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In long-standing diabetes mellitus, blood flow to essential organs including the retina is reduced owing to macrovascular and/or microvascular changes. Poor glycolytic pathway of glucose metabolism owing to tissue hypoxia caused by ischemia at capillary bed of essential organs produces excessive lactic acid and less of adenosine triphosphate, which lead to poor cellular function. The purpose of the study was to evaluate the relationship between increased anaerobic glycolysis and visual acuity in type 2 diabetes mellitus without retinopathy. Fifty patients of type 2 diabetes mellitus of 10-12 years duration, without retinopathy, constituted the study group. The controls were 50 age-matched healthy persons without diabetes mellitus. Blood lactate level and best-corrected visual acuity (BCVA) were measured in both the groups. The mean blood lactate level was 1.05 mM/l in the control group and 2.32 mM/l in the study group. BCVA of 20/20 (log MAR 0) was seen in 48 (96%) patients of the control group and in 27 (54%) patients of the study group. BCVA of 20/30 (log MAR 0.2) was seen in 23 (46%) patients in the study group and 2(4%) in the control group. Association of higher blood lactate level with decreased BCVA in the study group was statistically significant (P< 0.001).

Severe local muscle fatigue may be a precursor of repetition strain injuries (RSI). In any event it produces discomfort and limits production. This fatigue is evaluated by analysing the amplitude and frequency of the electromyographic signals of the extensor and flexor muscles during repetitive wrist extension against a constant torque. The absolute integral of the signal increased with extension angle but did not change with the exercise time period. This suggests that amplitude analysis is better for the evaluation of load, and frequency analysis is better in evaluating fatigue. The rate of decrease of the centre frequency with exercise time was also higher for the higher extension angle, and it was higher for female than for male subjects. Ulnar deviation did not affect the rate of fatigue in these experiments. The methodology used here shows promise for the evaluation of tool, job and layout design to prevent RSI. [ABSTRACT FROM PUBLISHER]

A 43-year-old man developed central serous choroidoretinopathy in his left eye following dacryocystorhinostomy operation on the same side. He was using xylometazoline nasal drops in his left nostril. Action of xylometazoline or the stress related to the operation or the effect of both factors played the role in the causation of this ocular condition. Omission of nasal drops or relief from stress resulted in full recovery of vision and complete resolution of symptoms within one month.

Objective: This study aimed to demonstrate the clinical equivalence of biosimilar QL1205 and reference ranibizumab, Lucentis, in patients with neovascular age-related macular degeneration (nAMD)., Design: This was a multicenter, double-masked, randomized, controlled phase III trial., Participants: Treatment-naive patients with active nAMD were randomly assigned to receive QL1205 or reference ranibizumab., Methods: Patients received intravitreal injection of QL1205 or reference ranibizumab at a dose of 0.5 mg in the study eye once every 4 weeks for 48 weeks., Main Outcome Measures: The primary end point was change in best-corrected visual acuity (BCVA) by ETDRS letters at week 8 compared with baseline level. Biosimilarity of QL1205 to reference ranibizumab was assessed with an equivalence range for the difference in BCVA letters between -3.49 and +3.49., Results: Between June 27, 2019 and June 8, 2021, 616 patients were randomized to the QL1205 group (n = 308) and the reference ranibizumab group (n = 308). The mean improvement of BCVA was +6.3 ± 9.13 ETDRS letters in the QL1205 group and +7.3 ± 8.82 ETDRS letters in the reference ranibizumab group at week 8. Both the 90% confidence interval (CI, -2.23 to 0.13) and 95% CI (-2.46 to 0.36) of the difference between the 2 treatment groups (P = 0.1434) were within the predefined equivalence range. Safety profiles were manageable in both groups., Conclusions: QL1205 was biosimilar to reference ranibizumab regarding clinical efficacy, ocular and systemic safety, as well as immunogenicity and pharmacokinetics profiles in the treatment of patients with nAMD., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024. Published by Elsevier Inc.)

Background: Esophageal cancer (EC) is an extremely aggressive tumor with one of the highest geographic, ethnic, and gender variations. Various factors including tobacco consumption, unhealthy diet, and socioeconomic status have been implicated in the etiology of EC. Despite the advent of modern treatments, the prognosis of EC is dismal. This study has been undertaken to review the clinical and pathologic profiles, treatment approach, and survival pattern in patients with EC in a tertiary care hospital in northeast India., Materials and Methods: A retrospective descriptive study was done with 179 EC patients presented to our department between January 2013 and December 2020. Statistical analysis was done by using IBM Statistical Package for the Social Sciences version 21. P- value <0.05 was considered significant., Results: The majority of the patients presented in the sixth decade of life from rural areas with male to female ratio of 3.7:1. Dysphagia was the most common presenting feature. High incidence of tobacco and alcohol use was found. Mid-esophagus is the most common site and squamous cell carcinoma is the most common type. Fifty-two (29.1%) and 71 (39.6%) patients presented in stages III and IV, respectively. Twenty-four (13.4%) patients presented with metastatic disease, the lung being the most common site. Patients were treated with surgery, chemotherapy, radiotherapy, or combination of any of these. Overall median survival for the EC patients was 6 months. Patients treated with concurrent chemoradiation had better survival., Conclusion: EC is a serious malignancy with a dismal prognosis due to the advanced stage at presentation. Larger clinical trials using new therapeutic strategies are the need of the hour., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Background: Brain metastasis increases morbidity and mortality in cancer patients. This study was undertaken to compare tumor response and treatment-related toxicities in patients treated with orally administered thalidomide concomitantly with whole brain radiotherapy to whole brain radiotherapy alone in brain metastases., Methods: This randomized control trial was conducted in radiation oncology department, RIMS among 42 patients of brain metastases distributed in two study arms during the period August 2018 to July 2020. Twenty patients in Arm-A received whole brain radiotherapy to a dose of 3,750 cGy in 15 fractions with concomitant oral thalidomide 200 mg daily in first week and 400 mg/day from second week of radiation onward till the end of radiotherapy, whereas 20 patients of Arm-B received whole brain radiation of 3,750 cGy in 15 fractions alone., Results: Patient characteristics were comparable. Median central nervous system progression free survival was 2 months for Arm-A and 3 months for Arm-B, whereas median overall survival study was 4 months for Arm-A and 3 months for Arm-B. Overall response rate in Arm-A was 56% and in Arm-B was 44%. Treatment-related toxicities were more in arm-A but were manageable., Conclusion: Addition of thalidomide to whole brain radiotherapy makes no significant difference. Though not statistically significant, but still, Arm-A had shown some percentage benefits. Further studies with larger sample sizes should be done., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Purpose: Retinal nerve fibre layer (RNFL) is a sensitive structure, which is affected by anaemia due to hypoxia. A timely detection of RNFL thinning may aid preventing devastating complications. Optical coherence tomography (OCT) measures RNFL thinning with accuracy and helps in detecting thinning of the retinal layer in anaemic patients. This study was destined to evaluate thinning of RNFL in anaemic patients and their correlation with the haemoglobin level., Methods: It was a prospective comparative study. Total of 151 patients were included in this study. Patients with retinal diseases were excluded from this study. After initial evaluation, haematological and ophthalmological parameters were measured. RNFL was measured with OCT and corroborated with the Hb level and analysed accordingly. EPI and SPSS softwares were used for detail analysis and the correlation between RNFL thinning and the Hb level. Initially, each eye was separately assigned a value (0, 1, and 2) (normal, borderline, and abnormal, respectively) as per the severity of thinning, and then, the sum of the scores of both eyes were considered as a separate variable, and a multiple linear regression analysis was performed with the independent variables., Results: RNFL thinning was found to be significant in each group of patients. There was a strong correlation of RNFL thinning with degree of anaemia., Conclusions: Thalassaemia, iron deficiency anaemia, and anaemia of chronic diseases are associated with the significant damage to RNFL. Degree of anaemia is the most important parameter for such thinning of the RNFL layer., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Suhana Datta et al.)

CCCTC-binding factor (CTCF) is a conserved transcription factor that performs diverse roles in transcriptional regulation and chromatin architecture. Cancer genome sequencing reveals diverse acquired mutations in CTCF , which we have shown functions as a tumour suppressor gene. While CTCF is essential for embryonic development, little is known of its absolute requirement in somatic cells and the consequences of CTCF haploinsufficiency. We examined the consequences of CTCF depletion in immortalised human and mouse cells using shRNA knockdown and CRISPR/Cas9 genome editing as well as examined the growth and development of heterozygous Ctcf ( Ctcf +/- ) mice. We also analysed the impact of CTCF haploinsufficiency by examining gene expression changes in CTCF -altered endometrial carcinoma. Knockdown and CRISPR/Cas9-mediated editing of CTCF reduced the cellular growth and colony-forming ability of K562 cells. CTCF knockdown also induced cell cycle arrest and a pro-survival response to apoptotic insult. However, in p53 shRNA-immortalised Ctcf +/- MEFs we observed the opposite: increased cellular proliferation, colony formation, cell cycle progression, and decreased survival after apoptotic insult compared to wild-type MEFs. CRISPR/Cas9-mediated targeting in Ctcf +/- MEFs revealed a predominance of in-frame microdeletions in Ctcf in surviving clones, however protein expression could not be ablated. Examination of CTCF mutations in endometrial cancers showed locus-specific alterations in gene expression due to CTCF haploinsufficiency, in concert with downregulation of tumour suppressor genes and upregulation of estrogen-responsive genes. Depletion of CTCF expression imparts a dramatic negative effect on normal cell function. However, CTCF haploinsufficiency can have growth-promoting effects consistent with known cancer hallmarks in the presence of additional genetic hits. Our results confirm the absolute requirement for CTCF expression in somatic cells and provide definitive evidence of CTCF 's role as a haploinsufficient tumour suppressor gene. CTCF genetic alterations in endometrial cancer indicate that gene dysregulation is a likely consequence of CTCF loss, contributing to, but not solely driving cancer growth.

Intron retention (IR) is widely recognized as a consequence of mis-splicing that leads to failed excision of intronic sequences from pre-messenger RNAs. Our bioinformatic analyses of transcriptomic and proteomic data of normal white blood cell differentiation reveal IR as a physiological mechanism of gene expression control. IR regulates the expression of 86 functionally related genes, including those that determine the nuclear shape that is unique to granulocytes. Retention of introns in specific genes is associated with downregulation of splicing factors and higher GC content. IR, conserved between human and mouse, led to reduced mRNA and protein levels by triggering the nonsense-mediated decay (NMD) pathway. In contrast to the prevalent view that NMD is limited to mRNAs encoding aberrant proteins, our data establish that IR coupled with NMD is a conserved mechanism in normal granulopoiesis. Physiological IR may provide an energetically favorable level of dynamic gene expression control prior to sustained gene translation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The purpose of the study was to evaluate the progression of glaucomatous field damage in patients with stable primary open angle glaucoma after an attack of myocardial infarction. In this case control study, 62 open angle glaucoma patients were selected and regularly followed up. Among 62 patients, 9 had an attack of myocardial infarction. The intra-ocular pressure and visual field progression of both the groups (myocardial infarction versus no myocardial infarction) were analysed. Three (33.3%) out of 9 patients who had suffered from myocardial infarction showed progressive visual field loss whereas only 9 (16.9%) out of 53 patients who did not suffer from myocardial infarction, showed progressive field changes. Both the groups had stable target intra-ocular pressure between 14 and 16 mm Hg. Myocardial infarction may adversely influence the progression of primary open angle glaucoma which is suspected to result from ischaemia induced neuronal loss and only control of intraocular pressure is not the only solution. We have to look for other drugs that prevents ischaemia induced neuronal damage.

Diabetic retinopathy is one of the most common complications in diabetes mellitus due to persistent hyperglycaemia. Various biochemical mechanisms have been suggested to cause this complication. The authors' present study which included 100 patients of type-2 diabetes mellitus with different stages of diabetic retinopathy and without retinopathy shows that initiation of diabetic retinopathy is associated with increased anaerobic glycolysis and accelerated oxidative stress. Progression of this complication is guided by increased secretion of vascular endothelial growth factors. It is our assumption that increased secretion of vascular endothelial growth factors in early part of this disease e.g. before occurrence of morphological abnormality may modify this complication.

A study was conducted to explore the effect of arsenic causing conjunctivitis, neuropathy and respiratory illness in individuals, with or without skin lesions, as a result of exposure through drinking water, contaminated with arsenic to similar extent. Exposed study population belongs to the districts of North 24 Parganas and Nadia, West Bengal, India. A total of 725 exposed (373 with skin lesions and 352 without skin lesions) and 389 unexposed individuals were recruited as study participants. Participants were clinically examined and interviewed. Arsenic content in drinking water, urine, nail and hair was estimated. Individuals with skin lesion showed significant retention of arsenic in nail and hair and lower amount of urinary arsenic compared to the group without any skin lesion. Individuals with skin lesion also showed higher risk for conjunctivitis ((odd's ratio) OR: 7.33, 95% CI: 5.05-10.59), peripheral neuropathy (OR: 3.95, 95% CI: 2.61-5.93) and respiratory illness (OR: 4.86, 95% CI: 3.16-7.48) compared to the group without any skin lesion. The trend test for OR of the three diseases in three groups was found to be statistically significant. Again, individuals without skin lesion in the exposed group showed higher risk for conjunctivitis (OR: 4.66, 95% CI: 2.45-8.85), neuropathy (OR: 3.99, 95% CI: 1.95-8.09), and respiratory illness (OR: 3.21, 95% CI: 1.65-6.26) when compared to arsenic unexposed individuals. Although individuals with skin lesions were more susceptible to arsenic-induced toxicity, individuals without skin lesions were also subclinically affected and are also susceptible to arsenic-induced toxicity and carcinogenicity when compared to individuals not exposed to arsenic.

Purpose: The aim of this study was to report on 2 cases of bilateral chronic conjunctivitis that were associated with the drinking of arsenic-contaminated underground water for a long time., Design: Interventional case reports comprised the study., Methods: This study was a review of clinical data and laboratory investigations., Results: Papillary conjunctivitis developed in 2 members of a family who has been drinking underground water for 15 years. There were severe dermatological changes, including hyperkeratosis, on palms and soles, hypo- and hyperpigmented lesions (rain-drop) on the abdomen, chest, and back. Arsenic levels estimated in the nails and hair of both patients were very high. The arsenic level of the drinking water was above the permissible limit. Histopathological examination of conjunctival tissue confirmed the inflammatory response of a papillary type; however, an arsenic estimation in conjunctival tissue was not possible. There were no inclusions of bodies in conjunctival smears stained with hematoxylin and eosin (H&E) stain. There was no response to the usual treatment for papillary conjunctivitis, which only subsided, along with a regression of dermatological changes, when patients were treated with the chelating agent, dimercaprol, and multivitamin preparations, as well as no longer drinking the contaminated water., Conclusions: This is a rare association and, to the best of our knowledge, the first report of successful treatment with dimercarpol. The source of arsenic was contaminated underground drinking water (from a deep tube-well). The pathophysiology is thought to be the result of an inflammatory response caused by accumulated arsenic in local tissues. Papillary conjunctivitis and dermatological changes can be successfully managed with dimercaprol and multivitamins. Further studies are required to find out the possible link between the papillary response of conjunctiva and arsenic accumulation within the body.

Complete development of eyes occurs between 8 and 11 years, though longitudinal growth of axial length may occur up to 13 years (approximately). Except a few, most of the eye diseases affecting adolescence age group are similar to adult type. Diseases like myopia, keratoconus, vernal keratoconjunctivitis, juvenile diabetic retinopathy and injuries to eye are exclusively diseases of adolescence that are commonly encountered. Psychologically, impact of eye disease on adolescent mind may be profound, thinking they might lose their eyesight. Early detection of diseases, prevention of injuries, health education and frequent eye check-up are essential.

A 7 year-old boy with unilateral septic cavernous sinus thrombosis following a pyoderma in the eyebrow is described. Problems in diagnosis and the role of magnetic resonance imaging (MRI) in the management are highlighted. Patient recovered with mild residual sequelae. The unique feature of this case was absence of chemosis and non-toxic presentation of the patient.

It is now proved that diabetic micro-angiopathy is caused by ischaemia at the capillary bed of retina due to reduced capillary blood flow in long standing type-2 diabetes mellitus. Deranged metabolic process due to chronic hypoxia at the tissue level produces visual and vascular dysfunction. Brimonidine tartrate, an alpha-2 agonist which is commonly used in glaucoma to protect retinal ganglion cells from pressure related ischaemia induced cell apoptosis, is administered in very early stage of non-proliferative diabetic retinopathy to reduce ischaemia at the capillary bed of retina. Improved visual acuity and decreased micro-aneurysm formation, which indicate elimination of ischaemic stimulus at the tissue level, are seen in long standing type-2 diabetes mellitus.

X-ray radiographic examination of the bone fracture healing process is a widely used method in the treatment and management of patients. Medical devices made of metallic alloys reportedly produce considerable artifacts that make the interpretation of radiographs difficult. Fiber reinforced polymer composite materials have been proposed to replace metallic alloys in certain medical devices because of their radiolucency, light weight, and tailorable mechanical properties. The primary objective of this paper is to provide a comparable radiographic analysis of different fiber reinforced polymer composites that are considered suitable for biomedical applications. Composite materials investigated consist of glass, aramid (Kevlar-29), and carbon reinforcement fibers, and epoxy and polyether-ether-ketone (PEEK) matrices. The total mass attenuation coefficient of each material was measured using clinical X-rays (50 kev). The carbon fiber reinforced composites were found to be more radiolucent than the glass and kevlar fiber reinforced composites.