Age distribution and metabolic disorders in people with Type 1 diabetes in Beijing and Shantou, China: a cross-sectional study.

AIMS: To examine whether the age profile of people with Type 1 diabetes differs from that of the general population and in what manner, and to study the clinical characteristics related to metabolic disorders among people with Type 1 diabetes in China. METHODS: We sequentially enrolled 849 people with Type 1 diabetes from hospital records review, inpatient wards and outpatient clinics. Data were collected via face-to-face interviews, medical records and venous blood samples. Beijing census data for 2011 were used to provide the general population statistics. Descriptive analysis of the results and tests for differences were performed. RESULTS: The median (interquartile range) age at diagnosis of diabetes was 16 (9-28) years and the duration of diabetes was 4 (1-8) years. The mean ± sd HbA1c concentration was 76±28 mmol/mol (9.1±2.5%). Compared with the general population, the population with Type 1 diabetes comprised more young individuals and fewer elderly individuals. The overall prevalence of metabolic syndrome among those with Type 1 diabetes was 10.1% (95% CI 7.9-12.2). People with metabolic syndrome were older and were diagnosed with diabetes at an older age. Hypertension and dyslipidaemia were more common in obese individuals with Type 1 diabetes than in their non-obese counterparts. CONCLUSIONS: Compared with the general population, people with Type 1 diabetes comprised more young and fewer elderly individuals. The prevalence of metabolic syndrome in the Type 1 diabetes population was 10.1%. Hypertension and dyslipidaemia were more prevalent in obese than non-obese individuals.

Single-Photon Interference due to Motion in an Atomic Collective Excitation.

We experimentally demonstrate the heralded generation of bichromatic single photons from an atomic collective spin excitation (CSE). The photon arrival times display collective quantum beats, a novel interference effect resulting from the relative motion of atoms in the CSE. A combination of velocity-selective excitation with strong laser dressing and the addition of a magnetic field allows for exquisite control of this collective beat phenomenon. The present experiment uses a diamond scheme with near-IR photons that can be extended to include telecommunications wavelengths or modified to allow storage and retrieval in an inverted-Y scheme.

Global estimates of diabetes prevalence for 2013 and projections for 2035.

INTRODUCTION: Diabetes is a serious and increasing global health burden and estimates of prevalence are essential for appropriate allocation of resources and monitoring of trends. METHODS: We conducted a literature search of studies reporting the age-specific prevalence for diabetes and used the Analytic Hierarchy Process to systematically select studies to generate estimates for 219 countries and territories. Estimates for countries without available source data were modelled from pooled estimates of countries that were similar in regard to geography, ethnicity, and economic development. Logistic regression was applied to generate smoothed age-specific prevalence estimates for adults 20-79 years which were then applied to population estimates for 2013 and 2035. RESULTS: A total of 744 data sources were considered and 174 included, representing 130 countries. In 2013, 382 million people had diabetes; this number is expected to rise to 592 million by 2035. Most people with diabetes live in low- and middle-income countries and these will experience the greatest increase in cases of diabetes over the next 22 years. CONCLUSION: The new estimates of diabetes in adults confirm the large burden of diabetes, especially in developing countries. Estimates will be updated annually including the most recent, high-quality data available.

The IDF Diabetes Atlas methodology for estimating global prevalence of hyperglycaemia in pregnancy.

INTRODUCTION: Hyperglycaemia is one of the most prevalent metabolic disorders occurring during pregnancy. Limited data are available on the global prevalence of hyperglycaemia in pregnancy. The International Diabetes Federation (IDF) has developed a methodology for generating estimates of the prevalence of hyperglycaemia in pregnancy, including hyperglycaemia first detected in pregnancy and live births to women with known diabetes, among women of childbearing age (20-49 years). METHODS: A systematic review of the literature for studies reporting the prevalence of gestational diabetes was conducted. Studies were evaluated and scored to favour those that were representative of a large population, conducted recently, reported age-specific estimates, and case identification was based on blood test. Age-specific prevalence data from studies were entered to produce estimates for five-year age groups using logistic regression to smooth curves, with age as the independent variable. The derived age-specific prevalence was adjusted for differences in diagnostic criteria in the underlying data. Cases of hyperglycaemia in pregnancy were derived from age-specific estimates of fertility and age-specific population estimates. Country-specific estimates were generated for countries with available data. Regional and global estimates were generated based on aggregation and extrapolation for 219 countries and territories. Available fertility rates and diabetes prevalence estimates were used to estimate the proportion of hyperglycaemia in pregnancy that may be due to total diabetes in pregnancy - pregnancy in women with known diabetes and diabetes first detected in pregnancy. RESULTS: The literature review identified 199 studies that were eligible for characterisation and selection. After scoring and exclusion requirements, 46 studies were selected representing 34 countries. More than 50% of selected studies came from Europe and North America and Caribbean. The smallest number of identified studies came from sub-Saharan Africa. The majority of studies were for high-income countries, although low- and middle-income countries were also represented. CONCLUSION: Prevalence estimates of hyperglycaemia in pregnancy are sensitive to the data from which they are derived. The IDF methodology is a transparent, reproducible, and modifiable method for estimating the burden of hyperglycaemia in pregnancy. More data are needed, in particular from developing countries, to strengthen the methodology.

Global estimates of the prevalence of hyperglycaemia in pregnancy.

AIMS: We estimated the number of live births worldwide and by IDF Region who developed hyperglycaemia in pregnancy in 2013, including total diabetes in pregnancy (known and previously undiagnosed diabetes) and gestational diabetes. METHODS: Studies reporting prevalence of hyperglycaemia first-detected in pregnancy (formerly termed gestational diabetes) were identified using PubMed and through a review of cited literature. A simple scoring system was developed to characterise studies on diagnostic criteria, year study was conducted, study design, and representation. The highest scoring studies by country with sufficient detail on methodology for characterisation and reporting at least three age-groups were selected for inclusion. Forty-seven studies from 34 countries were used to calculate age-specific prevalence of hyperglycaemia first-detected in pregnancy in women 20-49 years. Adjustments were then made to account for heterogeneity in screening method and blood glucose diagnostic threshold in studies and also to align with recently published diagnostic criteria as defined by the WHO for hyperglycaemia first detected in pregnancy. Prevalence rates were applied to fertility and population estimates to determine regional and global prevalence of hyperglycaemia in pregnancy for 2013. An estimate of the proportion of cases of hyperglycaemia in pregnancy due to total diabetes in pregnancy was calculated using age- and sex-specific estimates of diabetes from the IDF Diabetes Atlas and applied to age-specific fertility rates. RESULTS: The global prevalence of hyperglycaemia in pregnancy in women (20-49 years) is 16.9%, or 21.4 million live births in 2013. An estimated 16.0% of those cases may be due to total diabetes in pregnancy. The highest prevalence was found in the South-East Asia Region at 25.0% compared with 10.4% in the North America and Caribbean Region. More than 90% of cases of hyperglycaemia in pregnancy are estimated to occur in low- and middle-income countries. CONCLUSION: These are the first global estimates of hyperglycaemia in pregnancy and conform to the new WHO recommendations regarding diagnosis and also include estimates of live births in women with known diabetes. They indicate the importance of the disease from a public health and maternal and child health perspective, particularly in developing countries.

Miniaturized Hairs Maintain Contact with the Arrector Pili Muscle in Alopecia Areata but not in Androgenetic Alopecia: A Model for Reversible Miniaturization and Potential for Hair Regrowth.

BACKGROUND: Hair follicle miniaturization is the hallmark of male pattern hair loss (MPHL), female pattern hair loss (FPHL), and alopecia areata (AA). AA has the potential for complete hair regrowth and reversal of miniaturization. MPHL and FPHL are either irreversible or show only partial regrowth and minimal reversal of miniaturization. HYPOTHESIS: The arrector pili muscle (APM) attachment to the hair follicle bulge, a recognized repository of stem cells may be necessary for reversal of hair follicle miniaturization. MATERIALS AND METHODS: Sequential histological sections from MPHL, FPHL, AA, and telogen effluvium were used to create three-dimensional images to compare the relationship between the APM and bulge. RESULTS: In AA, contact was maintained between the APM and the bulge of miniaturized follicles while in MPHL and FPHL contact was lost. DISCUSSION: Contact between the APM and the bulge in AA may be required for reversal of hair follicle miniaturization. Maintenance of contact between miniaturized follicles in AA could explain the complete hair regrowth while loss of contact between the APM and the bulge in MPHL and FPHL may explain why the hair loss is largely irreversible. This loss of contact may reflect changes in stem cell biology that also underlie irreversible miniaturization.

A multi-tiered intervention to address behavioural and cognitive changes after diagnosis of primary brain tumour: a feasibility study.

PURPOSE: Untreated behavioural and cognitive changes after primary brain tumour (PBT) can result in challenging behaviours (CBs), with limited documentation on treatment approaches. This study explored the feasibility of employing a Behavioural Consultancy approach to manage CBs, targeting individuals with PBT, family and treating staff. METHODS: Participants were patients and families of two hospitals and health professionals from cancer/neurological services. A single-case experimental design piloted skill-based training and environmental changes in managing socio-behavioural impairments in a person with a low grade astrocytoma. A half-day workshop to train family members (n = 7) in compensatory strategy use to manage CBs after PBT was piloted. Finally, a 1-day workshop was provided to 43 health professionals in managing CBs after PBT. For both workshops, a pre-post impact evaluation was conducted employing a purpose-designed Strategies Use Measure. RESULTS: All three interventions demonstrated positive results. The single case showed a 71% decrease in the target behaviour (time spent talking) post-intervention. Some attrition to these gains was observed at two follow-up time points (3 and 5 months). Participants from both workshops demonstrated significant post-intervention increases in perceived knowledge of Strategy Use (family members z = 2.03, p < 0.05; health professionals z = 4.95, p < 0.00; Wilcoxon signed-rank test). CONCLUSIONS: These initial studies highlight the potential of employing an integrated multi-tiered intervention based on a Behavioural Consultancy model to manage CBs after PBT.

How not to get scar(r)ed: pointers to the correct diagnosis in patients with suspected primary cicatricial alopecia.

Primary cicatricial alopecias (PCAs) are a rare, but important, group of disorders that cause irreversible damage to hair follicles resulting in scarring and permanent hair loss. They may also signify an underlying systemic disease. Thus, it is of paramount importance that clinicians who manage patients with hair loss are able to diagnose these disorders accurately. Unfortunately, PCAs are notoriously difficult conditions to diagnose and treat. The aim of this review is to present a rational and pragmatic guide to help clinicians in the professional assessment, investigation and diagnosis of patients with PCA. Illustrating typical clinical and histopathological presentations of key PCA entities we show how dermatoscopy can be profitably used for clinical diagnosis. Further, we advocate the search for loss of follicular ostia as a clinical hallmark of PCA, and suggest pragmatic strategies that allow rapid formulation of a working diagnosis.

Central scalp alopecia photographic scale in African American women.

Central centrifugal cicatricial alopecia (CCCA) is a common but poorly understood cause of hair loss in African American women. A photographic scale was developed that captures the pattern and severity of the central hair loss seen with CCCA in order to help identify this problem in the general community and to potentially correlate clinical data with hair loss. The utility and reproducibility of this photographic scale was determined in a group of 150 African American women gathered for a health and beauty day who were evaluated by both four investigators experienced in the diagnosis of hair disorders and by the subjects themselves.

Management of primary cicatricial alopecias: options for treatment.

Primary cicatricial alopecias (PCAs) are a poorly understood group of disorders that result in permanent hair loss. Clinically, they are characterized not only by permanent loss of hair shafts but also of visible follicular ostia along with other visible changes in skin surface morphology, while their histopathological hallmark usually (although not always) is the replacement of follicular structures with scar-like fibrous tissue. As hair follicle neogenesis in adult human scalp skin is not yet a readily available treatment option for patients with cicatricial alopecias, the aim of treatment, currently, remains to reduce symptoms and to slow or stop PCA progression, namely the scarring process. Early treatment is the key to minimizing the extent of permanent alopecia. However, inconsistent terminology, poorly defined clinical end-points and a lack of good quality clinical trials have long made management of these conditions very challenging. As one important step towards improving the management of this under-investigated and under-serviced group of dermatoses, the current review presents evidence-based guidance for treatment, with identification of the strength of evidence, and a brief overview of clinical features of each condition. Wherever only insufficient evidence-based advice on PCA management can be given at present, this is indicated so as to highlight important gaps in our clinical knowledge that call for concerted efforts to close these in the near future.

The 'follicular trochanter': an epithelial compartment of the human hair follicle bulge region in need of further characterization.

Recent articles on hair follicle stem cells have summarized the current state of knowledge of what has been termed the hair follicle 'bulge'. During the course of immunohistological studies aimed at characterizing the expression of selected extracellular matrix proteins in the - as yet insufficiently characterized - niche of human bulge hair follicle stem cells, we have recently come across a largely forgotten, peculiar epithelial protrusion of the outer root sheath, which was visible in only a minority of all examined hair follicles. The morphology and immunoreactivity patterns of this structure, the 'follicular trochanter', are described herein.

Theoretical predictions for spatial covariance of the electroencephalographic signal during the anesthetic-induced phase transition: Increased correlation length and emergence of spatial self-organization.

In a recent series of papers, the authors have developed a stochastic theory to describe the electrical response of a spatially homogeneous cerebral cortex to infusion of a general anesthetic agent. We showed that by modeling the GABAergic (propofol-like) drug effect as a prolongation of the inhibitory postsynaptic impulse response, we obtain a prediction that there will be a hysteretically separated pair of first-order phase transitions in the population-average excitatory soma voltage, the first occurring at the point of induction of unconsciousness, and the second at the point of emergence from unconsciousness. In the present paper we generalize our earlier "zero-dimensional" homogeneous cortex to a one-dimensional (1D) line of cortical "mass," thus allowing for the possibility of spatial inhomogeneities in neural activity. Following the spirit of our earlier adiabatic ("slow membrane") philosophy, we impose a spatioadiabatic approximation that permits us to compute analytic expressions for changes in EEG (electroencephalographic) correlation length and EEG spatial covariance as a function of anesthetic effect. We establish that the correlation length of the EEG fluctuations is expected to increase at the approach to the transition points, and this finding is consistent with both the homogeneous-cortex prediction of increased correlation time ("critical slowing down") near transition, and the recent, comprehensive anesthetic study by John et al. [Conscious. Cogn. 10, 165 (2001)] reporting an increase in EEG coherence near the points of loss and recovery of consciousness. In addition, we find that if the long-range (corticocortical) excitatory-to-inhibitory connectivity in the 1D cortex is stronger than the long-range excitatory-to-excitatory connectivity, then the spatioadiabatic system can organize itself into large-amplitude spatial patterns ("dissipative structures") consisting of giant stationary quasiperiodic voltage fluctuations distributed along the cortical rod.

Update on cicatricial alopecia.

Cicatricial alopecia is an enigmatic group of hair disorders linked by the potential permanent loss of scalp hair follicles in involved areas. Progress in our understanding and treatment of these disorders has been stymied by the lack of clear diagnostic criteria for the current terms used to describe the various hair loss entities. Since all of these conditions evolve as the hair is destroyed or replaced, diagnosis is further made difficult by a lack of clinical and pathologic "snapshots" over the evolution of each disorder. Without some acceptance of general clinical and histological presentations in the early, mid and late stage of these disorders, one cannot begin to explore ways to make the diagnosis at a very early stage before significant follicular destraction has occurred (making the clinical diagnosis obvious) and when the damage is potentially repairable or progression preventable.

Prostate cancer: progression of prostate-specific antigen after external beam irradiation.

This paper is concerned with the development of a stochastic path of prostate-specific antigen (PSA) level after radiation treatment for prostate cancer. PSA is a biomarker for prostate cancer, higher levels of which indicate the seriousness of the cancer progression. Following the deterministic modeling of the data by the previous authors, Cox et al., this paper is concerned with the theoretical knowledge that could be gained by the stochastic modeling in discrete form of the PSA path over time. The expected value of the PSA level is computed and compared with the deterministic model and it is found that they are the same for about the first year after radiation therapy. The American Society for Therapeutic Radiology has set a consensus panel definition of biochemical failure following radiation therapy: the rise in three consecutive levels of PSA is considered to be a failure of the radiation therapy. Knowledge of the path of PSA presented in this paper would be useful in the management of the radiation treatment and in particular assessing quantitatively any clinically based policy for defining recurrence after radiation therapy. Application of the model is illustrated by fitting it to clinical data available in the University of Michigan cancer center.

Tobacco smoking in Tanzania, East Africa: population based smoking prevalence using expired alveolar carbon monoxide as a validation tool.

OBJECTIVES: To describe the prevalence of tobacco smoking in an urban East African population while using a simple validation procedure to examine the degree of under reporting in men and women. DESIGN: A cross sectional population based study in adults (15 years and over) with sampling from a well maintained census register. SETTING: Ilala Ilala, a middle income district of Dar es Salaam, Tanzania. SUBJECTS: An age and sex stratified random sample of 973 men and women. MAIN OUTCOME MEASURES: Self reported smoking status with correction by exhaled alveolar carbon monoxide (EACO). RESULTS: From the 605 participants (response rate 67.9%) age standardised (new world population) smoking prevalence, based on questionnaire and EACO, was 27.0% (95% confidence interval (CI) 20.8% to 33.2%) in males and 5.0% (95% CI 2.8% to 7.2%) in females. The age specific prevalence of smoking was highest in the age group 35-54 years (34.3%) for men and in the over 54 years group (16%) for women. Of those classified as smokers, 7.3% of men and 27.3% of women were reclassified as current smokers based on EACO (> or = 9 parts per million), after they had reported themselves to be an ex- or non-smoker in the questionnaire. CONCLUSIONS: The data suggest: (1) high rates of smoking among men in an urban area of East Africa; and (2) the importance of validating self reports of smoking status, particularly among women.

Activation of progelatinase A (MMP-2) by neutrophil elastase, cathepsin G, and proteinase-3: a role for inflammatory cells in tumor invasion and angiogenesis.

Gelatinase A (MMP-2), a matrix metalloproteinase (MMP) involved in tumor invasion and angiogenesis, is secreted as an inactive zymogen (proMMP-2) and activated by proteolytic cleavage. Here we report that polymorphonuclear neutrophil (PMN)-derived elastase, cathepsin G, and proteinase-3 activate proMMP-2 through a mechanism that requires membrane-type 1 matrix metalloproteinase (MT1-MMP) expression. Immunoprecipitation of human PMN-conditioned medium with a mixture of antibodies to elastase, cathepsin G, and proteinase-3 abolished proMMP-2 activation, whereas individual antibodies were ineffective. Incubation of HT1080 cells with either purified PMN elastase or cathepsin G or proteinase-3 resulted in dose-and time-dependent proMMP-2 activation. Addition of PMN-conditioned medium to MT1-MMP expressing cells resulted in increased proMMP-2 activation and in vitro invasion of extracellular matrix (ECM), but had no effect with cells that express no MT1-MMP. MMP-2 activation by PMN-conditioned medium or purified elastase was blocked by the elastase inhibitor alpha(1)-antitrypsin but not by Batimastat, an MMP inhibitor, showing that elastase activation of MMP-2 is not mediated by MMP activities. The PMN-conditioned medium-induced increase in cell invasion was blocked by Batimastat as well as by alpha(1)-antitrypsin, showing that PMN serine proteinases trigger a proteinase cascade that entails proMMP-2 activation: this gelatinase is the downstream effector of the proinvasive activity of PMN proteinases. These findings indicate a novel role for PMN-mediated inflammation in a variety of tissue remodeling processes including tumor invasion and angiogenesis.

Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss.

In androgenetic alopecia, or pattern hair loss, follicles undergo miniaturization, shrinking from terminal to vellus-like hairs. Traditionally, this process is thought to progress gradually over a number of follicular cycles. However, it is unlikely that miniaturization can be explained only by a series of progressively shorter anagen cycles. Simple calculations show that this process would take too long for significant miniaturization to occur secondary to shorter anagen cycles alone, especially in view of the latent lag period seen in pattern hair loss that occurs between the loss of a telogen hair and the appearance of an anagen hair. Evidence is presented to support a new concept that miniaturization is an abrupt, large-step process that also can be reversed in 1 hair cycle, as has been shown clinically, with confirmatory histologic evidence, in patients with pattern hair loss responding to finasteride treatment. It is hypothesized that the miniaturization seen with pattern hair loss may be the direct result of reduction in the cell number and, hence, size of the dermal papilla.

Human hair histogenesis for the mitochondrial DNA forensic scientist.

Analysis of mitochondrial DNA (mtDNA) sequence from human hairs has proven to be a valuable complement to traditional hair comparison microscopy in forensic cases when nuclear DNA typing is not possible. However, while much is known about the specialties of hair biology and mtDNA sequence analysis, there has been little correlation of individual information. Hair microscopy and hair embryogenesis are subjects that are sometimes unfamiliar to the forensic DNA scientist. The continual growth and replacement of human hairs involves complex cellular transformation and regeneration events. In turn, the analysis of mtDNA sequence data can involve complex questions of interpretation (e.g., heteroplasmy and the sequence variation it may cause within an individual, or between related individuals. In this paper we review the details of hair developmental histology, including the migration of mitochondria in the growing hair, and the related interpretation issues regarding the analysis of mtDNA data in hair. Macroscopic and microscopic hair specimen classifications are provided as a possible guide to help forensic scientists better associate mtDNA sequence heteroplasmy data with the physical characteristics of a hair. These same hair specimen classifications may also be useful when evaluating the relative success in sequencing different types and/or forms of human hairs. The ultimate goal of this review is to bring the hair microscopist and forensic DNA scientist closer together, as the use of mtDNA sequence analysis continues to expand.