Mild Hyperthermia-Induced Thermogenesis in the Endoplasmic Reticulum Defines Stress Response Mechanisms.

Previous studies reported that a mild, non-protein-denaturing, fever-like temperature increase induced the unfolded protein response (UPR) in mammalian cells. Our dSTORM super-resolution microscopy experiments revealed that the master regulator of the UPR, the IRE1 (inositol-requiring enzyme 1) protein, is clustered as a result of UPR activation in a human osteosarcoma cell line (U2OS) upon mild heat stress. Using ER thermo yellow, a temperature-sensitive fluorescent probe targeted to the endoplasmic reticulum (ER), we detected significant intracellular thermogenesis in mouse embryonic fibroblast (MEF) cells. Temperatures reached at least 8 °C higher than the external environment (40 °C), resulting in exceptionally high ER temperatures similar to those previously described for mitochondria. Mild heat-induced thermogenesis in the ER of MEF cells was likely due to the uncoupling of the Ca2+/ATPase (SERCA) pump. The high ER temperatures initiated a pronounced cytosolic heat-shock response in MEF cells, which was significantly lower in U2OS cells in which both the ER thermogenesis and SERCA pump uncoupling were absent. Our results suggest that depending on intrinsic cellular properties, mild hyperthermia-induced intracellular thermogenesis defines the cellular response mechanism and determines the outcome of hyperthermic stress.

Characterization of obesity-related diseases and inflammation using single cell immunophenotyping in two different diet-induced obesity models.

BACKGROUND: Obesity is a growing problem worldwide and a major risk factor for many chronic diseases. The accumulation of adipose tissue leads to the release of significant amounts of pro-inflammatory cytokines and adipokines, resulting in a low-grade systemic inflammation. However, the mechanisms behind the development of obesity-related diseases are not fully understood. Therefore, our study aimed to investigate the pathological changes and inflammatory processes at systemic level and in individual organs in two different diet-induced mouse obesity models. METHODS: Male C57BL6/J mice were fed by high-fat diet (HFD), high-fat/high-fructose diet (HFD + FR) or normal chow for 21 weeks starting at 3 months of age (n = 15 animals/group). Insulin resistance was tested by oral glucose tolerance test. Pathological changes were investigated on hematoxylin-eosin-stained liver and brown adipose tissue sections. The gene expression levels of adipokines and cytokines were analyzed by qPCR in adipose tissues, whereas serum protein concentrations were determined by multiplex immunoassays. Immunophenotyping of isolated blood, bone marrow and spleen cells was performed by single-cell mass cytometry. RESULTS: Weight gain, glucose intolerance and hepatic steatosis were more severe in the HFD + FR group than in the control and HFD groups. This was accompanied by a higher level of systemic inflammation, as indicated by increased expression of pro-inflammatory genes in visceral white adipose tissue and by a higher serum TNFα level. In addition, immunophenotyping revealed the increase of the surface expressions of CD44 and CD69 on various cell types, such as CD8+ and CD4 + T-cells, B-cells and macrophages, in animals with obesity. CONCLUSIONS: The combination of HFD with fructose supplementation promotes more properly the symptoms of metabolic syndrome. Therefore, the combined high-fat/high-fructose nutrition can be a more suitable model of the Western diet. However, despite these differences, both models showed immunophenotypic changes that may be associated with increased risk of obesity-related cancer.

The Use of the Symani Surgical System® in Emergency Hand Trauma Care.

Background: The use of robotic systems for microsurgery has gained popularity in recent years. Despite its drawbacks, such as increased learning time and lack of haptic feedback, robot-assisted microsurgery is beneficial for emergency care due to its reduced risk of tremor and fatigue. The Symani Surgical System® is 1 example of this advanced technology. The device offers a range of possibilities in the field of microsurgery by combining precision and dexterity, revolutionizing microsurgical procedures. This article explores the applications of the Symani in microsurgical procedures in emergency hand trauma care, highlighting its advantages and limitations. Material and Methods: We present the results of 62 anastomoses of blood vessels under .8 mm diameter after hand trauma. 31 anastomoses were conducted using the Symani Surgical System®, and the other 31 were done as a control group in hand-sewn technique. Study Sample: The patient characteristics, including sex, age, and risk factors, were matched. Results: We found no significant differences in the anastomosis surgery length when performed with the Symani (arterial 17.3 ± 1.9 min; venous 11.5 ± 1.3 min) vs the hand-sewn technique (arterial 16.1 ± 1.4 min; venous 10.2 ± 1.8 min). Additionally, the learning curve consistently decreased over time, with the 10th surgery taking 30% (arterial) less time. Conclusion: Our study indicates that robot-assisted microsurgery can help surgeons maintain a relaxed and focused state while producing results comparable to hand-sutured procedures in emergency care.

Reconstruction of an Extensive Segmental Radial Shaft Bone Defect by Vascularized 3D-Printed Graft Cage.

We report here a 46-year-old male patient with a 14 cm segmental bone defect of the radial shaft after third degree open infected fracture caused by a shrapnel injury. The patient underwent fixed-angle plate osteosynthesis and bone reconstruction of the radial shaft by a vascularized 3D-printed graft cage, including plastic coverage with a latissimus dorsi flap and an additional central vascular pedicle. Bony reconstruction of segmental defects still represents a major challenge in musculo-skeletal surgery. Thereby, 3D-printed scaffolds or graft cages display a new treatment option for bone restoration. As missing vascularization sets the limits for the treatment of large-volume bone defects by 3D-printed scaffolds, in the present case, we firstly describe the reconstruction of an extensive radial shaft bone defect by using a graft cage with additional vascularization.

Organization of Hannover Skin Bank: Sterile culture and procurement protocols for viable cryopreserved allogeneic skin grafts of living donors.

Preserved allogeneic donor skin still represents one of the gold standard therapies in temporary wound coverage in severely burned patients or chronic wounds. Allogeneic skin grafts are currently commercially available as cryo- or glycerol-preserved allografts through skin tissue banks all over the world. Most of the skin tissue banks rely on human cadaveric skin donations. Due to the chronic shortage of human allogeneic transplants, such as skin, and increasing costs in the procurement of allografts from other skin tissue banks, Hannover Medical School has been building up its own skin tissue bank based on allogeneic skin grafts from living donors who underwent surgical treatment (i.e., body-contouring procedures, such as abdominioplasties). This article presents procedures and protocols for the procurement and processing of allogeneic skin grafts according to national legislation and European regulations and guidelines. Beside protocols, initial microbiological data regarding the sterility of the harvested grafts are presented. The results currently form the basis for further investigations as well as clinical applications. In summary, a microbiological testing and acceptance procedure is presented that ensures adequate patient safety and skin viability.

Development of a Laser Microdissection-Coupled Quantitative Shotgun Lipidomic Method to Uncover Spatial Heterogeneity.

Lipid metabolic disturbances are associated with several diseases, such as type 2 diabetes or malignancy. In the last two decades, high-performance mass spectrometry-based lipidomics has emerged as a valuable tool in various fields of biology. However, the evaluation of macroscopic tissue homogenates leaves often undiscovered the differences arising from micron-scale heterogeneity. Therefore, in this work, we developed a novel laser microdissection-coupled shotgun lipidomic platform, which combines quantitative and broad-range lipidome analysis with reasonable spatial resolution. The multistep approach involves the preparation of successive cryosections from tissue samples, cross-referencing of native and stained images, laser microdissection of regions of interest, in situ lipid extraction, and quantitative shotgun lipidomics. We used mouse liver and kidney as well as a 2D cell culture model to validate the novel workflow in terms of extraction efficiency, reproducibility, and linearity of quantification. We established that the limit of dissectible sample area corresponds to about ten cells while maintaining good lipidome coverage. We demonstrate the performance of the method in recognizing tissue heterogeneity on the example of a mouse hippocampus. By providing topological mapping of lipid metabolism, the novel platform might help to uncover region-specific lipidomic alterations in complex samples, including tumors.

Correlation between Bacterial Wound Colonization and Skin-Graft Loss in Burn Patients.

Loss of skin grafts can be a dangerous complication during the early postoperative course of patients with extensive burns. A major risk factor for impaired healing of grafts is local wound infection due to bacterial colonization. Burn wounds are particularly prone to bacterial colonization. In this retrospective cohort study, we analyzed correlations between bacteria isolates from burn wounds and loss of skin grafts after surgical treatment. A cohort of patients with burn wounds who received split-skin grafts for wound coverage was divided into groups with and without loss of skin grafts. Demographics, comorbidities, trauma characteristics and bacterial isolates from wound cultures were reviewed and compared. Bacterial colonization isolated from burn wounds upon hospital admission was found to be a significant predictor of skin-graft loss. Additionally, an Abbreviated Burn Severity Index greater 6 predicted graft loss. When comparing bacterial swab results from admission with isolates from revision surgery after graft loss, causative pathogens were found to have changed.

Remodeling of Liver and Plasma Lipidomes in Mice Lacking Cyclophilin D.

In recent years, several studies aimed to investigate the metabolic effects of non-functioning or absent cyclophilin D (CypD), a crucial regulatory component of mitochondrial permeability transition pores. It has been reported that the lack of CypD affects glucose and lipid metabolism. However, the findings are controversial regarding the metabolic pathways involved, and most reports describe the effect of a high-fat diet on metabolism. We performed a lipidomic analysis of plasma and liver samples of CypD-/- and wild-type (WT) mice to reveal the lipid-specific alterations resulting from the absence of CypD. In the CypD-/- mice compared to the WT animals, we found a significant change in 52% and 47% of the measured 225 and 201 lipid species in liver and plasma samples, respectively. The higher total lipid content detected in these tissues was not accompanied by abdominal fat accumulation assessed by nuclear magnetic resonance imaging. We also documented characteristic changes in the lipid composition of the liver and plasma as a result of CypD ablation with the relative increase in polyunsaturated membrane lipid species. In addition, we did not observe remarkable differences in the lipid distribution of hepatocytes using histochemistry, but we found characteristic changes in the hepatocyte ultrastructure in CypD-/- animals using electron microscopy. Our results highlight the possible long-term effects of CypD inhibition as a novel therapeutic consideration for various diseases.

Netrin G1 Is a Novel Target Antigen in Primary Membranous Nephropathy.

BACKGROUND: Primary membranous nephropathy (MN) is caused by circulating autoantibodies binding to antigens on the podocyte surface. PLA2R1 is the main target antigen in 70%-80% of cases, but the pathogenesis is unresolved in 10%-15% of patients. METHODS: We used native western blotting to identify IgG4 autoantibodies, which bind an antigen endogenously expressed on podocyte membranes, in the serum of the index patient with MN. These IgG4 autoantibodies were used to immunoprecipitate the target antigen, and mass spectrometry was used to identify Netrin G1 (NTNG1). Using native western blot and ELISA, NTNG1 autoantibodies were analyzed in cohorts of 888 patients with MN or other glomerular diseases. RESULTS: NTNG1 was identified as a novel target antigen in MN. It is a membrane protein expressed in healthy podocytes. Immunohistochemistry confirmed granular NTNG1 positivity in subepithelial glomerular immune deposits. In prospective and retrospective MN cohorts, we identified three patients with NTNG1-associated MN who showed IgG4-dominant circulating NTNG1 autoantibodies, enhanced NTNG1 expression in the kidney, and glomerular IgG4 deposits. No NTNG1 autoantibodies were identified in 561 PLA2R1 autoantibodies-positive patients, 27 THSD7A autoantibodies-positive patients, and 77 patients with other glomerular diseases. In two patients with available follow-up of 2 and 4 years, both NTNG1 autoantibodies and proteinuria persisted. CONCLUSIONS: NTNG1 expands the repertoire of target antigens in patients with MN. The clinical role of NTNG1 autoantibodies remains to be defined.

Effect of HEAT therapy in patiEnts with type 2 Diabetes mellitus (HEATED): protocol for a randomised controlled trial.

INTRODUCTION: The burden of type 2 diabetes mellitus (T2DM) is increasing worldwide. Heat therapy has been found effective in improving glycaemic control. However, to date, there is a lack of randomised controlled studies investigating the efficacy of heat therapy in T2DM. Therefore, we aim to investigate whether heat therapy with natural thermal mineral water can improve glycaemic control in patients with T2DM. METHODS AND ANALYSIS: The HEAT therapy in patiEnts with type 2 Diabetes mellitus (HEATED) Study is a single-centre, two-arm randomised controlled trial being conducted at Harkány Thermal Rehabilitation Centre in Hungary. Patients with T2DM will be randomly assigned to group A (bath sessions in 38°C natural thermal mineral water) and group B (baths in thermoneutral water (30°C-32°C)). Both groups will complete a maximum of 5 weekly visits, averaging 50-60 visits over the 12-week study. Each session will last 30 min, with a physical check-up before the bath. At baseline, patients' T2DM status will be investigated thoroughly. Possible microvascular and macrovascular complications of T2DM will be assessed with physical and laboratory examinations. The short form-36 questionnaire will assess the quality of life. Patients will also be evaluated at weeks 4, 8 and 12. The primary endpoint will be the change of glycated haemoglobin from baseline to week 12. An estimated 65 patients will be enrolled per group, with a sample size re-estimation at the enrolment of 50% of the calculated sample size. ETHICS AND DISSEMINATION: The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (818-2/2022/EÜIG). Written informed consent is required from all participants. We will disseminate our results to the medical community and will publish our results in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT05237219.

Distinct Cellular Tools of Mild Hyperthermia-Induced Acquired Stress Tolerance in Chinese Hamster Ovary Cells.

Mild stress could help cells to survive more severe environmental or pathophysiological conditions. In the current study, we investigated the cellular mechanisms which contribute to the development of stress tolerance upon a prolonged (0-12 h) fever-like (40 °C) or a moderate (42.5 °C) hyperthermia in mammalian Chinese Hamster Ovary (CHO) cells. Our results indicate that mild heat triggers a distinct, dose-dependent remodeling of the cellular lipidome followed by the expression of heat shock proteins only at higher heat dosages. A significant elevation in the relative concentration of saturated membrane lipid species and specific lysophosphatidylinositol and sphingolipid species suggests prompt membrane microdomain reorganization and an overall membrane rigidification in response to the fluidizing heat in a time-dependent manner. RNAseq experiments reveal that mild heat initiates endoplasmic reticulum stress-related signaling cascades resulting in lipid rearrangement and ultimately in an elevated resistance against membrane fluidization by benzyl alcohol. To protect cells against lethal, protein-denaturing high temperatures, the classical heat shock protein response was required. The different layers of stress response elicited by different heat dosages highlight the capability of cells to utilize multiple tools to gain resistance against or to survive lethal stress conditions.

Major traumatic amputations and replantations of the upper extremity in Germany - National quality reports 2014-2018.

The treatment of traumatic major upper limb amputation is complex and of great urgency. Loss of time often represents a majorrestriction for replantation. Thus, logistical and infrastructural developments, such as the expansion of specialised hand trauma centres, are crucial for optimizing delivery of care. Surveillance represents the fundament for a proper, demand-adapted implementation of such therapeutical improvements. However, a comprehensive database for surveillance of these injuries does currently not exist in Germany or Europe. In this study quality reports of German hospitals from 2014 to 2018 were screened retrospectively for traumatic major upper extremity amputations and replantations. A total of 329 amputations and 87 replantations were recorded, accounting for an overall replantation rate (RR) of 26%. Most of the injuries affected the level of the wrist and forearm. Treatment of these injuries experienced an increasing centralisation to medical teaching facilities, which accounted for higher RRs compared with non-teaching facilities. The cumulatively most populous federal states handled most of the amputation injures in this five-year study period. Ratio calculations on the basis of population counts, however, revealed great discrepancies to these results, with Hamburg, Rhineland-Palatinate and Saarland accounting for the highest per capita incidences. In 2018 Germany was provided with 46 specialised hand trauma and replantation centres, which performed 45% of the replantations in that year, revealing a RR of 17%, compared to an overall RR of 14% in that year. Nevertheless, there might be potential for improvement in the geographical distribution of these specialised centres. The provision of highly specialised therapy in highly specialised centres for highly complex injuries is a future challenge in replantation surgery. This data is contributing to logistical improvements for a need-adapted expansion of these specialised hand trauma centres. The study demonstrates an approach of a standardised and comprehensive injury surveillance program based on national quality reports, while underlining the importance of such a national or rather European database for optimisations in medical care. Level of evidence IV.

An Identification and Characterization of the Axolotl (Ambystoma mexicanum, Amex) Telomerase Reverse Transcriptase (Amex TERT).

The Mexican axolotl is one of the few vertebrates that is able to replace its lost body parts during lifespan. Due to its remarkable regenerative abilities, the axolotl emerged as a model organism especially for limb regeneration. Telomeres and the telomerase enzyme are crucial for regeneration and protection against aging processes and degenerating diseases. Despite its relevance for regeneration, the axolotl telomerase and telomere length have not yet been investigated. Therefore, in the present paper, we reveal the sequence of the axolotl telomerase reverse transcriptase gene (Tert) and protein (TERT). Multiple sequence alignment (MSA) showed the known conserved RT- and TERT-specific motifs and residues found in other TERTs. In addition, we establish methods to determine the Tert expression (RT-PCR) and telomerase activity (Q-TRAP) of adult axolotl and blastema tissues. We found that both differentiated forelimb tissue and regenerating blastema tissue express Tert and show telomerase activity. Furthermore, blastema tissue appears to exhibit a higher Tert expression and telomerase activity. The presence of active telomerase in adult somatic cells is a decisive difference to somatic cells of non-regenerating vertebrates, such as humans. These findings indicate that telomere biology may play a key role in the regenerative abilities of cells.

Multifaceted Analyses of Isolated Mitochondria Establish the Anticancer Drug 2-Hydroxyoleic Acid as an Inhibitor of Substrate Oxidation and an Activator of Complex IV-Dependent State 3 Respiration.

The synthetic fatty acid 2-hydroxyoleic acid (2OHOA) has been extensively investigated as a cancer therapy mainly based on its regulation of membrane lipid composition and structure, activating various cell fate pathways. We discovered, additionally, that 2OHOA can uncouple oxidative phosphorylation, but this has never been demonstrated mechanistically. Here, we explored the effect of 2OHOA on mitochondria isolated by ultracentrifugation from U118MG glioblastoma cells. Mitochondria were analyzed by shotgun lipidomics, molecular dynamic simulations, spectrophotometric assays for determining respiratory complex activity, mass spectrometry for assessing beta oxidation and Seahorse technology for bioenergetic profiling. We showed that the main impact of 2OHOA on mitochondrial lipids is their hydroxylation, demonstrated by simulations to decrease co-enzyme Q diffusion in the liquid disordered membranes embedding respiratory complexes. This decreased co-enzyme Q diffusion can explain the inhibition of disjointly measured complexes I-III activity. However, it doesn't explain how 2OHOA increases complex IV and state 3 respiration in intact mitochondria. This increased respiration probably allows mitochondrial oxidative phosphorylation to maintain ATP production against the 2OHOA-mediated inhibition of glycolytic ATP production. This work correlates 2OHOA function with its modulation of mitochondrial lipid composition, reflecting both 2OHOA anticancer activity and adaptation to it by enhancement of state 3 respiration.

Lipids and Trehalose Actively Cooperate in Heat Stress Management of Schizosaccharomyces pombe.

Homeostatic maintenance of the physicochemical properties of cellular membranes is essential for life. In yeast, trehalose accumulation and lipid remodeling enable rapid adaptation to perturbations, but their crosstalk was not investigated. Here we report about the first in-depth, mass spectrometry-based lipidomic analysis on heat-stressed Schizosaccharomyces pombe mutants which are unable to synthesize (tps1Δ) or degrade (ntp1Δ) trehalose. Our experiments provide data about the role of trehalose as a membrane protectant in heat stress. We show that under conditions of trehalose deficiency, heat stress induced a comprehensive, distinctively high-degree lipidome reshaping in which structural, signaling and storage lipids acted in concert. In the absence of trehalose, membrane lipid remodeling was more pronounced and increased with increasing stress dose. It could be characterized by decreasing unsaturation and increasing acyl chain length, and required de novo synthesis of stearic acid (18:0) and very long-chain fatty acids to serve membrane rigidification. In addition, we detected enhanced and sustained signaling lipid generation to ensure transient cell cycle arrest as well as more intense triglyceride synthesis to accommodate membrane lipid-derived oleic acid (18:1) and newly synthesized but unused fatty acids. We also demonstrate that these changes were able to partially substitute for the missing role of trehalose and conferred measurable stress tolerance to fission yeast cells.

Treatment of hand infections using WALANT -when the anesthesiologist is not available: A retrospective cohort study.

BACKROUND: The aim of this study was to determine, if Wide Awake Local Anesthesia No Tourniquet (WALANT) can be used as an alternative method of providing anesthesia in management of deep infections of the hand. Since the advent of WALANT in 2003, infections of the hand have been regarded as a contraindication to its use. Occasional shortage of anesthesiologic manpower, especially during busy call hours and the current COVID-19 pandemic can lead to delay of treatment where urgent surgery is needed, to prevent progress of an infection, that can result in severe morbidity. METHODS: In the period from 2015 to 2020, 16 patients with various infections of the hand underwent 17 operations using WALANT in a Hand Trauma and Replantation Center (HTRC) in Germany. Retrospective cohort analysis of their operation reports, with emphasis on location of infection, time and duration of the operation, intraoperative incidents and complications were carried out. We also evaluated the need for revision surgery or necessity to convert to general anesthesia and factors causing delay till the time of surgery. RESULTS: No case of inadequate analgesia, the need to convert to general anesthesia, ischemic events or cardiovascular complications with the use of the WALANT solution containing adrenaline and lidocaine in the treatment of deep tissue infections.The highest priority of limb preservation was ensured as no patient progressed to amputation of a digit or the hand. There was a statistically significant difference (p ≤ 0.01) in delay from the time of admission until surgery of up to 9h24 m (SD±3h34 m) during the week and 4h10 m (SD±2h28 m) during the weekend. CONCLUSION: The status of infection as an absolute contraindication to the use of WALANT should be revised. Especially when human resources are limited, WALANT is an adequate technique to enable quick anesthesia for urgent treatment to prevent progression of hand infections.

Citizen science project characteristics: Connection to participants' gains in knowledge and skills.

BACKGROUND: Biodiversity is being lost rapidly and its conservation is thus one of the most urgent tasks today. For biodiversity conservation to be successful, the public needs to gain an awareness and understanding of biodiversity and its importance. Moreover, species experts are needed who have the skills necessary for identifying and recording biodiversity. Previous research showed that citizen science projects can contribute to educating the public about biodiversity. However, it is still unclear how project characteristics connect to participants' knowledge and skills and how citizen science projects should be designed if they are to foster participants' learning. AIM: We aimed to investigate specific characteristics of biodiversity citizen science projects that could potentially influence participants' learning. We explored the following project characteristics from both the project coordinators' and the participants' perspectives: information and training provided to participants, social interaction among participants, contact between participants and staff, and feedback and recognition provided to participants. METHODS AND RESULTS: In order to examine the extent to which these project characteristics are connected to participants' gains in knowledge and skills, we conducted a comprehensive study across 48 biodiversity citizen science projects in Europe and Australia. We found that participants' perceived gains in knowledge and skills were significantly related to the five project characteristics as reported by the participants: information received by the participants, training received by the participants, social interaction among participants, contact between participants and staff, and feedback and recognition received by the participants. CONCLUSION: We conclude that by deliberately designing citizen science projects to include features such as interaction and feedback, these projects could achieve higher learning outcomes for the participants. Thereby, suitable modes of communication between projects and their participants are crucial. We provide specific suggestions for the design of biodiversity citizen science projects and for future research on project characteristics and participant outcomes.

The Germline Marker Piwi Expressed in the Skin Layer of the Polychaete Perinereis wilsoni After Injury.

Nereidid polychaete Perinereis wilsoni is a homonomous metameric worm with a complete septum between each segment. Each segment has germ cells localized in the distal area of the parapodia. Perinereis wilsoni is also known to have high abilities of tissue regeneration; however, it is still unclear whether germ cells can regenerate in the healing tissue. To address this, we surgically operated the parapodia of an adult worm to remove germ cells from the segments and observed the germ cell regeneration using the germ cell genetic marker Pw-piwi. At day 20 post-surgical operation of the parapodia in one side of the segment, we found that Pw-piwi was expressed in the regenerating parapodia. We surgically operated the parapodia on both sides of the segment to remove the germ cells completely and it gave a similar result. However, before the expression of this gene marker in the regenerating parapodia, we observed that Pw-piwi was expressed in cells in the skin layer of the worm just after surgical operations. These Pw-piwi-positive cells were not observed in the un-operated worm. Our observations showed that germ cells of Perinereis wilsoni can regenerate even after the complete removal of germ cells from the defined habitat. The Pw-piwipositive cells that appeared in the skin layer after the disappearance of germ cells may be involved in the regeneration of new germ cells.

Male and Female Animals Respond Differently to High-Fat Diet and Regular Exercise Training in a Mouse Model of Hyperlipidemia.

Inappropriate nutrition and a sedentary lifestyle can lead to obesity, one of the most common risk factors for several chronic diseases. Although regular physical exercise is an efficient approach to improve cardiometabolic health, the exact cellular processes are still not fully understood. We aimed to analyze the morphological, gene expression, and lipidomic patterns in the liver and adipose tissues in response to regular exercise. Healthy (wild type on a normal diet) and hyperlipidemic, high-fat diet-fed (HFD-fed) apolipoprotein B-100 (APOB-100)-overexpressing mice were trained by treadmill running for 7 months. The serum concentrations of triglyceride and tumor necrosis factor α (TNFα), as well as the level of lipid accumulation in the liver, were significantly higher in HFD-fed APOB-100 males compared to females. However, regular exercise almost completely abolished lipid accumulation in the liver of hyperlipidemic animals. The expression level of the thermogenesis marker, uncoupling protein-1 (Ucp1), was significantly higher in the subcutaneous white adipose tissue of healthy females, as well as in the brown adipose tissue of HFD-fed APOB-100 females, compared to males. Lipidomic analyses revealed that hyperlipidemia essentially remodeled the lipidome of brown adipose tissue, affecting both the membrane and storage lipid fractions, which was partially restored by exercise in both sexes. Our results revealed more severe metabolic disturbances in HFD-fed APOB-100 males compared to females. However, exercise efficiently reduced the body weight, serum triglyceride levels, expression of pro-inflammatory factors, and hepatic lipid accumulation in our model.

Hot Bathtub, Cold Consequences-Misleading Wounds After Scald Injuries: A Retrospective Analysis.

Scalds in the elderly are frequently associated with the use of a bathtub and a disturbed consciousness. Therefore, the total burn surface area is often high. The initial clinical presentation displays a stark erythema of the skin, which frequently does not represent the true depth. The aim of this study was to characterize and assess medical features and outcome of scalds sustained in the bathtub. We conducted a retrospective study at a burn intensive care unit (BICU) between 2011 and 2018. Medical features as well as the treatment in these patients were statistically analyzed. We identified 16 patients and divided them into two groups regarding survival and lethality. The mean total burn surface area was 37.50 ± 19.47%. In 81.25% of the patients, we found a previous history of neurological or psychiatric disorders. Dementia and alcohol abuse were the most common triggers for the trauma. The statistical analysis showed a significant difference for the ABSI-score and the presence of multi organ failure (P-value .0462, respectively, .0004). Erythematous skin areas tended to progress into full thickness burns. We, therefore, coined the term "lobster redness" for these regions. Scalds sustained in the bathtub are devastating injuries. Initial assessment can be misleading and might delay early necrectomy. The wounds request even more attention, if the injuries occurred due to unconsciousness because of the longer exposure to heat. Early necrectomy should be considered. A biopsy with histological workup can be useful. Furthermore, we recommend special safety precautions for neurologically and psychiatrically affected patients.