Medical Sciences — Open Access Journal

Isolated adult rat ventricular cardiomyocytes (ARVC) adapt to the two-dimensional surface of culture dishes once they are isolated from the three-dimensional heart tissue. This process mimics aspects of cardiac adaptation to pressure overload and requires an initial breakdown of sarcomeric structures. The present study therefore aimed to identify key steps in this remodeling process. ARVC were cultured under serum-free or serum-supplemented conditions and their sizes and shapes were analyzed as well as apoptosis and the ability to disintegrate their sarcomeres. ARVC require serum-factors in order to adapt to cell culture conditions. More ARVC survived if they were able to breakdown their sarcomeres and mononucleated ARVC, which were smaller than binucleated ARVC, had a better chance to adapt. During the early phase of adaptation, proteasome subunit low molecular weight protein (LMP)-2 was induced. Inhibition of LMP-2 up-regulation by siRNA attenuated the process of successful adaptation. In vivo, LMP-2 was induced in the left ventricle of spontaneously hypertensive rats during the early phase of adaptation to pressure overload. In conclusion, the data suggest that breakdown of pre-existing sarcomeres is optimized by induction of LMP-2 and that it is required for cardiac remodeling processes, for example, occurring during pressure overload. Full article

Advances in both public health and medical interventions have resulted in a reduction in childhood mortality worldwide over the last few decades; however, children still have life-threatening conditions that require palliative care. Children’s palliative care is a specialty that differs from palliative care for adults in many ways. This paper discusses some of the challenges, and some of the recent advances in paediatric palliative care. Developing responsive services requires good epidemiological data, as well as a clarity on services currently available and a robust definition of the group of children who would benefit from palliative care. Once a child is diagnosed with a life-limiting condition or life-limiting illness, parents face a number of complex and difficult decisions; not only about care and treatment, but also about the place of care and ultimately, place of death. The best way to address the needs of children requiring palliative care and their families is complex and requires further research and the routine collection of high-quality data. Although research in children’s palliative care has dramatically increased, there is still a dearth of evidence on key components of palliative care notably decision making, communication and pain and symptom management specifically as it relates to children. This evidence is required in order to ensure that the care that these children and their families require is delivered. Full article

Exposure to air pollution and, in particular, to nitrogen dioxide (NO₂) or particulate pollutants less than 2.5 μm (PM2.5) or 10 μm (PM10) in diameter has been linked to thyroid (dys)function in pregnant women. We hypothesized that there may be a dose—effect relationship between air pollutants and thyroid function parameters. We retrospectively evaluated thyrotropin (TSH) in 293 women, NO₂, PM2.5 and PM10 levels in Athens. All the women were diagnosed with hypothyroidism for the first time during their pregnancy. Exposure to air pollution for each woman was considered according to her place of residence. Statistical analysis of age, pregnancy weight change, and air pollutants versus TSH was performed with ordinary least squares regression (OLS-R) and quantile regression (Q-R). A positive correlation for logTSH and PM2.5(r = +0.13, p = 0.02) was found, using OLS-R. Further analysis with Q-R showed that each incremental unit increase (for the 10th to the 90th response quantile) in PM2.5 increased logTSH(±SE) between +0.029 (0.001) to +0.025 (0.001) mIU/L (p < 0.01). The other parameters and pollutants (PM10 and NO₂) had no significant effect on TSH. Our results indeed show a dose—response relationship between PM2.5 and TSH. The mechanisms involved in the pathophysiological effects of atmospheric pollutants, in particular PM2.5, are being investigated. Full article

Breast cancer is the most commonly occurring cancer in women. There were over two-million new cases in world in 2018. It is the second leading cause of death from cancer in western countries. At the molecular level, breast cancer is a heterogeneous disease, which is characterized by high genomic instability evidenced by somatic gene mutations, copy number alterations, and chromosome structural rearrangements. The genomic instability is caused by defects in DNA damage repair, transcription, DNA replication, telomere maintenance and mitotic chromosome segregation. According to molecular features, breast cancers are subdivided in subtypes, according to activation of hormone receptors (estrogen receptor and progesterone receptor), of human epidermal growth factors receptor 2 (HER2), and or BRCA mutations. In-depth analyses of the molecular features of primary and metastatic breast cancer have shown the great heterogeneity of genetic alterations and their clonal evolution during disease development. These studies have contributed to identify a repertoire of numerous disease-causing genes that are altered through different mutational processes. While early-stage breast cancer is a curable disease in about 70% of patients, advanced breast cancer is largely incurable. However, molecular studies have contributed to develop new therapeutic approaches targeting HER2, CDK4/6, PI3K, or involving poly(ADP-ribose) polymerase inhibitors for BRCA mutation carriers and immunotherapy. Full article

Background: Critical care has evolved from a primary focus on short-term survival, with greater attention being placed on longer-term health care outcomes. It is not known how best to implement follow-up after critical care discharge. Study aims were to (1) assess the uptake and feasibility of telephone follow-up after a critical care stay and (2) profile overall physical status and recovery during the sub-acute recovery period using a telephone follow-up assessment. Methods: Adults who had been admitted to critical care units of St. James’s Hospital, Dublin, for >72 h were followed up by telephone 3–9 months post discharge from critical care. The telephone assessment consisted of a battery of questionnaires (including the SF-36 questionnaire and the Clinical Frailty Scale) and examined quality of life, frailty, employment status, and feasibility of telephone follow-up. Results: Sixty five percent (n = 91) of eligible participants were reachable by telephone. Of these, 80% (n = 73) participated in data collection. Only 7% (n = 5) expressed a preference for face-to-face hospital-based follow-up as opposed to telephone follow-up. For the SF-36, scores were lower in a number of physical health domains as compared to population norms. Frailty increased in 43.2% (n = 32) of participants compared to pre-admission status. Two-thirds (n = 48) reported being >70% physically recovered. Conclusion: Results showed that telephone follow-up is a useful contact method for a typically hard-to-reach population. Deficits in physical health and frailty were noted in the sub-acute period after discharge from critical care. Full article

Based on the latest GLOBOCAN data, bladder cancer accounts for 3% of global cancer diagnoses and is especially prevalent in the developed world. In the United States, bladder cancer is the sixth most incident neoplasm. A total of 90% of bladder cancer diagnoses are made in those 55 years of age and older, and the disease is four times more common in men than women. While the average 5-year survival in the US is 77%, the 5-year survival for those with metastatic disease is a measly 5%. The strongest risk factor for bladder cancer is tobacco smoking, which accounts for 50–65% of all cases. Occupational or environmental toxins likewise greatly contribute to disease burden (accounting for an estimated 20% of all cases), though the precise proportion can be obscured by the fact bladder cancer develops decades after exposure, even if the exposure only lasted several years. Schistosomiasis infection is the common cause of bladder cancer in regions of Africa and the Middle East and is considered the second most onerous tropical pathogen after malaria. With 81% of cases attributable to known risk factors (and only 7% to heritable mutations), bladder cancer is a prime candidate for prevention strategies. Smoking cessation, workplace safety practices, weight loss, exercise and schistosomiasis prevention (via water disinfection and mass drug administration) have all been shown to significantly decrease the risk of bladder cancer, which poses a growing burden around the world. Full article

Allogenic stem-cell therapies benefit patients in the treatment of multiple diseases; however, the side effects of stem-cell therapies (SCT) derived from the concomitant use of immune suppression agents often include triggering infection diseases. Thus, analysis is required to improve the detection of pathogen infections in SCT. We develop a polymerase chain reaction (PCR)-based methodology for the qualitative real-time DNA detection of cytomegalovirus (CMV), with reference to herpes simplex virus types 1 (HSVI), Epstein–Barr virus (EBV), and varicella-zoster virus (VZV) in blood, urine, solid tissues, and cerebrospinal fluid. This real-time PCR of 96-well plate format provides a rapid framework as required by the Food and Drug Administration (FDA) for clinical settings, including the processing of specimens, reagent handling, special safety precautions, quality control criteria and analytical accuracy, precisely reportable range (analyst measurement range), reference range, limit of detection (LOD), analytical specificity established by interference study, and analyte stability. Specifically, we determined the reportable range (analyst measurement range) with the following criteria: CMV copies ≥200 copies/mL; report copy/mL value; CMV copies ≤199 copies/mL; report detected but below quantitative range; CMV copies = 0 with report <200 copies/mL. That is, with reference range, copy numbers (CN) per milliliter (mL) of the LOD were determined by standard curves that correlated Ct value and calibrated standard DNA panels. The three repeats determined that the measuring range was 1E2~1E6 copies/mL. The standard curves show the slopes were within the range −2.99 to −3.65 with R² ≥ 0.98. High copy (HC) controls were within 0.17–0.18 log differences of DNA copy numbers; (2) low copy (LC) controls were within 0.17–0.18 log differences; (3) LOD was within 0.14–0.15 log differences. As such, we set up a fast, simple, inexpensive, sensitive, and reliable molecular approach for the qualitative detection of CMV pathogens. Conclusion: This real-time PCR of the 96-well plate format provides a rapid framework as required by the FDA for clinical settings. Full article

Vitamin D has displayed anti-cancer actions in numerous in vitro studies. Here, we investigated the anti-cancer actions of cholecalciferol, a vitamin D precursor, on a metastatic cervical cancer cell line, namely, CaSki. Experimental cultures were incubated for 72 h and treated with cholecalciferol (10–1000 ng/mL). In the present study, cell count, viability, proliferation and cell cycle were analyzed by a crystal violet assay, trypan blue assay, Ki67 proliferation, and a cell cycle assay, respectively. Biomarkers of apoptosis, necrosis, and autophagic cell death were measured by the Caspase 3/7 and Annexin V/7-AAD Muse™ assays, a LC3-II assay, and a lactate dehydrogenase release assay, respectively. The ultrastructural features of cell death were assessed by transmission electron microscopy. A statistical analysis was performed using a one-way ANOVA and Bonferroni’s post-hoc analysis test, and p < 0.05 is considered statistically significant here. The results identify statistical decreases in cell count and viability at high-dose treatments (100 and 1000 ng/mL). In addition, significant increases in apoptotic biochemical markers and apoptotic ultrastructure are shown to be present at high-dose treatments. In conclusion, high-dose cholecalciferol treatments inhibit cell count and viability, which are both mediated by apoptotic induction in the CaSki cell line. Full article

Prostate cancer and its associated treatments can cause significant and lasting morbidities, such as cardiovascular and sexual dysfunctions. Various interventions have attempted to prevent or mitigate these dysfunctions. This review summarises the available evidence on the effects of exercise training on markers of cardiovascular disease (as assessed via vascular health outcomes) and sexual health in this prevalent cancer population. Current studies predominantly report blood pressure outcomes as a marker of vascular health, as well as various questionnaires assessing sexual health parameters, in men on active treatment (i.e., hormone or radiation therapies) or post-treatment. Preliminary evidence suggests that exercise interventions may elicit improvements in sexual function, but not blood pressure, in these populations. Future studies in more advanced and varied prostate cancer populations (i.e., those on chemotherapies or immunotherapies, or undergoing active surveillance) are required to ascertain the duration, intensity and frequency of exercise that optimises the effects of exercise training on cardiovascular and sexual dysfunctions (and their relationship) in men during and following treatment for prostate cancer. Full article

Background: schistosomiasis is a neglected tropical disease caused by helminths of the genus Schistosoma. The disease has a worldwide distribution, with more cases occurring in Africa. Urogenital schistosomiasis caused by S. haematobium with its associated morbidity is prevalent in many areas of Ghana. Praziquantel is still the recommended drug of choice for schistosomiasis treatment, although a number of studies have reported sub-therapeutic effects and associated treatment failure. The current study, therefore, assessed whether persistent schistosomiasis, with its associated morbidity among children living in endemic areas within the Greater Accra Region of Ghana, is as a result of reinfection or suspected praziquantel resistance. Methodology: this was a longitudinal study involving a baseline and follow-up sampling after praziquantel treatment. Urine samples were collected from school children (whose parents had also consented) for the detection of S. haematobium ova using a sedimentation technique. The morbidity parameters were examined with urine chemistry strips, as well as microscopy. Viability was assessed using a modified hatchability technique, vital staining (0.4% trypan blue and 1% neutral red) and fluorescent (Hoechst 33258) microscopy. Infected individuals were treated with a single dose of praziquantel (40mg/kg). Resampling to determine reinfection was done sixth months post-treatment, after evidence of total egg clearance. For possible resistance assessment, egg counts and viability testing were conducted on the positive samples at the baseline, as well as weekly post-treatment follow-ups for 12 weeks. Results: out of the 420 school children sampled, 77 were initially positive but, after the sixth month sampling for reinfection assessment, eight out of the initial positives were infected again, giving a reinfection percentage of 10.4%. No suspected praziquantel resistance was recorded in the 21 positives detected out of the 360 sampled for suspected resistance assessment. The egg reduction rate increased weekly in the follow-up samples with a gradual reduction in the egg count. The study also recorded a gradual decrease in the percentage of live eggs after the first week; with all viability testing methods used complimenting each other. The morbidity parameters (proteinuria, haematuria and pyuria) changed between the baseline and post-treatment samples, eventually reducing to zero. Conclusions: the outcome of this study suggests that the persistent schistosomiasis, with its associated morbidity observed in these endemic communities, is not likely to be as a result of praziquantel resistance, but reinfection. Even though there was no suspected resistance observed in the study, there remains the need to continuously intensify the monitoring of praziquantel in other endemic communities. Full article

Hepatitis E virus (HEV) is a non-enveloped, positive-sense, single-stranded RNA icosahedral virus belongs to the genus Orthohepevirus within the Hepeviridae family. HEV infection can be asymptomatic, or it can cause icteric or fulminant hepatitis. Off late, there have been a number of publications reporting the extra-hepatic manifestations of HEV infection, and this systematic review is aimed at summarizing the available evidence in this regard. Two independent investigators searched PubMed, PubMed Central and Embase databases using the search string “(((hepatitis E) AND (Extrahepatic OR Extra-Hepatic))) OR ((Hepatitis E) AND (Neurology OR Cardiology OR Respiratory OR Lung OR Gastrointestinal OR musculoskeletal OR immunology OR pulmonary)) Filters: Abstract availability, English language, and Human studies”. The extra-hepatic manifestations reported in each of the selected articles were classified and reported as neurological, cardiovascular, and hematological and miscellaneous manifestations. The total number of various manifestations reported in our study were n = 324. These include neurological manifestations (n = 178/324 (54.94%)), cardiovascular and hematological manifestations (n = 113/324 (34.88%)), gastro-intestinal/pancreaticobiliary manifestations (n = 24/324 (7.41%)) and other rarer manifestations involving systems such as renal (n = 4/324; 1.24%), endocrine (n = 1/324; 0.31%), dermatology (n = 1/324; 0.31%), respiratory (n = 1/324; 0.31%), muscular (n = 1/324; 0.31%) and immune system (n = 1/324; 0.31%). Thus, HEV can have extra-hepatic manifestations affecting any system of the human body. Further research is needed to elucidate the underlying pathophysiological manifestations of these extra-hepatic manifestations and to prove causal association with HEV. Full article

The 6-minute walk test (6MWT) is not intended to document oxygen (O₂) desaturation during exertion but is often used for this purpose. Because of this, it only has modest reproducibility in determining the need for ambulatory O₂ therapy in patients with cardiopulmonary disease. The diagnostic and prognostic value of detecting exertional O₂ desaturation is still unknown. The aims of this study were to estimate the prevalence of O₂ desaturation during a 6MWT based on pulse oximetry measurements at the beginning and end of a 6MWT in a clinical population of patients with suspected cardiopulmonary disease and to determine whether the pulmonary function test (PFT) can predict exercise-induced desaturation during a 6MWT. This retrospective cohort study reviewed the results of the 6MWT and the PFT (i.e., spirometry, lung volumes, and diffusion capacity) of all patients who were evaluated for suspected cardiopulmonary disease at an academic medical center during a 5-year study period. The patients were categorized into three groups based on the change in O₂ saturation by pulse oximetry (SpO₂) from start to end of the 6MWT: (1) SpO₂ decreased by ≥3%; (2) SpO₂ unchanged (−2 ≤ Δ ≤ 0%); and (3) SpO₂ increased by ≥1%. Demographic, anthropometric, and lung function measurements were analyzed to determine which factors predicted O₂ desaturation during the 6MWT. Of the 319 patients who underwent the 6MWT and the PFT from November 2005 until December 2010 (mean age = 54 ± 0.78 years, 63% women, 58% Whites, body mass index = 29.63 ± 8.10 kg/m²), 113 (35%) had a decreased SpO₂, 146 (46%) had no change, and 60 (19%) had an increased SpO₂ from the start to end of test. Our bivariate analysis found age, spirometric measures, and diffusion capacity for carbon monoxide (DLCO) had statistically significant inverse associations with the SpO₂ change category (p < 0.001). Both a 3% and 4% drop in SpO₂ during the 6MWT were statistically significantly associated with an older age, a higher prevalence of obstruction, and reduced forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), FEV₁/FVC, DLCO and 6-minute walk distance (6MWD). Multivariable logistic regression analyses revealed that only DLCO was a significant independent predictor of the change in SpO₂ and a ≥ 4% O₂ desaturation during a 6MWT. Receiver operating curve analysis indicates DLCO cut-off of 45% is 82% sensitive and 40% specific in identifying ≥4% O₂ desaturators, with an area under the curve of 0.788 ± 0.039 (p < 0.001). The prevalence of a ≥ 3% oxygen desaturation via pulse oximetry during a 6MWT in our clinical population of patients with suspected cardiopulmonary disease was 35%. Although age, spirometric lung volumes, and DLCO had statistically significant unadjusted inverse associations with the change in SpO₂ during a 6MWT, the DLCO is the only significant independent predictor of both the magnitude of the change in SpO₂ and the occurrence of O₂ desaturation of at least 4%, respectively, during the test. Clinical Implications: A DLCO cut-off of 45% may be useful in identifying patients at risk for exertional hypoxemia during a 6MWT. Full article

Astrocytes are multi-functional cells, now recognized as critical participants in many brain functions. They play a critical physiological role in the clearance of neurotransmitters, such as glutamate and gamma-aminobutyric acid (GABA), and in the regulation of K⁺ from the space of synaptic clefts. Astrocytes also express the excitatory amino acid transporters (EAATs) and aquaporin-4 (AQP4) water channel, which are involved in both physiological functions and neurodegenerative diseases (ND). Some of the ND are the Alzheimer’s (AD), Huntington’s (HD), Parkinson’s diseases (PD), Cerebral edema, amyotrophic lateral sclerosis (ALS), and epilepsy pathological conditions in specific regions of the CNS. Parkinson’s disease is the second most common age-related neurodegenerative disorder, characterized by degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNpc). These project to the striatum, forming an important pathway within the basal ganglia. Mostly, PD has no clear etiology, and the mechanism of dopaminergic (DA) neuron loss is not well illustrated. The results of various studies suggest that astrocytes are involved in the pathophysiology of PD. Evidence has shown that the down-regulation of EAAT-2/GLT-1 and AQP4 expression is associated with PD pathogenesis. However, controversial results were reported in different experimental studies about the expression and function of EAAT-2/GLT-1 and AQP4, as well as their colocalization in different brain regions, and their involvement in PD development. Therefore, under neurological disorders, Parkinson’s disease is related to the genetic and phenotypic change of astrocytes’ biology. In this review, the authors summarized recent their research findings, which revealed the involvement of EAAT-2/GLT-1 and AQP4 expression, the physical interaction between EAAT-2/GLT-1 and AQP4 in astrocyte function, and their potential role in the development of PD in SNpc and Subthalamic nucleus (STN) of the basal ganglia nuclei. Full article

Despite advances in its prevention, pneumonia remains associated with high morbidity, mortality, and health costs worldwide. Studies carried out in the last decade have indicated that more patients with community-acquired pneumonia (CAP) now require hospitalization. In addition, pneumonia management poses many challenges, especially due to the increase in the number of elderly patients with multiple comorbidities, antibiotic-resistant pathogens, and the difficulty of rapid diagnosis. In this new call to action, we present a wide-ranging review of the information currently available on CAP and offer some reflections on ways to raise awareness of this disease among the general public. We discuss the burden of CAP and the importance of attaining better, faster microbiological diagnosis and initiating appropriate treatment. We also suggest that closer cooperation between health professionals and the population at large could improve the management of this largely preventable infectious disease that takes many lives each year. Full article

(1) Background: Present methods for drug susceptibility tests (DST) rely on culture methods that are sophisticated and relatively faster, or a slow and cheaper option. These methods frustrate disease control; therefore, there is a need for methods that incorporate key functions of microscopy and culture, with reduced cost burden and sophistry. Thus, the purpose of this study was to identify which, among the most commonly used (in Ghana) methods, can conveniently be used at health centers located in rural areas for effective DST determination of Mycobacterium tuberculosis (MTB). (2) Methods: Mycobacterium tuberculosis isolates were tested for their susceptibility to streptomycin, isoniazid, rifampicin, ethambutol (SIRE), and pyrazinamide by microscopic observation drug susceptibility (MODS) and BACTEC MGIT 960 methods. Evaluations were based on shorter turnaround periods, rapidity, ease of use, cost, etc. A comparative analysis was statistically expressed as kappa values. (3) Results: Endpoints for drug susceptibilities by MODS averaged 13 days (7–32), whilst that for BACTEC MGIT 960 was 10 days with a further 12 days to detect resistance. Therefore, a turnaround period of 22 days was needed for DST by BACTEC MGIT 960, compared to 13 days for MODS. There were differences in correlation levels between the two methods, as determined by their kappa values. (4) Conclusion: The MODS assay was found to be less costly, more user-friendly, and still able to be conveniently used at health centers located in rural areas known to be endemic for TB, particularly in Ghana. Full article

Here we investigate whether the presence of germinal vesicle-stage oocytes (GV− oocytes) reflects poor oocyte developmental competence (or quality). This was a prospective, non-randomised, cohort pilot-study involving 60 patients undergoing in vitro fertilization/ intracytoplasmic sperm injection for whom complete pregnancy outcome data were available. Patients in whom GV− oocytes were retrieved (GV+) at transvaginal oocyte retrieval (TVOR) were compared with those from whom no GVs were retrieved (GV−). We found that GV+ (n = 29) and GV− (n = 31) patients were similarly aged (35.4 vs. 36.4 years; p = 0.446). GV+ patients had a mean of 2.41 ± 2.03 GVs and comparable yields of MII oocytes to GV− patients (11 ± 6.88 vs. 8.26 ± 4.84; p = 0.077). Compared with GV− patients, GV+ patients had markedly lower implantation rates (11.8% vs. 30.2%; p = 0.022) as well as oocyte utilisation rates for clinical pregnancy (2.3% vs. 6.8%; p = 0.018) and live-birth (1.9% vs. 5.7%; p = 0.029). DNA damage levels measured using γH2AX immunostaining were not different in oocytes from women <36 years versus those ≥36 years (p = 0.606). Thus, patients who have GV− stage oocytes at TVOR exhibit poor oocyte quality reflected in reduced per-oocyte pregnancy success rates and uniformly high levels of oocyte DNA damage. Full article