Relative Energy Deficiency in Sport (RED-S): Scientific, Clinical, and Practical Implications for the Female Athlete.

Problem: If athletes develop low energy availability (LEA), it can lead to a Relative Energy Deficiency in Sport (RED-S) syndrome which has severe health consequences if not treated. Methodology: A narrative review of the most recent and pertinent literature on the topic, with special emphasis on women. Results: In assessing the current literature, we have synthesized: i) the scientific implications of LEA and RED-S, ii) the clinical manifestations of the conditions currently available for detection, as well as iii) the practical implications for healthcare and support for female athletes and teams in planning intervention or prevention strategies (maintaining EA >45 kcal/kg FFM/day). Discussion: The 'Female Athlete Triad" emerged in the 1990s as researchers understood more of the etiological adaptation of female athlete health to sports training. In the last 10 years, the scientific community has recognized that the 'Triad' approach was too narrow in focus, and the broader concept of RED-S emerged. Both the Triad and RED-S are consequences of a frequently prevalent LEA in athletes (<30 kcal/kg FFM/day). Developing LEA and RED-S compromises training adaptation, performance capacity, and health in athletes. For these reasons, it is critical that an athlete's support team recognize the behaviors that may indicate RED-S evolution. In this way, we can assist female athletes in reaching their full potential in sports while protecting their health.

Genomic instability and the role of radiation quality.

Genomic instability (GI) is a hallmark of tumorigenic progression and is observed as delayed genetic damage in the progeny of irradiated and unirradiated bystander cells. The expression of GI can be influenced by genotype, cell type and radiation quality. While several studies have demonstrated the induction of GI by high and low-linear energy transfer (LET) radiation, our work on human and mouse primary cell systems has shown LET-dependent differences in the induction and expression of GI. These differences might be attributed to differences in radiation track structure, dose rate, contribution of bystander cells and radiation dose. This paper reviews the role of radiation quality in the induction of GI and describe the possible mechanisms underlining the observed differences between radiation types on its induction. The experimental results presented suggest that dose might be the most significant factor in determining induction of GI after low-LET radiation.

Impact of acute undernutrition on growth, ileal morphology and nutrient transport in a murine model.

Undernutrition represents a major public health challenge for middle- and low-income countries. This study aimed to evaluate whether a multideficient Northeast Brazil regional basic diet (RBD) induces acute morphological and functional changes in the ileum of mice. Swiss mice (∼25 g) were allocated into two groups: i) control mice were fed a standard diet and II) undernourished mice were fed the RBD. After 7 days, mice were killed and the ileum collected for evaluation of electrophysiological parameters (Ussing chambers), transcription (RT-qPCR) and protein expression (western blotting) of intestinal transporters and tight junctions. Body weight gain was significantly decreased in the undernourished group, which also showed decreased crypt depth but no alterations in villus height. Electrophysiology measurements showed a reduced basal short circuit current (Isc) in the undernourished group, with no differences in transepithelial resistance. Specific substrate-evoked Isc related to affinity and efficacy (glutamine and alanyl-glutamine) were not different between groups, except for the maximum Isc (efficacy) induced by glucose. Transcription of Sglt1 and Pept1 was significantly higher in the undernourished group, while SN-2 transcription was decreased. No changes were found in transcription of CAT-1 and CFTR, while claudin-2 and occludin transcriptions were significantly increased in the undernourished group. Despite mRNA changes, SGLT-1, PEPT-1, claudin-2 and occludin protein expression showed no difference between groups. These results demonstrate early effects of the RBD on mice, which include reduced body weight and crypt depth in the absence of significant alterations to villus morphology, intestinal transporters and tight junction expression.

Human Rabies Post-Exposure Prophylaxis and Animal Rabies in Ontario, Canada, 2001-2012.

In Ontario, Canada, the implementation of an annual rabies control programme in wildlife that began in 1989 resulted in a marked, steady decrease in the number of animal rabies cases. The number of animal rabies cases decreased from 1870 in 1989 to 183 in 2000 (Nunan et al., 2002 Emerg Infect Dis 8, 214). In our study period, the number of animal rabies cases continued to decrease from 210 in 2001 to 28 in 2012. The marked decrease in animal rabies cases since 1989 has resulted in a decrease in the risk of human infection. A concomitant decrease in the number of rabies post-exposure prophylaxis (RPEP) administered was anticipated but failed to occur. The mean rate of RPEP, 13.9 RPEP administered per 100,000 persons, from 2001-2012 was approximately the same as the rate in the 1990 s. Two possible reasons that the rate of RPEP administration has not decreased include strict adherence to RPEP recommendations and administration of RPEP when it is not recommended. A reduction in the number of RPEP administered, consistent with the decrease in the animal rabies cases, would provide some financial savings for the government. Ideally, an increased use of the risk assessment approach in keeping with recent guidelines, rather than adhering to previous prescriptive recommendations for RPEP administration, coupled with a continuing low incidence of animal rabies cases will result in decreased, and yet appropriate, use of RPEP. Consideration should be given to identify how guidelines could be revised to more effectively target high-risk exposures and reduce the administration of RPEP for instances in which the risk of rabies virus exposure is exceedingly low.

Transient neovascularisation of the frog retina during optic nerve regeneration.

In conditions such as diabetic retinopathy, degenerative events in the retina are associated with neovascularisation. It is well established that a proportion of retinal ganglion cells die during optic nerve regeneration in the frog. The present study has determined whether neovascularisation takes place during this regenerative process. To do so, the pattern of blood vessels overlying the retinal ganglion cell layer was analysed in the frog Litoria (Hyla) moorei. We examined normal animals and those undergoing optic nerve regeneration following nerve crush. Blood vessels were visualised by perfusion with Indian ink and retinae were prepared as wholeamounts. In normal animals, the vascular tree was found to lie superficial to the nerve fibre layer and was more complex in regions overlying the area centralis and visual streak. After nerve crush, abnormal blood vessels transiently formed between the existing branches of the vascular tree. The new vessels were concentrated as an annulus centred on the optic nerve head and over the area centralis in midtemporal retina. The neovascularisation became most extensive between 6 and 10 weeks postcrush and disappeared by 12 weeks. The spatiotemporal sequence of neovascularisation suggests that it is triggered by accumulations of degenerating material formed as a proportion of the ganglion cells die during optic nerve regeneration.

Soluble IgG aggregates produced by heating remain stable on freeze-drying.

IgG aggregates produced by heating gamma globulin solutions were freeze-dried, kept at 4 degrees C and reconstituted up to 4 months later. By comparison with frozen (-20 degrees C) preparations, only minimal changes in biological reactivity and in physical integrity occurred during this period. These results demonstrate that freeze-dried preparations of heat-aggregated IgG are potentially useful as a reference reagent for the comparative evaluation and standardisation of immune complex assays.

Centrifugation of normal and rheumatoid arthritis blood on Ficoll-Hypaque and Ficoll-Nycodenz solutions.

Attempts to use the rapid single-step Ficoll-Hypaque centrifugation procedure for the purification of mononuclear and polymorphonuclear leucocytes from the blood of normal individuals and rheumatoid arthritis patients have sometimes been unsuccessful, largely because the erythrocytes would not sediment through the centrifugation medium. Re-evaluation of the factors (e.g. Ficoll concentration, temperature, and ratio of the diatrizoate salts) which affect these separations showed that under our conditions it was advantageous to use a medium with a lower viscosity (Ficoll concentration) and/or a higher osmotic strength (increased sodium diatrizoate: meglumine diatrizoate) than had been recommended previously (Ferrante and Thong, 1978; 1980; Ferrante et al., 1982). Higher osmotic strength media must be used for separating the components of blood from rheumatoid arthritis patients than from normal individuals because rheumatoid arthritis erythrocytes have a lower buoyant density than normal erythrocytes.

Development and aging of cell topography in the human retinal pigment epithelium.

PURPOSE: To determine how regional cell density of this tissue changes with age, the authors examined the topography of the human retinal pigment epithelium (RPE) in wholemounted tissue obtained from eyes aged 12 to 89 years, donated for corneas. METHODS: The RPE, with choroid attached, was wholemounted and stained with cresyl violet. From these preparations, the authors analyzed retinal area, RPE cell number, and cell density. RESULTS: Retinal pigment epithelial cell number is highly variable between persons but does not appear to be age related. Retinal area increases until approximately 30 years of age, but beyond this age individual variation masks further enlargement. The distinctive topography of the RPE changes markedly with age. There is a modification from the relatively homogeneous cell density distribution in the youngest retinas examined toward a more heterogeneous pattern in older retinas. From mid-adolescence, a band of larger cells appears at the extreme periphery, adjacent to the ora serrata, which gradually widens so that by 90 years of age, it occupies the outermost 30% of the retinal area. Cell density is highest in the central temporal retina, adjacent to the macula in the neural retina, throughout life. Cell density values in this region increase slightly with age, and the difference between this and surrounding regions becomes more marked with age. CONCLUSIONS: With no marked change in total cell number, peripheral RPE in humans enlarges in area throughout life, but the RPE in more central regions decreases in area.

Early childhood diarrhoea and helminthiases associate with long-term linear growth faltering.

BACKGROUND: Although the acute mortality from diarrhoeal diseases is well recognized, the potentially prolonged impact of early childhood diarrhoea on background growth and development is often overlooked. To examine the magnitude and duration of the association of early childhood enteric infections with growth faltering in later childhood, we investigated associations of early childhood diarrhoea (0-2 years) and intestinal helminthiases with nutritional status from age 2 to 7 years. METHODS: Twice-weekly diarrhoea surveillance and quarterly anthropometrics were followed from 1989 to 1998 in 119 children born into a Northeast Brazilian shantytown. RESULTS: Diarrhoea burdens at 0-2 years old were significantly associated with growth faltering at ages 2-7 years, even after controlling for nutritional status in infancy, helminthiases at 0-2 years old, family income, and maternal education by Pearson correlation, multivariate linear regression, and repeat measures analysis. The average 9.1 diarrhoeal episodes before age 2 years was associated with a 3.6 cm (95% CI : 0.6-6.6 cm) growth shortfall at age 7 years. Early childhood helminthiasis was also associated with linear growth faltering and a further 4.6 cm shortfall (95% CI : 0.8-7.9 cm) at age 7 years. CONCLUSIONS: Early childhood diarrhoea and helminthiases independently associate with substantial linear growth shortfalls that continue beyond age 6 years. Targeted interventions for their control may have profound and lasting growth benefits for children in similar settings.

Association of early childhood diarrhea and cryptosporidiosis with impaired physical fitness and cognitive function four-seven years later in a poor urban community in northeast Brazil.

To determine potential, long-term deficits associated with early childhood diarrhea and parasitic infections, we studied the physical fitness (by the Harvard Step Test) and cognitive function (by standardized tests noted below) of 26 children who had complete surveillance for diarrhea in their first 2 years of life and who had continued surveillance until 6-9 years of age in a poor urban community (favela) in Fortaleza in northeast Brazil. Early childhood diarrhea at 0-2 years of age correlated with reduced fitness by the Harvard Step Test at 6-9 years of age (P = 0.03) even after controlling for anthropometric and muscle area effects, anemia, intestinal helminths, Giardia infections, respiratory illnesses, and socioeconomic variables. Early childhood cryptosporidial infections (6 with diarrhea and 3 without diarrhea) were also associated with reduced fitness at 6-9 year of age, even when controlling for current nutritional status. Early diarrhea did not correlate with activity scores (P = 0.697), and early diarrhea remained significantly correlated with fitness scores (P = 0.035) after controlling for activity scores. Early diarrhea burdens also correlated in pilot studies with impaired cognitive function using a McCarthy Draw-A-Design (P = 0.01; P = 0.017 when controlling for early helminth infections), Wechsler Intelligence Scale for Children coding tasks (P = 0.031), and backward digit span tests (P = 0.045). These findings document for the first time a potentially substantial impact of early childhood diarrhea and cryptosporidial infections on subsequent functional status. If confirmed, these findings have major implications for calculations of global disability adjusted life years and for the importance and potential cost effectiveness of targeted interventions for early childhood diarrhea.

Small cell carcinoma of prostate: effectiveness of hormonal versus chemotherapy.

Small cell carcinoma of the prostate is rare and associated with a rapidly fatal course. Since 1977, 47 cases have been reported in the world literature with data from 3 additional cases presented herein. The purpose of our review was to determine the effectiveness of hormonal versus chemotherapy. Thirty-four of the 50 cases have known clinical histories. Four patients were not treated, and all were dead of their disease within an average of 2.75 months. Six patients were eliminated from our review because small cell carcinoma was discovered at autopsy. Another 5 cases were omitted because hormonal +/- chemotherapy had already been given for a previous diagnosis of adenocarcinoma, but no specific therapy was given once the small cell carcinoma developed. Of the remaining 19 cases, only 2 have survived. One is still alive forty-three months after hormonal treatment, and another is alive with disease six months after the initiation of hormonal therapy and chemotherapy. Five patients were given hormonal therapy only, and none of them responded. In 4 patients chemotherapy was given after hormonal therapy had failed, and they too died of their disease within a short period of time. However, an additional 8 patients were treated with immediate chemotherapy +/- hormonal therapy and had substantially longer clinical remissions. Therefore, although small cell carcinoma is a uniformly fatal disease, immediate chemotherapy should be considered to promote better clinical remissions.

Spontaneous mutation frequency and pattern in Big Blue mice fed a vitamin E-supplemented diet.

Endogenous oxidative DNA damage caused by normal cellular processes may play a vital role in carcinogenesis. To directly test the hypothesis that antioxidants will protect DNA from oxidative damage in vivo, Big Blue((R)) mice were fed either a control diet (66 IU vitamin E/kg diet) or a high-dose vitamin E diet containing 1000 IU vitamin E/kg diet of racemic d,l-alpha-tocopherol acetate from conception until 3 months of age. Using the standard Big Blue((R)) protocol, 15.5 million plaque forming units (pfu) were examined from five tissues (heart, liver, adipose tissue, thymus, and testis) of three control and three high-dose vitamin E supplemented male mice generating 433 mutants, which represented 373 independent mutations upon sequencing the lacI transgene. The alpha-tocopherol tissue concentration increased with high-dose vitamin E supplementation. In four of the tissues, individually or combined, mutation frequency changed little if any with vitamin E supplementation. In adipose tissue, which accumulated the highest levels of vitamin E, mutation frequency was significantly reduced with high-dose vitamin E supplementation (P = 0.047). Within the constraints of sample size, the pattern of mutation in adipose tissue was not altered significantly (P = 0.40). When data from all tissues were combined, a reduction in G:C --> T:A transversions was observed (P = 0.044). These results may have implications for cancer chemoprevention and provide insight into the efficacy of vitamin E supplementation in reducing spontaneous oxidative DNA damage in vivo. More dramatic alterations of mutation frequency and pattern may be observed with higher doses of vitamin E and substitution of the racemic supplement with d-alpha-tocopherol acetate.

Lip cancer in South Australia, 1977-1996.

Lip cancer (140 ICD-9, C00 ICD-10) is a form of oral cancer occurring at the junction between the oral cavity and the skin. Lip cancer has a distinctive global epidemiology that is notably different from cancer occurring at other intraoral sites. This study reviews and analyses the epidemiological data for lip cancer from the South Australian Central Cancer Registry between 1977 and 1996. During this 20-year period, 2716 cases of lip cancer (2095 male, 621 female) and 35 deaths from this disease (23 males, 12 females) were reported. The average age of diagnosis was 58.3 years in males and 66.0 years in females. Very high age-standardised incidence rates (over 15.0 per 100000 per annum in males and 4.0 per 100000 per annum in females) were found, giving the South Australian population amongst the highest incidence of lip cancer in the world. Also of considerable concern was the finding that, contrary to global trends, these rates showed a significant increase over the 20-year period in both sexes. Possible reasons for these findings are discussed.

Changes over time in the epidemiology of diarrhea and malnutrition among children in an urban Brazilian shantytown, 1989 to 1996.

BACKGROUND: Endemic diarrhea and its associated malnutrition remain leading causes of childhood morbidity and mortality in developing countries. This study was undertaken to describe changes in the incidence of diarrhea and prevalence of malnutrition among children in an urban Brazilian shantytown from 1989 to 1996. A secondary purpose was to examine associations between malnutrition and increased incidence and duration of diarrhea. METHODS: From August 1989 through December 1996 a dynamic birth cohort of 315 children was followed for surveillance of diarrhea and nutrition. Study homes were visited twice or thrice weekly to assess the occurrence of diarrhea. Length and weight of the subjects were measured quarterly. Poisson regression was used to test for associations between prior nutritional status and subsequent diarrhea during a quarter. Multiple regression was used to test for an association between nutritional status and episode duration. RESULTS: Declines in both age-adjusted attack rates (6.0 episodes/child-year in study year 3 [1991] to 2.5 episodes per child-year in study year 8 [1996] and days of diarrhea per child-year (30.8 days/child-year in year 3 to 8.5 days/child-year in year 8) were correlated with yearly improvements in mean nutritional status (R2= 0.84, P < 0.05, for mean length-for-age with mean number of episodes/child-year [corrected]. Both length- and weight-for-age were significant predictors of diarrhea incidence, including persistent episodes (> or =14 d), but not duration. CONCLUSIONS: These results demonstrate marked changes over time in the diarrhea burden and nutritional status of children in this population and provide further evidence of a significant association between malnutrition and increased incidence of diarrhea.

Mutation frequency is reduced in the cerebellum of Big Blue mice overexpressing a human wild type SOD1 gene.

Amyotrophic lateral sclerosis (ALS) is a progressive paralytic disorder caused by motor neuron degeneration. A similar disease phenotype is observed in mice overexpressing a mutant human hSOD1 gene (G93A, 1Gurd(1)). Mice transgenic for lacI (Big Blue) and human mutant (1Gurd(1), Mut hSOD1) or wild type (2Gur, Wt hSOD1) SOD1 genes were used to examine spontaneous mutation, oxidative DNA damage, and neurodegeneration in vivo. The frequency and pattern of spontaneous mutation were determined for forebrain (90% glia), cerebellum (90% neurons) and thymus from 5-month-old male mice. Mutation frequency is not elevated significantly and mutation pattern is unaltered in Mut hSOD1 mice compared to control mice. Mutation frequency is reduced significantly in the cerebellum of Wt hSOD1 mice (1.6x10(-5); P=0.0093; Fisher's Exact Test) compared to mice without a human transgene (2.7x10(-5)). Mutation pattern is unaltered. This first report of an endogenous factor that can reduce in vivo, the frequency of spontaneous mutation suggests potential strategies for lowering mutagenesis related to aging, neurodegeneration, and carcinogenesis.

Root resorption caused by impacted permanent teeth. Case report.

A case of severe external root resorption in several teeth caused by unerupted permanent teeth is presented along with the initial surgical treatment.

125 years of public health in the USA.

The past 125 years of public health in the United States are viewed from the perspective of the most significant public health areas of the 20th century as developed by the US Centers for Disease Control and Prevention. The long-term impacts and development of the areas include: immunizations, healthier mothers and babies, family planning, safer and healthier foods, fluoridation of drinking water, control of infectious diseases, decline in deaths from heart disease and stroke, recognition of tobacco as a health hazard, motor vehicle safety, and safer workplaces. The current and future of public health in the US is encapsulated in several developing areas, including: personal lifestyle modifications, politicalization of health, evolving knowledge base, knowledge transfer and globalization.

Walking for health: a nurse-managed activity.

One researcher has noted that forced inactivity leads to changes that are similar to those associated with the aging process, possibly indicating that some of the effects of aging may be due to inactivity rather than an intrinsic biologic process. The benefits of regular physical activity include improved cardiopulmonary function, lowered blood pressure, increased bone mineral content, increased muscle strength and joint flexibility, and improved psychological well-being. Walking is an excellent activity for seniors because it is a low impact sport, making the potential for injury low. A multi-faceted walking program managed by nurses can provide health promotion activities such as screenings, educational programs, weight-reduction classes, and health consultation. The sponsoring hospital, mall, and most importantly the walkers benefit from participation in such a program.

The potential for the use of personal computers in clinical forensic medicine.

This paper describes the use of a personal computer in clinical forensic medicine. It shows how a database can be easily created, updated for each new case by unqualified personnel, and then used to provide statistical data with a minimum resource input, without the need for great computer expertise. Databases will only recognise exactly identical abbreviations. Once created they can cross-reference data and provide individually tailored statistics. Registration with the Data Protection Agency is required in the UK in order to hold personal information on file. The results of 2201 cases entered on the database of one forensic physician show high levels of drug and alcohol abuse co-existing with unemployment and homelessness. 53% of individuals brought to police stations as a place of safety (under Section 136 of the Mental Health Act 1983) were in need of admission to a psychiatric hospital. 12% of those individuals were of no fixed abode. The potential for a national database linking forensic physicians on a national basis, pooling their data thereby creating a powerful statistical tool is clear.