Impact of alternative histopathology protocols in the dermatopathology laboratory: A prospective quality improvement study.

BACKGROUND: Histopathology protocols for processing dermatopathology specimens vary among laboratories. OBJECTIVE: To determine an optimal histopathology protocol to minimize cost and turnaround time (TAT) for biopsy specimens in a dermatopathology laboratory. METHODS: A prospective, 4-month study compared the mean cost and TAT of producing one versus two initial H&E slides, and zero versus three unstained slides that could be used for frequently used special or immunohistochemical (IHC) stains. RESULTS: For all cases, cost was lower for one versus two initial H&E slides, with an insignificant increase in TAT. Producing three vs zero unstained slides incurred higher cost, with no reduction in TAT. In a subset of cases in which frequently used special or IHC stains were performed, cost and TAT were optimized by producing one initial H&E and three unstained slides. CONCLUSION: A protocol of one initial H&E slide and zero unstained slides optimizes cost and TAT in our dermatopathology laboratory. Pigmented lesions and inflammatory dermatoses may benefit from the addition of unstained slides. Further study is needed to quantify this benefit and evaluate for other cases for which an alternative protocol is advantageous.

The role of body height as a co-factor of excess weight in Switzerland.

OBJECT: Excess weight (Body Mass Index [BMI] ≥25.0 kg/m2 ) is a major health issue worldwide, including in Switzerland. For high-income countries, little attention has been paid to body height in context of excess weight. The aim of this study is to assess the importance of body height as a co-factor for excess weight in multiple large nationwide data sets. DATA AND METHODS: In this comparative study, we included the largest nationwide and population-based studies in the fields of public health, nutrition and economics for Switzerland, as well as data of the medical examination during conscription for the Swiss Armed Forces, which contained information on BMI and, if possible, waist-to-height-ratio (WHtR) and waist-to-hip-ratio (WHR). RESULTS: The multinomial logistic regressions show that the probability of belonging to the excess weight category (BMI ≥25.0 kg/m2 ) decreased with increasing height in both sexes inall contemporary data sets. This negative association was shown to be constant, only among conscripts measured in the 1870s the association was positive, when increasing height was associated with a higher BMI. The negative association not only emerge in BMI, but also in WHtR and WHR. CONCLUSION: Our results emphasize the importance of body height as a co-factor of excess weight, suggesting a clear negative association between height and BMI, WHtR and WHR. Evidence indicates that both early-life environmental exposures and alleles associated with height may contribute to these associations. This knowledge could serve as further starting points for prevention programs in the field of public health.

Associations between hydration status, body composition, sociodemographic and lifestyle factors in the general population: a cross-sectional study.

BACKGROUND: Whole-body hydration status is associated with several health outcomes, such as dehydration, edema and hypertension, but little is known about the nonclinical determinants. Therefore, we studied the associations of sex, age, body composition, nutrition, and physical activity on several body hydration measures. METHODS: We assessed sociodemographic variables, dietary habits, and physical activity by questionnaire and body composition by bioelectric impedance analysis (BIA). We compared determinants between the sexes and calculated associations between determinants and BIVA hydration measures by multivariable linear regressions. RESULTS: A total of 242 adults from the general population (age 18-94, 47% women) were included. Women were younger, smaller, lighter, and had a smaller BMI (kg/m2) than men (p < 0.05). Women had less muscle mass, less visceral fat mass and less extracellular and intracellular water than men (p < 0.001). Women showed less intracellular water per extracellular water than men, while men showed higher phase angle values than women (both p < 0.001). Men had a stronger association of hydration measures with physical activity than women. Both sexes showed a decrease in hydration measures with age. CONCLUSIONS: Sex, age, body composition, and physical activity influence body hydration. There seem to be differences in body water regulation between the sexes. Especially interesting are factors susceptible to preventive measures such as physical activity.

Body mass index in young men in Switzerland after the national shutdowns during the COVID-19 pandemic: results from a cross-sectional monitoring study at the population level since 2010.

BACKGROUND: Owing to the coronavirus disease pandemic, the Swiss goverment imposed a shutdown twice in 2020, which may have changed diet and physical activity. Regarding the question of weight change during the pandemic, little information based on measured weight data is available. We aimed to investigate whether the body mass indices (BMIs) of young Swiss men after the two shutdowns in spring and fall 2020 differed from those of young men examined before the shutdowns. METHODS: We analysed young Swiss men's BMIs taken during mandatory recruitment for the Swiss Armed Forces at the cross-sectional (not individual longitudinal) monitoring level and across weeks of conscription between January 2010 and July 2021 (n = 373 016). These data allow for continuous health monitoring of young men at almost the population level (coverage, >90%). For statistical modelling, we used the generalized additive model (GAM) framework. RESULTS: We showed that the BMIs of the conscripts examined in the 15 weeks after the two shutdowns in spring and autumn 2020 were not or only slightly different from their baseline values. Sensitivity analyses revealed that this conclusion also holds if the BMI distribution or prevalence of excess weight is assessed. The GAM further showed the significant effects of individual and area-based measures of socioeconomic position and age on BMI. CONCLUSION: Our results suggest that lifestyle changes during the pandemic in young men might have been too modest to be reflected in body weight. However, longitudinal data and/or data on women, children, or the elderly may lead to different conclusions.

Public Health Interventions, Epidemic Growth, and Regional Variation of the 1918 Influenza Pandemic Outbreak in a Swiss Canton and Its Greater Regions.

Public health interventions implemented during the coronavirus disease 2019 (COVID-19) pandemic are based on experience gained from past pandemics. The 1918 influenza pandemic is the most extensively researched historical influenza outbreak. All 9335 reports available in the State Archives on 121 152 cases of influenza-like illness from the canton of Bern from 473 of 497 municipalities (95.2%) were collected; the cases were registered between 30 June 1918 and 30 June 1919. The overall incidence rates of newly registered cases per week for the 9 greater regions of Bern for both the first and second waves of the pandemic were calculated. Relative incidence rate ratios (RIRRs) were calculated to estimate the change in the slope of incidence curves associated with public health interventions. During the first wave, school closures (RIRR, 0.16 [95% CI, 0.15 to 0.17]) and restrictions of mass gatherings (RIRR, 0.57 [CI, 0.54 to 0.61]) were associated with a deceleration of epidemic growth. During the second wave, in autumn 1918, cantonal authorities initially reacted hesitantly and delegated the responsibility to enact interventions to municipal authorities, which was associated with a lack of containment of the second wave. A premature relaxation of restrictions on mass gatherings was associated with a resurgence of the epidemic (RIRR, 1.18 [CI, 1.12 to 1.25]). Strikingly similar patterns were found in the management of the COVID-19 outbreak in Switzerland, with a considerably higher amplitude and prolonged duration of the second wave and much higher associated rates of hospitalization and mortality.

Somatic PIK3R1 variation as a cause of vascular malformations and overgrowth.

PURPOSE: Somatic activating variants in the PI3K-AKT pathway cause vascular malformations with and without overgrowth. We previously reported an individual with capillary and lymphatic malformation harboring a pathogenic somatic variant in PIK3R1, which encodes three PI3K complex regulatory subunits. Here, we investigate PIK3R1 in a large cohort with vascular anomalies and identify an additional 16 individuals with somatic mosaic variants in PIK3R1. METHODS: Affected tissue from individuals with vascular lesions and overgrowth recruited from a multisite collaborative network was studied. Next-generation sequencing targeting coding regions of cell-signaling and cancer-associated genes was performed followed by assessment of variant pathogenicity. RESULTS: The phenotypic and variant spectrum associated with somatic variation in PIK3R1 is reported herein. Variants occurred in the inter-SH2 or N-terminal SH2 domains of all three PIK3R1 protein products. Phenotypic features overlapped those of the PIK3CA-related overgrowth spectrum (PROS). These overlapping features included mixed vascular malformations, sandal toe gap deformity with macrodactyly, lymphatic malformations, venous ectasias, and overgrowth of soft tissue or bone. CONCLUSION: Somatic PIK3R1 variants sharing attributes with cancer-associated variants cause complex vascular malformations and overgrowth. The PIK3R1-associated phenotypic spectrum overlaps with PROS. These data extend understanding of the diverse phenotypic spectrum attributable to genetic variation in the PI3K-AKT pathway.

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

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

Generalized infantile myofibromatosis with visceral involvement presenting as diffuse hypopigmented macules at birth.

The initial clinical presentation of infantile myofibromatosis can vary from subtle skin changes to large tumors. Here, we describe a case of congenital generalized infantile myofibromatosis which presented with diffuse hypopigmented macules, some with subtle atrophy and telangiectasia. Further workup revealed visceral involvement which led to treatment with systemic chemotherapy. Awareness of this rare clinical presentation is crucial to expedite workup and treatment given the poor prognosis in infants with visceral involvement.

Knuckle pads: an ancient disease frequently misdiagnosed because of minimal modern attention.

Knuckle pads are benign painless papules and nodules that most commonly appear on the extensor surfaces of the proximal interphalangeal joints. Knuckle pads are frequently misdiagnosed due to their location overlying joints, which can lead to costly interventions and patient discomfort for a relatively harmless condition. We describe a 44-year-old woman who presented with mildly painful nodules on multiple bilateral proximal interphalangeal joints. The patient did not have a family history of fibromatosis and the rheumatoid factor was negative. Histology showed mild epidermal hyperkeratosis, papillomatosis, and acanthosis with a deep dermal, poorly circumscribed, proliferative nodule made of spindled myofibroblasts without cytological atypia. The diagnosis of knuckle pads was established based on the clinical and morphological presentation of the nodules. Treatment with intralesional triamcinolone acetonide injection produced significant clinical improvement. Our findings highlight the challenging diagnosis of knuckle pads and the importance of increasing the familiarity of knuckle pads in modern medical practice.

Reactive angioendotheliomatosis associated with antiphospholipid syndrome.

Reactive angioendotheliomatosis (RAE) is an uncommon, benign, antiproliferative condition associated with systemic diseases that may cause occlusion or inflammation of the vascular lumina. A link between antiphospholipid syndrome (APS) and RAE has been reported a few times in the literature. Herein, we present a unique case of RAE diagnosed in a patient with primary APS who was well-managed on warfarin and rituximab with no recent thrombotic events. As RAE can precede or follow a diagnosis of APS, the presence of the condition indicates a need to workup for APS and to ensure those with the condition are adequately anticoagulated. However, as demonstrated in this case, the condition can still occur in patients who are adequately anticoagulated.

Changes in Biological Pathways During 6,000 Years of Civilization in Europe.

The beginning of civilization was a turning point in human evolution. With increasing separation from the natural environment, mankind stimulated new adaptive reactions in response to new environmental factors. In this paper, we describe direct signs of these reactions in the European population during the past 6,000 years. By comparing whole-genome data between Late Neolithic/Bronze Age individuals and modern Europeans, we revealed biological pathways that are significantly differently enriched in nonsynonymous single nucleotide polymorphisms in these two groups and which therefore could be shaped by cultural practices during the past six millennia. They include metabolic transformations, immune response, signal transduction, physical activity, sensory perception, reproduction, and cognitive functions. We demonstrated that these processes were influenced by different types of natural selection. We believe that our study opens new perspectives for more detailed investigations about when and how civilization has been modifying human genomes.

Rubella Vaccine Persistence Within Cutaneous Granulomas in Common Variable Immunodeficiency Disorder.

Common variable immunodeficiency disorder is a primary immunodeficiency disorder characterized by reduced levels of serum immunoglobulins and impaired antibody response. This condition may be associated with development of noninfectious granulomatous dermatitis of the skin which may be disfiguring and destructive. There are no published guidelines for the treatment of cutaneous granulomas in this patient population. In recent studies, rubella virus-positive cells in granulomas were localized to M2 macrophages which have an important role in wound healing and the secretion of immunoregulatory cytokines. We present a case of treatment-refractory, disfiguring common variable immunodeficiency disorder-associated granulomatous dermatitis. Immunofluorescence microscopy of the biopsy specimen confirmed the presence of rubella vaccine capsid proteins in M2 macrophages within the granuloma, a newly recognized phenomenon in this patient population. This knowledge may serve to identify future therapeutic targets or preventative strategies for granulomatous dermatitis in patients with primary immunodeficiency disorder.

Pulmonary arterial pressure at rest and during exercise in chronic mountain sickness: a meta-analysis.

Up to 10% of the more than 140 million high-altitude dwellers worldwide suffer from chronic mountain sickness (CMS). Patients suffering from this debilitating problem often display increased pulmonary arterial pressure (PAP), which may contribute to exercise intolerance and right heart failure. However, there is little information on the usual PAP in these patients.We systematically reviewed and meta-analysed all data published in English or Spanish until June 2018 on echocardiographic estimations of PAP at rest and during mild exercise in CMS patients.Nine studies comprising 287 participants fulfilled the inclusion criteria. At rest, the point estimate from meta-analysis of the mean systolic PAP was 27.9 mmHg (95% CI 26.3-29.6 mmHg). These values are 11% (+2.7 mmHg) higher than those previously meta-analysed in apparently healthy high-altitude dwellers. During mild exercise (50 W) the difference in mean systolic PAP between patients and high-altitude dwellers was markedly more accentuated (48.3 versus 36.3 mmHg) than at rest.These findings indicate that in patients with CMS PAP is moderately increased at rest, but markedly increased during mild exercise, which will be common with activities of daily living.

Cutaneous metastases of papillary renal cell carcinoma: A case report and review of the literature.

Papillary renal cell carcinoma (RCC) is an uncommon subtype of RCC that is typically encountered at early stages and has a high survival rate. Histopathology typically shows well-defined papillary architecture with tumor cells lining fibrovascular cores and can be further subdivided into type 1 and type 2 tumors based on cytology and genetic basis. Type 1 tumors have a single layer of basophilic cells and low nuclear atypia, while type 2 tumors have a pseudostratified layer of eosinophilic cells and high nuclear atypia. Some tumors have overlapping features of both types. We present a unique case of cutaneous metastases of papillary RCC with typical papillary architecture in the dermis and review the literature on this rare entity.

St. Catherine of Siena (1347-1380 AD): one of the earliest historic cases of altered gustatory perception in anorexia mirabilis.

St. Catherine of Siena suffered from an extreme form of holy fasting, a condition classified as anorexia mirabilis (also known as inedia prodigiosa). Historical and medical scholarships alike have drawn a comparison between this primaeval type of anorexia with a relatively common form of eating disorder among young women in the modern world, anorexia nervosa. St. Catherine's condition was characterised by a disgust for sweet taste, a condition also described in anorexia nervosa, and characterised by specific neurophysiological changes in the brain. St. Catherine's case may be considered one of the oldest veritable descriptions of altered gustation (dysgeusia). Moreover, a more compelling neurophysiological similarity between anorexia mirabilis and anorexia nervosa may be proposed.

Brief communication: Swimming and diving behavior in apes (Pan troglodytes and Pongo pygmaeus): first documented report.

Extant hominoids, including humans, are well known for their inability to swim instinctively. We report swimming and diving in two captive apes using visual observation and video recording. One common chimpanzee and one orangutan swam repeatedly at the water surface over a distance of 2-6 m; both individuals submerged repeatedly. We show that apes are able to overcome their negative buoyancy by deliberate swimming, using movements which deviate from the doggy-paddle pattern observed in other primates. We suggest that apes' poor swimming ability is due to behavioral, anatomical, and neuromotor changes related to an adaptation to arboreal life in their early phylogeny. This strong adaptive focus on arboreal life led to decreased opportunities to interact with water bodies and consequently to a reduction of selective pressure to maintain innate swimming behavior. As the doggy paddle is associated with quadrupedal walking, a deviation from terrestrial locomotion might have interfered with the fixed rhythmic action patterns responsible for innate swimming.

Associations between 3D surface scanner derived anthropometric measurements and body composition in a cross-sectional study.

BACKGROUND: 3D laser-based photonic scanners are increasingly used in health studies to estimate body composition. However, too little is known about whether various 3D body scan measures estimate body composition better than single standard anthropometric measures, and which body scans best estimate it. Furthermore, little is known about differences by sex and age. METHODS: 105 men and 96 women aged between 18 and 90 years were analysed. Bioelectrical Impedance Analysis was used to estimate whole relative fat mass (RFM), visceral adipose tissue (VAT) and skeletal muscle mass index (SMI). An Anthroscan VITUSbodyscan was used to obtain 3D body scans (e.g. volumes, circumferences, lengths). To reduce the number of possible predictors that could predict RFM, VAT and SMI backward elimination was performed. With these selected predictors linear regression on the respective body compositions was performed and the explained variations were compared with models using standard anthropometric measurements (Body Mass Index (BMI), waist circumference (WC) and waist-to-height-ratio (WHtR)). RESULTS: Among the models based on standard anthropometric measures, WC performed better than BMI and WHtR in estimating body composition in men and women. The explained variations in models including body scan variables are consistently higher than those from standard anthropometrics models, with an increase in explained variations between 5% (RFM for men) and 10% (SMI for men). Furthermore, the explained variation of body composition was additionally increased when age and lifestyle variables were added. For each of the body composition variables, the number of predictors differed between men and women, but included mostly volumes and circumferences in the central waist/chest/hip area and the thighs. CONCLUSIONS: 3D scan models performed better than standard anthropometric measures models to predict body composition. Therefore, it is an advantage for larger health studies to look at body composition more holistically using 3D full body surface scans.

The Mummy Explorer-a self-regulated open-access online teaching tool.

Background and objectives: Virtual teaching tools have gained increasing importance in recent years. In particular, the COVID-19 pandemic has reinforced the need for media-based and self-regulated tools. What is missing are tools that allow us to interlink highly interdisciplinary fields such as evolutionary medicine and, at the same time, allow us to adapt content to different lectures. Methodology: We designed an interactive online teaching tool, namely, the Mummy Explorer, using open-access software (Google Web Designer), and we provided a freely downloadable template. We tested the tool on students and lecturers of evolutionary medicine using questionnaires and improved the tool according to their feedback. Results: The tool has a modular design and provides an overview of a virtual mummy excavation, including the subfields of palaeopathology, paleoradiology, cultural and ethnographic context, provenance studies, paleogenetics, and physiological analyses. The template allows lecturers to generate their own versions of the tool for any topic of interest by simply changing the text and pictures. Tests undertaken with students of evolutionary medicine showed that the tool was helpful during their studies. Lecturers commented that they appreciated having a similar tool in other fields. Conclusions and implications: Mummy Explorer fills a gap in the virtual teaching landscape of highly interdisciplinary fields such as evolutionary medicine. It will be offered for free download and can be adapted to any educational topic. Translations into German and possibly other languages are in progress.