods of ancient Egyptian history and compares the general population with the existing mummies of the members of royal families. A sample of 259 adult Egyptian mummies originating from various collections and published sources with body lengths (long bone measures or/and overall measurements, CT data) were analyzed, and royal mummies were scored with respect to the level of consanguinity. Male royals were taller than males in the general ancient Egyptian population, while female royals were shorter than females in the general population. The body height variation of the royals is significantly reduced when compared with a pool of non-royal mummies. This provides evidence for inbreeding resulting from consanguineous marriages. However, there appears to be no correlation between the level of inbreeding and individual body height. The random sample of general population does not show signs of inbreeding. Due to the present lack of larger, technically and ethically challenging genetic studies, the selected non-invasive approach of body height is the most reliable indicator of sibling marriages of pharaohs based on direct physical evidence.