Cutaneous Collagenous Vasculopathy: A Rare Form of Microangiopathy Successfully Treated with a Combination of Multiplex Laser and Optimized Pulsed Light with a Review of the Literature.

Cutaneous collagenous vasculopathy (CCV) is a rare idiopathic microangiopathy of the cutaneous vasculature characterized histologically by the presence of dilated small blood vessels with flat endothelial cells and thickened walls containing hyaline material in the upper dermis. We report an elderly patient presenting with an extensive form of CCV involving the trunk, upper and lower limbs. She was treated with Multiplex PDL 595-nm/Nd:YAG 1,064-nm laser and optimized pulsed light. This approach, which has never been reported for CCV so far, resulted in a striking and almost complete clearance of the widespread lesions. We here review our knowledge about CCV and therapeutic options available with a survey of the literature.

If hunters end up in the emergency room: a retrospective analysis of hunting injuries in a swiss emergency department.

Aim. to characterize the mechanisms, patterns, and outcomes of nonfatal hunting-related injuries in patients presenting to Bern University Hospital, Switzerland, and compare these to reports of hunting injuries worldwide. Methods. patients presenting with hunting-related injuries to the Emergency Department at Bern University hospital from 2000 to 2014 were identified by retrospectively searching the department database using the keyword "hunt." Each case was analyzed in terms of the patient age and gender, the mechanism and pattern of injury, and management and patient follow-up. Results. 19 patients were identified. 16 were male with a mean age of 50 years (range: 16-74). Mechanisms of injury included firearm-related injuries, falls, and knife wounds. The most common patterns of injury were head injuries (7), followed by injuries to the upper (5) or lower limb (5) and trunk (2). Over half of the patients were admitted, and nine required emergency surgery. Conclusion. Nonfatal hunting accidents in Bern, Switzerland, are largely caused by firearms and falls and tend to occur in male hunters with a mean age of 50 years. The most common patterns of injury are orthopedic and head injuries, often requiring surgery. These findings are consistent with international studies of nonfatal hunting accidents.

Conserved regulation of proximodistal limb axis development by Meis1/Hth.

Vertebrate limbs grow out from the flanks of embryos, with their main axis extending proximodistally from the trunk. Distinct limb domains, each with specific traits, are generated in a proximal-to-distal sequence during development. Diffusible factors expressed from signalling centres promote the outgrowth of limbs and specify their dorsoventral and anteroposterior axes. However, the molecular mechanism by which limb cells acquire their proximodistal (P-D) identity is unknown. Here we describe the role of the homeobox genes Meis1/2 and Pbx1 in the development of mouse, chicken and Drosophila limbs. We find that Meis1/2 expression is restricted to a proximal domain, coincident with the previously reported domain in which Pbx1 is localized to the nucleus, and resembling the distribution of the Drosophila homologues homothorax (hth) and extradenticle (exd); that Meis1 regulates Pbx1 activity by promoting nuclear import of the Pbx1 protein; and that ectopic expression of Meis1 in chicken and hth in Drosophila disrupts distal limb development and induces distal-to-proximal transformations. We suggest that restriction of Meis1/Hth to proximal regions of the vertebrate and insect limb is essential to specify cell fates and differentiation patterns along the P-D axis of the limb.

Picea abies in Europe: distribution, habitat, usage and threats

Among the coniferous species, Norway spruce (Picea abies (L.) Karst.) is one of the most important trees in Europe both for economic and ecological aspects, with a long tradition of cultivation. It can be a big tree, reaching 50-60 m in height with a straight and regular trunk, particularly used for timber constructions, pulpwood for paper and furniture. This widespread species dominates the Boreal forests in Northern Europe and the subalpine areas of the Alps and Carpathian Mountains. Thanks to its high performances in different site conditions, it can also be found outside its natural distribution on lower elevations in more temperate forests. Norway spruce has been massively planted up to its niche limits, where it is particularly susceptible to heat and drought, due to its shallow root system. For this reason it is expected to be severely affected under global warming conditions. Disturbed and weakened plants can be easily attacked by rot fungi such as Heterobasidion annosum and Armillaria, or by the bark beetles Ips typographus, one of the most destructive spruce forest pests.

Neighbourhood abundance and small-tree survival in a lowland Bornean rainforest

Conspecific effects of neighbours on small-tree survival may have a role in tree population dynamics and community composition of tropical forests. This notion was tested with data from two 4-ha plots in lowland forest at Danum, Sabah (Borneo), for a 21-year interval (censuses at 1986, 1996, 2001, 2007). Species with ≥45 focal trees 10 to <100 cm stem girth per plot in 1986 were selected. Logistic regressions fitted mean focal tree size and mean inverse-distance-weighted basal area abundance of neighbours (within 20 m), for the periods over which each focus tree was alive. Coefficients of variation of neighbourhood basal area abundance, both spatially and temporally, quantified the changing environment of each focus tree. Fits were critically and individually evaluated, with corrections for spatial autocorrelation. Conspecific effects at Danum was generally very weak or non-existent: species’ mortality rates varied also across plots. The main reasons appear to be that (1) species were not dense enough to interact despite frequent although weak spatial aggregation, and their neighbourhoods were highly differing in species composition; and (2) these neighbourhoods were highly variable temporally, meaning that focus trees experienced stochastically fluctuating neighbourhood environments. Only one species, Dimorphocalyx muricatus, showed strong conspecific effects (varying between plots) which can be explained by its distinct ecology. This understorey species is highly aggregated on ridges and is drought-tolerant. That this functionally and habitat-specialized species, has implied intraspecific density-dependent feedback in its dynamics is a remarkable indication of the overall processes maintaining stability of the Danum forest.

Primary forest dynamics in lowland dipterocarp forest at Danum Valley, Sabah, Malaysia, and the role of the understorey

Changes in species composition in two 4–ha plots of lowland dipterocarp rainforest at Danum, Sabah, were measured over ten years (1986 to 1996) for trees greater than or equal to 10 cm girth at breast height (gbh). Each included a lower–slope to ridge gradient. The period lay between two drought events of moderate intensity but the forest showed no large lasting responses, suggesting that its species were well adapted to this regime. Mortality and recruitment rates were not unusual in global or regional comparisons. The forest continued to aggrade from its relatively (for Sabah) low basal area in 1986 and, together with the very open upper canopy structure and an abundance of lianas, this suggests a forest in a late stage of recovery from a major disturbance, yet one continually affected by smaller recent setbacks. Mortality and recruitment rates were not related to population size in 1986, but across subplots recruitment was positively correlated with the density and basal area of small trees (10 to <50 cm gbh) forming the dense understorey. Neither rate was related to topography. While species with larger mean gbh had greater relative growth rates (rgr) than smaller ones, subplot mean recruitment rates were correlated with rgr among small trees. Separating understorey species (typically the Euphorbiaceae) from the overstorey (Dipterocarpaceae) showed marked differences in change in mortality with increasing gbh: in the former it increased, in the latter it decreased. Forest processes are centred on this understorey quasi–stratum. The two replicate plots showed a high correspondence in the mortality, recruitment, population changes and growth rates of small trees for the 49 most abundant species in common to both. Overstorey species had higher rgrs than understorey ones, but both showed considerable ranges in mortality and recruitment rates. The supposed trade–off in traits, viz slower rgr, shade tolerance and lower population turnover in the understorey group versus faster potential growth rate, high light responsiveness and high turnover in the overstorey group, was only partly met, as some understorey species were also very dynamic. The forest at Danum, under such a disturbance–recovery regime, can be viewed as having a dynamic equilibrium in functional and structural terms. A second trade–off in shade–tolerance versus drought–tolerance is suggested for among the understorey species. A two–storey (or vertical component) model is proposed where the understorey–overstorey species’ ratio of small stems (currently 2:1) is maintained by a major feedback process. The understorey appears to be an important part of this forest, giving resilience against drought and protecting the overstorey saplings in the long term. This view could be valuable for understanding forest responses to climate change where drought frequency in Borneo is predicted to intensify in the coming decades.

Physical fitness of industrial firefighters

Firefighting is widely known to be one of the most physically demanding civilian occupations. A subset of this is Industrial Firefighting, which places similarly high physical demands on Industrial Firefighters. Although there are some studies on community firefighters, literature is scant on Industrial Firefighters and their physical fitness. ^ A cross-sectional study of Industrial Firefighters in Petrochemical companies in Texas was carried out in 1996–98 to assess their physical fitness and to develop a set of physical agility criteria useful in their selection and ongoing fitness for duty evaluations. ^ A physical agility criteria and a fitness scorecard was developed based on seven parameters (resting heart rate, diastolic blood pressure, aerobic capacity, muscle strength, muscle endurance, trunk flexibility and total body fat) of musculoskeletal and cardiorespiratory fitness. Each indicator received a minimum of 0 to a maximum of 20 points, based on individual performance. Therefore a minimum and maximum achievable score for the entire battery of tests was 0 and 140 respectively. Of the 111 study subjects, 5 (4.5%) were far above average, 31 (28%) above average, 46 (41.5 %) average, 29 (26%) below average and 0 (0%) far below average as deemed by the physical fitness scorecard. The mean score was 77 (±23) with a minimum and maximum score of 35 and 135 respectively. ^ Following univariate analysis an exploratory factor analysis to group variables and to assess the overall role of constituent variables in total fitness of a firefighter was developed. This was followed by a stepwise linear regression analysis using aerobic capacity as a dependent variable. ^ Finally, a graded implementation strategy was devised, such that all existing Industrial Firefighters would have an opportunity to improve or maintain their physical fitness at or above average level as deemed by the fitness scorecard. ^

Adiposity and the perilipin gene: The role of single locus and multilocus variation, obesity-related quantitative traits, and disease-related phenotypes in the Atherosclerosis Risk in Communities (ARIC) study

Obesity is a complex multifactorial disease and is a public health priority. Perilipin coats the surface of lipid droplets in adipocytes and is believed to stabilize these lipid bodies by protecting triglyceride from early lipolysis. This research project evaluated the association between genetic variation within the human perilipin (PLIN) gene and obesity-related quantitative traits and disease-related phenotypes in Non-Hispanic White (NHW) and African American (AA) participants from the Atherosclerosis Risk in Communities (ARIC) Study. ^ Multivariate linear regression, multivariate logistic regression, and Cox proportional hazards models evaluated the association between single gene variants (rs2304794, rs894160, rs8179071, and rs2304795) and multilocus variation (rs894160 and rs2304795) within the PLIN gene and both obesity-related quantitative traits (body weight, body mass index [BMI], waist girth, waist-to-hip ratio [WHR], estimated percent body fat, and plasma total triglycerides) and disease-related phenotypes (prevalent obesity, metabolic syndrome [MetS], prevalent coronary heart disease [CHD], and incident CHD). Single variant analyses were stratified by race and gender within race while multilocus analyses were stratified by race. ^ Single variant analyses revealed that rs2304794 and rs894160 were significantly related to plasma triglyceride levels in all NHWs and NHW women. Among AA women, variant rs8179071 was associated with triglyceride levels and rs2304794 was associated with risk-raising waist circumference (>0.8 in women). The multilocus effects of variants rs894160 and rs2304795 were significantly associated with body weight, waist girth, WHR, estimated percent body fat, class II obesity (BMI ≥ 35 kg/m2), class III obesity (BMI ≥ 35 kg/m2), and risk-raising WHR (>0.9 in men and >0.8 in women) in AAs. Variant rs2304795 was significantly related to prevalent MetS among AA males and prevalent CHD in NHW women; multilocus effects of the PLIN gene were associated with prevalent CHD among NHWs. Rs2304794 was associated with incident CHD in the absence of the MetS among AAs. These findings support the hypothesis that variation within the PLIN gene influences obesity-related traits and disease-related phenotypes. ^ Understanding these effects of the PLIN genotype on the development of obesity can potentially lead to tailored health promotion interventions that are more effective. ^

Comparative studies of Hox genes in mammalian limb and vertebral pattern formation

Divergence of anterior-posterior (AP) limb pattern and differences in vertebral column morphology are the two main examples of mammalian evolution. The Hox genes (homeobox containing gene) have been implicated in driving evolution of these structures. However, regarding Hox genes, how they contribute to the generation of mammalian morphological diversities, is still unclear. Implementing comparative gene expression and phenotypic rescue studies for different mammalian Hox genes could aid in unraveling this mystery. In the first part of this thesis, the expression pattern of Hoxd13 gene, a key Hox gene in the establishment of the limb AP pattern, was examined in developing limbs of bats and mice. Bat forelimbs exhibit a pronounced asymmetric AP pattern and offer a good model to study the molecular mechanisms that contribute to the variety of mammalian limbs. The data showed that the expression domain of bat Hoxd13 was shifted prior to the asymmetric limb plate expansion, whereas its domain in mice was much more symmetric. This finding reveals a correlation between the divergence of Hoxd13 expression and the AP patterning difference in limb development. The second part of this thesis details a phenotypic rescue approach by human HOXB1-9 transgenes in mice with Hoxb1-9 deletion, The mouse mutants displayed homeosis in cervical and anterior thoracic vertebrae. The human transgenes entirely rescued the mouse mutants, suggesting that these human HOX genes have similar functions to their mouse orthologues in anterior axial skeletal patterning. The anterior expressing human HOXB transgenes such as HOXB1-3 were expressed in the mouse embryonic trunk in a similar manner as their murine orthologues. However, the anterior boundary of human HOXB9 expression domain was more posterior than that of the mouse Hoxb9 by 2-3 somites. These data provide the molecular support for the hypothesis that Hox genes are responsible for maintaining similar anterior axial skeletal architectures cervical and anterior thoracic regions, but different architectures in lumbar and posterior thoracic regions between humans and mice. ^

BLOOD PRESSURE CHANGES IN RELATION TO DEMOGRAPHIC, ANTHROPOMETRIC, AND SEXUAL MATURATION VARIABLES IN U.S. HEALTH EXAMINATION SURVEY OF CHILDREN AND YOUTHS (UNITED STATES)

The determinants of change in blood pressure during childhood and adolescence were studied in a cohort of U.S. national probability sample of 2146 children examined on two occasions during the Health Examination Survey. Significant negative correlations between the initial level and the subsequent changes in blood pressure were observed. The multiple regression analyses showed that the major determinants of systolic blood pressure (SBP) change were change in weight, baseline SBP, and baseline upper arm girth. Race, time interval between examinations, baseline age, and height change were also significant determinants in SBP change. For the change in diastolic blood pressure (DBP), baseline DBP, baseline weight, and weight change were the major determinants. Baseline SBP, time interval and race were also significant determinants. Sexual maturation variables were also considered in the subgroup analysis for girls. Weight change was the most important predictor of the change in SBP for the group of girls who were still in the pre-menarchal or pre-breast maturation status at the time of the follow-up examination, and who had started to menstruate or to develop breast maturation at sometime between the two examinations. Baseline triceps skinfold thickness or initial SBP were more important variables than weight change for the group of girls who had already experienced menarche or breast maturation at the time of the initial survey. For the total group, pubic hair maturation was found to be a significant predictor of SBP change at the 5% significance level. The importance of weight change and baseline weight for the changes in blood pressure warrants further study. ^

The heart challenge: The effect of regular aerobic exercise on body fat distribution in third and fourth grade school children: A randomized clinical trial

The pattern of body fat distribution known as "centralized", and characterized by a predominance of subcutaneous fat on the trunk and a "pot belly", has been associated with an increased risk of chronic disease. These patterns of fat distribution, as well as the lifestyle habit variables associated with adult fatness and chronic morbidity clearly begin to develop during childhood, indicating the need for intervention and primary prevention of obesity, particularly the centralized form, during childhood or adolescence. The purpose of this study was to determine whether regular aerobic exercise could beneficially alter the distribution of body fat in 8 and 9 year old children. One hundred and eighty-eight participants were randomized into either a regular aerobic exercise treatment group or a standard physical education program control group. A variety of aerobic activities was used for intervention 5 days per week during physical education class for a period of 12 weeks. Fat distribution was measured by a number of the most commonly used indices, including ratios of body circumferences and skinfolds and indices derived from a principal components analysis. Change over time in average pulse rate was used to determine if intervention actually occurred. Approximately 10% of the students were remeasured, allowing the calculation of intra- and interexaminer measurement reliability estimates for all indices.^ This study group was comparable to the U.S. population, though the study children were slightly larger for certain measures. No effect of the exercise intervention was found. The most likely explanation for this was inadequacy of the intervention, as indicated by the lack of any change in average pulse rate with treatment. The results of the measurement reliability analysis are reported and indicate that body circumference ratios are more precise than skinfold ratios, particularly when multiple observers are used. Reliability estimates for the principal component indices were also high.^ It remains unclear whether the distribution of body fat can be altered with exercise. It is likely that this issue will remain undecided until one highly reliable, valid, and sensitive measure of fat distribution can be found. ^

A Pre-Clinical Assessment of Minocycline for Treatment of Chronic Neuropathic Pain after Spinal Cord Injury

Patients living with a spinal cord injury (SCI) often develop chronic neuropathic pain (CNP). Unfortunately, the clinically approved, current standard of treatment, gabapentin, only provides temporary pain relief. This treatment can cause numerous adverse side effects that negatively affect the daily lives of SCI patients. There is a great need for alternative, effective treatments for SCI-dependent CNP. Minocycline, an FDA-approved antibiotic, has been widely prescribed for the treatment of acne for several decades. However, recent studies demonstrate that minocycline has neuroprotective properties in several pre-clinical rodent models of CNS trauma and disease. Pre-clinical studies also show that short-term minocycline treatment can prevent the onset of CNP when delivered during the acute stage of SCI and can also transiently attenuate established CNP when delivered briefly during the chronic stage of SCI. However, the potential to abolish or attenuate CNP via long-term administration of minocycline after SCI is unknown. The purpose of this study was to investigate the potential efficacy and safety of long-term administration of minocycline to abolish or attenuate CNP following SCI. A severe spinal contusion injury was administered on adult, male, Sprague-Dawley rats. At day 29 post-injury, I initiated a three-week treatment regimen of daily administration with minocycline (50 mg/kg), gabapentin (50 mg/kg) or saline. The minocycline treatment group demonstrated a significant reduction in below-level mechanical allodynia and above- level hyperalgesia while on their treatment regimen. After a ten-day washout period of minocycline, the animals continued to demonstrate a significant reduction in below-level mechanical allodynia and above-level hyperalgesia. However, minocycline-treated animals exhibited abnormal weight gain and hepatotoxicity compared to gapabentin-treated or vehicle-treated subjects.The results support previous findings that minocycline can attenuate CNP after SCI and suggested that minocycline can also attenuate CNP via long-term delivery of minocycline after SCI (36). The data also suggested that minocycline had a lasting effect at reducing pain symptoms. However, the adverse side effects of long-term use of minocycline should not be ignored in the rodent model. Gabapentin treatment caused a significant decrease in below-level mechanical allodynia and below-level hyperalgesia during the treatment regimen. Because gabapentin treatment has an analgesic effect at the concentration I administered, the results were expected. However, I also found that gabapentin-treated animals demonstrated a sustained reduction in pain ten days after treatment withdrawal. This result was unexpected because gabapentin has a short half-life of 1.7 hours in rodents and previous studies have demonstrated that pre-drug pain levels return shortly after withdrawal of treatment. Additionally, the gabapentin-treated animals demonstrated a significant and sustained increase in rearing events compared with all other treatment groups which suggested that gabapentin treatment was not only capable of reducing pain long-term but may also significantly improve trunk stability or improve motor function recovery.

Cloning and molecular analysis of paraxis: A {\it trans\/}-acting factor required for somite maturation

During vertebrate embryogenesis, cells from the paraxial mesoderm coalesce in a rostral-to-caudal progression to form the somites. Subsequent compartmentalization of the somites yields the sclerotome, myotome and dermatome, which give rise to the axial skeleton, axial musculature, and dermis, respectively. Recently, we cloned a novel basic-Helix-Loop-Helix (bHLH) protein, called scleraxis, which is expressed in the sclerotome, in mesenchymal precursors of bone and cartilage, and in connective tissues. This dissertation focuses on the cloning, expression and functional analysis of a bHLH protein termed paraxis, which is nearly identical to scleraxis within the bHLH region but diverges in both its amino and carboxyl termini. During the process of mouse embryogenesis, paraxis transcripts are first detected at about day 7.5 post coitum within the primitive mesoderm lying posterior to the head and heart primordia. Subsequently, paraxis expression progresses caudally through the paraxial mesoderm, immediately preceding somite formation. Paraxis is expressed at high levels in newly formed somites before the first detectable expression of the myogenic bHLH genes, and as the somite becomes compartmentalized, paraxis becomes downregulated within the myotome.^ To determine the function of paraxis during mammalian embryogenesis, mice were generated with a null mutation in the paraxis locus. Paraxis null mice survived until birth, but exhibited severe foreshortening along the anteroposterior axis due to the absence of vertebrae caudal to the midthoracic region. The phenotype also included axial skeletal defects, particularly shortened bifurcated ribs which were detached from the vertebral column, fused vertebrae and extensive truncation and disorganization caudal to the hindlimbs. Mutant neonates also lacked normal levels of trunk muscle and exhibited defects in the dermis as well as the stratification of the epidermis. Analysis of paraxis -/- mutant embryos has revealed a failure of the somites to both properly epithelialize and compartmentalize, resulting in defects in somite-derived cell lineages. These results suggest that paraxis is an essential component of the genetic pathway regulating somitogenesis. ^