The incremental risk of fragility fractures in aging men.

INTRODUCTION: While the United States Preventative Services Task Force recommends osteoporosis screening for women 65 years and older, there is no definitive recommendation for routine osteoporosis screening in men. The purpose of this study was to determine the age at which the odds of fragility fractures (FFx) increase in men to help guide future policy discussions evaluating an optimal screening strategy in this population. METHODS: Men older than 49 years were identified in the PearlDiver Patient Records Database. Patients were excluded if they had a prior fragility fracture, if they were at high risk for osteoporosis due to comorbidities, or if they carried a diagnosis of and/or were on treatment for osteoporosis. The prevalence of FFx was trended for each age group. A stratum-specific likelihood ratio (SSLR) analysis was conducted to identify data-driven strata that maximize the incremental FFx risk by age for men. Logistic regression analyses controlling for potential confounders were conducted to test these identified strata. RESULTS: The incidence of FFx started to increase after the age of 64 years for men. Further, the identified data-driven age strata associated with a significant and incremental difference in fragility fractures were the following: 50-64, 65-69, 70-72, 73-75, 76-78, 79-80, and 81+. When compared to the youngest age stratum (50-64 years), multivariable regression showed the risk of fragility fracture incrementally increased starting in those aged 70-72 (RR, 1.31; 95% CI. 1.21-1.46; p < 0.001) with the highest risk in those aged 81+ (RR, 5.35; 95% CI, 5.10-5.62; p < 0.001). CONCLUSION: In men without a pre-existing history of osteoporosis, the risk of fragility fractures starts to increase after the age of 70. Further work building upon these data may help to identify a specific age at which routine bone health screening in males can help to minimize fractures and their associated morbidity and mortality.

Diffusion-weighted imaging of the orbit.

Orbital lesions compose a heterogeneous group of pathologies that often present with non-specific imaging findings on conventional magnetic resonance imaging (MRI) sequences (T1-and T2-weighted). Accordingly, the application of diffusion MRI offers an opportunity to further distinguish between lesions along this spectrum. Diffusion-weighted imaging (DWI) represents the simplest and most frequent clinically utilised diffusion imaging technique. Recent advances in DWI techniques have extended its application to the evaluation of a wider spectrum of neurological pathology, including orbital lesions. This review details the manifestations of select orbital pathology on DWI and underscores specific situations where diffusion imaging allows for increased diagnostic sensitivity compared to more conventional MRI techniques. These examples also describe preferred management for orbital lesions identified by DWI.

Predictive performance of the Garvan Fracture Risk Calculator: a registry-based cohort study.

The G arvan Fracture Risk Calculator predicts risk of osteoporotic fractures. We evaluated its predictive performance in 16,682 women and 2839 men from Manitoba, Canada, and found significant risk stratification, with a strong gradient across scores. The tool outperformed clinical risk factors and bone mineral density for fracture risk stratification. INTRODUCTION: The optimal model for fracture risk estimation to guide treatment decision-making remains controversial. Our objective was to evaluate the predictive performance of the Garvan Fracture Risk Calculator (FRC) in a large clinical registry from Manitoba, Canada. METHODS: Using the population-based Manitoba Bone Mineral Density (BMD) registry, we identified women and men aged 50-95 years undergoing baseline BMD assessment from September 1, 2012, onwards. Five-year Garvan FRC predictions were generated from clinical risk factors (CRFs) with and without femoral neck BMD. We identified incident non-traumatic osteoporotic fractures (OFs) and hip fractures (HFs) from population-based healthcare data sources to March 31, 2018. Fracture risk was assessed from area under the receiver operating characteristic curve (AUROC). Cox regression analysis and calibration ratios (5-year observed/predicted) were assessed for risk quintiles. All analyses were sex stratified. RESULTS: We included 16,682 women (mean age 66.6 + / - SD 8.7 years) and 2839 men (mean age 68.7 + / - SD 10.2 years). During a mean observation time of 2.6 years, incident OFs were identified in 681 women and 140 men and HFs in 199 women and 22 men. AUROC showed significant fracture risk stratification with the Garvan FRC. Tool predictions without BMD were better than from age or decreasing weight, and the tool with BMD performed better than BMD alone. Garvan FRC with BMD performed better than without BMD, especially for HF prediction (AUROC 0.86 in women, 0.82 in men). There was a strong gradient of increasing risk across Garvan FRC quintiles (highest versus lowest, hazard ratios women 5.75 and men 3.43 for any OF; women 101.6 for HF). Calibration differences were noted, with both over- and underestimation in risk. CONCLUSIONS: Garvan FRC outperformed CRFs and BMD alone for fracture risk stratification, particularly for HF, but may require recalibration for accurate predictions in this population.

Anatomage - the virtual dissection tool and its uses: A narrative review.

Advancement in technology has given students and institutes an educational, interactive, and diagnostic aid with virtual reality functionality known as the Anatomage table. This review analyses the various spheres of the medical field where the 3D virtual tool is being used and assesses its acceptability, convenience, and practical application. A search for relevant studies in various databases namely Pubmed, Embase, Wiley Library, and Google Scholar was performed, and the data was compiled to understand the use of the Anatomage table. The search yielded a total of 24 studies that focused on the use of the Anatomage table. Eleven articles focused on using Anatomage as a learning tool and 13 described the perception of the Table. Anatomage table offers an excellent tool for learning anatomy by virtual dissection. The tool is not only used as a teaching aid, but also as a diagnostic and planning tool in residency programs. Adding the tool as an educational aid boosts the existing curriculum and helps to counter the challenges with cadaveric dissection. The equipment cost and its maintenance charges may be a deciding factor for the underutilization of the tool in developing countries.

Role of Itolizumab in the Treatment of COVID-19 Patients, Admitted to ICU at a Tertiary Care Hospital.

BACKGROUND: Clinical studies have correlated severe deterioration of COVID-19 patients due to excessive and uncontrolled production of cytokines. There is a pressing need to explore therapies, which could prevent the cytokine storm rather than terminating it. AIMS AND OBJECTIVES: The aim of the study is to evaluate the effect of itolizumab on clinical outcomes of patients with moderate-severe COVID-19 disease admitted to ICU. The primary aim of the current study is to find out any mortality benefit in 14 days. The secondary aim is to assess the morbidity outcomes in terms of reduction in inflammatory markers and also the duration of hospital stays to assess the prognostication. MATERIALS AND METHODS: It is a retrospective case-control study in which laboratory-confirmed COVID-19 patients admitted to ICU were taken. A total of 62 patients were recruited, 31 patients received itolizumab (cases/treatment group) and 31 patients didn't receive itolizumab (designated as controls). RESULTS: Among the total patients recruited, 68% of the study population was male and 32% were female. A total of 12 patients expired among cases and 13 expired among controls. Overall mortality in both groups was noted to be almost similar. The control group showed mortality at lower computed tomography (CT) scores compared to the cases. There is a significant reduction in inflammatory markers, like interleukins-6 (IL-6) and D-dimer in cases compared to the control group. CONCLUSION: In conclusion, treating patients with cytokine storms before they require intubation/mechanical ventilation is crucial to preventing deaths. Itolizumab has shown no clinical benefit in critically ill COVID-19 patients, however, timely initiation of itolizumab therapy may serve as a key therapeutic option in preventing the mortality and morbidity outcomes in moderate-severe COVID-19 patients.

Evaluation of a novel sputum processing ReaSLR methodology for improving sensitivity of smear microscopy in clinical samples.

Background: Early case detection is a crucial step in the control of tuberculosis (TB). Sputum smear microscopy is the primary method of TB diagnosis in developing countries. The modified Petroff's method using sodium hydroxide at concentrations ranging between 2% and 4% to digest the specimen is widely used in developing countries. A novel ReaSLR (ReaMetrix's Sputum Liquefying Reagent) methodology has been proposed as a simple, easy, low-cost, and better alternative to conventional methods for sputum processing. This study was undertaken to evaluate the performance of the ReaSLR method of sputum processing in comparison with that of the modified Petroff's method. Methods: Early-morning sputum samples were collected. After preparing a direct smear, each sample was divided into two equal halves and processed by both the methods, i.e., modified Petroff's method and ReaSLR method. Direct smears were graded according to Revised National Tuberculosis Control Program grading, and smears prepared after processing by the two different methods were graded according to Center for Disease Control and Prevention grading. Smear microscopy results were compared taking culture results of samples processed by the modified Petroff's method as the gold standard. Results: The rate of smear positivity with the modified Petroff's method (22.22%) was found to be higher than that with direct smear microscopy (13.56%; p = 0.0002) and the ReaSLR method (17.32%; p = 0.04). The modified Petroff's method was found to be 26.76% more sensitive than direct microscopy and 15.59% more sensitive than the ReaSLR method. Conclusion: The ReaSLR method was not superior to the modified Petroff's method for smear microscopy. Although this method was more sensitive than the direct method in smear microscopy, the modified Petroff's method performed much better than the ReaSLR method.

Role of postoperative intact serum PTH as an early predictor of severe post-thyroidectomy hypocalcemia: a prospective study.

BACKGROUND: Post thyroidectomy hypocalcemia is a major sequel of thyroidectomy and continues to trouble the endocrinologists and the endocrine surgeons as there is no ideal predictive marker of hypocalcemia which has the potential to develop into a life-threatening complication. The role of early serum intact parathormone (iPTH) to predict post thyroidectomy hypocalcemia is becoming useful but the literature is still unclear regarding the optimal time of testing and the optimal cut-off value of serum iPTH. PATIENTS AND METHODS: This is a prospective cohort study of 111 patients who underwent total thyroidectomy in a tertiary care endocrine surgery referral unit. Serum iPTH was measured after 20 min and 4 h of surgery. Receiver-Operator characteristic Curve (ROC) was used to find out of the best cut-off value of S. iPTH 20 min and 4 h after surgery in predicting hypocalcemia. RESULTS: Hypocalcemia was noted in 60 (54%) out of 111 subjects who underwent total thyroidectomy. The best cut-off values of Serum iPTH to predict hypocalcemia was found to be 4.28 pmol/l at 20 min post total thyroidectomy with a sensitivity and specificity of 81.7% and 51%, respectively. In addition, patients with malignancy or central lymph nodal dissection were significantly over-represented in the hypocalcemia group with serum iPTH above the threshold level of 4.28 pmol/l. Below the cut off level, parenteral calcium supplementation was required in 23% (17/74) subjects while the rate was only 5.4% (2/37) patients when serum iPTH was above the cut-off level. CONCLUSIONS: The decline of serum iPTH below a specific level after surgery has predictive value together with other factors strictly related to patient, the thyroid disease itself and surgery. The risk of development of hypocalcemia and consequent need for calcium supplementation should be evaluated by clinical assessment along with serum PTH measurement.

Fetal ventricular strain in uncomplicated and selective growth-restricted monochorionic diamniotic twin pregnancies and cardiovascular response in pre-twin-twin transfusion syndrome.

OBJECTIVES: Our primary aim was to confirm whether intertwin discordance in ventricular strain and ductus venosus (DV) time intervals predicts twin-twin transfusion syndrome (TTTS). Secondary aims were to create gestational-age ranges for ventricular strain in uncomplicated monochorionic diamniotic (MCDA) twin pregnancies without selective intrauterine growth restriction (sIUGR) and to characterize the relationship of ventricular strain with gestational age in MCDA twin pregnancies with sIUGR that did not develop TTTS. METHODS: In the period 2015-2018, we enrolled 150 MCDA twin pregnancies consecutively into this prospective, blinded study of global longitudinal left and right ventricular strain. With the observer blinded to twin pairing and pregnancy outcome, videoclips of the four-chamber view, which had been recorded during ultrasound surveillance in the usual window for development of TTTS (16-26 completed gestational weeks), underwent offline measurement of strain. Uncomplicated MCDA twin pregnancies, without sIUGR, were used to test the association between strain, gestational age and estimated fetal weight using mixed-effects multilevel regression. Inter-rater reliability was tested in 208 strain measurements in 31 fetuses from pregnancies which did not develop TTTS and within-fetus variation was assessed in 16 such fetuses, in which multiple four-chamber views were taken on the same day. The effect of sIUGR on strain in otherwise uncomplicated MCDA twin pregnancy was analyzed. MCDA twin pregnancies were defined as 'pre-TTTS' when, having been referred for TTTS evaluation, they did not satisfy Quintero staging criteria, but subsequently developed TTTS requiring laser treatment. MCDA pregnancies which did not develop TTTS comprised the 'non-TTTS' group. Cardiovascular parameters measured in these cases included tissue Doppler parameters and DV early filling time as a percentage of the cardiac cycle (DVeT%). Intertwin strain and DVeT% discordance was compared between non-TTTS and pre-TTTS cases, matched for gestational age. RESULTS: Paired strain data were available for intertwin comparison in 127/150 MCDA twin pregnancies, comprising 14 pre-TTTS and 113 non-TTTS pregnancies, after exclusions. Scans were collected at a median frame rate of 97 (range, 28-220) Hz. Laser therapy was performed at a median gestational age of 20.6 (range, 17.2-26.6) weeks. There were no group differences in right (RV) or left (LV) ventricular strain discordance between 68/113 non-TTTS and 13/14 pre-TTTS MCDA twin pregnancies < 20 completed gestational weeks (RV, P = 0.338; LV, P = 0.932). DVeT% discordance > 3.6% was found in eight of 13 pre-TTTS pregnancies. In non-TTTS pregnancies, the estimated variability in ventricular strain within each twin during the day was high (RV, 19.7; LV, 12.9). However, within each pair (intertwin variation), variability was low (RV, 5.5; LV, 2.9). Interclass correlation reflecting the proportion of total variability represented by the variability between twin pairs was low (RV, 0.22; LV, 0.18). Both RV (P < 0.001) and LV (P = 0.025) strain showed a negative association with gestational age. Among non-TTTS MCDA twin pregnancies, LV strain was, on average, higher by 1.83 in sIUGR compared with normally grown fetuses (P = 0.023), with no statistically significant difference in RV strain (P = 0.271). CONCLUSIONS: Although ventricular strain has been reported previously as a possible predictor of developing TTTS, in this blinded, prospective study, we found no significant intergroup differences in ventricular strain in pre-TTTS compared with age-matched non-TTTS MCDA twin pregnancies. We recommend using DVeT% discordance as a more practical screening tool in MCDA twin pregnancies. This study also provides new information on the changes with gestational age, and the biological and technical variation, of global longitudinal ventricular strain in uncomplicated MCDA twin pregnancies and those with isolated sIUGR. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Intracranial vessel wall imaging: applications, interpretation, and pitfalls.

Vessel wall imaging (VWI) is being increasingly used as a non-invasive diagnostic method to evaluate the intra- and extracranial vascular bed. Whereas conventional vascular imaging primarily assesses the vessel lumen, VWI changes the focus of analysis toward the vessel wall. As the technical challenges of high spatial resolution, signal-to-noise ratio, and contrast-to-noise ratio and long scans times are addressed, interest in the clinical applications of this technique has steadily increased over the years. In this review, the authors will discuss the various applications of VWI as well as principles of interpretation and common imaging findings, focusing on intracranial atherosclerosis, vascular dissection, vasculitides (such as primary angiitis of the central nervous system (PACNS) and neurosarcoidosis), vasculopathies (such as reversible cerebral vasoconstriction syndrome (RCVS), cocaine-induced vasculopathy, moyamoya disease, and radiation-induced arteriopathy), aneurysms, and post-thrombectomy changes. The authors will also discuss the potential pitfalls of VWI and helpful cues to avoid being tricked.

Fulminant amebic colitis: An unusual postoperative complication of intraabdominal malignancy.

Amebiasis caused by protozoa Entamoeba histolytica (EH) is the third leading parasitic cause of human mortality. Although amebiasis is endemic in India, only about 10% of the infected individuals manifest disease. Clinical spectrum of amebiasis ranges from asymptomatic colonization to amebic colitis to hemorrhagic and fulminant colitis. Factors causing an invasive infection are not completely understood. Pathogen virulence, host immunity, and ability of the pathogen to evade host immune response play vital role in determining the disease course. Host factors such as immunocompromised states may make an individual susceptible to develop symptomatic infection. Malignancies usually result in chronic debilitation which may make the individual prone to develop invasive amebiasis with rapid progression. We report two cases of invasive amebiasis which developed a fulminant course in the immediate postoperative period after abdominal surgeries for visceral malignancies.

Silver nanoparticles (AgNPs) induced impairment of in vitro pollen performance of Peltophorum pterocarpum (DC.) K. Heyne.

Increasing use of silver nanoparticles (AgNPs) in myriad applications including electronics, medicines and agriculture has led to serious concerns regarding its release to plant ecosystems. Over the years, numerous studies have demonstrated the toxic impact of AgNPs in a variety of cell and tissue systems involved in vegetative growth across a wide range of plant species. However, assessing their impact on haploid phase of plant life cycle was restricted only to a study with Kiwifruit. In this study, in vitro pollen performance of Peltophorum pterocarpum at two endpoints i.e., germination and tube growth was assessed to evaluate the impact of nanoparticulate or ionic form of silver. Increasing concentrations of AgNO3/AgNPs significantly reduced the pollen germination and retarded the tube growth. The EC 50 values indicated a more potent toxic effect of AgNPs than AgNO3 on pollen germination as well as tube growth. Impairment of pollen performance was more pronounced at the stage of emergence of pollen tube. Extensive alterations in the muri and lumen of exine as revealed through SEM analysis and subsequent blockage of germpore might disrupt the emergence of pollen tube. The dynamics of pollen tube growth was analyzed with polynomial models of different degrees. A high degree of polynomial, the quintic model was able to approximate the real data points with highest coefficient of determination and smallest RMSE, compared to other models. An oscillating pattern of tube growth was portrayed with the passage of time in all the treatments that fits well with the established mechanistic oscillatory model of tube growth. It appears that exposure to AgNO3/AgNPs inhibited pollen germination and retarded tube growth without affecting the oscillatory behavior of tip-growth.

Prevalence of Abnormal Liver Function Tests in COVID-19 Patients at a Tertiary Care Centre.

BACKGROUND AND AIM: Coronavirus disease 2019 (COVID 2019) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is observed to cause liver dysfunction. We aimed to observe abnormal liver function tests (LFTs) in COVID-19 patients admitted in our hospital. METHODS: It was a cross- sectional study involving 105 COVID-19 patients who were admitted in our Hospital from 03-04-2020 to 02-05-2020. The COVID-19 positivity was defined on basis of real-time PCR. Thorough clinical examination and laboratory investigations including Complete Blood Count, Renal function Tests, Liver Function Tests, Chest X-ray, ECG, etc. were done. RESULTS: The total number of male and female patients were 64 and 41. Out of total 105 patients, 62 i.e. 59.04% had abnormal LFTs at time of admission. Out of these 62 patients, 44(70.9%) were Male and 18(29.03%) were female. Only 5(4.76%) patients had abnormal LFTs on repeat testing. Median Age of patients was 33years. Average stay of patients with Abnormal LFTs was 15 days (10-16 days) as compared to 10 days (7-11days) for patients with normal LFTs. CONCLUSION: The prevalence of Abnormal Liver function tests in patients of COVID-19 is 59.04%. Abnormal liver functions were more in males. The average stay in hospital for COVID-19 patients with abnormal LFTs was longer than those with normal LFTs.

Evaluation of Microscopic observation drug susceptibility (MODS) assay as a rapid, sensitive and inexpensive test for detection of tuberculosis and multidrug resistant tuberculosis.

BACKGROUND: Microscopic observation drug susceptibility (MODS) assay has been suggested as a low cost method for rapid, accurate detection of tuberculosis (TB) and multidrug resistant tuberculosis (MDR-TB). METHODS: A total of 2424 samples collected from 1063 eligible patients of suspected pulmonary or extrapulmonary TB were subjected to MODS assay. Performance of MODS was compared with culture and drug susceptibility testing (DST) by conventional solid Lowenstein-Jensen (LJ) media or liquid Mycobacteria Growth Indicator Tube (MGIT) culture. RESULTS: When compared to reference gold standard of positivity in either solid or liquid reference culture, the MODS assay had sensitivity, specificity, positive predictive value and negative predictive value of 91.3%, 98.2%, 96.0% and 95.9% respectively. MODS took a median time of 10.3 days to culture positivity as compared to 13.8 days using MGIT and 30.5 days using LJ culture. Culture and DST being concurrent in MODS, the median turnaround time for DST was the same as that for culture i.e. 10.3 days. The overall median turn around time for culture positivity and DST using manual MGIT and LJ medium was 23.6 days and 61.2 days respectively. The concordance between MODS culture and the reference susceptibility method was 97.7% for rifampicin, 95.6% for isoniazid, 98.5% for rifampicin and isoniazid. The cost of performing a single MODS assay was INR 200. CONCLUSION: MODS is a rapid and sensitive, yet simple and inexpensive test that may be helpful to enhance diagnostic accuracy, and case detection of TB and MDR-TB in resource constrained settings.

A study of hepatitis A virus seropositivity among children aged between 1 and 5 years of age: Implications for universal immunization.

BACKGROUND: Hepatitis A virus (HAV) causes an enterically transmitted viral disease mainly affecting children and endemic in many developing countries, including India. There is an epidemiological shift with an increased incidence of symptomatic cases among children. This study was conducted to assess the seroprevalence of HAV among young children aged below 5 years and the need for universal immunization. METHOD: This cross-sectional study was conducted at two tertiary care hospitals in Northern India, from Apr 2014 to Jul 2015, among healthy children aged between 1 and 5 years. The sample size was calculated based on the prevalence of HAV seropositivity of 40% among children aged <10 years [16-60%] and alpha error of 5%. Analysis of serum IgG against HAV was performed by enzyme-linked immunosorbent assay method, and results were analyzed. RESULTS: A total of 1084 children aged between 12 and 60 months were enrolled, with male-to-female ratio of 1.86:1. A total of 471 children (43.5%) were found to be positive for IgG against HAV. The seroprevalence of HAV was lower among younger children aged 12-23 months (odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.52-0.87, p = 0.03), which was statistically significant. Seropositivity of HAV was lower among boys and families consuming safe drinking water and having improved sanitation facilities. CONCLUSION: The study observed lower seropositivity against HAV among younger children, making them susceptible of contracting the disease. Possible underlying risk factors were younger age, unsafe drinking water, poor sanitation, and low education status of parents. Therefore, vaccination may be recommended as optional vaccine at one year of age, along with improved public health efforts for safe drinking water, hygiene practices, and food safety.

Divergent effects of AKI to CKD models on inflammation and fibrosis.

Chronic kidney disease (CKD) is a condition with significant morbidity and mortality that affects 15% of adults in the United States. One cause of CKD is acute kidney injury (AKI), which commonly occurs secondary to sepsis, ischemic events, and drug-induced nephrotoxicity. Unilateral ischemia-reperfusion injury (UIRI) without contralateral nephrectomy (CLN) and repeated low-dose cisplatin (RLDC) models of AKI to CKD demonstrate responses characteristic of the transition; however, previous studies have not effectively compared the pathogenesis. We demonstrate both models instigate renal dysfunction, inflammatory cytokine responses, and fibrosis. However, the models exhibit differences in urinary excretory function, inflammatory cell infiltration, and degree of fibrotic response. UIRI without CLN demonstrated worsening perfusion and function, measured with 99mTc-mercaptoacetyltriglycine-3 imaging, and physiologic compensation in the contralateral kidney. Furthermore, UIRI without CLN elicited a robust inflammatory response that was characterized by a prolonged polymorphonuclear cell and natural killer cell infiltrate and an early expansion of kidney resident macrophages, followed by T-cell infiltration. Symmetrical diminished function occurred in RLDC kidneys and progressively worsened until day 17 of the study. Surprisingly, RLDC mice demonstrated a decrease in inflammatory cell numbers relative to controls. However, RLDC kidneys expressed increased levels of kidney injury molecule-1 (KIM-1), high mobility group box-1 ( HMGB1), and colony stimulating factor-1 ( CSF-1), which likely recruits inflammatory cells in response to injury. These data emphasize how the divergent etiologies of AKI to CKD models affect the kidney microenvironment and outcomes. This study provides support for subtyping AKI by etiology in human studies, aiding in the elucidation of injury-specific pathophysiologic mechanisms of the AKI to CKD transition.

Efficacy of generic oral directly acting agents in patients with hepatitis C virus infection.

Novel direct-acting antivirals (DAAs) are now the standard of care for the management of hepatitis C virus (HCV) infection. Branded DAAs are associated with high sustained virological response at 12 weeks post-completion of therapy (SVR12), but are costly. We aimed to assess the efficacy of generic oral DAAs in a real-life clinical scenario. Consecutive patients with known HCV infection who were treated with generic-oral DAA regimens (May 2015 to January 2017) were included. Demographic details, prior therapy and SVR12 were documented. Four hundred and ninety patients (mean age: 38.9 ± 12.7 years) were treated with generic DAAs in the study time period. Their clinical presentations included chronic hepatitis (CHC) in 339 (69.2%) of cases, compensated cirrhosis in 120 (24.48%) cases and decompensated cirrhosis in 31 (6.32%) cases. Genotype 3 was most common (n = 372, 75.9%) followed by genotype 1 (n = 97, 19.8%). Treatment naïve and treatment-experienced (defined as having previous treatment with peginterferon and ribavirin) were 432 (88.2%) and 58 (11.8%), respectively. Generic DAA treatment regimens included sofosbuvir in combination with ribavirin (n = 175), daclatasvir alone (n = 149), ribavirin and peginterferon (n = 80), ledipasvir alone (n = 43), daclatasvir and ribavirin (n = 37), and ledipasvir and ribavirin (n = 6). Overall SVR12 was 95.9% (470/490) for all treatment regimens. SVR12 for treatment naïve and experienced patients was 97.0% (419/432) and 87.9% (51/58), respectively, P = .005. High SVR12 was observed with various regimens, irrespective of genotype and underlying liver disease status. There were no differences in SVR12 with 12 or 24 weeks therapy. No major adverse event occurred requiring treatment stoppage. Generic oral DAAs are associated with high SVR rates in patients with HCV infection in a real-life clinical scenario.

Phytostimulatory effect of silver nanoparticles (AgNPs) on rice seedling growth: An insight from antioxidative enzyme activities and gene expression patterns.

The knowledge on the mode of action, biocompatibility and ecological tolerance of silver nanoparticles (AgNPs) is gradually accumulating over the years with contradictory findings. Most of the studies indicated the toxic impact of AgNPs on plant growth and development, where induction of oxidative stress was considered to be one of the causal factors. The present study demonstrates the phytostimulatory effect of bio-synthesized silver nanoparticles (AgNPs) during seed germination and seedling growth of rice (Oryza sativa L., cv. Swarna) under in vitro condition. All the tested concentrations of AgNPs (10, 20, 40 ppm) promote both the shoot and root growth which was evident from the increased length and biomass of the seedlings. Exposure to AgNPs also significantly increased the chlorophyll a and carotenoid contents. The content and the pattern of distribution of phenolic metabolites among the different treatments are indicative of non-toxic impact of AgNP mimicking mild or no stress to the seedlings. Growth stimulation of rice seedlings by AgNPs was further supported by a low level of reactive oxygen species (ROS) concomitant with decreased amount of lipid peroxidation and H2O2 content, compared to control. In order to unravel the stimulatory impact of AgNPs on rice seedling growth, the present study also describes the AgNPs induced changes in antioxidative enzyme activity and related gene expression levels. Elevated levels of catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR) activities were recorded in all the AgNPs treated seedlings with improved growth. The activity of superoxide dismutase (SOD) was not significantly altered at low concentration of AgNPs. It appears that enzymes of ascorbate cycle, APX and GR are more active in ensuring protection against oxidative damage than SOD. There was significant up-regulation of CAT and APX gene expressions in seedlings exposed to AgNPs, whereas the expression level of CuZnSOD gene was decreased gradually with an increase in the concentration of AgNPs. The antioxidant enzyme activities and gene expression patterns coupled with the levels of H2O2 and lipid peroxidation indicates that the efficiency of redox reactions was increased in the presence of AgNPs and that accelerates the seedling growth.

Determination of seminal oxidation-reduction potential (ORP) as an easy and cost-effective clinical marker of male infertility.

Oxidative stress (OS) is an important contributing factor to male infertility. While previous methods to measure seminal OS are time-consuming and limited to the use of freshly produced semen, oxidation reduction potential (ORP) is easier and quicker to perform and can also be used in frozen semen. Therefore, this study evaluated the clinical utility of ORP as a potential marker of male infertility. ORP was measured in semen samples from 293 patients and 15 fertile controls and categorised according to WHO criteria as normozoospermic, oligozoospermic, asthenozoospermic, teratozoospermic and oligoasthenoteratozoospermic. Receiver operating characteristic (ROC) curves were generated to differentiate these categories. Semen parameters were significantly different when subjects were grouped as control and patients or between the patient and normozoospermic group for concentration and morphology. ORP levels were significantly different between the control and normozoospermic group. When subjects were grouped based on concentration, motility, morphology or a combination of these, the area under the ROC curve, sensitivity, specificity, positive predictive value and cut-off values were significantly different. These differences were significant when combined with ORP and grouped with any two sperm abnormalities. In conclusion, ORP is a quick, easy, cost-effective and reliable marker of semen quality as well as oxidative stress for use in a clinical setting.

Towards the identification of reliable sperm biomarkers for male infertility: A sperm proteomic approach.

Male infertility evaluation is mainly based on semen analysis. Thus, identification of additional diagnostic methods is valuable. The aim of this study was to analyse the sperm proteome of infertile men to identify the underlying mechanisms and reliable diagnostic biomarkers. This cross-sectional study consisted of 16 infertile men and seven proven fertile men. An LC-MS/MS approach was performed in five pooled samples of each group (proven fertile men, primary infertility and secondary infertility). Differentially expressed proteins were used for functional enrichment analyses, and the most central proteins involved in altered functions in both infertile groups and the testis-specific proteins were validated using Western blotting and immunocytochemistry. In total, 1,305 sperm proteins were identified, of which 102 were underexpressed and 15 were overexpressed proteins in both infertile groups. Underexpressed proteins were mostly related to protein post-translational modification and folding, especially BAG6, HSPA2 and SPA17. Validation analysis revealed an underexpression of BAG6 in infertile men, whereas HSPA2 and SPA17 expressions did not differ between the groups. No differences were observed in the sperm localisation of these proteins. An overexpression of HIST1H2BA-a testis-specific protein-was observed in both proteomic approaches. Therefore, BAG6 and HIST1H2BA are potential candidates for male infertility biomarkers.

Reactive oxygen species impact on sperm DNA and its role in male infertility.

Reactive oxygen species (ROS) have been extensively studied as a cause of male infertility. Excessive levels of ROS coupled with a deficiency in antioxidants can lead to oxidative stress (OS), which in turn can lead to nuclear and mitochondrial DNA damage, telomere shortening, epigenetic alterations and Y chromosomal microdeletions. In this review, we discuss how OS induces DNA damage and the types of DNA damage that can occur. We also briefly touch on the clinical consequences of OS-induced DNA damage.