Fungal diversity in the soil Mycobiome: Implications for ONE health.

Today, over 300 million individuals worldwide are afflicted by severe fungal infections, many of whom will perish. Fungi, as a result of their plastic genomes have the ability to adapt to new environments and extreme conditions as a consequence of globalization, including urbanization, agricultural intensification, and, notably, climate change. Soils and the impact of these anthropogenic environmental factors can be the source of pathogenic and non-pathogenic fungi and subsequent fungal threats to public health. This underscores the growing understanding that not only is fungal diversity in the soil mycobiome a critical component of a functioning ecosystem, but also that soil microbial communities can significantly contribute to plant, animal, and human health, as underscored by the One Health concept. Collectively, this stresses the importance of investigating the soil microbiome in order to gain a deeper understanding of soil fungal ecology and its interplay with the rhizosphere microbiome, which carries significant implications for human health, animal health and environmental health.

Aging of the adrenal gland and its impact on the stress response.

This article discusses the physiological and anatomical changes of adrenal gland with age and the effects this has overall on how the organ responds to stress. Physiological changes entail a decrease in adrenocorticoid hormone secretion however cortisol levels remain intact leading to a disruptive stress response. Additionally, loss of zonation of the organ also occurs. Both characteristics in combination with chronic stress affect overall health. Complex interplay between adrenal aging and stress responsiveness is confounded further by the impact they expel on other systems, such as the thyroid hormone. The body undergoes age-related transformations modifying rate of cellular growth, differentiation, senescence, and hormone production. Given the multiplicity and complexity of hormones, their production must be considered to develop appropriate interventions to mitigate its effect on age related diseases in health.

Microbial Therapy and Breast Cancer Management: Exploring Mechanisms, Clinical Efficacy, and Integration within the One Health Approach.

This comprehensive review elucidates the profound relationship between the human microbiome and breast cancer management. Recent findings highlight the significance of microbial alterations in tissue, such as the gut and the breast, and their role in influencing the breast cancer risk, development, progression, and treatment outcomes. We delve into how the gut microbiome can modulate systemic inflammatory responses and estrogen levels, thereby impacting cancer initiation and therapeutic drug efficacy. Furthermore, we explore the unique microbial diversity within breast tissue, indicating potential imbalances brought about by cancer and highlighting specific microbes as promising therapeutic targets. Emphasizing a holistic One Health approach, this review underscores the importance of integrating insights from human, animal, and environmental health to gain a deeper understanding of the complex microbe-cancer interplay. As the field advances, the strategic manipulation of the microbiome and its metabolites presents innovative prospects for the enhancement of cancer diagnostics and therapeutics. However, rigorous clinical trials remain essential to confirm the potential of microbiota-based interventions in breast cancer management.

Burnout and motivation to study medicine among students during the COVID-19 pandemic.

Aim: To investigate medical students' burnout and motivation levels in each of the six years of their studies during the COVID-19 pandemic and identify independent predictors of burnout and motivation. Methods: An anonymous cross-sectional survey was sent to the students of all six years within our school. Burnout was measured with the adapted Oldenburg Burnout Inventory questionnaire (OLBI-S) and motivation with the updated Strength of Motivation for Medical School (SMMS-R) questionnaire. Univariate analysis was performed with the Kruskal-Wallis test and Spearman's correlation, while multivariable analysis with linear regression models. Results: A total of 333 medical students (52% of student body) responded. Higher burnout levels correlated with lower motivation to study medicine (rho = -0.30, p < 0.001). Burnout levels differed between the six years of medical studies, peaking in years two and four whereas being the lowest in year one (p = 0.01). Motivation levels differed significantly as well, peaking in years one and four whereas being the lowest in years five and six (p = 0.012). In the multivariable linear regression models, being a female (b = 2.22, p = 0.016), studying in the fourth year vs. first year (b = 2.54, p = 0.049), having a perceived beginner/intermediate vs. advanced/expert technology level (b = 2.05, p = 0.032) and a perceived poor school support system (b = 6.35, p < 0.001) were independently associated with higher burnout levels. Furthermore, studying in the fifth year vs. first year (b = -5.17, p = 0.019) and a perceived poor school support system (b = -3.09, p = 0.01) were independently associated with a reduced motivation to study medicine. Conclusion: Our study highlighted potential areas for intervention to decrease the rate of burnout and low motivation among medical students. However, further research is needed to unravel the full effect of the pandemic on medical students.

Age-related modifications in CYP-dependent drug metabolism: role of stress.

Accumulating clinical evidence indicates extensive inter-individual variations in the effectiveness and adverse effects of standard treatment protocols, which are largely attributed to the multifactorial regulation of the hepatic CYP-dependent drug metabolism that is connected with either transcriptional or post-translational modifications. Age and stress belong to the most important factors in CYP gene regulation. Alterations in neuroendocrine responses to stress, which are associated with modified hypothalamo-pituitary-adrenal axis function, usually accompany ageing. In this light, ageing followed by a decline of the functional integrity of organs, including liver, a failure in preserving homeostasis under stress, increased morbidity and susceptibility to stress, among others, holds a determinant role in the CYP-catalyzed drug metabolism and thus, in the outcome and toxicity of pharmacotherapy. Modifications in the drug metabolizing capacity of the liver with age have been reported and in particular, a decline in the activity of the main CYP isoforms in male senescent rats, indicating decreased metabolism and higher levels of the drug-substrates in their blood. These factors along with the restricted experience in the use of the most medicines in childhood and elderly, could explain at an extent the inter-individual variability in drug efficacy and toxicity outcomes, and underscore the necessity of designing the treatment protocols, accordingly.

Adipose-Derived Stem Cells and Tacrolimus Improve Nerve Regeneration in a Rat Sciatic Nerve Defect Model.

This study compared the effect of undifferentiated adipose-derived stem cells (ADSCs) vs tacrolimus (FK506) in peripheral nerve regeneration in a rat sciatic nerve complete transection model. Forty Wistar rats were equally distributed in four groups. In the SHAM surgery group, the sciatic nerve was exposed and no further intervention was done. In the conduit-alone group (the SLN group), a 10-mm nerve gap was created and bridged with a fibrin conduit filled in with normal saline. In the FK506 group, the fibrin conduit was injected with soluble FK506. In the ADSC group, the conduit was impregnated with undifferentiated ADSCs. Nerve regeneration was assessed by means of walking track analysis, electromyography, and neurohistomorphometry. Clinically and microscopically, nerve regeneration was achieved in all groups at 12 weeks. Walking track analysis confirmed functional recovery in the FK506 and ADSC groups, but there was no difference between them. Recovery in function was also achieved in the SLN group, but it was inferior (P<.05). Electromyography demonstrated superior nerve regeneration in the FK506 and ADSC groups compared with the SLN group (P<.05), with no difference between the FK506 and ADSC groups. Similarly, histology showed no difference between the FK506 and ADSC groups, although both outperformed the SLN group (P<.05). No complications were observed. Successful peripheral nerve regeneration can be accomplished after a 10-mm nerve defect treated with nerve conduits. Superior nerve regeneration may be expected when the conduits are loaded with undifferentiated ADSCs or FK506, with similar outcomes for ADSCs and FK506. [Orthopedics. 2023;46(6):e353-e361.].

Health worker education during the COVID-19 pandemic: global disruption, responses and lessons for the future-a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis identified early evidence quantifying the disruption to the education of health workers by the COVID-19 pandemic, ensuing policy responses and their outcomes. METHODS: Following a pre-registered protocol and PRISMA/AMSTAR-2 guidelines, we systematically screened MEDLINE, EMBASE, Web of Science, CENTRAL, clinicaltrials.gov and Google Scholar from January 2020 to July 2022. We pooled proportion estimates via random-effects meta-analyses and explored subgroup differences by gender, occupational group, training stage, WHO regions/continents, and study end-year. We assessed risk of bias (Newcastle-Ottawa scale for observational studies, RοB2 for randomized controlled trials [RCT]) and rated evidence certainty using GRADE. RESULTS: Of the 171 489 publications screened, 2 249 were eligible, incorporating 2 212 observational studies and 37 RCTs, representing feedback from 1 109 818 learners and 22 204 faculty. The sample mostly consisted of undergraduates, medical doctors, and studies from institutions in Asia. Perceived training disruption was estimated at 71.1% (95% confidence interval 67.9-74.2) and learner redeployment at 29.2% (25.3-33.2). About one in three learners screened positive for anxiety (32.3%, 28.5-36.2), depression (32.0%, 27.9-36.2), burnout (38.8%, 33.4-44.3) or insomnia (30.9%, 20.8-41.9). Policy responses included shifting to online learning, innovations in assessment, COVID-19-specific courses, volunteerism, and measures for learner safety. For outcomes of policy responses, most of the literature related to perceptions and preferences. More than two-thirds of learners (75.9%, 74.2-77.7) were satisfied with online learning (postgraduates more than undergraduates), while faculty satisfaction rate was slightly lower (71.8%, 66.7-76.7). Learners preferred an in-person component: blended learning 56.0% (51.2-60.7), face-to-face 48.8% (45.4-52.1), and online-only 32.0% (29.3-34.8). They supported continuation of the virtual format as part of a blended system (68.1%, 64.6-71.5). Subgroup differences provided valuable insights despite not resolving the considerable heterogeneity. All outcomes were assessed as very-low-certainty evidence. CONCLUSION: The COVID-19 pandemic has severely disrupted health worker education, inflicting a substantial mental health burden on learners. Its impacts on career choices, volunteerism, pedagogical approaches and mental health of learners have implications for educational design, measures to protect and support learners, faculty and health workers, and workforce planning. Online learning may achieve learner satisfaction as part of a short-term solution or integrated into a blended model in the post-pandemic future.

Shift to emergency remote preclinical medical education amidst the Covid-19 pandemic: A single-institution study.

The Covid-19 pandemic disrupted medical education, shifting it towards emergency remote delivery. This cross-sectional study aimed to assess the impact of the pandemic on preclinical medical education and identify predictors of the virtual learning experience and perceived stress. An anonymous survey was delivered electronically to the students of the authors' medical school that attended either histology or pathology. This survey contained two scales, the virtual learning experience (VLE) and the perceived stress scale-10 (PSS-10). A total of 173/255 (68%) responded, showing a positive perception towards the remote delivery of both courses. An exploratory factor analysis was performed on the VLE scale items and four new dimensions were formed: "course quality and learning outcomes", "student motivation", virtual against F2F learning", and "virtual laboratory sessions". The following significant predictors of enhanced VLE, in at least one dimension, were identified: female gender, pathology course, final examination grade >80%, lower perceived stress levels, studying in home country, and holding of another degree before medical school. In addition, the following predictors were significantly associated with higher levels of student perceived stress: female gender, pathology course, studying away from home, and suboptimal internet connection. Notably, the quality of internet connection was significantly associated with the students' final examination performance. Concerning the best mode for future delivery of both courses, most students proposed a blended, rather than an entirely on-campus or online approach. In conclusion, despite its problems, a high-quality remote preclinical medical education was possible in the authors' school and offered tremendous opportunities for future improvement.

Clinical significance of P-class pumps in cancer.

P-class pumps are specific ion transporters involved in maintaining intracellular/extracellular ion homeostasis, gene transcription, and cell proliferation and migration in all eukaryotic cells. The present review aimed to evaluate the role of P-type pumps [Na+/K+ ATPase (NKA), H+/K+ ATPase (HKA) and Ca2+-ATPase] in cancer cells across three fronts, namely structure, function and genetic expression. It has been shown that administration of specific P-class pumps inhibitors can have different effects by: i) Altering pump function; ii) inhibiting cell proliferation; iii) inducing apoptosis; iv) modifying metabolic pathways; and v) induce sensitivity to chemotherapy and lead to antitumor effects. For example, the NKA ß2 subunit can be downregulated by gemcitabine, resulting in increased apoptosis of cancer cells. The sarcoendoplasmic reticulum calcium ATPase can be inhibited by thapsigargin resulting in decreased prostate tumor volume, whereas the HKA α subunit can be affected by proton pump inhibitors in gastric cancer cell lines, inducing apoptosis. In conclusion, the present review highlighted the central role of P-class pumps and their possible use and role as anticancer cellular targets for novel therapeutic chemical agents.

COVID-19 pandemic and cardiovascular disease: where do we stand?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) which recently has been characterized as a pandemic by the World Health Organization (WHO) having killed almost 250,000 people worldwide as of May 4th, 2020. Despite the fact that SARS-CoV-2 seems to predominantly affect the respiratory system leading to pneumonia and acute respiratory distress syndrome, it is now evident that it may also affect the cardiovascular system in multiple ways. The current paper is a review of the most recent literature regarding SARS-CoV-2 infection and its associated main cardiovascular clinical manifestations. Cardiovascular disease represents a prevalent underlying comorbidity associated with increased mortality rates among COVID-19 affected individuals. In addition, various cardiovascular manifestations have been linked to the viral insult, including among others acute coronary syndromes, myocarditis, acute heart failure, cardiac injury, arrhythmias and acute pulmonary embolism. Further studies are required in order to establish the complicated association between SARS-CoV-2 infection and its effects on the cardiovascular system. Our knowledge regarding diagnostic approaches, therapeutic management and preventive measures is constantly enriched throughout an abundance of ongoing research in the respective fields.

Gastric ischemic preconditioning may reduce the incidence and severity of anastomotic leakage after οesophagectomy: a systematic review and meta-analysis.

Anastomotic leakage after esophagectomy is a severe and life-threatening complication. Gastric ischemic preconditioning is a strategy for the improvement of anastomotic healing. Aim of this systematic review and meta-analysis is to investigate the impact of gastric ischemic preconditioning on postoperative morbidity. A systematic literature search was performed to identify studies comparing patients undergoing gastric ischemic preconditioning before esophagectomy with nonpreconditioned patients. Meta-analysis was conducted for the overall incidence of anastomotic leakage, severe anastomotic leakage, anastomotic stricture, postoperative morbidity, and mortality. Mantel-Haenszel odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed concerning preconditioning technique, the interval between preconditioning and surgery and the extent of preconditioning. Fifteen cohort studies were identified. Gastric preconditioning was associated with reduced overall incidence of anastomotic leakage (OR 0.73; 95% CI, 0.53-1.0; P = 0.050) and severe anastomotic leakage (OR 0.27; 95% CI, 0.14-0.50; P < 0.010), but not with anastomotic stricture (OR 1.18; 95% CI 0.38 to 3.66; P = 0.780), major postoperative morbidity (OR 1.03; 95% CI 0.45 to 2.36; P = 0.940) or mortality (OR 0.69; 95% CI 0.39 to 1,23; P = 0.210). Subgroup analyses did not identify any differences between embolization and ligation while increasing the interval between preconditioning and esophagectomy as well as the extent of preconditioning might be beneficial. Gastric ischemic preconditioning may be associated with a reduced incidence of overall and severe anastomotic leakage. Randomized studies are necessary to further evaluate its impact on leakage, refine the technique and define patient populations that will benefit the most.

Three-dimensional printing in anatomy teaching: current evidence.

PURPOSE: The critical literature review investigates the extent to which the current evidence supports that three-dimensional printing (3DP) could play an important role in human anatomy education. METHODS: PubMed, ERIC, and Cochrane databases were searched for papers dealing with the outcomes of 3DP implementation in human undergraduate anatomy education. The following data were extracted from each paper: authors, year of publication, type of study (comparative or not), number of participants, level of outcome according to Kirkpatrick hierarchy, influence of 3DP on acquisition of anatomical knowledge and skills, as well as perceptions about the 3DP use in anatomy teaching. RESULTS: Eight papers were eligible for analysis. All of them comprised comparison of 3DP with other anatomy teaching tools. Two papers evaluated only students' perceptions about 3DP, while six papers explored its impact on students' knowledge. The 3DP was statistically significantly superior to two-dimensional images in terms of the investigated parameters. However, comparison between 3DP and cadavers' dissection by students did not take place in any study. CONCLUSION: The 3DP implementation in anatomy education showed promising outcomes. However, the lack of studies which compared the educational effectiveness of 3DP with that of cadavers' dissection is highlighted. It seems that 3DP could certainly be used as an adjunct to cadavers' dissection. Further research could clarify if 3DP could obtain a more prominent role in anatomy pedagogy compared to other anatomy teaching modalities.

Silicone tubes with thyroid hormone (Τ3) and BDNF as an alternative to autografts for bridging neural defects.

The way thyroid hormone works in peripheral nerve regeneration has not been fully elucidated, although studies have shown that it has a strong positive effect on nerve regeneration. It is argued that its action is probably stronger than the neurotrophic factors that have been used for some time. It is hypothesized that the use of thyroid hormone in the nerve tubes has a beneficial effect on nerve regeneration to the extent that the results of its use are comparable to those of the autograft technique in bridging small nerve deficits. In this experimental study, we examined the effect of thyroid hormone and BDNF (Brain Derived Neurotrophic Factor) on the repair of 10 mm nerve defects when administered within silicone nerve tubes and compared the results with the autograft method. Thyroid hormone promotes nerve regeneration mainly by increasing its speed and its effect on the maturation of nerve fibers compared to the other groups where the nerve deficit was bridged by entubulation. Also, better organization and the absence of intraneural fibrosis, compared to the other groups, may argue for the action of thyroid hormone in regulating the inflammatory response. Functionally, the AG group showed better results compared to the other groups by the end of the study (16 weeks).