Inherited retinal disorders: a genotype-phenotype correlation in an Indian cohort and the importance of genetic testing and genetic counselling.

PURPOSE: Recent advances in sequencing technologies have enabled radical and rapid progress in the genetic diagnosis of inherited retinal disorders (IRDs). Although the list of gene variations continues to grow, it lacks the genetic etiology of ethnic groups like South Asians. Differences in racial backgrounds and consanguinity add to genetic heterogeneity and phenotypic overlaps. METHODS: This retrospective study includes documented data from the Gen-Eye clinic from years 2014 to 2019. Medical records and pedigrees of 591 IRD patients of Indian origin and genetic reports of 117 probands were reviewed. Genotype-phenotype correlations were performed to classify as correlating, non-correlating and unsolved cases. RESULTS: Among the 591 patients, we observed a higher prevalence of clinically diagnosed retinitis pigmentosa (38.9%) followed by unspecified diagnoses (28.5%). Consanguinity was reported to be high (55.6%) in this cohort. Among the variants identified in 117 probands, 36.4% of variants were pathogenic, 19.2% were likely pathogenic, and 44.4% were of uncertain significance. Among the pathogenic and likely pathogenic variants, autosomal recessive inheritance showed higher prevalence. About 35% (41/117) of cases showed genotype-phenotype correlation. Within the correlating cases, retinitis pigmentosa and Stargardt disease were predominant. Novel variants identified in RP, Stargardt, and LCA are reported here. CONCLUSION: This first-of-a-kind report on an Indian cohort contributes to existing knowledge and expansion of variant databases, presenting relevant and plausible novel variants. Phenotypic overlap and variability lead to a differential diagnosis and hence a clear genotype-phenotype correlation helps in precise clinical confirmation. The study also emphasizes the importance of genetic counselling and testing for personalized vision care in a tertiary eye hospital.

Kinetic and equilibrium modeling of biosorption of nickel (II) and cadmium (II) on brewery sludge.

In the current study, utilization of industrial waste brewery sludge for the biosorption of nickel (II) and cadmium (II) has been explored. The suitable conditions for the effective removal of Ni (II) and Cd (II) from aqueous solutions were examined. The kinetic evaluation showed that the biosorption process using the sludge followed pseudo-second order kinetics. In the presence of a metal co-ion, competitive and preferential biosorption was observed. The Langmuir model and Freundlich model were able to describe the sorption equilibrium for biosorption of Ni (II) and Cd (II) ions in single and dual metal systems. The effects of co-ion concentrations onto mono-component isotherm parameters (Langmuir and Freundlich) were studied and the inhibitory effect of co-ion concentration was observed. The effective reusability of biomass was assessed by three cycles of sorption-desorption. The sludge, owing to its high biosorption intensity and large availability from the local supply, is a better biosorbent for the treatment of Ni (II) and Cd (II) contaminated water.

Echocardiographic abnormalities in cirrhosis & their correlation with severity of cirrhosis using Child-Pugh score among patients in a tertiary care hospital.

BACKGROUND & OBJECTIVES: Child-Pugh score (CPS) is a widely used prognostic marker in cases of cirrhosis and pulmonary arterial hypertension (PAH). However, the role of this score in the quantification of severity of PAH is not well studied. In mild cases, echocardiography is more sensitive. This study was done to assess the association between echocardiography and severity of cirrhosis using CPS. METHODS: A cross-sectional study was done from April to June 2014 in 42 patients with cirrhosis using a pre-tested semi-structured interview schedule. RESULTS: There was no significant association between echocardiographic changes and CPS in patients with liver cirrhosis. INTERPRETATION & CONCLUSIONS: Advising an echocardiographic evaluation may prove beneficial in patients of Child-Pugh Grades B and C. However, more extensive studies are required to confirm the same.

Shear stress effects on production of exopolymeric substances and biofilm characteristics during phenol biodegradation by immobilized Pseudomonas desmolyticum (NCIM2112) cells in a pulsed plate bioreactor.

This article reports studies on a continuous pulsed plate bioreactor (PPBR) with the cells of Pseudomonas desmolyticum (NCIM2112) immobilized on granular activated carbon (GAC) used as a biofilm reactor for biodegradation of phenol. Almost complete removal of 200 ppm phenol could be achieved in this bioreactor. Biofilm structure and characteristics are influenced by hydrodynamic and shear conditions in bioreactors. In this article, the effect of shear stress induced by frequency of pulsation on biofilm characteristics during the startup period in the PPBR is reported. The startup time decreased with the increase in frequency of pulsation. The formation of biofilm in PPBR was found to have three phases: accumulation, compaction, and plateau. The effect of frequency on production of exoploymeric substances (EPS) such as, protein, carbohydrate, and humic substance is reported. An increase in shear stress induced by the frequency of pulsation increased the production of exopolymeric substances in the biofilm during startup of the bioreactor. Increase in shear stress caused a decrease in biofilm thickness and an increase in dry density of the biofilm. Increase in shear stress resulted in a smoother and thinner biofilm surface with more compact and dense structure.

In vitro and in vivo anticancer effects of mevalonate pathway modulation on human cancer cells.

BACKGROUND: The increasing usage of statins (the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) has revealed a number of unexpected beneficial effects, including a reduction in cancer risk. METHODS: We investigated the direct anticancer effects of different statins approved for clinical use on human breast and brain cancer cells. We also explored the effects of statins on cancer cells using in silico simulations. RESULTS: In vitro studies showed that cerivastatin, pitavastatin, and fluvastatin were the most potent anti-proliferative, autophagy inducing agents in human cancer cells including stem cell-like primary glioblastoma cell lines. Consistently, pitavastatin was more effective than fluvastatin in inhibiting U87 tumour growth in vivo. Intraperitoneal injection was much better than oral administration in delaying glioblastoma growth. Following statin treatment, tumour cells were rescued by adding mevalonate and geranylgeranyl pyrophosphate. Knockdown of geranylgeranyl pyrophosphate synthetase-1 also induced strong cell autophagy and cell death in vitro and reduced U87 tumour growth in vivo. These data demonstrate that statins main effect is via targeting the mevalonate synthesis pathway in tumour cells. CONCLUSIONS: Our study demonstrates the potent anticancer effects of statins. These safe and well-tolerated drugs need to be further investigated as cancer chemotherapeutics in comprehensive clinical studies.

Peginterferon and ribavirin for treatment of recurrent hepatitis C disease in HCV-HIV coinfected liver transplant recipients.

Achievement of a sustained virologic response (SVR) with antiviral therapy significantly improves graft survival in hepatitis C virus (HCV) monoinfected liver transplant (LT) patients. Risks and benefits of HCV therapy in HCV-human immunodeficiency virus (HIV) coinfected LT recipients are not well established. Among 89 HCV-HIV LT recipients in the HIVTR cohort, 39 (23% Black, 79% genotype 1, 83% fibrosis stage ≤ 1) were treated with peginterferon-a2a or a2b plus ribavirin for a median 363 days (14-1373). On intent-to-treat basis, 22% (95% CI: 10-39) and 14% (95% CI: 5-30) achieved an end-of-treatment response (EOTR) and SVR, respectively. By per-protocol analysis (completed 48 weeks of therapy ± dose reductions), 42% and 26% had EOTR and SVR, respectively. Severe adverse events occurred in 85%, with 26% hospitalized with infections and 13% developing acute rejection. Early discontinuations and dose reductions occurred in 38% and 82%, respectively, despite use of growth factors in 85%. Eighteen of 39 treated patients (46%) subsequently died/had graft loss, with 10 (26%) attributed to recurrent HCV. In conclusion, SVR rates are low and tolerability is poor in HCV-HIV coinfected transplant recipients treated with peginterferon and ribavirin. These results highlight the critical need for better tolerated and more efficacious HCV therapies for HCV-HIV coinfected transplant recipients.

Uptake of certain heavy metals from contaminated soil by mushroom--Galerina vittiformis.

Remediation of soil contaminated with heavy metals has received considerable attention in recent years. In this study, the heavy metal uptake potential of the mushroom, Galerina vittiformis, was studied in soil artificially contaminated with Cu (II), Cd (II), Cr (VI), Pb (II) and Zn (II) at concentrations of 50 and 100mg/kg. G. vittiformis was found to be effective in removing the metals from soil within 30 days. The bioaccumulation factor (BAF) for both mycelia and fruiting bodies with respect to these heavy metals at 50mg/kg concentrations were found to be greater than one, indicating hyper accumulating nature by the mushroom. The metal removal rates by G. vittiformis was analyzed using different kinetic rate constants and found to follow the second order kinetic rate equation except for Cd (II), which followed the first order rate kinetics.

Reduction of hexavalent chromium by a novel Ochrobactrum sp. - microbial characteristics and reduction kinetics.

A Gram negative hexavalent chromium (Cr(VI)) reducing bacteria, Ochrobactrum sp. Cr-B4 (genbank accession number: JF824998) was isolated from the aerator water of an activated sludge process of a wastewater treatment facility of a dye and pigment based specialty chemical industry. It showed a resistance for 1000 mg L(-1) Cr(VI). It exhibited resistance against other heavy metal ions like Ni(2+) (900 mg L(-1) ), Cu(2+) (500 mg L(-1) ), Pb(2+) (800 mg L(-1) ), and Cd(2+) (250 mg L(-1) ), Zn(2+) (700 mg L(-1) ), Fe(3+) (800 mg L(-1) ), and against selected antibiotics. Cr-B4 could efficiently reduce 200 mg L(-1) Cr(VI) completely in nutrient and LB media and could convert Cr(VI) to Cr(III) efficiently. Cr(VI) reduction in nutrient media followed allosteric enzyme kinetics with Km values of 59.39 mg L(-1) and Vmax values of 47.03 mg L(-1) h(-1) . The reduction in LB media followed Michaelis-Menten kinetics with Km values of 99.52 mg L(-1) and Vmax of 77.63 mg L(-1) h(-1) . Scanning electron micrograms revealed the presence of extracellular polymeric secretions.

Inhibitory and stimulating effect of single and multi-metal ions on hexavalent chromium reduction by Acinetobacter sp. Cr-B2.

Potential application of chromium reducing bacteria for industrial scale wastewater treatment demands that effect of presence of other metal ions on rate of Cr(VI) reduction be investigated, as industrial wastewaters contain many toxic metal ions. In the current study, the effect of different heavy metal ions (nickel, zinc, cadmium, copper, lead, iron) on chromium reduction by a novel strain of Acinetobacter sp. Cr-B2 that shows high tolerance up to 1,100 mg/L and high Cr(VI) reducing capacity was investigated. The alteration in Cr(VI) reduction capacity of Cr-B2 was studied both in presence of individual metal ions and in the presence of multi-metal ions at different concentrations. The study showed that the Cr(VI) reduction rates decreased in presence of Ni(2+), Zn(2+) and Cd(2+) when present individually. Pb(2+) at lower concentration did not show significant effect while Cu(2+) and Fe(3+) stimulated the rate of Cr(VI) reduction. In the studies on multi-metal ions, it was observed that in presence of Cu(2+) and Fe(3+), the inhibiting effect of Ni(2+), Zn(2+), Cd(2+) and Pb(2+) on Cr(VI) reduction was reduced. Each of these metals affect the overall rate of Cr(VI) reduction by Cr-B2. This work highlights the need to consider the presence of other heavy metal ions in wastewater when assessing the bioreduction of Cr(VI) and while designing the bioreactors for the purpose, as rate of reduction is altered by their presence.

A simple technique for the direct bonding of a lingual retainer: a clinical hint.

The direct bonding of a fixed wire retainer often poses clinical difficulties. While there are several possible techniques, the present paper describes a simple method employing a ball clasp (S handle) to assist in the stabilisation of the wire to be attached. The advantages and disadvantages are indicated.

Permanent mandibular canine(s) impaction: expansion of our understanding.

INTRODUCTION: Eruption disturbances, tooth size and specific malocclusions are known to be genetically influenced. The clinical association between these traits may indicate common genetic controls. OBJECTIVES: A cross-sectional clinical study was designed to test the null hypothesis that the maximum mesiodistal crown diameter (MMD) of maxillary and mandibular central and lateral incisors and the prevalence of various classes of incisor relationships (Class I, II/1, II/2 and III) do not differ between the subjects with and without permanent mandibular canine(s) impaction. METHODS: Dental models of 43 subjects diagnosed with mandibular canine(s) impaction (Impaction Group - IG) were compared with those of 86 subjects of a control reference sample (Control Group - CG). Independent t-test and chi-square tests were used to determine the association between mandibular canine(s) impaction and the MMD of the incisors and the incisor relationship, respectively. The likelihood of various incisor relationships between the IG and CG were evaluated according to odds ratios. RESULTS: A fourfold increase (p < 0.0001) in the overall frequency of Class II/2 incisor relationship was observed in the IG when compared to controls. CONCLUSIONS: The null hypothesis was rejected. Subjects with mandibular canine(s) impaction appeared to be characterised with wider incisors and a remarkably high rate of Class II/2 malocclusion. This information assists the understanding of genetically controlled dental anomalies, which are likely to coexist with mandibular canine(s) impaction.

Leiomyosarcoma of the bone: Unveiling the mystery of a spindly ossein.

ABSTRACT: Leiomyosarcoma (LMS) represents one of the most common soft tissue sarcomas, involving various anatomical sites like the retroperitoneum, genitourinary tract, and extremities. LMS of the bone is extremely rare, with a 0.7% incidence of all primary malignant bone tumors. They are histologically identical to the leiomyosarcomas of other sites but pose a diagnostic dilemma due to their rarity and varied presentation when it manifests as a bony lesion.

Nutrition and diet for dry eye disease: Insights toward holistic management.

Dry eye disease (DED) is one of the most common eye problems in the aging population. Hyperosmolarity triggers the immune response in DED and consequently activates the self-perpetuating immune cycle, leading to chronic damage of the ocular surface. This event causes symptoms such as a burning sensation, irritation, redness, photophobia, and blurred vision in DED patients. Subsequently, the quality of life gets significantly affected. The rising demand for DED management and treatment solutions, and the desirable outcomes from innovative therapies that draw global interest provide evidence to demonstrate the role of diet and nutrition in DED. Nutritional deficiency and a Westernized diet contribute to the chronic systemic progression of DED symptoms. It has been revealed in several published studies that the use of nutrients and dietary supplements improves the ocular surface and acts as a protective factor against DED. - We reviewed nutrition and dietary aspects in managing DED and its associated consequences, based on published studies, and reached an evidence-based conclusion.

Restoring Vitality: The Science and Practice of Pulp Revascularization in Endodontics.

Pulp revascularization is an emerging treatment modality in endodontics aimed at preserving the vitality and function of immature permanent teeth with necrotic pulp and apical periodontitis. This review provides a comprehensive examination of the current state of pulp revascularization, encompassing its rationale, clinical procedures, indications, contraindications, advantages, limitations, and potential future prospects. By critically analyzing the existing literature and clinical experiences, this review aims to offer insights into the efficacy, challenges, and potential advancements in the field of pulp revascularization.

A Clinical Study of Anterior Abdominal Wall Hernias and Its Management: A Medical College Experience.

Objective We aim to evaluate the various risk factors contributing to the occurrence of anterior abdominal wall hernias and assess the various surgical modalities. Materials and methods This prospective observational research was conducted between 2022 and 2024 at a tertiary care health center, involving 100 participants with an anterior abdominal wall hernia diagnosis aged over 14 years. The study excluded patients under 14 years with bleeding diathesis, inherited coagulopathies, inguinal or femoral hernias, or recurrent ventral hernias. Participants underwent detailed clinical examinations and biochemical evaluations and underwent a primary ultrasonography (USG)/contrast-enhanced computed tomography (CECT) to determine defect size. Risk factors were documented, including age, gender, occupation, body mass index (BMI), comorbidities, previous surgery history, multiparity, smoking, chronic straining due to constipation or benign prostatic hyperplasia (BPH), malnutrition, chronic steroid use, chronic renal failure, and chronic liver disease. The surgical procedure was determined by the same surgical team for all cases. Standard antibiotic prophylaxis and preoperative painting/draping protocols were followed in all cases. Intraoperatively, intraoperative time (in hours) was documented. Postoperative parameters included pain, hematoma formation, seroma formation, surgical site infections (SSIs), and early recurrence. These intra- and postoperative findings constituted the primary outcome parameters. Secondary outcome parameters included hospital stay duration and time taken to return to work. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 16 (IBM SPSS Statistics, Armonk, NY) software. Results The study analyzed the occurrence of ventral hernias in 100 patients, with the fourth decade having the highest occurrence (n=42 (42%)). The majority of the participants were male (female: n=47 (47%), male: n=53 (53%)). The majority of the participants were laborers, and 24% (n=24) were office workers. The study found that hypertension, diabetes mellitus, and chronic obstructive pulmonary disease were risk factors for hernias. Other risk factors included obesity, previous history of surgery, multiparity, smoking, chronic straining, malnutrition, and chronic steroid use. The most common type of ventral hernia was umbilical hernia (n=33 (33%)), followed by paraumbilical hernias (n=30 (30%)), and incisional hernias (n=20 (20%)). Of the 100 patients, 74% underwent open hernia repair, with the mean operation time being minimal in cases managed with laparoscopic repair (2.5±0.67 hours). Postoperative pain was highest with the Rives-Stoppa (RS) repair with component separation group. The incidence of surgical site infection was the maximum among cases of open anatomical repair (41.7%), followed by RS repair (31.3%), while it was the minimum in laparoscopic repair (3.7%). Early recurrence was lower in the laparoscopic group (n=1 (3.7%)). Conclusion The study highlights risk factors for abdominal wall hernia and management approaches. Understanding these is crucial for identifying and preventing recurrence. Surgeons must choose the right surgical approach based on patient health and symptoms to achieve desired outcomes and minimize complications. In addition, surgical expertise, availability of resources, and knowledge of what works best for the surgeon constitute important determinants of surgical outcomes.

Hydatid Cyst in the Thigh: An Unusual Extra-hepatic Site.

Echinococcus granulosus, a cystic parasite, is the cause of hydatid illnesses. The liver and lungs are the most commonly affected organs. In this study, we report a rare instance of a hydatid cyst of the thigh. A 42-year-old male had been experiencing swelling on his left thigh that gradually increased in size. Upon examination, a firm, non-tender swelling measuring 12 x 8 x 8 cm at the lateral aspect of the left thigh was present. The diagnosis of a hydatid cyst in the thigh was confirmed by magnetic resonance imaging (MRI). The patient underwent surgical intervention and had an uneventful recovery post-operatively. The treatment for a hydatid cyst in the thigh, a rare parasitic condition that presents as a painless swelling and is typically diagnosed through MRI, involves en bloc resection. Therefore, surgeons must consider hydatidosis as a potential diagnosis when evaluating swelling in the thigh.

Comprehensive analysis of systemic, metabolic, and molecular changes following prospective change to low-carbohydrate diet in adults with type 2 diabetes mellitus in India.

Purpose: South Asians, especially Indians, face higher diabetes-related risks despite lower body mass index (BMI) compared with the White population. Limited research connects low-carbohydrate high-fat (LCHF)/ketogenic diets to metabolic changes in this group. Systematic studies are needed to assess the long-term effects of the diet, such as ocular health. Method: In this prospective, observational study, 465 candidates aged 25-75 years with type 2 diabetes included with institutional ethics approval. A total of 119 subjects were included in the final study assessment based on the availability of pathophysiological reports, tears, and blood samples collected at baseline, 3rd, and 6th months. Serum and tear samples were analyzed by an enzyme-linked lectinsorbent assay, to examine secreted soluble protein biomarkers, such as IL-1ß (interleukin 1 Beta), IL-6 (interleukin 6), IL-10 (interleukin 10), IL-17A (interleukin 17A), MMP-9 (matrix metalloproteinase 9), ICAM-1 (intercellular adhesion molecule 1), VEGF-A (vascular endothelial growth factor A), and TNF-α (tumor necrosis factor-alpha). A Wilcoxon test was performed for paired samples. Spearman's correlation was applied to test the strength and direction of the association between tear biomarkers and HbA1c. p-value of < 0.05 was considered significant. Results: After a 3- and 6-month LCHF intervention, fasting blood sugar decreased by 10% (Δ: -14 mg/dL; p < 0.0001) and 7% (Δ: -8 mg/dL; p < 0.0001), respectively. Glycated hemoglobin A1c levels decreased by 13% (Δ: -1%; p < 0.0001) and 9% (Δ: -0.6%; p < 0.0001). Triglycerides reduced by 22% (Δ: -27 mg/dL; p < 0.0001) and 14% (Δ: -19 mg/dL; p < 0.0001). Total cholesterol reduced by 5.4% (Δ: -10.5 mg/dL; p < 0.003) and 4% (Δ: -7 mg/dL; p < 0.03), while low-density lipoprotein decreased by 10% (Δ: -11.5 mg/dL; p < 0.003) and 9% (Δ: -11 mg/dL; p < 0.002). High-density lipoprotein increased by 11% (Δ: 5 mg/dL; p < 0.0001) and 17% (Δ: 8 mg/dL; p < 0.0001). At the first follow-up, tear proteins such as ICAM-1, IL-17A, and TNF-α decreased by 30% (Δ: -2,739 pg/mL; p < 0.01), 22% (Δ: -4.5 pg/mL; p < 0.02), and 34% (Δ: -0.9 pg/mL; p < 0.002), respectively. At the second follow-up, IL-1ß and TNF-α reduced by 41% (Δ: -2.4 pg/mL; p < 0.05) and 34% (Δ: -0.67 pg/mL; p < 0.02). Spearman's correlation between HbA1c and tear analytes was not statistically significant. Conclusion: The LCHF diet reduces the risk of hyperglycemia and dyslipidemia. Changes in tear fluid protein profiles were observed, but identifying promising candidate biomarkers requires validation in a larger cohort.

The effect of surface conditioning techniques on the shear bond strength of zirconia-reinforced lithium silicate ceramic following adhesive cementation - An in vitro study.

Aim: The aim of this study was to determine the effect of different surface conditioning techniques on the bond strength between zirconia-reinforced lithium silicate (ZLS) ceramics and resin cement. Materials and Methods: Fifty samples of ZLS ceramic were used and allotted into five groups with 10 samples per group based on the type of surface conditioning technique. The ceramic specimens were crystallized and embedded into acrylic resin. The five groups were group 1 (negative control-without surface treatment); group 2 (10% hydrofluoric [HF] acid + silanization); group 3 (10% HF acid only); group 4 (self-etching ceramic primer [SECP]); and group 5 (experimental laboratory sealing of the conditioned surface). Resin cylinders were bonded using self-adhesive resin cement and were subjected to thermocycling after 24 h storage. The shear bond strength was tested with a universal testing machine. Statistical Analysis Used: One-way ANOVA was used for comparing five groups (P < 0.05 was considered significant). Results: Group 4 showed the highest mean bond strength value (23.4 MPa ± 2.21 MPa). A statistically significant difference was noted between group 4 and all the other groups tested in the study (P < 0.05). Conclusion: It can be concluded that the SECP can be considered an alternative to the conventional protocol of HF acid and silane application for the surface conditioning of ZLS ceramic.

Wind turbine with line-side PMSG FED DC-DC converter for voltage regulation.

This article represents a novel study of the design and analysis of a wind turbine system that includes a line-side permanent magnet synchronous generator (PMSG) with an ultra-step-up DC-DC converter for voltage regulation. Integrating renewable energy sources such as wind power into the grid requires efficient and reliable power conversion systems to handle fluctuating power and ensure a stable power supply. The wind turbine system utilizes a PMSG, which offers several advantages over traditional induction generators, including higher efficiency, reduced maintenance, and better power quality. The line-side configuration allows for increased control and flexibility, allowing the system to respond dynamically to grid conditions. This wind turbine system involves the integration of a grid-side PMSG-fed DC-DC converter between the PMSG and the grid. The converter enables a seamless flow of electricity between the wind turbine and the grid. By actively controlling the intermediate circuit voltage, the converter efficiently regulates the output voltage of the wind turbine and thus enables constant power generation regardless of fluctuating wind speeds. The simulation outcomes illustrate the efficacy of the proposed system in achieving voltage regulation and seamless integration with the grid. Performance is evaluated under various operating conditions and compared to conventional wind turbines.