circRNAs (hsa_circ_00156, hsa_circ _000224, and hsa_circ _000520) are novel potential biomarkers in hepatocellular carcinoma.

Circular RNAs (circRNAs) are a newly validated type of noncoding RNAs recently found to be deregulated in several human cancers. More accurate and specific noninvasive biomarkers are strongly needed for better diagnosis and prognosis of hepatocellular carcinoma (HCC). We performed a bioinformatics analysis to retrieve a novel panel of circRNAs potentially relevant to HCC. We examined their expression in the sera of 68 patients with HCC, 60 patients with chronic hepatitis C, and 36 healthy controls using quantitative polymerase chain reaction. We examined the performance characteristics of the selected circRNA biomarker panel in comparison with alpha-fetoprotein (AFP). In addition, we performed a survival analysis to correlate between their expression levels and patient survival. The circRNAs hsa_circ _00224 and hsa_circ _00520 showed a strong biomarker potential with relatively high sensitivities and specificities compared with AFP. The combined panel including the three circRNAs showed superior performance characteristics relative to those of AFP. The median follow-up period was 26 months. hsa_circ_00520 expression has been shown to be associated with relapse-free survival (P < 0.005). circRNAs hsa_circ_00156, hsa_circ_000224, and hsa_circ_000520 are novel potential biomarkers of high sensitivity and specificity, which could potentially be used in the diagnosis of HCC.

Nootkatone Mitigated Melamine-Evoked Hepatotoxicity by Featuring Oxidative Stress and Inflammation Interconnected Mechanisms: In Vivo and In Silico Approaches.

Melamine (ML) is a common environmental contaminant, commonly used in food fraud, representing a serious health hazard and jeopardizing human and animal health. Recently, nootkatone (NK), a naturally occurring sesquiterpenoid, has garnered considerable attention due to its potential therapeutic advantages. We investigated the potential mechanisms underlying the protective effects of NK against ML-induced liver injury in rats. Five groups were utilized: control, ML, NK10, ML-NK5, and ML-NK10. ML induced substantial hepatotoxicity, including considerable alterations in biochemical parameters and histology. The oxidative distress triggered by ML increased the generation of malondialdehyde (MDA) and nitric oxide (NO) and decreased levels of reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. In addition, decreased expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and increased nuclear factor kappa beta (NF-κB) expression levels were observed in hepatocytes, which indicated the occurrence of inflammatory changes following ML exposure. These alterations were alleviated by NK supplementation in a dose-dependent manner. The data revealed that the favorable effects of NK were attributed, at least in part, to its antioxidant and anti-inflammatory properties. Moreover, our results were supported by molecular docking studies that revealed a good fit and interactions between NK and antioxidant enzymes. Thus, the current study demonstrated that NK is a potential new food additive for the prevention or treatment of ML-induced toxicity.

Molecular Epidemiology and Genetic Diversity of the Enteric Protozoan Parasite Blastocystis sp. in the Northern Egypt Population.

Blastocystis sp. is currently reported as the most frequent single-celled eukaryote inhabiting the intestinal tract of humans and a wide range of animal groups. Its prevalence is especially higher in developing countries linked with fecal peril. Despite a growing interest in this enteric protozoan, certain geographical regions potentially at high risk of infection, such as North Africa, remain under-investigated. Therefore, a large-scale molecular epidemiological survey, including 825 participants presenting digestive disorders or not, was conducted in five governorates located in Northern Egypt. A real-time polymerase chain reaction (qPCR) assay was performed to identify the parasite in stool samples, followed by direct sequencing of the positive PCR products for subtyping and genotyping of the corresponding isolates. The overall prevalence was shown to reach 72.4% in the Egyptian cohort, coupled with a variable frequency depending on the governorate (41.3 to 100%). Among the 597 positive participants, a large proportion of them (39.4%) presented mixed infections, as determined by sequencing. The remaining individuals with single infection were predominantly colonized by subtype 3 (ST3) (48.3%) followed by ST1 (39.5%), ST2 (10.8%), ST14 (1.1%), and ST10 (0.3%). This was the first report of ST10 and ST14 in North Africa. Age, sex, digestive symptoms, and health status of the participants or contact with animals were not identified as significant risk factors for Blastocystis sp. occurrence or affecting the ST distribution. In contrast, substantial variations in the prevalence and ST distribution of the parasite were reported according to the governorate. Genotyping of isolates revealed the lower intra-ST diversity for ST3, followed by ST1 and then ST2. By combining subtyping and genotyping data, a widespread inter-human transmission was strongly suggested for ST3 within the Egyptian cohort. Regarding ST1 and ST2, additional animal or environmental sources of infection by these STs have been proposed, whereas the few cases of colonization by ST10 and ST14 were likely the result of zoonotic transmission from bovid. These investigations clearly emphasized the active circulation of Blastocystis sp. in Northern Egypt and the necessity for health authorities to implement prevention campaigns towards the population and quality control of drinking water, with the aim of reducing the burden of this enteric protozoan in this endemic country.

Effect of docosahexaenoic acid as a chemopreventive agent on experimentally induced hamster buccal pouch carcinogenesis.

PURPOSE: The current study was directed to investigate the effectiveness of docosahexaenoic acid (DHA) as a chemopreventive agent on experimentally induced hamster buccal pouch (HBP) carcinogenesis. MATERIAL AND METHODS: In this study we used 40 Syrian male hamsters, five weeks old, were divided into 4 groups (GI, GII, GIII, and GIV) of 10 animals in each as follows, GI: Topical application of liquid paraffin alone (thrice a week for 14 weeks), GII: Topical application of 7, 12 dimethyl benz[a]anthracene (DMBA) alone (0.5% in liquid paraffin, thrice a week for 14 weeks), GIII: Topical application of DMBA (0.5% in liquid paraffin, thrice a week for 14 weeks) + Oral administration of DHA (125 mg/kg b.w. in 1 ml distilled water by oral gavage, thrice a week for 14 weeks on alternative days of DMBA application), GIV: Oral administration of DHA alone (125 mg/kg b.w. in 1 ml distilled water by oral gavage, thrice a week for 14 weeks). RESULTS: Gross observations and histopathological findings revealed that, in GI: normal stratified squamous epithelium, in GII: well and moderately differentiated squamous cell carcinoma (SCC), in GIII: variable results ranges from hyperkeratosis, hyperkeratosis and focal hyperplasia, mild dysplasia, and well differentiated SCC with superficial invasion of tumor cells not extended to deeper areas, while in GIV: normal similar to GI. Immunohistochemical results indicated that oral DHA treatment to DMBA treated hamsters restored the normal expression of bcl-2. CONCLUSION: Our results indicated that DHA has the potential to be a dietary chemopreventive agent due to its capacity to improve carcinogen detoxification and to block/suppress the initiation and promotion stages of experimentally produced HBP carcinogenesis.

Histological and immunohistochemical study of brain damage in traumatic brain injuries in children, depending on the survival period.

Numerous studies showed that, at present, traumatic brain injury (TBI) is one of the main causes of death in young adults, but also a main cause of disabilities at all ages. For these reasons, TBI are continuously investigated. In our study, we evaluated the histopathological (HP) and immunohistochemical (IHC) changes that occurred in the brain in underage patients after a severe TBI depending on the survival period. We histopathologically and immunohistochemically analyzed a number of 22 cases of children, deceased in Dolj County, Romania, following some severe TBI, undergoing autopsy within the Institute of Forensic Medicine in Craiova between 2015-2020. Patients were divided into three groups depending on the survival period, namely: (i) patients who died during the first 24 hours of the accident; (ii) patients who died after seven days of survival; (iii) patients who died after 15 days of survival. Microscopic examinations of the brain fragments, collected during the necropsy examination, showed that the traumatic agent caused primary injuries in all brain structures (cerebral parenchyma, meninges, blood vessels). However, HP injuries ranged in size and intensity from one area to another of the brain. In patients with a longer survival period, there was observed the presence of smaller primary injuries and larger secondary injuries. There was also observed a growth in the number of meningo-cerebral microscopic injuries, depending on the increase of the survival period.

Hyperosmotic Stress Induces a Specific Pattern for Stress Granule Formation in Human-Induced Pluripotent Stem Cells.

Stress granules (SGs) are assemblies of selective messenger RNAs (mRNAs), translation factors, and RNA-binding proteins in small untranslated messenger ribonucleoprotein (mRNP) complexes in the cytoplasm. Evidence indicates that different types of cells have shown different mechanisms to respond to stress and the formation of SGs. In the present work, we investigated how human-induced pluripotent stem cells (hiPSCs/IMR90-1) overcome hyperosmotic stress compared to a cell line that does not harbor pluripotent characteristics (SH-SY5Y cell line). Gradient concentrations of NaCl showed a different pattern of SG formation between hiPSCs/IMR90-1 and the nonpluripotent cell line SH-SY5Y. Other pluripotent stem cell lines (hiPSCs/CRTD5 and hESCs/H9 (human embryonic stem cell line)) as well as nonpluripotent cell lines (BHK-21 and MCF-7) were used to confirm this phenomenon. Moreover, the formation of hyperosmotic SGs in hiPSCs/IMR90-1 was independent of eIF2α phosphorylation and was associated with low apoptosis levels. In addition, a comprehensive proteomics analysis was performed to identify proteins involved in regulating this specific pattern of hyperosmotic SG formation in hiPSCs/IMR90-1. We found possible implications of microtubule organization on the response to hyperosmotic stress in hiPSCs/IMR90-1. We have also unveiled a reduced expression of tubulin that may protect cells against hyperosmolarity stress while inhibiting SG formation without affecting stem cell self-renewal and pluripotency. Our observations may provide a possible cellular mechanism to better understand SG dynamics in pluripotent stem cells.

Bimalleolar pathological fracture in a patient with chronic tophaceous gout.

Gout is one of the most common types of inflammatory arthritis. Four stages have been described in its evolution: asymptomatic hyperuricemia, acute gouty arthritis, intercritical gout and chronic tophaceous gout. Monosodium urate crystals deposits are more frequently encountered in hyaline cartilage, tendon sheaths, articular bursae, bone epiphysis, synovium, and skin. Pathological fractures that occur at the formation sites of gout tophi have been rarely described in gout. Bimalleolar fractures often occur following a trauma. We present the case of a 56-year-old patient, diagnosed with chronic gout for over 12 years, with tophi in the upper and lower limbs, who presented accusing mechanical pain in the left tibio-tarsal joint and impaired function of the hands. The clinical examination showed bilateral multiple destructive gout tophi in the hands, forearms, elbows, feet, ankles, and lower legs, while the left ankle exhibited an important varus deformity. Computed tomography examination of the left ankle showed multiple gout tophi with bone erosions and a bimalleolar pathological fracture. The patient underwent pharmacological treatment, physical therapy and the ankle was immobilized in a knee-ankle-foot orthosis, with subsequent orthopedic surgical treatment for fracture fixation, to improve functional status. We have chosen to present this case given the multiple disabilities of the patient, which have improved following the rehabilitation treatment.

Epidemiology of geriatric syndromes among older people residing in six old-age homes of Delhi-NCR.

Introduction: The frequency of geriatric syndromes (GSs) such as cognitive impairment (CI), depression, and malnutrition among older people residing in old-age homes (OAHs) of Delhi-National Capital Territory Region (NCR) has not been reported. The availability of such data determines the quality of health care. The present study aims to assess the frequency of GS among residents of six OAHs in Delhi-NCR. Materials and Methods: The study was carried out after obtaining informed written consent from all participants. The team comprising doctors, physiotherapists, and nurses visited the OAHs and assessed GSs using a psychometrically validated screening tool ICT-BRIEF 30. Other standard tools such as Snellen's chart, whisper voice test, mini nutritional assessment, time up and go test score, Mini-Cog, and geriatric depression scale 5 were used to assess vision, hearing, nutrition, mobility, cognition, and mood, respectively. Results: Out of 131 participants, low vision was observed in 69.47%, hearing impairment in 20.61%, malnutrition in 12.9%, risk of fall in 18.32%, CI in 46.56%, and depression in 62.59% of the participants. Hearing impairment was found to be significantly associated with quality of life and cognition. Conclusion: The present study from Delhi showed high frequency of vision impairment, CI, frailty, depression, and malnutrition in older people residing in OAHs. 20% of the participants had functional loss due to various reasons. Hence, the owner/caretaker of OAHs of Delhi/NCR needs to be proactive in screening the residents for various GSs to provide quality care to the residents.

Cardiac Hemodynamics and Slight Regression of Left Ventricular Mass Index in a Group of Hemodialysed Patients.

Chronic kidney disease (CKD) is a major health problem and has a growing prevalence in Romania and worldwide. The concept of chronic kidney disease (CKD) is defined by abnormal kidney function and/or structure persisting for more than 3 months, influencing patients health. Patients with chronic kidney disease have a 20-30 times greater risk for cardiovascular morbidity and mortality than similar individuals without chronic kidney disease. We conducted a prospective observational study that included 33 patients on hemodialysis. All patients were performing hemodialysis for at least 6 months, 3 sessions per week at a private Haemodialysis Centre in Craiova. Left ventricular hypertrophy has a high prevalence in dialysis patients and increased left ventricular mass index (LVMI) is a major cardiovascular risk factor. We concluded that concentric and eccentric ventricular hypertrophy are present simultaneously in hemodialysis patients, LVH regression is possible, but requires an interventional approach on cardiovascular risk factors (anemia, blood pressure, secondary hyperparathyroidism) in hemodialysis patients, patients on dialysis with a higher fistula flow, over 1170ml/min have heart failure, and the fistula's constant increased flow is a risk factor for heart failure with a high flow.

Managing Low Back Pain in Primary Care.

Low back pain (LBP) is one of the most common pathologies for which patients present for consultation in primary medical practice. The objective of the study was to determine the number of patients with LBP who presented to the general practitioner 's (GP) office between October 2019 and March 2020, to determine risk factors, favoring factors and their correlation with clinical data obtained after performing the clinical examination, with paraclinical data obtained by imaging investigation. 347 patients, aged between 17 and 82 years, were included in the study, presenting a sex ratio of men: women of approximately 2: 1. The main pain symptoms of the patients were: localized pain in the lumbar spine, radicular pain, referred to the lower limbs, subjective sensitivity disorders felt in the lower limbs, distal motor deficit in the lower limbs, paravertebral muscle contractions and the feeling of instability in the low back. The main risk factors were smoking, the existence of a trauma to the lumbar spine, sedentary lifestyle, maintaining a prolonged fixed position and intense physical exercise, either occasionally or daily. Among the patients included in the study, a number of 93 patients required the granting of medical leave both by the attending GP and by other specialists. Regardless of the etiology and pathophysiological mechanisms involved in the occurrence of LBP, therapeutic management should aim to stop pain symptoms and prevent recurrences.

Severe traumatic brain injury (TBI) - a seven-year comparative study in a Department of Forensic Medicine.

Deaths caused by traumatic brain injury (TBI) increase in incidence every year worldwidely, mainly in developing countries. Thus, World Health Organization (WHO) estimates that in 2020, TBI will become the third main cause of death. In our study, we evaluated the deaths caused by TBI recorded within the Institute of Forensic Medicine of Craiova, Romania, between 2011 and 2017. Therefore, according to age, the cases were divided into two groups: people aged 0-18 years old (including 18 years old) and people aged over 18 years old (a total of 1005 cases, of which 971 were adults and 34 included in the age group 0-18 years old). In both groups, most patients were males from the rural area. In adults, falling was the main legal entity of the cases, followed by car accidents (which were the most common in children). In both groups, in car accidents, most of them were pedestrians and car occupants. Various aggressions (human, animal, self-injury) were found in 94 (9.68%) of the adult cases and in four (11.76%) cases of children. Another parameter under study was the blood alcohol concentration, being observed that most of the subjects with positive blood alcohol content died from car accidents. By evaluating the Glasgow Coma Scale (GCS) score as a prognostic factor, most of the subjects presented third and fourth degree coma at admission; still, 5.14% of the adult patients who deceased had GCS score 15 at admission, death occurring probably by developing some intracranial hematomas in time. Regarding the morphology of the lesions, most patients presented various forms of cranial fractures, 185 (19.05%) adults in association with extradural hemorrhages∕hematomas, but also there were four cases with extradural hematomas without any cranial fractures. In children, there was highlighted a single case of extradural hemorrhage under the fracture line. Seventy-eight percent of the adults and 44.12% of children presented subdural hematomas associated with other meningo-cerebral lesions. Also, 83.63% of the adults and 97% of children presented brain contusions. In both groups, brain laceration was observed in approximately 50% of the cases.

Potential Toxic Effect of Bisphenol A on the Cardiac Muscle of Adult Rat and the Possible Protective Effect of Omega-3: A Histological and Immunohistochemical Study.

Bisphenol A (BPA) is intensely used in the production of polycarbonate plastics and epoxy resins. Recently, BPA has been receiving increased attention due to its link to various health problems that develop after direct or indirect human exposure. Previous studies have shown the harmful effect of high doses of BPA; however, the effect of small doses of BPA on disease development is controversial. The aim of this study was to investigate the effect of a low dose of BPA on the rat myocardium and to explore the outcome of coadministration of Omega-3 fatty acid (FA). Thirty adult male rats were divided equally into control group, BPA-treated group (1.2 mg/kg/day, intraperitoneally for 3 weeks), and BPA and Omega-3-treated group (received BPA as before plus Omega-3 at a daily dose of 300 mg/kg/day orally) for 3 weeks. Exposure to BPA resulted in structural anomalies in the rat myocardium in the form of disarrangement of myofibers, hypertrophy of myocytes, myocardial fibrosis, and dilatation of intramyocardial arterioles. On the other hand, mast cell density and media-to-lumen area ratio were not significantly altered. Interestingly, concomitant administration of Omega-3 FAs with BPA significantly reduced BPA-induced changes and provided a protective effect to the myocardium. In conclusion, exposure to a low dose of BPA could potentially lead to pathological alterations in the myocardium, which could be prevented by administration of Omega-3 FA.

Frostbite arthropathy - a rare case of osteoarthritis, review of the literature and case presentation.

Frostbite affects more commonly the northern population then it was suspected earlier, but wherever cold winter occurs, cold caused lesions are reported. Most often, it is described as soft tissue lesions, but deeper structures like tendons, ligaments, muscles, cartilage or bones can be affected. All extremities can be involved; lesions can lead to necrosis and amputations. First documented cases were described during military actions, but occupational or recreational activities can also be a risk factor for frostbite. Frozen or frostbite arthropathy is a rare cause of osteoarthritis. Usually, arthritis appears after a long time after frostbite, it can be decades apart. Frostbite arthropathy can result in different debilitating conditions. The current review describes the most important changes in frostbite and a rare but very serious late complication, which lead to arthropathy.

Complex evaluation in patients with knee osteoarthritis.

Knee osteoarthritis (KOA) is a very common, slowly progressive and incurable articular disease resulting in the breakdown of cartilage and bone in the joint, which causes significant discomfort, pain and disability, with a significant socio-economic impact. The aim of our observational study for patients with symptomatic KOA was to investigate the changes of C-terminal telopeptide of type II collagen (CTX-II) in serum pre and post a complex rehabilitation program and to establish the correlation between all studied parameters [clinical, functional, serum CTX-II (sCTX-II) and histological aspects obtained through arthroscopy]. During 2016-2017, we performed an observational study including 24 patients, between 59 and 76 years old, diagnosed with KOA. Studied patients were completely assessed before (T1) and four months after a complex rehabilitation program (T2). The measured parameters were stiffness, pain, and physical function and we used the Visual Analogue Scale (VAS) for pain, with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), sCTX-II value obtained by enzyme-linked immunosorbent assay (ELISA) test, histological assessment of knee cartilage after arthroscopy. In the histological assessment of our patients, we observed that the cells of the superficial areas were round and hypertrophic, the cartilage tissue had few proteoaminoglycans and glycosaminoglycans, with an airy aspect of the matrix and degenerate cells, numerically reduced. After positive diagnosis, the complete treatment, including the rehabilitation program, seems to be the ideal option for improving the CTX-II values, as well as the quality of life in KOA patients.

Immunohistochemical analysis of bone metabolism in osteonecrosis of the femoral head.

Osteonecrosis of the femoral head occurs because of the suppression of blood circulation. At the level of the area affected by the ischemic phenomenon, there are two types of events, in the first stage there is necrosis of the cellular elements, followed by a reparatory phase of the spongy bone tissue. The objective of the study was the histological and immunohistochemical (IHC) analysis of bone metabolism in the repair phase. We observed the action of the main cells involved in the remodeling, the osteoblasts and the osteoclasts, following the reaction of the markers of their activity: osteoprotegerin, osteonectin, osteopontin. We included 23 patients diagnosed with femoral head osteonecrosis, stage II, Ficat and Arlet classification, biological material required for histological and IHC analysis being obtained during hip arthroplasty. Regardless of the age or presence of risk factors, the reaction to osteoprotegerin was mildly positive, being only highlighted at the level of the reactive dividing line, being absent in the other areas, indicating a reduced activity of inhibiting differentiation and activation of osteoclasts, also highlighted with classical histology methods, the affected area being well-defined and we could observe the necrotic tissue resorption by osteoclasts. The intense positive reaction of osteopontin and osteonectin, especially at the line of demarcation, is due to the increase in the number of osteoblasts required for the synthesis of neoformation bone tissue. We believe that the aspects revealed by our study can be a track in finding new-targeted therapies useful in stopping the development of the disease.

Hand enchondroma - complete evaluation and rehabilitation.

Enchondroma, the most frequently reported primary tumor in the long bones of the hand, is a common benign cartilaginous tumor, defined more exactly as a benign mature hyaline cartilaginous tumor that is located into the medullar space of the tubular bones. Between 2012 and 2018, we performed an observational study on six patients (two males and four females), aged 16 to 49 years old (mean 29.5 years), who were diagnosed during routine physical examinations with isolated enchondroma in their hand. The tumor was more frequently located in their proximal phalanges (four patients), while two patients had middle phalange tumors. The most common digit involved was the little finger (five patients), followed by the ring finger (one patient). The symptoms, which prompted surgical interventions, were: enlargement without fracture (two patients), pain or limitation of mobility (four patients), pain without pathological fracture (six patients). Studied patients were completely assessed before the treatment program (surgical intervention and rehabilitation program). The measured parameters and scales used were Visual Analogue Scale (VAS), Health Assessment Questionnaire (HAQ) scale for functional status and histological exam. For both VAS and HAQ, we observed a statistically significant difference between the initial and final evaluations, with p=0.03 and p=0.035, respectively. Histological assessment and differential diagnosis are essential for the post-surgical treatment and rehabilitation program.

Emerging role of nutrition and the non-coding landscape in type 2 diabetes mellitus: A review of literature.

With the advent of recent advances in molecular techniques and whole genome sequencing, we have come to know that the non-coding landscape (including non-coding RNAs, tRNAs and even telomeres) plays a major role in the regulation of cellular processes. Furthermore, the deregulation of this landscape has been found to contribute to and even bring about the pathogenesis of a large number of diseases. One of such diseases is diabetes mellitus (type 2 specifically) whose incidence rate and global burden is constantly increasing. Nutrition has been proven to be a key player in the development, onset and control of type 2 diabetes mellitus. Additionally, non-coding DNA based molecular markers are emerging as biomarkers of T2D, susceptibility, and perhaps dietary supplements can modulate non-coding DNA based markers expression and function in T2D management. In this review, we provide a brief overview of the developmental origins and genetics of type 2 diabetes mellitus, how each component of the non-coding landscape contributes to the development and progression of the disease and finally we discuss how dietary interventions modulate the non-coding landscape in T2D.

A morpho-functional study using PEP/LVET ratio and global longitudinal strain in patients with dilated cardiomyopathy.

AIM: To assess left ventricular (LV) systolic function and morphology in patients with severe dilated cardiomyopathy (DCM), using both conventional and a complex technique, speckle-tracking echocardiography, and evaluate the correlation between pre-ejection period and left ventricular ejection period (PEP/LVET) ratio, global longitudinal strain (GLS), and severity of the condition. PATIENTS, MATERIALS AND METHODS: Seventeen patients were enrolled after rigorous criteria. Echocardiography was performed in conventional and speckle-tracking mode, in all patients with DCM, in sinus rhythm. LV dimensions, volumes and ejection fraction (LVEF) were measured. PEP/LVET ratio was obtained from apical 5-chamber axis and was defined as the time between QRS onset and LV ejection reported to LV ejection period. Speckle-tracking imaging was performed in offline mode and GLS was obtained from parasternal 4-, 3-, 2-chamber apical view, by averaging longitudinal peak systolic strain of all 17 LV-segments. RESULTS: New York Heart Association (NYHA) functional class correlated significantly with LVEF (-0.82; p=0.0006), PEP/LVET (0.86; p=0.001) or GLS (0.85; p=0.0002). Considerable correlations were between mitral regurgitation (MR) severity and LVEF (-0.65; p=0.01) or PEP/LVET (0.69; p=0.0059), but higher were between MR severity and GLS (0.76; p=0.0018). Tricuspid regurgitation (TR) grading correlated statistically with LVEF (-0.62; p=0.01), PEP/LVET and GLS (0.6; p=0.018; and 0.62; p=0.014, respectively). As opposed to the parameters in conventional echocardiography, GLS correlated with DCM etiology (p=0.0046) and with the gender (p=0.048). CONCLUSIONS: This study demonstrates that, in patients with DCM, assessment of cardiac dyssynchrony can be accurately accomplished by combining parameters in conventional and in speckle-tracking echocardiography.

Epigenetic regulation of immune checkpoints: another target for cancer immunotherapy?

Epigenetic changes in oncogenes and tumor-suppressor genes contribute to carcinogenesis. Understanding the epigenetic and genetic components of tumor immune evasion is crucial. Few cancer genetic mutations have been linked to direct correlations with immune evasion. Studies on the epigenetic modulation of the immune checkpoints have revealed a critical interaction between epigenetic and immune modulation. Epigenetic modifiers can activate many silenced genes. Some of them are immune checkpoints regulators that turn on immune responses and others turn them off resulting in immune evasion. Many forms of epigenetic inheritance mechanisms may play a role in regulation of immune checkpoints including: covalent modifications, noncoding RNA and histone modifications. In this review, we will show how the potential interaction between epigenetic and immune modulation may lead to new approaches for specific epigenome/immunome-targeted therapies for cancer.

Clinical importance of pharmacogenetics in the treatment of hepatitis C virus infection.

Globally, over 4% of the world population is affected by hepatitis C virus (HCV) infection. The current standard of care for hepatitis C infection is combination therapy with pegylated interferon and ribavirin for 48 weeks, which yield a sustained virological response in only a little over half of the patients with genotype 1 HCV. We investigated the clinical importance of pharmacogenetics in treatment efficacy and prediction of hematotoxicity. A total of 148 patients infected with HCV were enrolled. All patients were treated for a period of 48 weeks or less with pegylated interferon and ribavirin. Four genotypes were investigated: inosine triphosphatase (ITPA) rs1127354, C20orf194 rs6051702, interferon lambda (IFNL)3 rs8099917, IFNL3÷4 rs12979860 in the population from southwestern Romania. Genetic variants for rs129798660 and rs6051702 proved once more to represent an indisputable clinical tool for predicting sustained virological response (SVR) (69.23%, chi-square p=0.007846, p<0.05 and 63.29%, chi-square p=0.007846, p<0.05, respectively). ITPA genetic variants protect against ribavirin-induced hemolytic anemia and C20orf194 also proved to be protective against thrombocytopenia. These clinical findings strengthen the belief that pharmacogenetics should play a constant role in treatment decisions for patients infected with hepatitis C virus.