MATURE TESTICULAR TERATOMA IN PEDIATRIC PATIENT: A CASE REPORT

Objective: To report our experience on management of testicular teratoma in pediatric patient. Case(s) presentation: A 2-years-old boy presented with progressive mass in his left testis. The mass was found 3 months ago but became larger in a few days. The patient had no other genitourinary complaint. Vital signs were within normal limits. A hard and tender mass in the left scrotum sized 5x4x2.5 cm was palpated from the physical examination. An imaging study with Computed Tomography (CT) Scan revealed an enhancement in the left scrotum mass area. There was no ring enhancement in pelvic and paraaortic lymph nodes. The laboratory examination within normal limit. Inguinal radical orchiectomy was performed, and histopathological examination revealed a mature testicular teratoma of the left testis. Discussion: Testicular teratoma in children is usually benign. Testicular germ cell tumors generally have a good prognosis with current therapy. Post-orchiectomy management depends on the histology type, staging, and tumor markers. Conclusion: Testicular teratoma is a rare case and can cause minimal symptoms until it grows significantly. Testicular teratoma should be considered in the differential diagnosis of non-traumatic painless progressive scrotal mass. Inguinal radical orchiectomy may be considered as the primary management.

LncRNAs and Rheumatoid Arthritis: From Identifying Mechanisms to Clinical Investigation

Rheumatoid arthritis (RA) is a systemic chronic autoinflammatory disease, and the synovial hyperplasia, pannus formation, articular cartilage damage and bone matrix destruction caused by immune system abnormalities are the main features of RA. The use of Disease Modifying Anti-Rheumatic Drugs (DMARDs) has achieved great advances in the therapy of RA. Yet there are still patients facing the problem of poor response to drug therapy or drug intolerance. Current therapy methods can only moderate RA progress, but cannot stop or reverse the damage it has caused. Recent studies have reported that there are a variety of long non-coding RNAs (LncRNAs) that have been implicated in mediating many aspects of RA. Understanding the mechanism of LncRNAs in RA is therefore critical for the development of new therapy strategies and prevention strategies. In this review, we systematically elucidate the biological roles and mechanisms of action of LncRNAs and their mechanisms of action in RA. Additionally, we also highlight the potential value of LncRNAs in the clinical diagnosis and therapy of RA.

The effectiveness of a fixed double combination (bisoprolol, perindopril) in patients with stable coronary artery disease and arterial hypertension different degrees

The aim – to evaluate the hypotensive and antianginal efficacy of a fixed double combination (bisoprolol, perindopril) in patients with coronary artery disease (CAD) and concomitant hypertension.Materials and methods. The study involved 170 cardiologists from various regions of Ukraine. Each researcher selected 15 consecutive outpatients with coronary heart disease who came for a regular visit. Inclusion criteria: age over 18 years old, blood pressure (BP) above 140/90 mm Hg, heart rate (HR) above 60 bpm, bisoprolol as part of antihypertensive therapy in the last ≥ 3 months. The study included two visits. At each visit, the patient’s objective status was assessed; an individual questionnaire with office systolic and diastolic blood pressure, heart rate, ECG data, clinical manifestations of CAD, risk factors, lifestyle features, concomitant diseases, current therapy was filled out. Medication adherence was also evaluated, the therapy was corrected if necessary and the presence of side effects and adverse events was registered. We analyzed the levels of BP and HR at the beginning and at the end of the study, the percentage of achievement of the recommended levels of these indicators, the antianginal efficacy of treatment and adherence to therapy in patients with CAD and different degrees of hypertension after 4 weeks of treatment.Results and discussion. 2785 patient questionnaires were provided by doctors, 1747 patients were included in substudy. The mean age of the patients was 60.9±10.2 years old, men – 57.1 %, women – 42.9 %. The diagnosis of coronary artery disease was based on: chest pain – 554 (31.7 %), a history of documented myocardial infarction – 935 (53.5 %), coronary ventriculography – 536 (30.7 %), revascularization (CABG/stenting) – 344 (19.8 %) patients. The use of a fixed combination of previously taken drugs (perindopril, bisoprolol) for 4 weeks allows to reduce heart rate and blood pressure effectively (HR ≤ 70 bpm reached 84.9 % of patients, BP ≤ 140/90 mm Hg – 86.9 %), to reduce the number of angina attacks (from 4.48, 4.5 and 4.7 per week at the beginning of the study to 2.4; 2.9 and 2.3 per week in patients with 1, 2 and 3 degrees of hypertension, respectively) and the need for nitroglycerin from from 4.5; 4.9 and 5.9 tab per week up to 2.4; 2.9 and 2.3 tab per week. The most significant absolute decrease of BP and HR was in patients with a more severe degree of hypertension (decrease systolic BP was – 40.8 mm Hg, diastolic BP – 21.4 mm Hg, HR – 21.8 bpm).Conclusions. The study demonstrated that the use of the fixed combination of bisoprolol and perindopril in patients with coronary artery disease and concomitant hypertension (different degrees) helps to improve treatment efficacy, to achieve recommended levels of blood pressure and heart rate, also has a significant antianginal effect (reliable decrease of the number of angina attacks and the need to take nitroglycerin) and increases adherence to therapy.

Establishment of a monoclonal antibody against human NTCP that blocks HBV infection

Hepatitis B virus (HBV) infects 240 million people worldwide. Current therapy profoundly suppresses HBV replication but requires long-term maintenance therapy. Therefore there is still a medical need for an efficient HBV cure. HBV enters host cells by binding via the preS1-domain of the viral L protein to the Na + /Taurocholate Cotransporting Polypeptide (NTCP). Thus, NTCP should be a key target for the development of anti-HBV therapeutics. Indeed, Myrcludex B, a synthetic form of the myristoylated preS1 peptide, effectively reduces HBV/HDV infection and has been approved as Hepcludex® in Europe for the treatment of patients with chronic hepatitis D virus (HDV) infection. We established a monoclonal antibody (mAb) N6HB426-20 that recognizes the extracellular domain of human NTCP and blocks HBV entry in vitro into human liver cells but has much less of an inhibitory effect on bile acid uptake. In vivo , administration of the N6HB426-20 mAb prevented HBV viremia for an extended period of time after HBV inoculation in a mouse model system without strongly inhibiting bile acid absorption. Among the extracellular loops (ECLs) of NTCP, regions of amino acids (aa) 84-87 in ECL1 and aa 157-165 near ECL2 of transmembrane domain 5 are critically important for HBV/HDV infection. Epitope-mapping and the 3D model of the NTCP structure suggested that the N6HB426-20 mAb may recognize aa 276/277 at the tip of ECL4 and interfere with an binding of HBV to the aa 84-87 region. In summary, we identified an in vivo neutralizing NTCP-targeting antibody capable of preventing HBV infection. Further improvements in efficacy of this drug will pave the way for its clinical applications. IMPORTANCE A number of entry inhibitors are being developed to enhance the treatment of HBV patients with oral nucleos(t)ide analogues (NA). To amplify the effectiveness of NA therapy, several efforts have been made to develop therapeutic mAbs with neutralizing activity against HBs antigens. However, the neutralizing effect of these mAbs may be muted by a large excess of HBsAg-positive noninfectious particles in the blood of infected patients. The advantage of NTCP-targeted HBV entry inhibitors is that they remain effective regardless of viral genotype, viral mutations and the presence of subviral particles. Although N6HB426-20 requires a higher dose than Myrcludex to obtain equivalent suppression of HBV in a model mouse system, it maintained the inhibitory effect for a long time post administration in proportion to the half-life of an IgG mAb. We believe that further improvements will make this antibody a promising treatment option for patients with chronic hepatitis B.

Risk of Suicidal Events in Youths Taking Atomoxetine Compared with Those on Methylphenidate; An Observational Cross-Sectional Study

Background: Stimulants such as methylphenidate and atomoxetine, a nonstimulant norepinephrine reuptake inhibitor, are approved for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Associations between the use of methylphenidate or atomoxetine with suicidal ideation and suicide-related behavior have been reported in the literature. The present study aimed to compare the effects of atomoxetine with that of methylphenidate on suicidal ideation and behavior in children and adolescents. Methods: Children and adolescents between 7 to 17 years of age with the diagnosis of ADHD, based on DSM-5 criteria, were included in this observational, cross sectional study. The suicidal ideation was assessed among children and adolescents who have been receiving either atomoxetine or methylphenidate for at least 12 months prior to entering the study. A Farsi version of Positive and Negative Suicide Ideation (PANSI) inventory was applied for the assessment. Differences among age groups, duration of therapy and comparison of positive and negative scores in both genders were analyzed using t-test. In addition, a one-way analysis of variance (ANOVA) was applied to examine the differences in positive and negative scores among different age groups. Moreover, chi-square and Fisher’s exact tests were performed to examine the effects of past history of drugs and other present illnesses on suicidal ideation. P-value of <0.05 was considered as significant. Results: A total of 57 students between 7 to 17 years of age were enrolled in this study. Twenty-eight patients have been taking atomoxetine at doses of 10 to 60 mg/day while 29 were on methylphenidate 7.50-55 mg/day. The mean positive and negative scores in the atomoxetine group were found to significantly differ (P=0.001) from those in the methylphenidate group. No risk of suicidal ideation was detected in the atomoxetine group, while in the methylphenidate group 15 out of 29 patients (51.7%) scored above the cutoff point. In terms of the relationship between suicidal ideation and history of other drugs prior to the current therapy and other concurrent disorders, chi-square test showed no significant difference in methylphenidate group (P=0.100 and 0.500 respectively). This analysis was not considered in atomoxetine group due to the absence of suicidal ideation. Conclusion: The authors of this study suggest that atomoxetine may be a safer choice than methylphenidate for the treatment of ADHD when suicidal ideation is a concern. In this regard, monitoring suicidal ideation and behavior along with family education should be considered in all children and adolescents suffering ADHD.

Breast Cancer Drug Repurposing a Tool for a Challenging Disease

Drug repurposing is one of the best strategy for drug discovery. There are several examples where drug repurposing has revolutionized the drug development process, such as metformin developed for diabetes and is now employed in polycystic ovarian syndrome. Drug repurposing against breast cancer is currently a hot topic to look upon. With the continued rise in breast cancer cases, there is a dire need for new therapies that can tackle it in a better way. There is a rise of resistance to current therapies, so drug repurposing might produce some lead candidates that may be promising to treat breast cancer. We will highlight the breast cancer molecular targets, currently available drugs, problems with current therapy, and some examples that might be promising to treat it.

Redox dyshomeostasis strategy for tumor therapy based on nanomaterials chemistry

This review summarizes the current progress of the redox dyshomeostasis (RDH) strategy for tumor therapy. This strategy makes tumor cells more sensitive to current therapy patterns through using nanomaterials to disrupt redox homeostasis.

Comparison Of Collagen-Curcumin Blend (Collaper Rtu)With Intralesional Steroid Injections in Oral Submucous Fibrosis a Randomized, Open-Label Interventional Study.

Introduction: Oral Submucous Fibrosis (OSMF) is a precancerous condition characterized by limited mouth opening, burning sensation, stiffness, and blanching of the oral mucosa induced by areca nut eating. With any of the current therapy regimens, complete regression of the illness has not been accomplished in all patients. Curcumin is a yellow pigment found in curry powder that has antioxidant, anti-inflammatory, and pro-apoptotic properties. As a result, interventional research was conducted to determine the efficacy of Collaper RTu a proprietary collagen-curcumin based product in patients with OSMF.Setting and design: Forty patients with clinically and histologically confirmed Oral Submucous Fibrosis participated in a randomized open label interventional research. Method & materials: For the research, forty patients with clinically and histologically verified Oral Submucous Fibrosis were randomly assigned to one of two groups. The first group was given a weekly intralesional injection of 4 mg Dexamethasone and 1500 I.U Hyaluronidase, whereas the second was given two Collagen-Curcumin pills (Collaper Rtu 60mg Collagen with 100 mg Curcumin) every day for three months. On a weekly basis, the improvement of burning sensation, interincisal distance, and tongue protrusion was assessed.Results: From early to late stages, the burning feeling improved in both groups. Collaper Rtu was found to eliminate the burning feeling. In groups 1 and 2, the mean increase in interincisal distance was 3.13 mm and 1.25 mm, respectively. The interincisal distance improved significantly in both groups by the end of the first month. When compared to group 2, group 1's tongue protrusion recovered faster at the conclusion of the first month. Conclusion: Collaper RTu is useful and effective in lowering the burning feeling in people with early OSMF.

Precision Therapy for Invasive Fungal Diseases

Invasive fungal infections (IFI) are a common infection-related cause of death in immunocompromised patients. Approximately 10 million people are at risk of developing invasive aspergillosis annually. Detailed study of the pharmacokinetics (PK) and pharmacodynamics (PD) of antifungal drugs has resulted in a better understanding of optimal regimens for populations, drug exposure targets for therapeutic drug monitoring, and establishing in vitro susceptibility breakpoints. Importantly, however, each is an example of a “one size fits all strategy”, where complex systems are reduced to a singularity that ensures antifungal therapy is administered safely and effectively at the level of a population. Clearly, such a notion serves most patients adequately but is completely counter to the covenant at the centre of the clinician–patient relationship, where each patient should know whether they are well-positioned to maximally benefit from an antifungal drug. This review discusses the current therapy of fungal infections and areas of future research to maximise the effectiveness of antifungal therapy at an individual level.