Estimation of sex and age of "virtual skeletons"--a feasibility study

This article presents a feasibility study with the objective of investigating the potential of multi-detector computed tomography (MDCT) to estimate the bone age and sex of deceased persons. To obtain virtual skeletons, the bodies of 22 deceased persons with known age at death were scanned by MDCT using a special protocol that consisted of high-resolution imaging of the skull, shoulder girdle (including the upper half of the humeri), the symphysis pubis and the upper halves of the femora. Bone and soft-tissue reconstructions were performed in two and three dimensions. The resulting data were investigated by three anthropologists with different professional experience. Sex was determined by investigating three-dimensional models of the skull and pelvis. As a basic orientation for the age estimation, the complex method according to Nemeskéri and co-workers was applied. The final estimation was effected using additional parameters like the state of dentition, degeneration of the spine, etc., which where chosen individually by the three observers according to their experience. The results of the study show that the estimation of sex and age is possible by the use of MDCT. Virtual skeletons present an ideal collection for anthropological studies, because they are obtained in a non-invasive way and can be investigated ad infinitum.

Cellular senescence of white blood cells in very long-term survivors after allogeneic hematopoietic stem cell transplantation: the role of chronic graft-versus-host disease and female donor sex

In this single-center, cross-sectional study, we evaluated 44 very long-term survivors with a median follow-up of 17.5 years (range, 11-26 years) after hematopoietic stem cell transplantation. We assessed the telomere length difference in human leukocyte antigen-identical donor and recipient sibling pairs and searched for its relationship with clinical factors. The telomere length (in kb, mean +/- SD) was significantly shorter in all recipient blood cells compared with their donors' blood cells (P < .01): granulocytes (6.5 +/- 0.9 vs 7.1 +/- 0.9), naive/memory T cells (5.7 +/- 1.2 vs 6.6 +/- 1.2; 5.2 +/- 1.0 vs 5.7 +/- 0.9), B cells (7.1 +/- 1.1 vs 7.8 +/- 1.1), and natural killer/natural killer T cells (4.8 +/- 1.0 vs 5.6 +/- 1.3). Chronic graft-versus-host disease (P < .04) and a female donor (P < .04) were associated with a greater difference in telomere length between donor and recipient. Critically short telomeres have been described in degenerative diseases and secondary malignancies. If this hypothesis can be confirmed, identification of recipients at risk for cellular senescence could become part of monitoring long-term survivors after hematopoietic stem cell transplantation.

HIV infection disrupts the sympatric host-pathogen relationship in human tuberculosis

The phylogeographic population structure of Mycobacterium tuberculosis suggests local adaptation to sympatric human populations. We hypothesized that HIV infection, which induces immunodeficiency, will alter the sympatric relationship between M. tuberculosis and its human host. To test this hypothesis, we performed a nine-year nation-wide molecular-epidemiological study of HIV-infected and HIV-negative patients with tuberculosis (TB) between 2000 and 2008 in Switzerland. We analyzed 518 TB patients of whom 112 (21.6%) were HIV-infected and 233 (45.0%) were born in Europe. We found that among European-born TB patients, recent transmission was more likely to occur in sympatric compared to allopatric host-pathogen combinations (adjusted odds ratio [OR] 7.5, 95% confidence interval [95% CI] 1.21-infinity, p = 0.03). HIV infection was significantly associated with TB caused by an allopatric (as opposed to sympatric) M. tuberculosis lineage (OR 7.0, 95% CI 2.5-19.1, p<0.0001). This association remained when adjusting for frequent travelling, contact with foreigners, age, sex, and country of birth (adjusted OR 5.6, 95% CI 1.5-20.8, p = 0.01). Moreover, it became stronger with greater immunosuppression as defined by CD4 T-cell depletion and was not the result of increased social mixing in HIV-infected patients. Our observation was replicated in a second independent panel of 440 M. tuberculosis strains collected during a population-based study in the Canton of Bern between 1991 and 2011. In summary, these findings support a model for TB in which the stable relationship between the human host and its locally adapted M. tuberculosis is disrupted by HIV infection.

New anthropometry-based age- and sex-specific reference values for urinary 24-hour creatinine excretion based on the adult Swiss population.

BACKGROUND Urinary creatinine excretion is used as a marker of completeness of timed urine collections, which are a keystone of several metabolic evaluations in clinical investigations and epidemiological surveys. The current reference values for 24-hour urinary creatinine excretion rely on observations performed in the 1960s and 1970s in relatively small and mostly selected groups, and may thus poorly fit to the present-day general European population. The aim of this study was to establish and validate anthropometry-based age- and sex-specific reference values of the 24-hour urinary creatinine excretion on adult populations with preserved renal function. METHODS We used data from two independent Swiss cross-sectional population-based studies with standardised 24-hour urinary collection and measured anthropometric variables. Only data from adults of European descent, with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m(2) and reported completeness of the urinary collection were retained. A linear regression model was developed to predict centiles of the 24-hour urinary creatinine excretion in 1,137 participants from the Swiss Survey on Salt and validated in 994 participants from the Swiss Kidney Project on Genes in Hypertension. RESULTS The mean urinary creatinine excretion was 193 ± 41 μmol/kg/24 hours in men and 151 ± 38 μmol/kg/24 hours in women in the Swiss Survey on Salt. The values were inversely correlated with age and body mass index (BMI). Based on current reference values (177 to 221 μmol/kg/24 hours in men and 133 to 177 μmol/kg/24 hours in women), 56% of the urinary collections in the whole population and 67% in people >60 years old would have been considered as inaccurate. A linear regression model with sex, BMI and age as predictor variables was found to provide the best prediction of the observed values and showed a good fit when applied to the validation population. CONCLUSIONS We propose a validated prediction equation for 24-hour urinary creatinine excretion in the general European population, based on readily available variables such as age, sex and BMI, and a few derived normograms to ease its clinical application. This should help healthcare providers to interpret the completeness of a 24-hour urine collection in daily clinical practice and in epidemiological population studies.

Age-specific and sex-specific weight gain norms to monitor antiretroviral therapy in children in low-income and middle-income countries.

BACKGROUND Viral load and CD4% are often not available in resource-limited settings for monitoring children's responses to antiretroviral therapy (ART). We aimed to construct normative curves for weight gain at 6, 12, 18, and 24 months following initiation of ART in children, and to assess the association between poor weight gain and subsequent responses to ART. DESIGN Analysis of data from HIV-infected children younger than 10 years old from African and Asian clinics participating in the International epidemiologic Databases to Evaluate AIDS. METHODS The generalized additive model for location, scale, and shape was used to construct normative percentile curves for weight gain at 6, 12, 18, and 24 months following ART initiation. Cox proportional models were used to assess the association between lower percentiles (< 50th) of weight gain distribution at the different time points and subsequent death, virological suppression, and virological failure. RESULTS Among 7173 children from five regions of the world, 45% were underweight at baseline. Weight gain below the 50th percentile at 6, 12, 18, and 24 months of ART was associated with increased risk of death, independent of baseline characteristics. Poor weight gain was not associated with increased hazards of virological suppression or virological failure. CONCLUSION Monitoring weight gain on ART using age-specific and sex-specific normative curves specifically developed for HIV-infected children on ART is a simple, rapid, sustainable tool that can aid in the identification of children who are at increased risk of death in the first year of ART.

Drug suicide: a sex-equal cause of death in 16 European countries

Background There is a lack of international research on suicide by drug overdose as a preventable suicide method. Sex- and age-specific rates of suicide by drug self-poisoning (ICD-10, X60-64) and the distribution of drug types used in 16 European countries were studied, and compared with other self-poisoning methods (X65-69) and intentional self-injury (X70-84). Methods Data for 2000-04/05 were collected from national statistical offices. Age-adjusted suicide rates, and age and sex distributions, were calculated. Results No pronounced sex differences in drug self-poisoning rates were found, either in the aggregate data (males 1.6 and females 1.5 per 100,000) or within individual countries. Among the 16 countries, the range (from some 0.3 in Portugal to 5.0 in Finland) was wide. 'Other and unspecified drugs' (X64) were recorded most frequently, with a range of 0.2-1.9, and accounted for more than 70% of deaths by drug overdose in France, Luxembourg, Portugal and Spain. Psychotropic drugs (X61) ranked second. The X63 category ('other drugs acting on the autonomic nervous system') was least frequently used. Finland showed low X64 and high X61 figures, Scotland had high levels of X62 ('narcotics and hallucinogens, not elsewhere classified') for both sexes, while England exceeded other countries in category X60. Risk was highest among the middle-aged everywhere except in Switzerland, where the elderly were most at risk. Conclusions Suicide by drug overdose is preventable. Intentional self-poisoning with drugs kills as many males as females. The considerable differences in patterns of self-poisoning found in the various European countries are relevant to national efforts to improve diagnostics of suicide and appropriate specific prevention. The fact that vast majority of drug-overdose suicides came under the category X64 refers to the need of more detailed ICD coding system for overdose suicides is needed to permit better design of suicide-prevention strategies at national level.

Age, microbiota, and T cells shape diverse individual IgA repertoires in the intestine

Intestinal immunoglobulin A (IgA) ensures host defense and symbiosis with our commensal microbiota. Yet previous studies hint at a surprisingly low diversity of intestinal IgA, and it is unknown to what extent the diverse Ig arsenal generated by somatic recombination and diversification is actually used. In this study, we analyze more than one million mouse IgA sequences to describe the shaping of the intestinal IgA repertoire, its determinants, and stability over time. We show that expanded and infrequent clones combine to form highly diverse polyclonal IgA repertoires with very little overlap between individual mice. Selective homing allows expanded clones to evenly seed the small but not large intestine. Repertoire diversity increases during aging in a dual process. On the one hand, microbiota-, T cell-, and transcription factor RORγt-dependent but Peyer's patch-independent somatic mutations drive the diversification of expanded clones, and on the other hand, new clones are introduced into the repertoire of aged mice. An individual's IgA repertoire is stable and recalled after plasma cell depletion, which is indicative of functional memory. These data provide a conceptual framework to understand the dynamic changes in the IgA repertoires to match environmental and intrinsic stimuli.

Benefits of Induced Host Responses against an Ectoparasite

As a consequence of the deleterious effects of parasites on host fitness, hosts have evolved responses to minimize the negative impact of parasite infection. Facultative parasite-induced responses are favoured when the risk of infection is unpredictable and host responses are costly. In vertebrates, induced responses are generally viewed as being adaptive, although evidence for fitness benefits arising from these responses in natural host populations is lacking. Here we provide experimental evidence for direct reproductive benefits in flea-infested great tit nests arising from exposure during egg production to fleas. In the experiment we exposed a group of birds to fleas during egg laying (the exposed group), thereby allowing for induced responses, and kept another group free of parasites (the unexposed group) over the same time period. At the start of incubation, we killed the parasites in both groups and all nests were reinfested with fleas. If induced responses occur and are adaptive, we expect that birds of the exposed group mount earlier responses and achieve higher current reproductive success than birds in the unexposed group. In agreement with this prediction, our results show that birds with nests infested during egg-laying have (i) fewer breeding failures and raise a higher proportion of hatchlings to hedging age; () offspring that reach greater body mass, grow longer feathers, and hedge earlier, and (iii) a higher number of recruits and first-year grandchildren than unexposed birds. Flea reproduction and survival did not differ significantly between the two treatments. These results provide the first evidence for the occurrence and the adaptiveness of induced responses against a common ectoparasite in a wild population of vertebrates. [References: 50]

[A descriptive epidemiological study on canine babesiosis in the Lake Geneva region]

A descriptive study was carried out in the district of the Lake Geneva between March 1, 2005 and August 31,2006 to assess the incidence and prevalence of canine babesiosis, to genotype the Babesia species occurring, to assess the most frequently clinical signs found and to address the potential of autochthonous transmission. This included a data assessment on the different tick-populations occurring in the area and on the prevalence of Babesia-DNA in these ticks. A total of 56 veterinary practices participated in the study. By blood smear and PCR, Babesia canis canis was found in 12 out of 21 cases with suspected babesiosis. In an additional 13th case, the parasite could only be detected by PCR. All autochthonous cases originated from the Western part of the Lake Geneva region. Clinical signs in affected dogs included inappetence, apathy, anemia, fever, hemoglobinuria and thrombocytopenia. There were no risk factors with regard to age, sex and breed. Most cases were diagnosed during the spring periods of 2005 and 2006 (11 cases) and two cases in autumn 2005, coinciding with the main activity period of Dermacentor reticulatus, the main vector of B. canis canis. A total of 495 ticks were collected on patients by the veterinarians, 473 were identified as Ixodes sp., 7 as Rhipicephalus sanguineus and 15 as Dermacentor reticulatus. While Ixodes sp. was found in the whole study area, D. reticulatus and R. sanguineus occurred only in the Western part till Lausanne. PCR and sequencing yielded B. canis canis positivity in 3 D. reticulatus specimen, these three ticks were collected from two different dogs both suffering from babesiosis. All R. sanguineus were negative by Babesia-PCR. Global warming, ecological changes in the potential habitat of ticks, increasing host- and vector-populations and increasing mobility of dog owners may be responsible for an emergence situation of infection risk for Babesia spp. by time. E.g., Dermacentor reticulatus has become autochtonously prevalent already till Lausanne in the Lake Geneva region, and further surveillance is suggested to tackle this problem.

Sex differences in cryptogenic stroke with patent foramen ovale

BACKGROUND: Sex differences in patients with patent foramen ovale (PFO) and cryptogenic stroke have not been systematically analyzed. We aimed to determine sex influences on demographics, vascular risk factors, clinical manifestations, stroke location, and clinical outcome. METHODS: One thousand two hundred eighty-eight consecutive patients with ischemic stroke or transient ischemic attack (TIA) were admitted to a single stroke center. All patients underwent a complete stroke workup including clinical examination, standard blood tests, cerebral and vascular imaging, transesophageal echocardiography, and 24-hour electrocardiography. In 500 patients, no definite etiology could be established (cryptogenic stroke/TIA). Of them, 167 patients (107 men and 60 women, mean age 52 +/- 13 years) had an PFO. RESULTS: The prevalence of PFO in patients with cryptogenic stroke or TIA was higher in men than in women (38% vs 28%, P = .014). Stroke severity and the prevalence of risk factors did not differ between the 2 sexes. There was an independent association between male sex and stroke location in the posterior cerebral circulation (OR 3.0, 95% CI 1.4-6.5, P = .006). Men and women did not differ in respect to PFO grade, prevalence of right-to-left shunt at rest, or coexistence of atrial septal aneurysm. Clinical outcome at 3 months was similar in both sexes. CONCLUSION: Patent foramen ovale was more prevalent in men than in women with cryptogenic stroke. There were no sex influences on age, risk factors, echocardiographic characteristics of PFO, or clinical outcome. Male sex was independently associated with stroke in the posterior cerebral circulation.

Host- rather than virus-related factors reduce health-related quality of life in hepatitis C virus infection

BACKGROUND: Hepatitis C virus (HCV) infection is associated with decreased health-related quality of life (HRQOL). Although HCV has been suggested to directly impair neuropsychiatric functions, other factors may also play a role. PATIENTS AND METHODS: In this cross-sectional study, we assessed the impact of various host-, disease- and virus-related factors on HRQOL in a large, unselected population of anti-HCV-positive subjects. All individuals (n = 1736) enrolled in the Swiss Hepatitis C Cohort Study (SCCS) were asked to complete the Short Form 36 (SF-36) and the Hospital Anxiety Depression Scale (HADS). RESULTS: 833 patients (48%) returned the questionnaires. Survey participants had significantly worse scores in both assessment instruments when compared to a general population. By multivariable analysis, reduced HRQOL (mental and physical summary scores of SF-36) was independently associated with income. In addition, a low physical summary score was associated with age and diabetes, whereas a low mental summary score was associated with intravenous drug use. HADS anxiety and depression scores were independently associated with income and intravenous drug use. In addition, HADS depression score was associated with diabetes. None of the SF-36 or HADS scores correlated with either the presence or the level of serum HCV RNA. In particular, SF-36 and HADS scores were comparable in 555 HCV RNA-positive and 262 HCV RNA-negative individuals. CONCLUSIONS: Anti-HCV-positive subjects have decreased HRQOL compared to controls. The magnitude of this decrease was clinically important for the SF-36 vitality score. Host and environmental, rather than viral factors, seem to impact on HRQOL level.

Stroke events, and case fatalities in Switzerland based on hospital statistics and cause of death statistics

OBJECTIVE: In Switzerland there is a shortage of population-based information on stroke incidence and case fatalities (CF). The aim of this study was to estimate stroke event rates and both in- and out-of-hospital CF rates. METHODS: Data on stroke diagnoses, coded according to I60-I64 (ICD 10), were taken from the Federal Hospital Discharge Statistics database (HOST) and the Cause of Death database (CoD) for the year 2004. The number of total stroke events and of age- and gender-specific and agestandardised event rates were estimated; overall CF, in-hospital and out-of-hospital, were determined. RESULTS: Among the overall number of 13 996 hospital discharges from stroke (HOST) the number was lower in women (n = 6736) than in men (n = 7260). A total of 3568 deaths (2137 women and 1431 men) due to stroke were recorded in the CoD database. The number of estimated stroke events was 15 733, and higher in women (n = 7933) than in men (n = 7800). Men presented significantly higher age-specific stroke event rates and a higher age-standardised event rate (178.7/100 000 versus 119.7/100 000). Overall CF rates were significantly higher for women (26.9%) than for men (18.4%). The same was true of out-of-hospital CF but not of in-hospital CF rates. CONCLUSION: The data on estimated stroke events obtained indicate that stroke discharge rate underestimates the stroke event rate. Out-of-hospital deaths from stroke accounted for the largest proportion of total stroke deaths. Sex differences in both number of total stroke events and deaths could be explained by the higher proportion of women than men aged 55+ in the Swiss population.

Cortical and trabecular bone mineral density in transsexuals after long-term cross-sex hormonal treatment: a cross-sectional study

The aim of this study was to explore the effect of long-term cross-sex hormonal treatment on cortical and trabecular bone mineral density and main biochemical parameters of bone metabolism in transsexuals. Twenty-four male-to-female (M-F) transsexuals and 15 female-to-male (F-M) transsexuals treated with either an antiandrogen in combination with an estrogen or parenteral testosterone were included in this cross-sectional study. BMD was measured by DXA at distal tibial diaphysis (TDIA) and epiphysis (TEPI), lumbar spine (LS), total hip (HIP) and subregions, and whole body (WB) and Z-scores determined for both the genetic and the phenotypic gender. Biochemical parameters of bone turnover, insulin-like growth factor-1 (IGF-1) and sex hormone levels were measured in all patients. M-F transsexuals were significantly older, taller and heavier than F-M transsexuals. They were treated by cross-sex hormones during a median of 12.5 years before inclusion. As compared with female age-matched controls, they showed a significantly higher median Z-score at TDIA and WB (1.7+/-1.0 and 1.8+/-1.1, P < 0.01) only. Based on the WHO definition, five (who did not comply with cross-sex hormone therapy) had osteoporosis. F-M transsexuals were treated by cross-sex hormones during a median of 7.6 years. They had significantly higher median Z-scores at TEPI, TDIA and WB compared with female age-matched controls (+0.9+/-0.2 SD, +1.0+/-0.4 SD and +1.4+/-0.3 SD, respectively, P < 0.0001 for all) and reached normal male levels except at TEPI. They had significantly higher testosterone and IGF-1 levels (p < 0.001) than M-F transsexuals. We conclude that in M-F transsexuals, BMD is preserved over a median of 12.5 years under antiandrogen and estrogen combination therapy, while in F-M transsexuals BMD is preserved or, at sites rich in cortical bone, is increased to normal male levels under a median of 7.6 years of androgen treatment in this cross sectional study. IGF-1 could play a role in the mediation of the effect of androgens on bone in F-M transsexuals.

Sex differences in the prevalence and clinical outcomes of subclinical peripheral artery disease in the Health, Aging, and Body Composition (Health ABC) study

The objective of the study was to determine if there are sex-based differences in the prevalence and clinical outcomes of subclinical peripheral artery disease (PAD). We evaluated the sex-specific associations of ankle-brachial index (ABI) with clinical cardiovascular disease outcomes in 2797 participants without prevalent clinical PAD and with a baseline ABI measurement in the Health, Aging, and Body Composition study. The mean age was 74 years, 40% were black, and 52% were women. Median follow-up was 9.37 years. Women had a similar prevalence of ABI < 0.9 (12% women versus 11% men; P = 0.44), but a higher prevalence of ABI 0.9-1.0 (15% versus 10%, respectively; P < 0.001). In a fully adjusted model, ABI < 0.9 was significantly associated with higher coronary heart disease (CHD) mortality, incident clinical PAD and incident myocardial infarction in both women and men. ABI < 0.9 was significantly associated with incident stroke only in women. ABI 0.9-1.0 was significantly associated with CHD death in both women (hazard ratio 4.84, 1.53-15.31) and men (3.49, 1.39-8.72). However, ABI 0.9-1.0 was significantly associated with incident clinical PAD (3.33, 1.44-7.70) and incident stroke (2.45, 1.38-4.35) only in women. Subclinical PAD was strongly associated with adverse CV events in both women and men, but women had a higher prevalence of subclinical PAD.