Prevalence of Hearing Loss in Type 2 Diabetes Mellitus and Its Association with Severity of Diabetic Neuropathy

Purpose This study assessed the prevalence of hearing loss (HL) in patients with Type 2 Diabetes (T2DM) and its relationship with the presence and severity of diabetic neuropathy. Methods Patients between the ages of 30 to 60 years (both ages inclusive) with T2DM were recruited and divided into three groups. Group 1 included patients without neuropathy. Group 2 had patients with mild neuropathy. Group 3 had patients with moderate and severe neuropathy. After informed consent hearing threshold was assessed using pure tone audiometry (PTA). Results Of the 200 patients recruited, the prevalence of hearing loss was overall 81%. The prevalence was 66.7% in group 1, 80.9% in group 2 and 87.6% in group 3 (p=0.009). Among patients with moderate to severe neuropathy (group 3) 33.3% had clinically significant hearing loss (p=0.015). Age, gender, presence of neuropathy and severity of neuropathy were associated with increased risk of developing hearing loss. Severity of hearing loss worsened with increase in severity of neuropathy. Conclusions Age, gender and severity of neuropathy were associated with increased risk of developing hearing loss. Screening for hearing loss in patients with moderate to severe diabetic neuropathy using self-report questionnaires can help in timely diagnosis and treatment.

Cellular Prion Protein Is Essential for Myocardial Regeneration but Not the Recovery of Left Ventricular Function from Apical Ballooning

This study tested the hypothesis that cellular prion protein (PrPC) played an essential role in myocardial regeneration and recovery of left ventricular ejection fraction (LVEF) from apical takotsubo cardiomyopathy (TCM) induced by transaortic constriction (TAC). In vitro study was categorized into G1 (H9C2), G2 (H9C2-overexpression-PrPC), G3 (H9C2-overexpression-PrPC + Stelazine/1 uM), and G4 (H9C2 + siRNA-PrPC), respectively. The results showed that the protein expressions of PrPC, cell-stress signaling (p-PI3K/p-Akt/p-m-TOR) and signal transduction pathway for cell proliferation/division (RAS/c-RAF/p-MEK/p-ERK1/2) were lowest in G1, highest in G2, significantly higher in G3 than in G4 (all p < 0.001). Adult-male B6 mice (n = 30) were equally categorized in group 1 (sham-control), group 2 (TAC) for 14 days, then relieved the knot and administered BrdU (50 ug/kg/intravenously/q.6.h for two times from day-14 after TAC) and group 3 (TAC + Stelazine/20 mg/kg/day since day 7 after TAC up to day 21 + BrdU administered as group 2), and animals were euthanized at day 28. The results showed that by day 28, the LVEF was significantly higher in group 1 than in groups 2/3 and significantly higher in group 3 than in group 2, whereas the LV chamber size exhibited an opposite pattern of LVEF (all p < 0.0001). The protein expressions of PrPC/p-PI3K/p-Akt/p-m-TOR/cyclin D/cyclin E and cellular-proliferation biomarkers (Ki67/PCNA/BrdU) exhibited an opposite pattern of LVEF (all p < 0.0001) among the three groups, whereas the protein expressions of RAS/c-RAF/p-MEK/p-ERK1/2 were significantly and progressively increased from groups 1 to 3 (all p < 0.0001). In conclusion, PrPC participated in regulating the intrinsic response of cell-stress signaling and myocardial regeneration but did not offer significant benefit on recovery of the heart function in the setting of TCM.

Effect of cogon grass root ethanol extract on fatty acid binding protein 4 and oxidative stress markers in a sepsis mouse model

Background: Sepsis causes several immunological and metabolic alterations that induce oxidative stress. The modulation of fatty acid-binding protein 4 (FABP4) has been shown to worsen this condition. Extract of cogon grass root (ECGR) contains flavonoids and isoeugenol compounds that exhibit anti-inflammatory and antioxidant properties. This study aimed to assess the effects of ECGR on FABP4 and oxidative stress–related factors in a sepsis mouse model. Methods: Twenty-nine male mice (Mus musculus) of the Deutsche Denken Yoken strain were divided into four groups: group 1, control; group 2, mice treated with 10 μL/kg body weight (BW) lipopolysaccharide (LPS); and groups 3 and 4, mice pre-treated with 90 and 115 mg/kg BW, respectively, and then treated with 10 μL/kg BW LPS for 14 d. Blood, liver, lymph, and cardiac tissue samples were collected and subjected to histological and complete blood examinations. Antioxidant (Glutathione peroxidase 3 (GPx3) and superoxide dismutase), FABP4 levels, and immune system-associated biomarker levels (TNF-α, IL-6 and IL-1β ) were measured. Results: Significant increases in platelet levels (p = 0.03), cardiomyocyte counts (p =0.004), and hepatocyte counts (p = 0.0004) were observed in group 4 compared with those in group 2. Conversely, compared with those in group 2, there were significant decreases in TNF-α expression in group 3 (p = 0.004), white pulp length and width in group 4 (p = 0.001), FABP4 levels in groups 3 and 4 (p = 0.015 and p = 0.012, respectively), lymphocyte counts in group 4 (p = 0.009), and monocyte counts (p = 0.000) and polymorphonuclear cell counts in the livers (p = 0.000) and hearts (p = 0.000) of groups 3 and 4. GPx3 activity was significantly higher in group 3 than in group 1 (p = 0.04). Conclusions: ECGR reduces FABP4 level and modulating oxidative stress markers in sepsis mouse model.

Evaluating the blood toxicity of functionalized graphene-arginine with anticancer drug ginsenoside Rh2 in balb/c mouse model with breast cancer

Background: Gensenoside Rh2 is an anticancer drug with low toxicity and stability in the body. The aim of this study was to evaluate the blood toxicity of functionalized graphene-arginine with anticancer drug ginsenoside Rh2 in balb/c mouse model with breast cancer. Materials and Methods: Graphene-Arginine (G-Arg) and Graphene-Arginine-ginsenoside Rh2 (G-Arg-Rh2) were synthesized using microwave method. For evaluation of blood toxicity, 32 mice with breast tumors were randomly divided into 4 groups: control (3mg/kg 6 mg / kg PBS sterile), group 1 (6 mg / kg ginsenoside), group 2 (3 mg / kg G-Arg), and group 3 (3 mg / kg G-Arg-Rh2). Treatment was done intravenously once every three days for 32 days. Finally, blood factors were also examined by sampling from the heart. Results: Complete functionalization was proven by FTIR and Raman. Examination of blood factors showed that white blood cells had a very small increase. Anova test showed significant difference among four groups in term of WBC count (p=0.016). Pair sample T test showed that there was significant difference between control and group 1(p=0.036) and control and group 2 (p=0.036). There was no significant difference between control and group 3 (p=0.051). Other blood factors had no significant difference among examined groups (p>0.05). Conclusion: Based on results, after treatment with all designed nanostructures, only white blood cells had a very small increase and inflammatory reactions were statistically similar in all groups. This indicates the high efficiency of designed drug.

Recombinant Human Interferon-Gamma: Prospects for the Treatment of Chronic Epstein-Barr Viral Infection

Infection of Epstein-Barr virus (EBV) is about 90% among people over the age of 40. The EBV causes a chronic infection that is characterized by chronic or recurrent symptoms and persists for a long time. Recombinant interferon-gamma (IFN-γ) has high clinical and antiviral efficacy in the treatment of herpesvirus infections. 110 patients with chronic EBV infection were examined. The patients were divided into three groups for different treatment regimens: Group 1—IFN-γ therapy (15 injections of Ingaron i/m, 500,000 IU every other day); Group 2—valaciclovir (Valtrex 500 mg × 2 times/day, orally for 2 months); Group 3—valganciclovir (Valcyte 450 mg × 2 times/day, orally for 2 months) and IFN-γ (10–20 injections of Ingaron i/m, 500,000 IU every other day). The best results were obtained in group 3–73.07% negative PCR. In this group, the combination of valganciclovir + IFN-γ was different. We showed that the efficacy of therapy in patients with chronic EBV is determined by the duration of INF-γ administration. We also determined spontaneous and induced production of IFN-α and -γ cytokines in serum and in lymphocyte culture. We demonstrated that in patients with an initially low level of induced IFN-γ, the production of this cytokine significantly increased in three months after the end of therapy.

Dimethylarginines in Children after Anti-Neoplastic Treatment

Background and Objectives: According to a recent Cochrane systematic review, renal impairment can develop in 0–84% of childhood cancer survivors in the future. The renal function impairment in this patient group can be related to nephrectomy, nephrotoxic agents therapy, abdominal radiotherapy, and combinations of these treatment methods. In this study, in a population of patients after anti-neoplastic therapy, with particular emphasis on patients after Wilms’ tumour treatment, we compared new substances which play role in the chronic kidney disease (CKD) pathogenesis (asymmetric dimethylarginine—ADMA, symmetric dimethylarginine—SDMA) with standard renal function markers (e.g., creatinine and cystatin C in serum, creatinine in urine, etc.) to assess the usefulness of the former. Materials and Methods: Eighty-four children, without CKD, bilateral kidney tumours, congenital kidney defects, or urinary tract infections, with a minimum time of 1 year after ending anti-neoplastic treatment, aged between 17 and 215 months, were divided into three groups: group 1—patients after nephroblastoma treatment (n = 21), group 2—after other solid tumours treatment (n = 44), and group 3—after lymphoproliferative neoplasms treatment (n = 19). The patients’ medical histories were taken and physical examinations were performed. Concentrations of blood urea nitrogen (BUN), creatinine, cystatin C, C-reactive protein (CRP), ADMA, and SDMA in blood and albumin in urine were measured, and a general urine analysis was performed. The SDMA/ADMA ratio, albumin–creatine ratio, and estimated glomerular filtration rate (eGFR) were calculated. eGFR was estimated by three equations recommended to the paediatric population by the KDIGO from 2012: the Schwartz equation (eGFR1), equation with creatinine and urea nitrogen (eGFR2), and equation with cystatin C (eGFR3). Results: Both the eGFR1 and eGFR2 values were significantly lower in group 1 than in group 3 (eGFR1: 93.3 (83.1–102.3) vs. 116.5 (96.8–126.9) mL/min/1.73 m2, p = 0.02; eGFR2: 82.7 (±14.4) vs. 94.4 (±11.9) mL/min/1.73 m2, p = 0.02). Additionally, there were weak positive correlations between SDMA and creatinine (p < 0.05, r = 0.24), and cystatin C (p < 0.05, r = 0.32) and weak negative correlations between SDMA and eGFR1 (p < 0.05, r = −0.25), eGFR2 (p < 0.05, r = −0.24), and eGFR3 (p < 0.05, r = −0.32). Conclusions: The usefulness of ADMA and SDMA in the diagnosis of renal functional impairment should be assessed in further studies. eGFR, calculated according to equations recommended for children, should be used in routine paediatric practice.

Does the Conjunctivochalasis Accompanied by Pseudoexfoliation Syndrome Affect the Ocular Surface and Anterior Segment Structures?

Purpose: Probability of coexistence of conjunctivochalasis and pseudoexfoliation syndrome (PES) in same individual may increase with aging. We investigated effects of conjunctivochalasis accompanied by PES on ocular surface (OS) and anterior segment (AS) structures.Methods: Cases with only conjunctivochalasis were determined as group-1 (n=62), cases with conjunctivochalasis accompanied by PES as group-2 (n=45), and healthy cases as group-3 (n=56). OS and AS parameters of groups were compared.Results: Compared to group-1, group-2 had higher grade-3 conjunctivochalasis (17.7% vs 46.7%, p=0.039), greater mean grade of conjunctivochalasis (MGC) (1.72±0.24 vs 2.29±0.32, p=0.036), higher total conjunctivochalasis score (TCS) (4.27±1.13 vs 6.12±1.35, p=0.025), shorter tear-film break-up time (TBUT) (9.17±2.53 vs 5.41±1.32, p=0.010), greater OS disease index (OSDI)-score (16.28±3.15 vs 27.36±4.12, p=0.037). Compared to group-3, both group-1 and group-2 had shorter TBUT (group 3-1: p=0.004; group 3-2: p<0.001) and greater OSDI score (group 3-1: p=0.042; group 3-2: p=0.019). Schirmer tests, central corneal thicknesses, keratometries, axial lengths, anterior chamber depths and lens thicknesses of groups were similar (p>0.05). In group-1 and group-2, as age increased, both MGC (r=0.349, p=0.043; r=0.403, p=0.022, respectively) and TCS (r=0.322, p=0.046; r=0.372, p=0.031) increased. In group-2, as both MGC and TCS increased, TBUT (r=-0.370, p=0.034; r=-0.401, p=0.025) decreased and OSDI score (r=0.338, p=0.045; r=0.362, p=0.040) increased.Conclusions: To our knowledge, this was the first study comprehensively investigating effects of conjunctivochalasis accompanied by PES on OS and AS structures together. We found that conjunctivochalasis might cause OS disease, while presence of PES in conjunctivochalasis cases might worsen OS disease and conjunctivochalasis findings.

Embolism to the main limb arteries in patients with atrial fibrillation

Introduction. Acute limb ischemia due to embolism in patients with atrial fibrillation remains poorly studied. Objective – to study the clinical significance and role of atrial fibrillation (AF) in the development of embolism to the bifurcation of the aorta and the main arteries of the limbs. Materials and methods. Treatment results of 1816 patients with acute ischemia of the extremities due to embolism treated at a specialized vascular surgical department for the past 30 years were analyzed. 1611 (88.7 %) of them had AF. The distribution into studied groups was according to the period time factor. Group 1 (n = 744) consisted of patients admitted in the period from 1991 to 2000; in group 2 (n = 568) – admitted in the period from 2001 to 2010, in group 3 (n = 299) – from 2011 to 2020. Methods included clinical examination, electrocardiography, Doppler-ultrasound, echocardiography. Results. The role of rheumatic heart disease as a cause of AF has decreased over the past decades by almost 10 times (from 19.5 % in group 1 to 2.0 % in group 3). Currently, the main background diseases for the development of AF are arterial hypertension and various forms of coronary artery disease. Embolism in patients with AF may develop in the arteries of all vascular areas of the systemic circulation, but in the practice of a vascular surgeon more often in the main arteries of minor caliber – the brachial (24.5 %) and popliteal (13.0 %). Multiple embolisms to various vascular areas were found in 2.8 % of patients. Urgent surgical revascularization of the limb by open embolectomy was performed in 1481 (91.9 %) patients that allowed 1348 (83.7 %) to be discharged with limb-sparing. Conclusion. In patients with acute limb ischemia of embologenic ethiology, comorbid AF has 88.7 % of them. Urgent embolectomy allows 83.7 % of patients to be discharged without limb amputation. Hospital mortality in the period 1991–2000 was 15.6 %, the last decade has been reduced to 7.4 %.