External workload and cognitive performance of a tactical military scenario-based field exercise.

INTRODUCTION: Military personnel must manage a multitude of competing physiological and cognitive stressors while maintaining high levels of performance. Quantifying the external workload and cognitive demands of tactical military field exercises closely simulating operational environments, will provide a better understanding of stressors placed on personnel to inform evidence-based interventions. METHODS: Thirty-one soldiers completing a dismounted 48 hours tactical field exercise, participated in the study. External workload was quantified using a wrist-worn triaxial accelerometer, with cognitive function (Go-/No-Go, N-back, psychomotor vigilance task and subjective workload ratings (NASA-TLX) assessed pre-exercise, mid-exercise and postexercise. Physical activity was described using Euclidian Norm Minus One (mg), with moderate vigorous physical activity (MVPA) and sedentary light physical activity (SLPA) as ≥ or <113 mg, respectively. Changes in general cognitive performance (total accuracy-speed trade-off (ASTO) % change) and function outcome variables (overall mean reaction time, ASTO and number of correct and missed responses) were calculated for each assessment from pre-exercise, to mid-exercise and postexercise. RESULTS: For the exercise duration (50:12±02:06 hh:mm) participants spent more time completing SLPA compared with MVPA (1932±234 vs 1074±194 min; p<0.001), equating to 33% of the time spent completing MVPA. Overall cognitive performance decreased over the exercise (pre-to-post: -249). However, the largest decrement was observed pre-to-mid (-168). Perceived mental demand associated with the cognitive assessments significantly increased over the duration of the exercise (pre-: 33; mid-: 38 and post-: 51; χ2 F(2) = 26.7, p = <0.001, W=0.477) which could suggest that participants were able to attenuate a further decline in cognitive performance by investing more effort/mental resources when completing assessments. CONCLUSION: The study successfully quantified the physical activity, and subsequent impact on cognitive function, in soldiers completing a 48 hours tactical field exercise. Further research is needed to better understand how physiological stressors interact with cognitive function during military operations.

Fate of Quasiparticles at High Temperature in the Correlated Metal Sr_{2}RuO_{4}.

We study the temperature evolution of quasiparticles in the correlated metal Sr_{2}RuO_{4}. Our angle resolved photoemission data show that quasiparticles persist up to temperatures above 200 K, far beyond the Fermi liquid regime. Extracting the quasiparticle self-energy, we demonstrate that the quasiparticle residue Z increases with increasing temperature. Quasiparticles eventually disappear on approaching the bad metal state of Sr_{2}RuO_{4} not by losing weight but via excessive broadening from super-Planckian scattering. We further show that the Fermi surface of Sr_{2}RuO_{4}-defined as the loci where the spectral function peaks-deflates with increasing temperature. These findings are in semiquantitative agreement with dynamical mean field theory calculations.

Changes in physical performance during British Army Junior Entry, British Army Standard Entry and Royal Air Force Basic Training.

INTRODUCTION: The purpose was to quantify physical performance in men and women during British Army Junior Entry (Army-JE), British Army Standard Entry (Army-SE) and Royal Air Force (RAF) basic training (BT). DESIGN: Prospective longitudinal study. METHODS: 381 participants ((339 men and 42 women) n=141 Army-JE, n=132 Army-SE, n=108 RAF) completed a 2 km run, medicine ball throw (MBT) and isometric mid-thigh pull (MTP), pre-BT and post-BT. To examine changes in pre-BT to post-BT physical test performance, for each course, paired Student t-test and Wilcoxon test were applied to normally and non-normally distributed data, respectively, with effect sizes reported as Cohen's D and with rank biserial correlations, respectively. A one-way between-subjects analysis of variance (ANOVA) (or Welch ANOVA for non-normally distributed data) compared performance between quartiles based on test performance pre-BT. Where the main tests statistic, p value and effect sizes identified likely effect of quartile, post hoc comparisons were made using Games-Howell tests with Tukey's p value. Data are presented as mean±SD, with statistical significance set at p<0.05. RESULTS: During BT, 2 km run time improved by 13±46 s (-2.1%±8.1%), 30±64 s (-4.8%±12.3%) and 24±27 s (-4.5%±5.1%) for Army-JE, Army-SE and RAF, respectively (all p<0.005). MBT distance increased by 0.27±0.28 m (6.8%±7.0%) for Army-JE (p<0.001) and 0.07±0.46 m (2.3%±10.9%) for Army-SE (p=0.040), but decreased by 0.08±0.27 m (-1.4%±6.0%) for RAF (p=0.002). MTP force increased by 80±281 n (10.8%±27.6%) for Army-JE (p<0.001) and did not change for Army-SE (-36±295 n, -0.7%±20.6%, p=0.144) or RAF (-9±208 n, 1.0±17.0, p=0.603). For all tests and cohorts, participants in the lowest quartile of pre-BT performance scores demonstrated greater improvements, compared with participants in the highest quartile (except Army-JE MBT, ∆% change similar between all quartiles). CONCLUSIONS: Changes in physical performance were observed for the three fitness tests following the different BT courses, and recruits with the lowest strength and aerobic fitness experienced greatest improvements.

Buried graphene heterostructures for electrostatic doping of low-dimensional materials.

The fabrication and characterization of steep slope transistor devices based on low-dimensional materials requires precise electrostatic doping profiles with steep spatial gradients in order to maintain maximum control over the channel. In this proof-of-concept study we present a versatile graphene heterostructure platform with three buried individually addressable gate electrodes. The platform is based on a vertical stack of embedded titanium and graphene separated by an intermediate oxide to provide an almost planar surface. We demonstrate the functionality and advantages of the platform by exploring transfer and output characteristics at different temperatures of carbon nanotube field-effect transistors with different electrostatic doping configurations. Furthermore, we back up the concept with finite element simulations to investigate the surface potential. The presented heterostructure is an ideal platform for analysis of electrostatic doping of low-dimensional materials for novel low-power transistor devices.

Unloader bracing in osteoarthritis of the knee - Is there a direct effect on the damaged cartilage?

BACKGROUND: Unloading knee braces represent a conservative treatment option for non-pharmalogical management of unicompartmental osteoarthritis of the knee. Though there is consensus on the clinical effectiveness of unloading, the effect mechanism of bracing remains part of a debate. Our study was designed to assess the effect of unloader bracing on damaged cartilage via MRI cartilage mappings. METHODS: Fourteen patients (7 female, 7 male, mean age 43.1 ± 9.4 years) with unicompartmental cartilage wear in knees with varus or valgus malalignment were enrolled. Clinical scores, radiographs and MR-graphic properties (T2/T2* mapping, T1 Delayed Gadolinium Enhanced MRI of the cartilage (dGEMRIC) mapping, high-resolution PDw sequences) of knee cartilage were recorded before and three months after brace use. RESULTS: Bracing the knees for a mean of 14.4 ± 2.0 weeks (range 11 to 18 weeks) resulted in significant pain reduction (VAS changed from 5.9 ± 2.0 to 2.0 ± 1.3, p < 0.001) and improvement in knee function (KOOS increased from 42.1 ± 22.7 to 64.8 ± 18.7, p < 0.001). In the affected cartilage regions T2 relaxation times significantly decreased from 56.1 ± 11.4 ms to 46.5 ± 11.2 ms (p < 0.05). No changes in T1-dGEMRIC and T2* relaxation times, thickness or the extent of the damaged cartilage area could be detected. CONCLUSIONS: Our results suggest, that unloader bracing improves the biochemical properties of the damaged cartilage by increasing collagen and proteoglycan concentration as well as decreasing the cartilage edema.

Insulin expression in ß cells is reduced within islets before islet loss in diabetic cats.

OBJECTIVES: Diabetes mellitus is a common condition that requires intensive treatment and markedly impacts the welfare of affected cats. The aim of this study was to identify diabetes mellitus-associated perturbations in the feline pancreatic islet microenvironment. The utility of "clear, unobstructed brain/body imaging cocktails and computational analysis" (CUBIC) for three-dimensional pancreatic analysis was investigated. METHODS: Formalin-fixed paraffin-embedded tissues from cats with diabetes mellitus, or control cats without pancreatic pathology, were retrospectively identified. Immunohistochemistry for synaptophysin and ionised calcium binding adaptor molecule 1, and immunofluorescence for insulin and synaptophysin, were used to assess changes in islets. An image analysis pipeline was developed to analyse images acquired from two-dimensional immunofluorescence. CUBIC was used to optically clear selected pancreas samples before immunofluorescence and deep three-dimensional confocal microscopy. RESULTS: Diabetic cats have a significant reduction in synaptophysin-positive islet area. Whilst islets from diabetic patients have similar numbers of ß cells to islets from control cats, significantly lower intensity of insulin expression can be observed in the former. CUBIC facilitates clear visualisation of pancreatic islets in three dimensions. CLINICAL SIGNIFICANCE: The data presented support the theory that there is a decrease in function of ß cells before their destruction, suggesting a potentially significant step in the pathogenesis of feline diabetes mellitus. In parallel, we demonstrate CUBIC as a valuable new tool to visualise the shape of feline pancreatic islets and to interrogate pathology occurring in the islets of diabetic pets.

Pan-cancer analysis of genomic scar patterns caused by homologous repair deficiency (HRD).

Homologous repair deficiency (HRD) is present in many cancer types at variable prevalence and can indicate response to platinum-based chemotherapy and PARP inhibition. We developed a tumor classification system based on the loss of function of genes in the homologous recombination repair (HRR) pathway. To this end, somatic and germline alterations in BRCA1/2 and 140 other HRR genes were included and assessed for the impact on gene function. Additionally, information on the allelic hit type and on BRCA1 promoter hypermethylation was included. The HRDsum score including LOH, LST, and TAI was calculated for 8847 tumors of the TCGA cohort starting from genotyping data and for the subcohort of ovarian cancer also starting from WES data. Pan-cancer, deleterious BRCA1/2 alterations were detected in 4% of the tumors, while 18% of the tumors were HRD-positive (HRDsum ≥ 42). Across 33 cancer types, both BRCA1/2 alterations and HRD-positivity were most prevalent in ovarian cancer (20% and 69%). Pan-cancer, tumors with biallelic deleterious alterations in BRCA1/2 were separated strongly from tumors without relevant alterations (AUC = 0.89), while separation for tumors with monoallelic deleterious BRCA1/2 alterations was weak (AUC = 0.53). Tumors with biallelic deleterious alterations in other HHR genes were separated moderately from tumors without relevant alterations (AUC = 0.63), while separation for tumors with such monoallelic alterations was weaker (AUC = 0.57). In ovarian cancer, HRDsum scores calculated from WES data correlated strongly with HRDsum scores calculated from genotyping data (R = 0.87) and were slightly (4%) higher. We comprehensively analyzed HRD scores and their association with mutations in HRR genes in common cancer types. Our study identifies important parameters influencing HRD measurement and argues for an integration of HRDsum score with specific mutational profiles.

Intestinal and extraintestinal neoplasms in patients with NTHL1 tumor syndrome: a systematic review.

Germline biallelic pathogenic variants (PVs) in NTHL1 have since 2015 been associated with the autosomal recessive tumor predisposition syndrome: NTHL1 tumor syndrome or NTHL1-associated polyposis. In this systematic review, we aim to systematically investigate the phenotypic and genotypic spectrum of the condition including occurrence of both benign and malignant tumors. The databases PubMed, EMBASE, and Scopus were searched. The search was conducted the 25th of august 2021. We included patients with germline PVs, both heterozygous and homo-/compound heterozygous carriers. Twenty-one papers were selected including 47 patients with biallelic PVs in NTHL1 in 32 families. Twenty-three out of 47 patients (49%) were diagnosed with colorectal cancer (CRC) (mean age: 55, range: 31-73) and 12 out of 22 female patients (55%) were diagnosed with breast cancer (mean age: 49, range: 36-63). Apart from three, all patients who underwent a colonoscopy, had colonic adenomas (93%), and three patients (6%) had duodenal adenomatosis. We also identified 158 heterozygous carriers of germline PVs in NTHL1. Twenty-six out of 68 (38%) heterozygous carriers, who underwent colonoscopy, had colonic polyps or adenomas. Twenty-nine heterozygous carriers (18%) were diagnosed with CRC and 59 (49%) with breast cancer. We observed a high frequency of early onset CRC and breast cancer in patients with NTHL1 tumor syndrome. Subsequently, colorectal, breast, and endometrial cancer screening programs are recommended for NTHL1 biallelic carriers. Trial registry PROSPERO: CRD42021275159.

Young children spontaneously invent three different types of associative tool use behaviour.

Associative Tool Use (ATU) describes the use of two or more tools in combination, with the literature further differentiating between Tool set use, Tool composite use, Sequential tool use and Secondary tool use. Research investigating the cognitive processes underlying ATU has shown that some primate and bird species spontaneously invent Tool set and Sequential tool use. Yet studies with humans are sparse. Whether children are also able to spontaneously invent ATU behaviours and at what age this ability emerges is poorly understood. We addressed this gap in the literature with two experiments involving preschoolers (E1, N = 66, 3 years 6 months to 4 years 9 months; E2, N = 119, 3 years 0 months to 6 years 10 months) who were administered novel tasks measuring Tool set, Metatool and Sequential tool use. Participants needed to solve the tasks individually, without the opportunity for social learning (except for enhancement effects). Children from 3 years of age spontaneously invented all of the types of investigated ATU behaviours. Success rates were low, suggesting that individual invention of ATU in novel tasks is still challenging for preschoolers. We discuss how future studies can use and expand our tasks to deepen our understanding of tool use and problem-solving in humans and non-human animals.

Management of COVID-19 ICU-survivors in primary care: - a narrative review.

Many survivors of critical illness suffer from long-lasting physical, cognitive, and mental health sequelae. The number of affected patients is expected to markedly increase due to the COVID-19 pandemic. Many ICU survivors receive long-term care from a primary care physician. Hence, awareness and appropriate management of these sequelae is crucial. An interdisciplinary authorship team participated in a narrative literature review to identify key issues in managing COVID-19 ICU-survivors in primary care. The aim of this perspective paper is to synthesize important literature to understand and manage sequelae of critical illness due to COVID-19 in the primary care setting.

Air pollution-induced tanning of human skin.

BACKGROUND: Melanism is more frequent in animals living in polluted areas on urban-industrial sites. Given that an increasing number of people are exposed to elevated air pollution levels, it is possible that environmental pollutants affect melanogenesis in human skin. Epidemiological studies have shown that exposure to traffic-related air pollutants such as diesel exhaust particles (DEP) is associated with more clinical signs of hyperpigmentation. However, mechanistic evidence linking DEP exposure to pigmentation has been elusive. OBJECTIVES: To develop an ex␣vivo skin model to allow for repetitive topical application of relevant ambient DEP, and to provide proof of concept in humans. METHODS: We measured skin pigmentation, melanin and pigmentation-associated gene expression, and evaluated oxidative stress. RESULTS: Repetitive exposure of ex␣vivo skin to DEP at nontoxic concentrations increased skin pigmentation. This increase was visible to the naked eye, time dependent, and associated with an increase in melanin content and the transcription of genes involved in de novo melanin synthesis. Similarly, in healthy participants (n = 76), repetitive topical application of DEP at nontoxic concentrations increased skin pigmentation. DEP-induced pigmentation was mediated by an oxidative stress response. After the application of DEP, epidermal antioxidants were depleted, lipid peroxidation and oxidative DNA damage were enhanced, and in a vehicle-controlled, double-blind clinical study DEP-induced pigmentation was prevented by the topical application of an antioxidant mixture. CONCLUSIONS: Similar to solar radiation, air pollutants cause skin tanning. As eumelanin is an antioxidant, it is proposed that this response serves to protect human skin against air pollution-induced oxidative stress.

Multidisciplinary barriers to addressing tobacco cessation during an inpatient psychiatric hospitalization.

Tobacco use and resultant health complications disproportionately impact individuals with psychiatric disorders. Inpatient psychiatric hospitalizations provide an opportunity to initiate tobacco treatment. In this study, electronic medical record review identified demographic and clinical information, smoking status, and tobacco cessation treatment offered for adults hospitalized on two acute, non-smoking psychiatric units in Massachusetts from January 2016 to March 2018. We additionally conducted semi-structured interviews with 15 inpatient nursing, psychiatry, psychology and social work providers regarding their tobacco cessation treatment practices and perceived facilitators and barriers to addressing tobacco use on psychiatric inpatient units. Chart review identified 1099 of 3140 (35%) people admitted reporting daily tobacco smoking. On discharge, 5 (0.005%) of inpatient smokers received a prescription for varenicline, 43 (0.04%) for dual-nicotine replacement therapy, 211 (19.2%) for nicotine patch, and 5 (0.005%) for bupropion. Barriers to inpatient smoking cessation treatment initiation identified in qualitative interviews included: 1) smoking cessation as low priority, 2) smoking cessation as the responsibility of outpatient providers, 3) lack of education about tobacco treatment, and 4) treatment discussions framed as preventing withdrawal. Given the potential to impact a large percentage of psychiatric tobacco users, future interventions should investigate provision of tobacco cessation counseling and pharmacotherapy in inpatient settings, with interventions that take into account the barriers and opportunities presented in this study.

Validation of a combined ELISA to detect IgG, IgA and IgM antibody responses to SARS-CoV-2 in mild or moderate non-hospitalised patients.

BACKGROUND: Frequently SARS-CoV-2 results in mild or moderate disease with potentially lower concentrations of antibodies compared to those that are hospitalised. Here, we validated an ELISA using SARS-CoV-2 trimeric spike glycoprotein, with targeted detection of IgG, IgA and IgM (IgGAM) using serum and dried blood spots (DBS) from adults with mild or moderate disease. METHODS: Targeting the SARS-CoV-2 trimeric spike, a combined anti-IgG, IgA and IgM serology ELISA assay was developed using 62 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 624 COVID-19 negative samples. The assay was validated using 73 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 359 COVID-19 negative serum samples with an additional 81 DBSs. The assay was further validated in 226 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 426 COVID-19 negative clinical samples. RESULTS: A sensitivity and specificity of 98.6% (95% CI, 92.6-100.0), 98.3% (95% CI, 96.4-99.4), respectively, was observed following validation of the SARS-CoV-2 ELISA. No cross-reactivities with endemic coronaviruses or other human viruses were observed, and no change in results were recorded for interfering substances. The assay was stable at temperature extremes and components were stable for 15 days once opened. A matrix comparison showed DBS to correlate with serum results. Clinical validation of the assay reported a sensitivity of 94.7% (95% CI, 90.9-97.2%) and a specificity of 98.4% (95% CI, 96.6-99.3%). CONCLUSIONS: The human anti-IgGAM SARS-CoV-2 ELISA provides accurate and sensitive detection of SARS-CoV-2 antibodies in non-hospitalised adults with mild or moderate disease. The use of dried blood spots makes the assay accessible to the wider community.

[Comparison between oral fluid samples and pooled serum samples for the detection of antibodies against Porcine Reproductive and Respiratory Syndrome Virus in weaning pig herds]. / Vergleich von Speichelproben und ­gepoolten Serumproben für den ­Nachweis von Antikörpern gegen das Porzine Reproduktive und Respiratorische ­Syndrom Virus in ­Aufzuchtbeständen.

INTRODUCTION: Monitoring of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) in pig farms is performed usually by testing for antibodies against PRRSV in serum samples. A new method is the detection of PRRSV antibodies in porcine saliva. In this study serum samples and saliva were collected in nine farms suspicious for PRRSV and tested for the presence of PRRSV antibodies. In total 220 serum and 41 saliva samples were taken from pigs at the age of 8 weeks (± 1 week). One saliva and one pooled serum sample (1:5) were tested from each pen. In total 11 (Cut-off 0.4/0.3) or 14 (Cut-off 0.2) serum samples and 23 saliva out of 41 pens were positive for PRRSV antibodies. Cohen`s Kappa testing showed a moderate agreement (κ = 0.446). Saliva samples compared to pooled serum samples were very sensitive, the specificity was 60 and 67, respectively.

INTRODUCTION: La surveillance du virus du syndrome reproducteur et respiratoire porcin (PRRSV) dans les élevages de porcs est généralement effectuée en recherchant des anticorps contre le PRRSV dans des échantillons de sérum. Une nouvelle méthode est la détection des anticorps anti-­PRRSV dans la salive porcine. Dans cette étude, des échantillons de sérum et de salive ont été prélevés dans neuf exploitations suspectes de PRRSV et testés quant à la présence d'anticorps PRRSV. Au total, 220 échantillons de sérum et 41 échantillons de salive ont été prélevés sur des porcs à l'âge de 8 semaines (± 1 semaine). De chaque boxe, un échantillon de salive et un échantillon de sérums regroupé (1: 5) ont été testés. Au total, 11 échantillons de sérum (seuil 0,4/0,3) ou 14 (seuil 0,2) et 23 de salive sur 41 boxes étaient positifs quant aux anticorps anti-PRRSV. Le test Kappa de Cohen a montré une corrélation modérée (κ = 0,446). Les échantillons de salive étaient très sensibles par rapport aux échantillons de sérum regroupés, la spécificité n'était toutefois que de 60 respectivement 67.

Pre-clinical testing of human size magnesium implants in miniature pigs: Implant degradation and bone fracture healing at multiple implantation sites.

Two miniature pig models to assess safety and performance of degradable osteosynthesis implants are presented. Both models provide multiple implantation sites with human size implants. In the first model, different types of magnesium plates and screws for fracture fixation were used to study local and systemic safety aspects in 14 Göttingen minipigs. Implant degradation, gas release and accumulation of alloying elements in organs were assessed for non-coated and plasmaelectrolytic coated magnesium implants and compared to the titanium reference. The observed implant degradation was mostly uniform and did not seem to depend on the implantation site and implant condition. The coating was effective in delaying initial gas release and degradation. No rare earth alloying elements could be detected in local lymph nodes, kidneys, livers or spleens. In the second model with Göttingen und Yucatan minipigs, full osteotomies were inflicted to four different anatomical sites and treated with magnesium plates and screws to assess fracture healing performance. Two Göttingen pilot minipigs showed promising results including a mandible osteosynthesis which healed within 6 weeks. The subsequent study was compromised by the more massive jaws of the used Yucatan minipigs. Three out of seven animals had to be sacrificed within two months as the stability of magnesium and titanium reference implants in the mandible was surpassed. In conclusion, the resorbable magnesium implants showed promising in vivo properties. For the analysis of human standard sized implants under full chewing load conditions, lighter Göttingen minipigs were more suitable than heavier Yucatan minipigs.

[Apps in clinical use in orthopedics and trauma surgery : The status quo in Germany]. / Klinischer Einsatz mobiler Applikationen in der Orthopädie und Unfallchirurgie in Deutschland : Eine Bestandsaufnahme.

In the course of digitalization the smartphone is penetrating more and more areas of life giving the user mobile and almost ubiquitous access to the internet and other web applications. The advantages of mHealth are an integral part in some areas of patient care but in contrast to other disciplines, routine integration of mobile devices into orthopedics and trauma surgery is still in its infancy. A survey among German orthopedists and trauma surgeons revealed which kind of apps have become established in everyday clinical practice to date. Apps published by representative institutions such as the AO Foundation demonstrated the highest usage rates. In summary, the number of regularly used apps is low; however, the causes of this lack of acceptance have not yet been conclusively clarified. The authors of this study proclaim a significant increase in the use of mHealth and mobile devices in daily clinical practice in the future.

A randomized controlled proof-of-concept trial of digoxin and furosemide in adults with cutaneous warts.

BACKGROUND: Topical ionic contraviral therapy (ICVT) with digoxin and furosemide inhibits the potassium influx on which DNA viruses rely for replication. Therefore, ICVT was hypothesized to be a potential novel treatment for cutaneous warts. OBJECTIVES: To assess the clinical efficacy, safety and tolerability of ICVT in adults with cutaneous warts. The secondary objective was to gain insight into the underlying working mechanism of ICVT. METHODS: Treatment with ICVT was assessed for efficacy, safety and tolerability in a single- centre, randomized, double-blind, placebo-controlled phase IIA trial. Eighty adult patients with at least two cutaneous warts (plantar or common) were randomized to one of four treatments: digoxin + furosemide (0·125%), digoxin (0·125%), furosemide (0·125%) or placebo. The gel was administered once daily for 42 consecutive days. Predefined statistical analysis was performed with a mixed-model ancova. The trial was registered at ClinicalTrials.gov with number NCT02333643. RESULTS: Wart size and human papillomavirus (HPV) load reduction was achieved in all active treatment groups. A statistically significant reduction in wart diameter of all treated warts was shown in the digoxin + furosemide treatment group vs. placebo (-3·0 mm, 95% confidence interval -4·9 to -1·1, P = 0·002). There was a statistically significant reduction in the HPV load of all treated warts in the digoxin + furosemide group vs. placebo (-94%, 95% confidence interval -100 to -19, P = 0·03). With wart size reduction, histologically and immunohistochemically defined viral characteristics disappeared from partial and total responding warts. CONCLUSIONS: This study demonstrates the proof of concept for the efficacy of topical ICVT in adults with cutaneous warts.

[Is the discharge letter still relevant? : Chances and risks of "Medical apps" in orthopedics and traumatology]. / Ist der Entlassungsbrief noch zeitgemäß? : Chancen und Risiken von "Medical Apps" in Orthopädie und Unfallchirurgie.

CURRENT SITUATION: The discharge letter currently represents the gold standard of the information and transfer document in the field of inpatient orthopedic and trauma patient care. In the age of digitization, the smartphone is penetrating more and more areas of life as an omnipresent internet access medium and is thus fundamentally influencing the awareness of our society. Whereas the use of applications on smartphones is already well established today, the range of medical apps is rudimentary. The potential of apps on smartphones as an innovative digital communication medium is undeniable, but the currently available medical apps in orthopedics and trauma surgery are available to a small patient clientele only. FORECAST: Currently, the use of medical apps is not an adequate alternative to the discharge letter. However, it is only a matter of time before the innovative potential of applications is used as a communication tool in outpatient and inpatient care. It is, therefore, essential to start creating the legal, ethical and medical framework and to establish a relevant regulatory body.