Med. Sci., Volume 10, Issue 2 (June 2022) – 13 articles

Underwater plasma discharge temporally produces several reactive radicals and/or free chlorine molecules in water, which is responsible for antimicrobial activity. Hence, it can simply sanitize tap water without disinfectant treatment. Additionally, the spraying technique using cleaning water exploits deep application in the narrow and curved vaginal tract of patients. Herein, we attempted a clinical trial to evaluate the vaginal cleaning effect of spraying plasma-activated water (PAW) to patients with vaginitis (46 patients). The efficacy was compared with treatment with betadine antiseptics used to treat bacterial vaginosis (40 patients). To evaluate the cleaning effect, Gram staining of the vaginal secretions was conducted before and after spraying PAW or betadine treatment (BT). Consequently, PAW-sprayed (PAWS) patients (22.3%) showed a better vaginal cleaning effect against Gram-positive and -negative bacteria than BT patients (14.4%). Moreover, 18 patients in the BT group showed worsened vaginal contamination, whereas five patients in the PAWS group showed worsened vaginal contamination. Taken together, the noncontact method of spraying cleaning water to the vagina exhibited a reliable vaginal cleaning effect without further bacterial infection compared with BT. Therefore, we suggest a clinical application of the spraying method using PAW for vaginal cleaning to patients with vaginitis without disinfectants and antibiotics. Full article

Valvular heart disease is a rapidly growing cause of global cardiovascular morbidity and mortality with diverse and evolving geographic distribution. The prevalence of rheumatic heart disease, the most common valvular heart disease (affecting approximately 41 million people), has been rising in developing nations, likely due to the expansion of the young adult population and the decrease in premature mortality that has resulted from improved access to antibiotics, microbiological testing, and echocardiography. Rheumatic heart disease has also been rising among the impoverished and, often, indigenous populations of developed nations, spurring public health initiatives that are aimed at alleviating healthcare disparities. Aortic valve stenotic disease is the most commonly occurring valvular pathology in developed nations (afflicting 9 million people worldwide) and its prevalence has been increasing with population aging and the increased prevalence of atherosclerosis. Aortic regurgitation is associated with diastolic, but not systolic, hypertension and it has likewise seen a rise in the developed world. Mitral regurgitation affects 24 million people worldwide, with great variability between and among nations. Primary mitral regurgitation arises as a consequence of myxomatous degeneration and mitral valve prolapse, which is largely due to genetic predispositions, while secondary mitral regurgitation accounts for 65% of cases and arises secondary to dilation and heart failure. Tricuspid regurgitation has become more prevalent in developed nations due to the increased usage of intracardiac pacemakers. Infective endocarditis prevalence has also grown in developed nations, likely due to population aging and the increased utilization of transcatheter valve replacement and prosthetic valves as interventions against the previously discussed valvular pathologies. Full article

Polyamine biosynthesis is frequently dysregulated in cancers, and enhanced flux increases intracellular polyamines necessary for promoting cell growth, proliferation, and function. Polyamine depletion strategies demonstrate efficacy in reducing tumor growth and increasing survival in animal models of cancer; however, mechanistically, the cell-intrinsic and cell-extrinsic alterations within the tumor microenvironment underlying positive treatment outcomes are not well understood. Recently, investigators have demonstrated that co-targeting polyamine biosynthesis and transport alters the immune landscape. Although the polyamine synthesis-targeting drug 2-difluoromethylornithine (DFMO) is well tolerated in humans and is FDA-approved for African trypanosomiasis, its clinical benefit in treating established cancers has not yet been fully realized; however, combination therapies targeting compensatory mechanisms have shown tolerability and efficacy in animal models and are currently being tested in clinical trials. As demonstrated in pre-clinical models, polyamine blocking therapy (PBT) reduces immunosuppression in the tumor microenvironment and enhances the therapeutic efficacy of immune checkpoint blockade (ICB). Thus, DFMO may sensitize tumors to other therapeutics, including immunotherapies and chemotherapies. Full article

The rate of venous thromboembolism in COVID-19 patients has been reported to be 30% (deep vein thrombosis 20% and pulmonary embolism 18%). This has been shown to be higher in COVID-19 patients admitted to the ICU. Prophylactic anticoagulation may be sufficient at ward level, but not in intensive care. A retrospective chart review was undertaken in a large university hospital. The review included 276 patients from COVID-19 Wave 1, COVID-19 Wave 2, influenza, and community-acquired pneumonia groups. The timeframe included patients admitted between 23 February 2014 and 12 May 2021. Clinical characteristics, outcomes, blood results, rates of venous thromboembolism, and anticoagulation status were recorded. The incidence of venous thromboembolism in COVID-19 Wave 1, COVID-19 Wave 2, influenza, and community-acquired pneumonia was 10.91%, 13.69%, 13.33%, and 6.81%, respectively (p = 0.481). The incidence of pulmonary embolism was 7.27%, 10.95%, 3.33%, and 5.68%, respectively (p = 0.350). The incidence of deep vein thrombosis was 5.45%, 5.48%, 10.00%, and 1.14%, respectively (p = 0.117). Although most patients were prophylactically anticoagulated, venous thromboembolism still occurred. Venous thromboembolism remains an important differential to consider in critically ill COVID-19 patients. The current literature does not advise therapeutic anticoagulation for thromboprophylaxis in the ICU. Full article

Evidence continues to emerge that the social determinants of health play a role in adverse outcomes related to COVID-19, including increased morbidity and mortality, increased risk of long COVID, and vaccine adverse effects. Therefore, a more nuanced understanding of the biochemical and cellular pathways of illnesses commonly associated with adverse social determinants of health is urgently needed. We contend that a commitment to understanding adverse outcomes in historically marginalized communities will increase community-level confidence in public health measures. Here, we synthesize emerging literature on mast cell disease, and the role of mast cells in chronic illness, alongside emerging research on mechanisms of COVID illness and vaccines. We propose that a focus on aberrant and/or hyperactive mast cell behavior associated with chronic underlying health conditions can elucidate adverse COVID-related outcomes and contribute to the pandemic recovery. Standards of care for mast cell activation syndrome (MCAS), as well as clinical reviews, experimental research, and case reports, suggest that effective and cost-efficient remedies are available, including antihistamines, vitamin C, and quercetin, among others. Primary care physicians, specialists, and public health workers should consider new and emerging evidence from the biomedical literature in tackling COVID-19. Specialists and researchers note that MCAS is likely grossly under-diagnosed; therefore, public health agencies and policy makers should urgently attend to community-based experiences of adverse COVID outcomes. It is essential that we extract and examine experiential evidence of marginalized communities from the broader political–ideological discourse. Full article

Ovarian cancer accounts for 3% of the total cancers in women, yet it is the fifth leading cause of cancer deaths among women. The BRCA1/2 germline and somatic mutations confer a deficiency of the homologous recombination (HR) repair pathway. Inhibitors of poly (ADP-ribose) polymerase (PARP), another important component of DNA damage repair, are somewhat effective in BRCA1/2 mutant tumors. However, ovarian cancers often reacquire functional BRCA and develop resistance to PARP inhibitors. Polyamines have been reported to facilitate the DNA damage repair functions of PARP. Given the elevated levels of polyamines in tumors, we hypothesized that treatment with the polyamine synthesis inhibitor, α-difluoromethylornithine (DFMO), may enhance ovarian tumor sensitivity to the PARP inhibitor, rucaparib. In HR-competent ovarian cancer cell lines with varying sensitivities to rucaparib, we show that co-treatment with DFMO increases the sensitivity of ovarian cancer cells to rucaparib. Immunofluorescence assays demonstrated that, in the presence of hydrogen peroxide-induced DNA damage, DFMO strongly inhibits PARylation, increases DNA damage accumulation, and reduces cell viability in both HR-competent and deficient cell lines. In vitro viability assays show that DFMO and rucaparib cotreatment significantly enhances the cytotoxicity of the chemotherapeutic agent, cisplatin. These results suggest that DFMO may be a useful adjunct chemotherapeutic to improve the anti-tumor efficacy of PARP inhibitors in treating ovarian cancer. Full article

Cardiovascular diseases are largely represented in patients with cancer and appear to be important side effects of cancer treatments, heavily affecting quality of life and leading to premature morbidity and death among cancer survivors. In particular, treatments for breast cancer have been shown to potentially play serious detrimental effects on cardiovascular health. This review aims to explore the available literature on breast cancer therapy-induced side effects on heart and vessels, illustrating the molecular mechanisms of cardiotoxicity known so far. Moreover, principles of cardiovascular risk assessment and management of cardiotoxicity in clinical practice will also be elucidated. Chemotherapy (anthracycline, taxanes, cyclophosphamide and 5-fluorouracil), hormonal therapy (estrogen receptor modulator and gonadotropin or luteinizing releasing hormone agonists) and targeted therapy (epidermal growth factor receptor 2 and Cyclin-dependent kinases 4 and 6 inhibitors) adverse events include arterial and pulmonary hypertension, supraventricular and ventricular arrhythmias, systolic and diastolic cardiac dysfunction and coronary artery diseases due to different and still not well-dissected molecular pathways. Therefore, cardiovascular prevention programs and treatment of cardiotoxicity appear to be crucial to improve morbidity and mortality of cancer survivors. Full article

Molecular and histopathological analysis of melanoma subtypes has revealed distinct epidemiological, genetic, and clinical features. However, immunotherapy for advanced metastatic melanoma patients does not differ based on subtype. Response to immune checkpoint inhibitors (ICI) has been shown to vary, therefore, predictive biomarkers are needed in the design of precision treatments. Targeted sequencing and histopathological analysis (CD8 and CD20 immunohistochemistry) were performed on subtypes of metastatic melanoma (cutaneous melanoma (CM, n = 10); head and neck melanoma (HNM, n = 7); uveal melanoma (UM, n = 4); acral lentiginous melanoma (AM, n = 1) and mucosal melanoma (MM, n = 1) treated with ICI). Progression-free survival (PFS) was significantly associated with high CD8 expression (p = 0.025) and mutations in DNA damage repair (DDR) pathway genes (p = 0.012) in all subtypes but not with CD20 expression. Our study identified that immune cell infiltration and DDR gene mutations may have an impact in response to ICI treatment in metastatic melanoma but differs among subtypes. Therefore, a comprehensive understanding of the immune infiltration cells’ role and DDR gene mutations in metastatic melanoma may identify prognostic biomarkers. Full article

Prostate cancer therapy for locally advanced and metastatic diseases includes androgen deprivation therapy (ADT). Second-generation antiandrogens have a role in castration-resistant prostate cancer. Nevertheless, some patients do not respond to this therapy, and eventually all the patients became resistant. This is due to modifications to intracellular signaling pathways, genomic alteration, cytokines production, metabolic switches, constitutional receptor activation, overexpression of some proteins, and regulation of gene expression. The aim of this review is to define the most important mechanisms that drive this resistance and the newest discoveries in this field, specifically for enzalutamide and abiraterone, with potential implications for future therapeutic targets. Furthermore, apalutamide and darolutamide share some resistance mechanisms with abiraterone and enzalutamide and could be useful in some resistance settings. Full article

Parasites of the genus Leishmania cause a variety of devastating and often fatal diseases in humans and domestic animals worldwide. The need for new therapeutic strategies is urgent because no vaccine is available, and treatment options are limited due to a lack of specificity and the emergence of drug resistance. Polyamines are metabolites that play a central role in rapidly proliferating cells, and recent studies have highlighted their critical nature in Leishmania. Numerous studies using a variety of inhibitors as well as gene deletion mutants have elucidated the pathway and routes of transport, revealing unique aspects of polyamine metabolism in Leishmania parasites. These studies have also shed light on the significance of polyamines for parasite proliferation, infectivity, and host–parasite interactions. This comprehensive review article focuses on the main polyamine biosynthetic enzymes: ornithine decarboxylase, S-adenosylmethionine decarboxylase, and spermidine synthase, and it emphasizes recent discoveries that advance these enzymes as potential therapeutic targets against Leishmania parasites. Full article

Skin wound repair has been the central focus of clinicians and scientists for almost a century. Insights into acute and chronic wound healing as well as scarring have influenced and ameliorated wound treatment. Our knowledge of normal skin notwithstanding, little is known of acute and chronic wound repair of genital skin. In contrast to extra-genital skin, hypertrophic scarring is uncommon in genital tissue. Chronic wound healing disorders of the genitals are mostly confined to mucosal tissue diseases. This article will provide insights into the differences between extra-genital and genital skin with regard to anatomy, physiology and aberrant wound repair. In light of fundamental differences between genital and normal skin, it is recommended that reconstructive and esthetic surgery should exclusively be performed by specialists with profound expertise in genital wound repair. Full article

The effect of thyroid function on semen parameters has been studied in pathological conditions in small studies. With this research work, we aimed to study thyroid hormone effects on semen parameters in 130 men who were evaluated for couple subfertility. Our study was cross-sectional. We noted semen volume, sperm concentration, total sperm count, testosterone levels and thyrotropin (TSH) levels. The analysis included ordinary least squares regression (OLS-R), quantile regression (QR) and segmented line regression (SR). Using OLS-R, a weak negative correlation was found between the logTSH levels and semen volume (r = −0.16, r² = 0.03, p = 0.05). In Q-R, each incremental unit increase in logTSH decreased the mean semen volume between −0.78 ± 0.44 and −1.33 ± 0.34 mL (40–60th response quantile) and between −1.19 ± 0.71 and −0.61 ± 0.31 mL (70–90th response quantile) (p = 0.049). With SR, a biphasic relationship of sperm concentration with TSH was noted (positive turning to negative, peaking at TSH = 1.22 μIU/mL). Thus, a weak negative association between the TSH levels and semen volume was noted, showing a trough within the usual normal range for TSH. Moreover, a biphasic relationship between the sperm concentration and TSH was also noted, peaking at approximately mid-normal TSH levels. Based on our results, TSH explained slightly less than 3% of the variation in semen volume and 7% of the sperm concentration (thus, other factors, which were not studied here, have a more important effect on it). Full article

We performed a systematic review and meta-analysis to evaluate the association whether the female gender was associated with an increased chance of left ventricular ejection fraction (LVEF) in patients with heart failure with reduced ejection fraction (HFrEF). We searched the databases of MEDLINE and EMBASE from inception to 18 January 2022. Included studies were published studies evaluating or reporting characteristics of patients with HF with recovered LVEF. Data from each study were combined using a random-effects model, the generic inverse variance method of DerSimonian and Laird, to calculate odd ratios (OR) and 95% confidence intervals (CI). Eighteen studies were included in the analysis with a total of 12,270 patients (28.2% female). Female gender was associated with an increased chance of LVEF recovery (pooled OR = 1.50, 95% CI = 1.21–1.86, p-value < 0.001, I² = 74.5%). In our subgroup analysis, female gender was associated with an increased chance of LVEF recovery when defined as LVEF > 50% (pooled OR = 1.78, 95% CI = 1.45–2.18, p-value < 0.001, I² = 0.0%), and LVEF > 40–45% (pooled OR = 1.45, 95% CI = 1.09–1.91, p-value = 0.009, I² = 79.2%), but not in LVEF > 35 (OR = 2.18, 95% CI = 0.94–5.05, p-value = 0.06). Our meta-analysis demonstrated that the female gender is associated with an increased chance of LVEF recovery. This association was not statistically significant in the subgroup that defined LVEF recovery as LVEF > 35%. Full article