Life

Spaceflight (SF) increases the risk of developmental, regenerative, and physiological disorders in animals and humans. Astronauts, besides bone loss, muscle atrophy, and cardiovascular and immune system alterations, undergo ocular disorders affecting posterior eye tissues, including the retina. Few studies revealed abnormalities in the development and changes in the regeneration of eye tissues in lower vertebrates after SF and simulated microgravity. Under microgravity conditions, mammals show disturbances in the retinal vascular system and increased risk of oxidative stress that can lead to cell death in the retina. Animal studies provided evidence of gene expression changes associated with cellular stress, inflammation, and aberrant signaling pathways. Experiments using retinal cells in microgravity-modeling systems in vitro additionally indicated micro-g-induced changes at the molecular level. Here, we provide an overview of the literature and the authors’ own data to assess the predictive value of structural and functional alterations for developing countermeasures and mitigating the SF effects on the human retina. Further emphasis is given to the importance of animal studies on the retina and other eye tissues in vivo and retinal cells in vitro aboard spacecraft for understanding alterations in the vertebrate visual system in response to stress caused by gravity variations. Full article

Porto-mesenteric vein thrombosis (PVT) is a well-recognized but uncommon disease entity in patients with and without cirrhosis. Given the complexity of these patients, there are many differing treatment algorithms depending on the individual circumstances of a given patient. The focus of this review is primarily patients with cirrhosis, with an emphasis on liver transplantation considerations. The presence of cirrhosis substantially affects work-up, prognosis, and management of these patients and will substantially affect the patient treatment and have additional implications for prognosis and long-term outcomes. Here, we review the incidence of portal vein thrombosis in known cirrhotic patients, medical and interventional treatment options that are currently used, and, in particular, how to approach cirrhotic patients with PVT who are awaiting liver transplantation. Full article

While fetal growth is dependent on many factors, optimal placental function is a prerequisite for a normal pregnancy outcome. The majority of fetal growth-restricted (FGR) pregnancies result from placental insufficiency (PI). The insulin-like growth factors (IGF1 and IGF2) stimulate fetal growth and placental development and function. Previously, we demonstrated that in vivo RNA interference (RNAi) of the placental hormone, chorionic somatomammotropin (CSH), resulted in two phenotypes. One phenotype exhibits significant placental and fetal growth restriction (PI-FGR), impaired placental nutrient transport, and significant reductions in umbilical insulin and IGF1. The other phenotype does not exhibit statistically significant changes in placental or fetal growth (non-FGR). It was our objective to further characterize these two phenotypes by determining the impact of CSH RNAi on the placental (maternal caruncle and fetal cotyledon) expression of the IGF axis. The trophectoderm of hatched blastocysts (9 days of gestation, dGA) were infected with a lentivirus expressing either a non-targeting sequence (NTS RNAi) control or CSH-specific shRNA (CSH RNAi) prior to embryo transfer into synchronized recipient ewes. At ≈125 dGA, pregnancies were fitted with vascular catheters to undergo steady-state metabolic studies. Nutrient uptakes were determined, and tissues were harvested at necropsy. In both CSH RNAi non-FGR and PI-FGR pregnancies, uterine blood flow was significantly reduced (p ≤ 0.05), while umbilical blood flow (p ≤ 0.01), both uterine and umbilical glucose and oxygen uptakes (p ≤ 0.05), and umbilical concentrations of insulin and IGF1 (p ≤ 0.05) were reduced in CSH RNAi PI-FGR pregnancies. Fetal cotyledon IGF1 mRNA concentration was reduced (p ≤ 0.05) in CSH RNAi PI-FGR pregnancies, whereas neither IGF1 nor IGF2 mRNA concentrations were impacted in the maternal caruncles, and either placental tissue in the non-FGR pregnancies. Fetal cotyledon IGF1R and IGF2R mRNA concentrations were not impacted for either phenotype, yet IGF2R was increased (p ≤ 0.01) in the maternal caruncles of CSH RNAi PI-FGR pregnancies. For the IGF binding proteins (IGFBP1, IGFBP2, IGFBP3), only IGFBP2 mRNA concentrations were impacted, with elevated IGFBP2 mRNA in both the fetal cotyledon (p ≤ 0.01) and maternal caruncle (p = 0.08) of CSH RNAi non-FGR pregnancies. These data support the importance of IGF1 in placental growth and function but may also implicate IGFBP2 in salvaging placental growth in non-FGR pregnancies. Full article

Atrial fibrillation (AF) is a very common arrhythmia that mainly affects older individuals. The mechanism of atrial fibrillation is complex and is related to the pathogenesis of trigger activation and the perpetuation of arrhythmia. The pulmonary veins in the left atrium arei confirm that onfirm the most common triggers due to their distinct anatomical and electrophysiological properties. As a result, their electrical isolation by ablation is the cornerstone of invasive AF treatment. Multiple factors and comorbidities affect the atrial tissue and lead to myocardial stretch. Several neurohormonal and structural changes occur, leading to inflammation and oxidative stress and, consequently, a fibrotic substrate created by myofibroblasts, which encourages AF perpetuation. Several mechanisms are implemented into daily clinical practice in both interventions in and the medical treatment of atrial fibrillation. Full article

Angiogenic T (Tang) cells and endothelial progenitor cells (EPCs) play a role in maintaining vascular integrity and repair. This study considers the association between them and Behçet disease (BD) and disease activity. Fifty patients with BD and forty-five age- and gender-matched healthy controls were included in the study. The participants’ demographic, clinical, and laboratory characteristics were recorded, and their blood Tang cell and EPC counts were determined. Fifty patients were diagnosed with BD, consisting of 24 females and 26 males. The blood Tang cell (3.5 ± 1.2 cells/μL in patients, 4 ± 0.9 cells/μL in controls, p = 0.046)) and EPC (2.9 ± 0.9 cells/μL in patients, 3.7 ± 1 cells/μL in controls, p = 0.001) counts were significantly lower for the patient group with BD than for the control group. The blood Tang cell (42.5 ± 4.9% in active patients, 48.9 ± 7.9% in inactive patients, p = 0.001) and EPC (35.5 ± 6.4% in active patients, 41.2 ± 6.3% in inactive patients, p = 0.004) levels were lower for the patient group with active BD than for the inactive patient group. A weak positive correlation was present between the blood Tang cell and EPC percentage values in BD (r: 0.318, p = 0.002). It was determined that Tang cell and EPC counts are lower in BD, and these reductions become more profound with increasing disease activity. This situation may prevent the development of a sufficient immune response against a disease with a course of chronic inflammation or may trigger the formation of autoreactive immunity. A reduction in Tang cells and EPCs may serve as a marker or predictor of vascular damage in BD patients and represents the progression of vascular injury. Full article

WRKY gene family is one of the largest transcription factor families involved in various physiological processes of plants. Flax (Linum usitatissimum) is an important stem fiber crop, and it is also an economically important crop in natural fiber and textile industries around the world. In this study, 105 WRKY genes were obtained by screening the whole genome of flax. There were 26 in group I, 68 in group II, 8 in group III and 3 in group UN. The characteristics of the WRKY motif and gene structure in each group are similar. The promoter sequence of WRKY genes includes photoresponsive elements, core regulatory elements and 12 cis-acting elements under abiotic stress. Similar to A. thaliana and Compositae plants, WRKY genes are evenly distributed on each chromosome, with segmental and tandem repeated events, which play a major role in the evolution of WRKY genes. The flax WRKY gene family is mainly concentrated in group I and group II. This study is mainly based on genome-wide information to classify and analyze the flax WRKY gene family, laying a foundation for further understanding the role of WRKY transcription factors in species evolution and functional analysis. Full article

This study aimed to evaluate the diagnostic capability of isolated-check visual evoked potential (icVEP) for primary open-angle glaucoma (POAG) via comparison with visual field (VF) tests and pattern visual evoked potential (PVEP). This cross-sectional study enrolled 68 subjects, including 33 POAG patients and 35 controls. All subjects underwent a complete ophthalmic examination, including icVEP, PVEP, and VF tests. The diagnostic performance, the area under the receiver operating characteristic curve (AUC), the integrated discrimination index (IDI), and the net reclassification index (NRI) were calculated. The clinical benefits of the three tests were compared via decision curve analysis (DCA) of the signal-to-noise ratio (SNR) from icVEP, the P100 latency and amplitude of 1° and 0.25° checks from the PVEP, pattern standard deviation (PSD), and mean deviation (MD) from the VF test. The SNR, MD and PSD, PVEP P100 latency of 0.25° checks, and P100 amplitude (both 1° and 0.25° checks) showed significant differences between the POAG and control groups (* p < 0.05), except for the P100 latency of 1° checks. Regarding diagnostic ability, the three tests, AUC, IDI, and NRI, showed no significant difference (p > 0.05). The DCA showed that the clinical benefits of icVEP (SNR) were comparable to those of VF (MD and PSD) and better than those of PVEP (P100 latency and amplitude). In addition, no significant difference was found in the consistency analysis of the qualitative comparison between the icVEP, VF, and PVEP (McNemar p > 0.05). In this study, icVEP showed a diagnostic ability for early to moderate POAG patients comparable to VF and PVEP. IcVEP might be applied as a supplementary psychophysical examination method in addition to VF examinations for special POAG populations who have difficulty cooperating with the VF examination. Full article

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, originally used for diabetes mellitus, are gaining more popularity for other indications, owing to their positive cardiovascular and renal effects. SGLT2 inhibitors reduce heart failure (HF) hospitalization and improve cardiovascular outcomes in patients with type 2 diabetes. Later, SGLT2 inhibitors were evaluated in patients with HF with reduced ejection fraction (HFREF) and had beneficial effects independent of the presence of diabetes. Recently, reductions in cardiovascular outcomes were also observed in patients with HF with preserved ejection fraction (HFPEF). SGLT2 inhibitors also reduced renal outcomes in patients with chronic kidney disease. Overall, these drugs have an excellent safety profile with a negligible risk of genitourinary tract infections and ketoacidosis. In this review, we discuss the current data on SGLT2 inhibitors in special populations, including patients with acute myocardial infarction, acute HF, right ventricular (RV) failure, left ventricular assist device (LVAD), and type 1 diabetes. We also discuss the potential mechanisms behind the cardiovascular benefits of these medications. Full article

(1) Background: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the first two decades of life. One third of cases appear in the head and neck, with 60% of these being embryonal type. RMS is extremely rare in adults, comprising only 1% of adult malignancies, and of those, only 3.3% are rhabdomyosarcomas. (2) Case report: A 46 y.o. male presented with a 1 cm exophytic pediculated painless lesion on the dorsum of his tongue, with progressive growth for 3 months. An excisional biopsy revealed an “embryonal rhabdomyosarcoma with fusocellular areas, with negative rearrangement for gen FOXO1A, negative MDM2 (only focal positivity), and positive INI-1”. Subsequent contrast-enhanced MRI concluded the presence of a lesion with imprecise margins in the right half-tongue, 15 × 8 × 7 mm (longitudinal x transverse x craniocaudal), compatible with a sarcoma. The patient underwent a partial centrolingual glossectomy followed by reconstruction with a buccinator muscle local flap. After surgery, he received chemotherapy with eight cycles of VAC (vincristine, actinomycin, and cyclophosphamide) protocol. The patient is now disease free after 42 months, with good tongue function. (3) Discussion and conclusions: Embryonal RMS is an extremely rare sarcoma in adults, and the location in the tongue is even more exceptional (only two more similar cases are reported in the literature). The prognosis in adults is significantly poorer than in children. A complete margin-free resection with an adequate chemotherapy protocol is the treatment of choice in cases such as these. Full article

Motor neuron diseases (MNDs) are a heterogeneous group of disorders that affect the cranial and/or spinal motor neurons (spMNs), spinal sensory neurons and the muscular system. Although they have been investigated for decades, we still lack a comprehensive understanding of the underlying molecular mechanisms; and therefore, efficacious therapies are scarce. Model organisms and relatively simple two-dimensional cell culture systems have been instrumental in our current knowledge of neuromuscular disease pathology; however, in the recent years, human 3D in vitro models have transformed the disease-modeling landscape. While cerebral organoids have been pursued the most, interest in spinal cord organoids (SCOs) is now also increasing. Pluripotent stem cell (PSC)-based protocols to generate SpC-like structures, sometimes including the adjacent mesoderm and derived skeletal muscle, are constantly being refined and applied to study early human neuromuscular development and disease. In this review, we outline the evolution of human PSC-derived models for generating spMN and recapitulating SpC development. We also discuss how these models have been applied to exploring the basis of human neurodevelopmental and neurodegenerative diseases. Finally, we provide an overview of the main challenges to overcome in order to generate more physiologically relevant human SpC models and propose some exciting new perspectives. Full article

The purpose of the present study was to document pathological findings on retromode imaging in choroidal nevi and evaluate its diagnostic validity, using the confocal scanning laser ophthalmoscope Nidek Mirante (cSLO). A total of 41 choroidal nevi from 41 patients were included. All patients underwent multicolor fundus (mCF), infrared reflectance (IR), green fundus autofluorescence (FAF), dark-field (DF) and retromode (RM) imaging and optical coherence tomography (OCT) scans. We investigated retromode images to evaluate choroidal nevus features by comparing the results with those of mCF, IR, FAF, DF and OCT. In 100% of available images, retromode scanning laser ophthalmoscopy was able to detect choroidal nevi with a characteristic “hypo-retro-reflective” pattern, even the cases not visible on mCF, IR and FAF images. It also made it possible to delineate the margins of lesions with the highest rate of sharpness and accuracy among the imaging modalities examined. These findings seem to demonstrate how RM-SLO is an innovative diagnostic tool to detect and follow up choroidal nevi in a fast, reliable and non-invasive way. Full article

Purpose: The association between COVID-19 and hypercoagulability is well established. This is a case of a patient with systemic lupus erythematosus (SLE) who developed unilateral renal vein thrombosis following COVID-19, the third case described in the international literature so far. Methods: Clinical, laboratory characteristics and outcomes of the patient were described in detail. Literature review was performed on MEDLINE database via Pubmed. Search items included COVID-19, renal infarction, and renal thrombosis. A total of fifty-three cases were located. Of these, only two patients had renal vein thrombosis but none of them carried a diagnosis of SLE. However, six cases have been published so far involving SLE patients in whom thromboembolic events developed following COVID-19, but none of them experienced renal vein thrombosis. Conclusion: The present case adds a new piece to the emerging puzzle of COVID-19 associated hypercoagulability, especially among patients with autoimmune diseases. Full article

Background: The thesis on which this paper is based intended to investigate whether the result of the microbiological vaginal swab has an influence on the outcome of the fertility treatment. Methods: The microbiological vaginal swabs of patients who received fertility treatment at Saarland University Hospital were evaluated. Depending on the microorganisms detected, the swab result was classified as inconspicuous, intermediate, or conspicuous. The SPSS software was used to determine the correlation between the swab result and the outcome of the fertility treatment. Results: Dysbiosis was associated with a worse outcome of fertility treatment. The pregnancy rate with a conspicuous swab was 8.6%, whereas it was 13.4% with an inconspicuous swab. However, this association was not statistically significant. Furthermore, an association of endometriosis with dysbiosis was found. Endometriosis was more frequent with a conspicuous swab result than with an inconspicuous result (21.1% vs. 17.7%), yet the correlation was not statistically significant. However, the absence of lactobacilli was significantly associated with endometriosis (p = 0.021). The association between endometriosis and a lower pregnancy rate was also statistically significant (p = 0.006). Conclusion: The microbiological vaginal and cervical swabs can be used as predictors for the success of fertility treatments. Further studies are needed to assess the impact of transforming a dysbiotic flora into a eubiotic environment on the success of fertility treatments. Full article

The COVID-19 pandemic, starting in 2020, has presented a major challenge in terms of early diagnosis and the subsequent containment and management of severe cases. The spread of viruses such as monkeypox in non-endemic countries is now creating new difficulties for healthcare professionals. Proper case definition and clinical examination are crucial for the early identification of suspected cases. For this reason, we performed a review of the literature in order to report the first signs, which are useful for healthcare providers for early case identification. Since 2022 to date, 86,930 laboratory-confirmed cases and 1051 probable cases have been reported worldwide, and of these, 116 were fatal cases and, for the first time, most of the cases were registered in countries that have not historically reported monkeypox and that lack direct or immediate epidemiological links to areas of West or Central Africa where the disease is endemic. Patients with Monkeypox experience prodromal symptoms, such as fever, fatigue, headache, muscle aches, and a rash after an incubation period of 5–21 days. The disease is usually self-limiting within 2–4 weeks but can lead to complications, such as pneumonia, encephalitis, kidney injury, and myocarditis in children, pregnant individuals, and those with weakened immune systems. The case–fatality ratio is between 1 and 10%. Today, prevention campaigns and the control of human monkeypox are the best weapons to prevent infection and stop transmission. Prevention strategies, such as avoiding contact with sick or dead animals, and the proper preparation of all foods containing animal meat or parts, should be adopted. Furthermore, close contact with infected people or contaminated materials should be avoided to prevent human-to-human transmission. Full article

This report describes the case of a 65-year-old man who presented with gross hematuria and a history of pelvic salvage radiotherapy for prostate cancer. Cystoscopy and transurethral resection of the bladder revealed urothelial carcinoma. Subsequently, disseminated bone metastases were detected with normal prostate-specific antigen (PSA) levels, and palliative radiotherapy and systemic chemotherapy were administered. Because gross hematuria can appear in both acute/chronic cystitis and bladder cancer in patients who have undergone pelvic radiotherapy for prostate cancer, close follow-up along with a detailed evaluation is needed. In addition, because prostate cancer disease progression with normal PSA levels may be associated with specific pathological findings, a detailed evaluation of symptoms and a careful review of pathologic reports are important. Full article

The accumulation of body fat due to an imbalance between calorie intake and energy expenditure is called obesity. Metabolic syndrome increases the risk of heart disease, type 2 diabetes, and stroke. The purpose of this study was to determine the effect of Jatropha tanjorensis (J.T.) and Fraxinus micrantha (F.M.) leaf extracts on high-fat diet-induced obesity in rats. Normal control, high-fat diet (HFD) control, orlistat standard, and test groups were created using male Albino Wistar rats (n = 6 per group) weighing 190 ± 15 g. Except for the control group, all regimens were administered orally and continued for 6 weeks while on HFD. Evaluation criteria included body weight, food intake, blood glucose, lipid profile, oxidative stress, and liver histology. High-Performance Thin Layer Chromatography (HPTLC) analysis was performed using a solvent system (7:3 hexane: ethyl acetate for sitosterol solution and Jatropha tanjorensis extracts and 6:4 hexane: ethyl acetate: 1 drop of acetic acid for esculetin and Fraxinus micrantha extracts). There were no deaths during the 14 days before the acute toxicity test, indicating that aqueous and ethanolic extracts of both J.T. and F.M. did not produce acute toxicity at any dose (5, 50, 300, and 2000 mg/kg). The ethanolic and aqueous extracts of J.T. and F.M. leaves at 200 and 400 mg/kg/orally showed a reduction in weight gain, feed intake, and significant decreases in serum glucose and lipid profile. As compared to inducer HFD animals, co-treatment of aqueous and ethanolic extract of both J.T. and F.M. and orlistat increased the levels of antioxidant enzymes and decreased lipid peroxidation. The liver’s histological findings showed that the sample had some degree of protection. These results indicate that ethanolic samples of J.T. have antidiabetic potential in diabetic rats fed an HFD. The strong antioxidant potential and restoration of serum lipid levels may be related to this. Co-treatment of samples JTE, JTAQ, FME, FMAQ and orlistat resulted in an increase in antioxidant enzymes and reduction in lipid peroxidation as compared to inducer HFD animals. We report, for the first time, on using these leaves to combat obesity. Full article

Akkermansia muciniphila is a mucin-degrading bacterium of the intestinal niche, exerting beneficial effects on the host metabolic profile. Accumulating evidence indicated Akkermansia as a promising therapeutic probiotic against metabolic disorders such as obesity, type 2 diabetes and cardiovascular diseases. However, in specific intestinal microenvironments, its excessive enrichment may be not beneficial. Conditions like inflammatory bowel disease (IBD), Salmonella typhimurium infection or post-antibiotic reconstitution may not benefit from Akkermansia supplementation. Furthermore, using Akkermansia in patients with endocrine and gynecological disorders—such as polycystic ovary syndrome (PCOS) or endometriosis—that have a higher risk of developing IBD, should be critically evaluated. In addition, a cautionary note comes from the neurological field, as the gut microbiota of patients suffering from Parkinson’s disease or multiple sclerosis exhibits a characteristic signature of Akkermansia municiphila abundance. Overall, considering these controversial points, the use of Akkermansia should be evaluated on an individual basis, avoiding risking unexpected effects. Full article

The robust regulation of the cell cycle is critical for the survival and proliferation of bacteria. To gain a comprehensive understanding of the mechanisms regulating the bacterial cell cycle, it is essential to accurately quantify cell-cycle-related parameters and to uncover quantitative relationships. In this paper, we demonstrate that the quantification of cell size parameters using microscopic images can be influenced by software and by the parameter settings used. Remarkably, even if the consistent use of a particular software and specific parameter settings is maintained throughout a study, the type of software and the parameter settings can significantly impact the validation of quantitative relationships, such as the constant-initiation-mass hypothesis. Given these inherent characteristics of microscopic image-based quantification methods, it is recommended that conclusions be cross-validated using independent methods, especially when the conclusions are associated with cell size parameters that were obtained under different conditions. To this end, we presented a flexible workflow for simultaneously quantifying multiple bacterial cell-cycle-related parameters using microscope-independent methods. Full article

Annular dermatoses are a heterogeneous and extremely diverse group of skin diseases, which share in common annular, ring-like patterns with centrifugal spreading. Numerous skin diseases can sometimes display annular lesions, but some specific skin conditions are originally annular. We take the opportunity to review here mainly the causes of primary annular erythemas and their differential diagnoses, but also the rare causes of annular purpuras. Full article