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Our study compared the diagnostic accuracy of the 10% alcohol-formalin cell-block (CB) technique against traditional smears (CS) in serous effusions over 1 year. CB outperformed CS by detecting 7 missed cases and diagnosing 177 benign, 5 suspicious and 26 malignant cases compared to CS's 180 benign, 9 suspicious and 19 malignant cases. Using histopathology as a gold standard, CB showed a sensitivity of 96.4%, specificity of 98.3% and diagnostic accuracy of 98.1%, significantly higher than CS's 79.3% sensitivity, specificity of 97.7% and 95.2% accuracy. Using a 10% alcohol-formalin method, CB also excelled in cytomorphological characterization, especially in background elements, cellularity and cellular architecture. CB offered improved diagnostic accuracy and allowed extra sections for additional tests. In resource-constrained settings, combining CS and CB enhances cytological assessment., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The glenopolar angle (GPA), usually ranges from 30° to 45°. GPA measures the tilt of the plane of the glenoid cavity in relation to the axis of the body of the scapula passing from the superior pole of the glenoid cavity to the inferior angle of the scapula. It is essential to assess the results of surgeries for dislocated shoulders. Worse long-term outcomes can arise from glenoid misalignment in scapular neck fractures. When evaluating prognosis and planning therapy for shoulder injuries including scapular fractures, GPA assessment is essential. Still, there is a dearth of data on the normal range of GPA and its contributing elements, which calls for more study. The purpose of this study is to determine typical GPA values by utilizing radiographs and a sizable sample of scapular bone specimens., Methods: In this study, the GPA was assessed in 50 chest radiographs of anteroposterior (AP) view and Neer's view of individuals as well as 100 dried scapulae of any gender. The mean GPA obtained using the various methods was then statistically compared., Findings: All scapulae had an average GPA of 42.6°. Twenty-nine scapulae had GPA observations higher than 45°, with an average of 47.2°. Twenty-seven scapulae had GPA measurements below 40°, averaging 37.3°. Right-sided 62 scapulae with an average GPA of 43.1° were present. Thirty-eight of left-side scapulae had a GPA of 41.7° on average. It was determined that the 1.6° mean difference in GPA between the two groups was not statistically significant. The Kolmogorov-Smirnov test verified that the GPA data had a normal distribution. The homogeneity of variances across various measuring techniques was confirmed using Levene's test. The average GPA measured using the dry scapula approach was 42.6°, the average GPA measured using the AP view was 39.8°, and the average GPA measured using the Neer I view was 42.3°. The GPA means from these three approaches differed considerably (p=0.0014) according to a one-way Analysis of Variance (ANOVA). Fisher's least significant difference post hoc testing showed that the scapular bone specimens and the Neer I view revealed significantly higher GPA values than AP shoulder radiographs. The GPA values obtained from the osteological group and the Neer I perspective had a mean difference of 0.21°, which was practically identical and suggested that there was no statistically significant difference between these approaches., In Summary: In order to diagnose and treat a variety of shoulder joint diseases, this study estimates the normal values of scapular GPA. Furthermore, it offers support for improved implant design in the context of Indian shoulder joint replacement and repair. Using every measurement technique, the GPA values on the right and left sides did not differ significantly. GPA results from various measuring methods varied significantly, which emphasizes the significance of methodological consistency in clinical and research settings., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethical Committee issued approval 604/IEC/IGIMS dated 18/12/2018. I hereby affirm that the Institutional Ethical Committee or Ethics Committee has approved the research conducted for this article. The protocols and methodologies employed in this study have been carefully reviewed and deemed ethically sound in accordance with the established guidelines and regulations. Furthermore, all necessary permissions and consent procedures have been obtained from relevant participants or stakeholders involved in this research. The confidentiality and anonymity of participants have been rigorously maintained, and their rights and welfare have been upheld throughout the course of this study. This statement affirms the ethical integrity and compliance of the research conducted upholding the highest standards of ethical conduct. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kumari et al.)

Recently, the 5-HT 7 receptor has achieved greater attention in research fraternity due to the involvement of neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) in several neurological disorders. Targeting this neuroreceptor, we have synthesized six compounds named as butyl-benzoxazolone substituted piperazinium derivatives (BBOP) derivatives, abbreviated as L1-L6. These compounds have been evaluated for their binding interaction with BSA through photophysical and in-silico approaches. The UV absorption of these compounds with BSA at λ max  = 280 nm, showed an optical density (O.D.) in the range of 0.5-0.9, i.e., 21%-53% (L1 max  = 1.4, L5 min  = 0.7385) at varied concentrations (17 μM-114 μM). For fluorescence studies, the K sv value varied inversely with temperature, which confirmed the static mechanism of quenching with L1 showing maximum quenching. The parameters (ΔH, ΔS) obtained from the thermodynamic study for interaction between BSA and L1-L6 were correlated with in-silico (molecular docking) data. The in-silico docking study showed hydrophobic and the Van der Waals forces were the most significant forces. Amino acid residues ARG 217 & TRP 213 (Sudlow Site I) and LYS 116 & GLU 125 (Sudlow Site II) of BSA were primarily involved in H-bonding.Furthermore, the catalytic activity of BSA for hydrolyzingdifferent chemical entities have monitored in the presence of L1-L6 through esterase-like assay with p-NPA as a substrate, to get more insight about the interaction with catalytic residues (LYS 414, LYS 413, and TYR 411) in BSA at site II. These findings showed the potential of these 5-HT7 markers as promising ligands with appropriate drug likeliness characteristics., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Although studies of the sacral corridor dimension have been reported in the European population, little attention has been paid to this issue in the Asian population. The purpose of the study is to estimate the safe dimension of the corridor to avoid neurovascular damage during the fixation of the sacral fracture. The study aimed to examine the cephalocaudal (vertical) and the anteroposterior diameter of the bony passage in the upper three sacral segments. The study further examines the effect of age and sex on corridor dimensions at different sacral levels. Three-dimensionally reconstructed sacra from computed tomography of normal subjects were included in the study. Cephalocaudal and anteroposterior diameters were measured in coronal and axial sections using Geomagic Freeform Plus software. Anteroposterior diameter of the sacral corridor at the first, second, and third sacral segments are significantly higher in males ( P =0.013, 0.0011, and <0.0001, respectively). The length of the sacrum also revealed sexual dimorphism ( P <0.00016). The anteroposterior diameter of the second sacral segment (ap-S2c) correlated moderately with the first sacral anteroposterior diameter (ap-S1c) (R=0.519, P <0.001). The ap-S2c exhibited a moderate correlation to the third sacral segment (ap-S3c) (R=0.677, P <0.001). The sacral corridor at the level of S1 has the largest cephalocaudal (18.25 mm) and anteroposterior diameter (17.11 mm). Placement of the screw in the first sacral corridor may avoid damage to the neurovascular bundle during the fixation of the sacral fracture.

In the West, National Early Warning Score 2 (NEWS2) is commonly applied to predict the severity of illness using only bedside variables unlike the extensive Pneumonia Severity Index (PSI). The objective of this study was to compare these scores as mortality predictors in patients admitted with community acquired pneumonia (CAP). This cross-sectional study was conducted in Jinnah Postgraduate Medical Centre, Karachi, Pakistan, for six months in 2020 on 116 patients presenting with CAP. Cases of aspiration pneumonia, hospital acquired pneumonia, pulmonary tuberculosis, pulmonary embolism, and pulmonary oedema were excluded. In-hospital mortality was taken as the outcome of this study. The mean age of the participants was 46.9±20.5 years. The in-hospital mortalities were 45(38.8%). NEWS2 was 97.8% sensitive but only 15.5% specific in predicting the outcome, whereas PSI was less sensitive (68.9%) but more specific (50.7%), which showed that in comparison with PSI, NEWS2 is a more sensitive mortality predicting score among hospitalised CAP patients.

Heavy metal pollution is a significant global health concern, posing risks to both the environment and human health. Exposure to heavy metals happens through various channels like contaminated water, food, air, and workplaces, resulting in severe health implications. Heavy metals also disrupt the gut's microbial balance, leading to dysbiosis characterized by a decrease in beneficial microorganisms and proliferation in harmful ones, ultimately exacerbating health problems. Probiotic microorganisms have demonstrated their ability to adsorb and sequester heavy metals, while their exopolysaccharides (EPS) exhibit chelating properties, aiding in mitigating heavy metal toxicity. These beneficial microorganisms aid in restoring gut integrity through processes like biosorption, bioaccumulation, and biotransformation of heavy metals. Incorporating probiotic strains with high affinity for heavy metals into functional foods and supplements presents a practical approach to mitigating heavy metal toxicity while enhancing gut health. Utilizing probiotic microbiota and their exopolysaccharides to address heavy metal toxicity offers a novel method for improving human health through modulation of the gut microbiome. By combining probiotics and exopolysaccharides, a distinctive strategy emerges for mitigating heavy metal toxicity, highlighting promising avenues for therapeutic interventions and health improvements. Further exploration in this domain could lead to groundbreaking therapies and preventive measures, underscoring probiotic microbiota and exopolysaccharides as natural and environmentally friendly solutions to heavy metal toxicity. This, in turn, could enhance public health by safeguarding the gut from environmental contaminants., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ca 9 Y(VO 4 ) 7 phosphor activated with Er 3+ ions have been developed by the urea-aided solution combustion technique. XRD profiles assisted with Rietveld refinement executed over-developed Er 3+ -activated Ca 9 Y(VO 4 ) 7 powder, revealed a trigonal phase with the R3c space group. The electron microscope techniques namely TEM and SEM characterize the size and surface-linked qualities of the developed nanopowder, respectively. The uniform distribution of various elements in the nanocrystalline sample is authenticated by an energy-dispersive spectroscopy (EDS) system. The E g (band gap) value of 3.64 eV for Ca 9 Y 0.9 Er 0.1 (VO 4 ) 7 and 3.74 eV for Ca 9 Y(VO 4 ) 7 has been estimated. Upon 382 nm excitation, Er 3+ : Ca 9 Y(VO 4 ) 7 phosphor gives rise to the bright green emission owing to the 4 S 3/2 → 4 I 15/2 transition. The concentration quenching after 10 mol% composition of trivalent erbium ions is attributed to dipole-dipole interlinkages in accordance with Dexter's theory. The radiative lifetime (1.1083 ms), non-radiative rates (0.2079 ms - 1 ), quantum efficiency (79%), along with colorimetric parameters i.e. CIE x (= 0.2577), y (= 0.4566), and CCT quantities offer Ca 9 Y 0.9 Er 0.1 (VO 4 ) 7 as a proficient green radiating nanomaterial for RGB phosphors in solid-state applications., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Heart failure (HF) patients frequently present with comorbidities such as atrial fibrillation (AF) or other cardiovascular conditions, elevating their risk of thromboembolic events. Consequently, anticoagulation therapy is often considered for thromboprophylaxis, although its initiation in HF patients is complicated by concomitant bleeding risk factors. This review explores the paradoxical relationship between HF, increased bleeding risk, and the potential benefits of anticoagulation. Through an examination of existing evidence from clinical trials, observational studies, and meta-analyses, we aim to elucidate the role of anticoagulation in HF patients with increased bleeding risk. Despite guidelines recommending anticoagulation for certain HF patients with AF or other thromboembolic risk factors, uncertainty persists regarding the optimal management strategy for those at heightened risk of bleeding. The review discusses the pathophysiological mechanisms linking HF and thrombosis, challenges in bleeding risk assessment, and strategies to minimize bleeding risk while optimizing thromboprophylaxis. Shared decision-making between clinicians and patients is emphasized as essential for individualized treatment plans that balance the potential benefits of anticoagulation against the risk of bleeding complications. Furthermore, it examines emerging anticoagulant agents and their potential role in HF management, highlighting the need for further research to delineate optimal management strategies and inform evidence-based practice. In conclusion, while anticoagulation holds promise for improving outcomes in HF patients, careful consideration of patient-specific factors and ongoing research efforts are essential to optimize therapeutic strategies in this population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Saeed et al.)

Diversely substituted methoxy derivatives of arylpiperazinyl-alkyl benzothiazolone has been evaluated as specific probe for 5HT 7 . To determine the best methoxy derivative for 5HT 7 receptor affinity, we synthesised a number of 2-benzothiazolone arylalkyl piperazine derivatives. In-vitro/vivo studies with C-2 substituted [ 11 C]ABT showed 5HT 7 specific binding. The radiochemical purity of [ 11 C]ABT was found to be more than 99% with radiochemical stability persistence for more than 1.5 hr at 25 °C. The interaction of BSA and ABT has been analysed by photophysical studies for better understanding of properties such as adsortion, distribution, metabolism and elemination (ADME). The interaction between ABT and BSA was analyzed by using the UV-vis and fluorescence spectra. UV-vis spectra analyzed the changes in primary structure of BSA on its interaction with ABT. ABT showed quenched fluorescence emission intensity of tryptophan residues in BSA via static quenching mechanism. This study might help to understand how ABT binds to serum protein or subsequently to know the ADME of this drug candidate., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The gut-brain axis (GBA) is a two-way communication system that is influenced by signals from the nervous system, hormones, metabolism, the immune system, and microbes. The GBA may play a key role in gastrointestinal and neurological illnesses. Signaling events from the gut can regulate brain function. As a result, mounting data point to a connection between autoimmune disorders (AIDs), both neuroinflammatory and neurodegenerative diseases, and the GBA. Clinical, epidemiological, and experimental studies have shown that a variety of neurological illnesses are linked to alterations in the intestinal environment, which are suggestive of disease-mediated inter-organ communication between the gut and the brain. This review's objective is to draw attention to the clinical and biological relationship between the gut and the brain, as well as the clinical importance of this relationship for AIDs, neurodegeneration, and neuroinflammation. We also discuss the dysbiosis in the gut microbiota that has been linked to various AIDs, and we make some assumptions about how dietary changes such as prebiotics and probiotics may be able to prevent or treat AIDs by restoring the composition of the gut microbiota and regulating metabolites., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Khawar et al.)

Quantification of bacterial colonies on an agar plate is a daily routine for a microbiologist to determine the number of viable microorganisms in the sample. In general, microbiologists perform a visual assessment of bacterial colonies which is time-consuming (takes 2 min per plate), tedious, and subjective. Some automatic counting algorithms are developed that save labour and time, but their results are affected by the non-illumination on an agar plate. To improve this, the present manuscript aims to develop an inexpensive and efficient device to acquire S.aureus images via an automatic counting method using image processing techniques under real laboratory conditions. The proposed method (P&#95;ColonyCount) includes the region of interest extraction and color space transformation followed by filtering, thresholding, morphological operation, distance transform, and watershed technique for the quantification of isolated and overlapping colonies. The present work also shows a comparative study on grayscale, K, and green channels by applying different filter and thresholding techniques on 42 images. The results of all channels were compared with the score provided by the expert (manual count). Out of all the proposed method (P&#95;ColonyCount), the K channel gives the best outcome in comparison with the other two channels (grayscale and green) in terms of precision, recall, and F-measure which are 0.99, 0.99, and 0.99 (2 h), 0.98, 0.99, and 0.98 (4 h), and 0.98, 0.98, 0.98 (6 h) respectively. The execution time of the manual and the proposed method (P&#95;ColonyCount) for 42 images ranges from 19 to 113 s and 15 to 31 s respectively. Apart from this, a user-friendly graphical user interface is also developed for the convenient enumeration of colonies without any expert knowledge/training. The developed imaging device will be useful for researchers and teaching lab settings., Competing Interests: Declaration of Competing Interest The author declares that they have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Hepatitis E virus (HEV) is a major cause of epidemic water-borne hepatitis in tropical and subtropical countries in areas with poor sanitary conditions. The infection by HEV in children is frequent but typically asymptomatic or manifested only as a very mild disease without jaundice, and usually, it often goes undiagnosed. In this case report, the authors describe a case of hepatitis-E-induced cholestasis in a child., Case Presentation: An 8-year-old male child presented to a Pediatrics emergency with fever and features of acute cholestasis. On abdominal examination, there was non-tender hepatomegaly. The rest of the systemic examinations were normal. Ultrasonography findings were suggestive of acute hepatitis. The liver biopsy report showed hepatic cholestasis and hepatitis. The serological test for hepatitis E IgM was positive. The child was managed symptomatically., Conclusion: Although cholestasis is uncommon in children with HEV infection, it should be considered for non-improving clinical status in children with hepatitis. Also, patients with jaundice and Hepatitis E should be followed up by treating physicians until resolution occurs. To the authors' knowledge, this is the first case report from Nepal describing cholestasis in a child due to HEV infection., Competing Interests: There are no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Due to heterogeneity in the organs involved and a variety of influencing factors, a wide range of clinical manifestations are possible in systemic lupus erythematosus (SLE). In our knowledge, a combination of leg ulcer and dysentery as presenting symptoms of SLE has never been reported previously., Patient Concerns: A 13-year-old female child presented with a chronic wound over right medial malleolus for 6 months, and passing of watery stool, later mixed with blood, for 4 days. On examination, she had a fever of 38.5°C. Lab reports revealed anemia, thrombocytopenia, proteinuria, and features of urinary tract infection. Renal biopsy showed membranous glomerulonephropathy. She was positive for antinuclear antibodies (ANA) and antidouble stranded DNA (anti-dsDNA). Immunofluorescence revealed reduced C4 and C3 levels. Abdominal ultrasound showed symmetrical circumscribed thickening, and edematous cecum and ascending colon., Diagnosis: The patient was diagnosed with SLE based on the Systemic Lupus International Collaborating Clinics classification criteria., Interventions: The patient was treated with prednisolone, hydroxychloroquine, metronidazole, ciprofloxacin, trypsin-chymotrypsin, zinc, calcium, and calcitriol tablets., Outcomes: Fever subsided within 3 days of treatment. Gastrointestinal symptoms subsided within 1 week of treatment. On 31 day of treatment, the wound had been reduced and showed features of healing., Conclusion: Dysentery and leg ulcers can be the manifestations of SLE. Therefore, SLE should also be considered when a patient presents with such symptoms. Any suspicion of infection in SLE should be treated aggressively with antibiotics., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: We examined the associations between the 6-year incidence of age-related macular degeneration (AMD) and vision-related quality of life (VRQoL), and the contribution of presenting visual acuity (VA), in an Asian population., Methods: Fundus images from the Singapore Chinese Eye Study, a population-based cohort study (baseline: 2009-2011; follow-up: 2015-2017), were graded using a modified Wisconsin age-related maculopathy grading system. Incident AMD was defined as no baseline AMD in both eyes and early/late AMD in the worse eye at follow-up. Presenting VA was assessed using the logarithm of the minimum angle of resolution chart at 4 m under standard lighting conditions with habitual correction. Multiple linear regression models determined the associations between AMD incidence with changes in the Rasch-transformed scores of the Reading, Mobility and Emotional VRQoL domains of the 32-item Impact of Visual Impairment (IVI-32) questionnaire, adjusted for traditional confounders. The contribution of presenting VA to changes in VRQoL was also estimated., Results: Of the 2251 participants without AMD at baseline (mean age (SD): 57.7 (9) years, 51.4% women), 101 (4.5%) and 11 (0.5%) developed incident early and late AMD at follow-up, respectively. Incident late AMD was associated with significant 30.3%, 32.5% and 30.9% decrements in Reading, Mobility and Emotional IVI scores, respectively. The contribution of presenting VA ranged between 1.62% and 4.35% of the observed decrements. No significant associations were noted with incident early AMD., Conclusion: Incident late AMD had a substantial impact on all aspects of VRQoL, with presenting VA contributing only minimally to this longitudinal relationship., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Efforts are underway to improve the diagnosis and treatment for neurological disorders like depression, anxiety, epilepsy, and schizophrenia. The G-protein-coupled receptors (GPCRs) 5-HT 7   receptor, the most recently identified member of 5-HT receptor family dysregulation has an association with various central nervous system (CNS) disorders and its ligands have an edge as potential therapeutics. Here, we report the synthesis, characterization, and biological evaluation of diversely substituted methoxy derivatives of 2-benzoxazolone arylpiperazine for targeting 5-HT 7  receptors. Out of all derivatives, only C-2 substituted derivative, 3-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)benzoxazol-2(3H)-one/ABO demonstrate a high affinity for human 5-HT 7 receptors. [ 11 C]ABO was obtained by O-methylation of desmethyl-precursor using [ 11 C]CH 3 OTf in the presence of NaOH giving a high radiochemical yield of 25 ± 12% (decay-corrected, n = 7) with stability up to 1.5 h postradiolabeling. In vitro autoradiography displays binding of [ 11 C]ABO in accordance with 5-HT 7 distribution with a decrease of approximately 80% and 40% activity in the hippocampus and cerebellum brain region when administered with 10 µM cold ligand. Prefatory positron emission tomography scan results in Sprague-Dawley (SD) rat brain revealed fast and high radioactivity build-up in 5-HT 7 receptor-rich regions, namely, the hippocampus (2.75 ± 0.16 SUV) and the cerebral cortex (2.27 ± 0.02 SUV) establishing selective targeting of [ 11 C]ABO. In summary, these pieces of data designate [ 11 C]ABO as a promising 5-HT 7  receptor ligand that can have possible roles in clinics after its further optimization on different animal models., (© 2022 Wiley Periodicals LLC.)

The translocator protein (TSPO, 18 kDa) is one of the most promising biomarker to understand the role of neuroinflammation in human as well as in different animal species. Here we report a new TSPO-selective ligand 2-(5-(2-(bis(pyridin-2-yl methyl)amino)acetamido)-2-oxobenzo[d] oxazol-3(2H)-yl)-N-methyl-N-phenylacetamide, BBPA, which is supposed to be a potential probe to understand the role of TSPO in neuro-glial interaction through SPECT modality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cognitive function is a crucial determinant of human capital. The Lancet Commission (2020) has recognized air pollution as a risk factor for dementia. However, the scientific evidence on the impact of air pollution on cognitive outcomes across the life course and across different income settings, with varying levels of air pollution, needs further exploration. A systematic review was conducted, using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Guidelines to assess the association between air pollution and cognitive outcomes across the life course with a plan to analyze findings as per the income status of the study population. The PubMed search included keywords related to cognition and to pollution (in their titles) to identify studies on human participants published in English until 10 July 2020. The search yielded 84 relevant studies that described associations between exposure to air pollutants and an increased risk of lower cognitive function among children and adolescents, cognitive impairment and decline among adults, and dementia among older adults with supportive evidence of neuroimaging and inflammatory biomarkers. No study from low- and middle-income countries (LMICs)was identified despite high levels of air pollutants and high rates of dementia. To conclude, air pollution may impair cognitive function across the life-course, but a paucity of studies from reLMICs is a major lacuna in research.

Quantitative changes in expression level of 5HT 1A are somewhere related to common neurological disorders such as anxiety, major depression and schizophrenia. We have designed EDTA conjugated SPECT imaging probe for localization of 5HT 1A receptor in brain. For designing SPECT probe we have employed the concept of bivalent approach and a homodimeric system with desirable pharmacokinetics of 5HT 1A imaging. 99m Tc-EDHT was also evaluated for its stability through serum stability assay and glutathione challenge experiment. Biodistribution study showed the highest accumulation of radioactivity in kidney which depicted the renal mode of excretion from the body. However in brain the uptake of 1.21% ID per gram was observed in initial 5 min of drug administration. On blocking the receptor this percent get decreased to 0.97% ID per gram. The regional distribution in brain was also performed which showed the accumulation of drug in cerebellum, cortex and hippocampus part, which are already known for 5HT 1A expression. Dynamic study in rabbit is also in support of results derived from biodistribution and blood kinetics experiment. These finding suggest that 99m Tc-EDHT holds promising place for further optimization before nuclear medicine applications in different animal species., (Copyright © 2021. Published by Elsevier Inc.)

Apple scar skin viroid (ASSVd), the type member of the genus Apscaviroid, induces symptoms only on fruits, which include colour dappling, russeting, cracking and distortion. Studies on viroid incidence were conducted during past five years and incidence up to 90.0 percent was recorded in commercial apple cultivars (Royal Delicious, Red Delicious, Red Gold, Golden Delicious). From 2015 to 2018, forty apple orchards were surveyed in different blocks of Shimla district of Himachal Pradesh and fruits in six orchards were found with typical symptoms of apple scar skin viroid infection without symptoms on leaves. The presence of ASSVd in symptomatic fruits and symptomless leaves were confirmed by RT- PCR. It was also revealed that ASSVd infection not only deteriorate the quality of apple fruits but cause large losses in term of yield, as 17.80 quintal less fruit production was recorded in the affected orchards with loss in net return up to Rs. 3,91,102/- per hectare (72.68% loss in net return per hectare)., (© Indian Virological Society 2020.)

The present work demonstrates the application of a composite of the zeolite imidazole framework (ZIF-67) and reduced graphene oxide (rGO), synthesized via a simple hydrothermal route for the sensitive sensing of ammonia. The successful synthesis of ZIF-67 and rGO composite was confirmed with structural and spectroscopic characterizations. A porous structure and a high surface area (1080 m 2 g -1 ) of the composite indicate its suitability as a gas sensing material. The composite material was coated as a thin film onto interdigitated gold electrodes. The sensor displays a change in its chemoresistive property (i.e., resistance) in the presence of ammonia (NH 3 ) gas. A sensor response of 1.22 ± 0.02 [standard deviation (sd)] is measured for 20 ppm of NH 3 , while it shows a value of 4.77 ± 0.15 (sd) for 50 ppm of NH 3 . The fabricated sensor is reproducible and offers a stable response, while also providing tolerance against humidity and some other volatile compounds. The average response and recovery times of the sensor, for 50 ppm NH 3 concentration, are found to be 46.5 ± 2.12 (sd) and 66.5 ± 2.12 (sd) s, respectively. The limit of detection of the sensor was found to be 74 ppb., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Background/aims: In order to address the eye care needs of the increasing numbers of elderly Chinese globally, there is a need for comprehensive understanding on the longitudinal trends of age-related eye diseases among Chinese. We herein report the key findings from the baseline Singapore Chinese Eye Study (SCES-1), and describe the rationale and methodology of the 6-year follow-up study (SCES-2)., Methods: 3353 Chinese adults who participated in the baseline SCES-1 (2009-2011) were invited for the 6-year follow-up SCES-2 (2015-2017). Examination procedures for SCES-2 included standardised ocular, systemic examinations and questionnaires identical to SCES-1. SCES-2 further included new examinations such as optical coherence tomography angiography, and questionnaires to evaluate health impact and economic burden of eye diseases., Results: In SCES-1, the age-adjusted prevalence of best-corrected low vision (VA<6/12, better-seeing eye) and blindness (VA<6/60, better-seeing eye) were 3.4% and 0.2%, respectively. The prevalence rates for glaucoma, age related macular degeneration, and diabetic retinopathy (among diabetics) were 3.2%, 6.8%, 26.2%, respectively. Of the 3033 eligible individuals from SCES-1, 2661 participated in SCES-2 (response rate=87.7%). Comparing with those who did not attend SCES-2, those attended were younger, had higher SES (all p<0.001), but less likely to be a current smoker, to have diabetes, hypertension, hyperlipidaemia (all p≤0.025)., Conclusions: Building on SCES-1, SCES-2 will be one of the few longitudinal population-based eye studies to report incidence, progression, and risk factors of major age-related eye diseases. Findings from this cohort may offer new insights, and provide useful reference information for other Chinese populations elsewhere., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The aim of this study was to determine whether cataract surgery was associated with age-related macular degeneration (AMD) development in Asian patients., Design: Longitudinal cohort study., Methods: Participants from the Singapore Malay and Indian Eye Studies were recruited between 2004 and 2015. A total of 6790 late-AMD-free eyes from 3475 individuals were followed for 6 years on average. Multivariable regression analysis using generalized estimating equations determined associations between cataract surgery and the incidence of any, early, and late AMD., Results: The mean age (SD) of participants was 55.5 (9.1) years; 48.1% were male; 11.3% of eyes had cataract surgery recorded; incident any, early, and late AMD developed in 238 (3.6%), 222 (3.4%), and 29 (0.4%) eyes, respectively. Operated eyes had higher incidence of late AMD [1.4% vs 0.3%; adjusted risk ratio (RR): 3.47, 95% confidence interval (CI) 1.40-8.57], but not early AMD (6.0% vs 3.0%, adjusted RR: 1.12, 95% CI 0.76-1.64) or any AMD (6.9 vs 3.2%, adjusted RR: 1.23, 95% CI 0.85-1.78)., Conclusions: Our data are consistent with findings in population-based Caucasian studies that cataract surgery may be associated with incidence of late AMD. However, the absolute risk of late AMD development remains low and physicians should continue to balance the benefits and risks of cataract surgery in elderly patients.

This paper presents research work about the design and fabrication of a 44-layer optical reflective notch filter. The performance of the fabricated notch filter was studied at normal (0°) and oblique (45°) incidence angle. In addition, the paper also discusses a three-layer broadband antireflective coating on both sides of the multilayer stack to suppress the ripples in the passband region. The thickness-modulated reflective stack of the filter was designed by using the materials A l 2 O 3 (1.63) and S i O 2 (1.46). Optimization of the multilayer stack was carried out by using the damped least-squares algorithm. The theoretical and experimental results from the ion-assisted e-beam deposited samples for single notch reflective filters are presented. Good agreement in the design and experimental results was observed when the deposition process was controlled by time of evaporation. Further, the filter was characterized for the optical properties by using a UV-VIS-NIR spectrophotometer, surface morphology and protective properties using field emission scanning electron microscopy, a coherence correlation interferometer, and water contact angle.

Aims: Diabetes is a major public health problem in migrants and ethnic minorities worldwide. We determined the incidence and risk factors of diabetic retinopathy (DR) in migrant Indians living in Singapore., Methods: We included data from 759 Indian adults with diabetes, who participated in the baseline (aged 40-80 years, 2007-2009) and 6-year follow-up 2012-2015 of the Singapore Indian Eye Study. Retinal photographs were graded for the presence and severity of DR using modified Airlie House Classification. Incidence was assessed in participants who were free of DR at baseline visit (n=501), while progression in those with DR but free of proliferative DR at baseline visit (n=189). Risk factors included demographic, lifestyle, socioeconomic, family history, genes, duration of diabetes, glycaemic control, insulin use, ocular and clinical factors., Results: The 6-year age-standardised DR incidence and progression were 21.89% and 33.45%, respectively. HbA1c (risk ratio (RR) 1.41, 95% CI 1.28 to 1.55 per unit increase), current smoking (RR 1.63, 95% CI 1.02 to 2.62) and insulin use (RR 2.63, 95% CI 1.44 to 4.82) were associated with higher incidence, whereas estimated cerebrospinal fluid pressure (RR 0.90, 95% CI 0.82 to 0.98) and body mass index (BMI) (RR 0.74, 95% CI 0.60 to 0.93) were associated with lower incidence of DR. Higher HbA1c (RR 1.26, 95% CI 1.13 to 1.42), BMI (RR 1.26, 95% CI 1.02 to 1.56) and estimated cerebrospinal fluid pressure (RR 1.11, 95% CI 1.02 to 1.21) were associated with DR progression. The population attributable risk of HbA1c >8% was 41.29% and 49.63% for DR incidence and progression., Conclusion: DR incidence and progression in migrant Indians living in Singapore was more than double that reported in Indians living in urban India. Consistent with past studies, poor glycaemic control was an important predictor for incidence and progression of DR., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Arterial stiffness has been associated with diabetic retinopathy; however, the information is limited in Asians. We aim to examine the association of central arterial stiffness with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus patients in Singapore., Methods: Arterial stiffness was estimated by carotid-femoral pulse wave velocity and augmentation index using applanation tonometry method. Digital colour fundus photographs from 1,203 patients were assessed for diabetic retinopathy. Diabetic retinopathy severity was categorized into non-proliferative diabetic retinopathy and proliferative diabetic retinopathy. Logistic regression model was used to evaluate the associations of diabetic retinopathy with pulse wave velocity and augmentation index., Results: Diabetic retinopathy was diagnosed in 391 (32.5%) patients, including 271 non-proliferative diabetic retinopathy and 108 proliferative diabetic retinopathy. Diabetic retinopathy have higher pulse wave velocity (11.2 ± 3.3 vs 9.5 ± 2.6 m/s, p  < 0.001) and augmentation index (28.4 ± 9.4 vs 26.1 ± 10.6%, p  < 0.001) than non-diabetic retinopathy. After multivariable adjustment, pulse wave velocity [odds ratio = 1.11 (95% confidence interval = 1.05-1.17), p  < 0.001] and augmentation index [odds ratio = 1.03 (95% confidence interval = 1.01-1.04), p  = 0.009] was associated with diabetic retinopathy. In severity analyses, pulse wave velocity was associated with non-proliferative diabetic retinopathy [odds ratio = 1.10 (95% confidence interval = 1.03-1.17), p  = 0.002] and proliferative diabetic retinopathy [odds ratio = 1.15 (95% confidence interval = 1.06-1.25), p  = 0.001] ( p -trend < 0.001). Augmentation index showed significant associations with non-proliferative diabetic retinopathy [odds ratio = 1.02 (95% confidence interval = 1.01-1.04), p  = 0.008], but not with proliferative diabetic retinopathy [odds ratio = 1.01 (95% confidence interval = 0.98-1.04), p  = 0.36] ( p -trend = 0.03)., Conclusion: Central arterial stiffness was associated with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus patients, suggesting its etiologic implication in diabetic retinopathy.

The association between objective measures of body composition (BC) with type 2 diabetes (T2DM) is inconclusive. We conducted a systematic review and meta-analysis to examine the association between several body composition (BC) indices assessed using dual energy X-ray absorptiometry (DXA), and T2DM. Using PRISMA guidelines, we searched for observational studies investigating BC measures, including total body fat mass (BFM), visceral fat mass (VFM), subcutaneous fat mass (SFM), and fat free mass (FFM); and T2DM. Of 670 titles initially identified, 20 were included. High VFM was consistently associated with T2DM. For every kg increase in VFM, the odds of having T2DM increased by two-fold for males (OR 2.28 [95% CI 1.42 to 3.65], p = 0.001) and more than 4-fold for females (OR 4.24 [1.64 to 11.02], p = 0.003). The presence of T2DM was associated with 2-fold higher odds of low FFM (OR 2.38 [1.44 to 3.95]). We found evidence that greater VFM is a risk factor for prevalent and incident T2DM. While the presence of T2DM is associated with reduced FFM; the relationship between FFM and BFM with T2DM remains unclear. Reducing VFM and increasing FFM through lifestyle changes may reduce the risk of T2DM and mitigate its deleterious effect on BC, respectively.

Aim: We aim to examine the association of plasma leucine-rich-α-2-glycoprotein 1 (LRG1) with diabetic retinopathy (DR) in type 2 diabetes., Methods: At baseline visit, plasma LRG1 levels were assessed using ELISA. Central arterial stiffness was estimated by carotid-femoral pulse wave velocity (PWV). At follow-up visit (median = 3.2 years), digital color fundus photographs were assessed for DR. DR severity was categorized into non-proliferative DR (NPDR) and proliferative DR (PDR)., Results: DR was diagnosed in 396 (32.8%) of 1206 patients. DR has higher LRG1 than non-DR (19.5 ± 11.3vs.16.9 ± 8.9 μg/ml, p ≪ 0.001). After adjustment, LRG1 was not associated with DR (OR = 1.2, [95% CI, 0.96-1.30], p = 0.16). LRG1 was higher in PDR (n = 107) than NPDR (n = 270) (23.2 ± 15.4vs.18.1 ± 8.9 μg/ml, n = 270, p ≪ 0.001). After adjustment, with 1-SD increase in LRG1, the relative risk of NPDR and PDR was 0.99 ([0.83-1.18], p = 0.91) and 1.42 ([95% CI, 1.14-1.76], p = 0.002) (p-trend = 0.01), respectively. We didn't observe significant improvement in AUC after adding LRG1 into the model. Baseline PWV mediated 12.0% of the association between LRG1 and PDR (p = 0.03)., Conclusion: Baseline plasma LRG1 is associated with PDR, suggesting it maybe a promising biomarker for prediction for advanced proliferative stages of DR. The mediation result indicates the potential benefit of ameliorating central arterial stiffness to prevent PDR., (Copyright © 2019. Published by Elsevier Inc.)

Background/aims: To assess the independent impact of diabetic retinopathy (DR) on three domains of vision-related quality of life (VRQoL) in a Chinese Singapore population., Methods: The Singapore Chinese Eye Study (n=3353; 2009-2011) was a population-based, prospective, cross-sectional study conducted at the Singapore Eye Research Institute. The study population included 292 adults with diabetes, with and without DR. DR (better eye) was categorised as presence and absence of any DR; severity of DR (no vision-threatening DR (VTDR); severe non-proliferative DR (NPDR); PDR and/or clinically significant macular oedema and VTDR). Our main outcome was VRQoL which was measured using Rasch-calibrated scores from the 'Reading', 'Mobility' and 'Emotional' domains of the Impact of Vision Impairment questionnaire. The relationship between DR and VRQoL was assessed using multiple linear regression models., Results: Of the 292 individuals (mean age 61.35 ± 9.66 years; 55.8% male), 201 (68.8%), 49 (16.8%), 20 (6.8%), 22 (7.5%) and 27 (9.2%) had no DR, minimal-mild NPDR, moderate-severe NPDR, PDR and VTDR, respectively. Any DR and VTDR were independently associated with 6% and 12% worse Reading scores and 7% and 18% poorer Emotional well-being, respectively, compared with those without DR. These associations persisted after separate adjustment for visual impairment and presenting visual acuity. No significant difference was found in the Mobility domain between persons with and without DR., Conclusions: We documented that DR, particularly VTDR, was independently associated with restrictions in Reading and Emotional well-being. Understanding factors underlying the detrimental DR-VRQoL relationship may optimise rehabilitation outcomes for individuals with DR., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) [year]. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Staphylococcus aureus is a notorious pathogen which often causes nosocomial and community attained infections. These infections steadily increased after evolving the resistance due to indecorous practice of antibiotics and now become a serious health issue. Ouabain is a Na + /K + -ATPase inhibitor that leads to increase the heart contraction in patients with congestive heart failure., Methods: In the present study, in vitro antimicrobial effect of ouabain together with aminoglycosides was determined against clinical and non-clinical S. aureus strains. Using checkerboard, Gentamycin uptake and biofilm assays, we analysed he interactions of ouabain with aminoglycosides., Results: Ouabain induced the staphylocidal potency of aminoglycosides by remarkably reducing the MIC of gentamycin (GEN) by 16 (0.25 μg/mL), 8 folds (0.5 μg/mL) amikacin (AMK); and 16 folds (1.0 μg/mL) with kanamycin (KAN), compared to their individual doses. OBN severely reduced cell viability within 60 min with GEN (1 μg/mL), KAN (2 μg/mL) and 90 min with AMK (1 μg/mL). This bactericidal effect was enhanced due to GEN uptake potentiated by 66% which led to increase the cell permeability as revealed by leakage of bacterial ATP and nitrocefin assay. The biofilm adherence disrupted by 80 and 50% at 5 mg/mL and 1.5 mg/mL OBN and 50 and 90% biofilm formation was inhibited at 5 mg/mL (MBIC 50 ) and 10 mg/mL (MBIC 90 ), respectively. Moreover, OBN with GEN further induced biofilm inhibition by 67 ± 5% at pH 7.0., Conclusions: Taken together, we established that OBN synergizes the antimicrobial activity of aminoglycosides that induces cell killing due to intracellular accumulation of GEN by disturbing cell homeostasis. It may be proven an effective approach for the treatment of staphylococcal infections.

Objective: The aim of our case-control study was to determine expression of VEGFA mRNA in placentae of preeclamsia (PE) versus uncomplicated pregnancy to further clarify its differential expression in pregnancy hypertensive disorders., Study Design: The PE group was subdivided into severe and non-severe; those with or without HELLP syndrome and placental VEGFA characteristics were compared for these cohorts. Additionally, the neonatal and maternal outcomes were recorded. The quantification of placental VEGFA was done using quantitative real-time PCR and results were expressed as fold change., Results: Out of 42 PE cases, 23 (55%) were non-severe and 19 cases (45%) were severe PE. Out of 19 severe PE patients, 8 (42%) were HELLP syndrome (complete HELLP) and remaining 11 (58%) were non-HELLP severe PE. Compared to controls, the true fold change in PE, HELLP, non-HELLP, severe PE, non-severe PE was - 2.186, - 13.333, - 6.698, - 8.950 and 1.466, respectively., Conclusions: Our results showed a lowered VEGFA expression in PE placentae compared to uncomplicated controls. The finding of initial increase of VEGFA in non-severe PE and subsequent marked lowering in HELLP strengthens the existing hypothesis of decompensated VEGF being a major role player in PE., Competing Interests: The authors declare that they have no conflict of interest.Informed consent was obtained from all individual participants included in the study.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Background: Fluctuation of kidney function may signify intra-glomerular microvascular hemodynamic instability. We aim to examine the association of long-term serum creatinine and estimated glomerular filtration rate variability with diabetic retinopathy., Methods: We included type 2 diabetes mellitus patients who attended the Diabetes Centre in 2011-2014 and were followed up (median = 3.2 years). Digital colour fundus photographs were assessed for diabetic retinopathy at follow-up. Diabetic retinopathy severity was categorized into non-proliferative diabetic retinopathy and proliferative diabetic retinopathy. We conducted a nested case-control study involving 177 diabetic retinopathy (118 non-proliferative diabetic retinopathy, 50 proliferative diabetic retinopathy) and 327 age- and gender-matched non-diabetic retinopathy. Serum creatinine measured before follow-up visit was obtained (⩾3 readings/patient). Variability was calculated as intra-individual standard deviation/√ n/( n - 1)., Results: Diabetic retinopathy have higher adjusted-serum creatinine-standard deviation than non-diabetic retinopathy [9.1 (4.9-21.6) vs 5.4 (3.4-10.1) µM, p < 0.001]. After multivariable adjustment, adjusted-serum creatinine-standard deviation was associated with diabetic retinopathy [odds ratio = 1.47, 95% confidence interval (1.02-2.10), p = 0.04]. The area under the curve increased significantly after adding adjusted-serum creatinine-standard deviation [0.70 (0.65-0.75) vs 0.72 (0.68-0.77), p < 0.03]. Proliferative diabetic retinopathy have higher adjusted-serum creatinine-standard deviation than non-proliferative diabetic retinopathy [15.5 (6.6-39.7) vs 7.47 (4.52-17.8) µM, p < 0.001]. After adjustment, adjusted-serum creatinine-standard deviation remained associated with non-proliferative diabetic retinopathy [1.48 (1.04-2.12), p = 0.03] and proliferative diabetic retinopathy [2.43 (1.34-4.39), p = 0.003; p-trend = 0.002]. Similar findings were observed for estimated glomerular filtration rate variability., Conclusion: Serum creatinine and estimated glomerular filtration rate variability is associated with the presence and severity of diabetic retinopathy independent of intra-individual means. This may inform novel therapeutic strategies aiming to achieve stable renal function in type 2 diabetes mellitus.

To evaluate the association between serum carotenoids and quantitative measures of retinal vasculature in elderly Singapore Chinese subjects. The following details were collected in 128 healthy subjects: sociodemographics, lifestyle information, medical and drug history, and anthropometric measurements. Serum concentrations of carotenoids were estimated in fasting venous blood using high performance liquid chromatography. Retinal vascular parameters were quantitatively measured from retinal photographs using a computer-assisted program (Singapore I Vessel Assessment). The mean age of the population was 54.1 years (range 40 to 81 years). In multiple linear regression analysis, per SD decrease in retinal arteriolar caliber [β = 0.045 (0.003 to 0.086), p = 0.036], per SD increase in retinal venular caliber [β = -0.045 (-0.086 to -0.003), p = 0.036] and per SD increase in arteriolar branching angle [β = -0.039 (-0.072 to -0.006), p = 0.021] were associated with decreased serum lutein. Per SD increase in retinal venular tortuosity [β = -0.0075 (-0.0145 to -0.0004), p = 0.039] and per SD increase in arteriolar branching angle (β = -0.0073 [-0.0142 to -0.0059], p = 0.041) were associated with decreased serum zeaxanthin. None of the other carotenoids demonstrated meaningful relationship with quantitative measures of retinal vasculature. Lower levels of lutein and zeaxanthin demonstrated significant relationship with adverse quantitative measures of retinal vasculature in elderly healthy subjects., Competing Interests: Alexandra Health Private Limited does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: The introduction of tyrosine kinase inhibitors has transformed the care of patients with chronic myeloid leukemia, with survival approaching that of healthy individuals. Current-day challenges in chronic myeloid leukemia care include adherence to tyrosine kinase inhibitor therapy. We studied adherence from resource-constrained settings and tried to analyze the factors responsible for nonadherence in these individuals. We also correlated adherence to current molecular status., Patients and Methods: This was a single-center, cross-sectional, observational study from north India. It consisted of a questionnaire-based survey in which a one-to-one interview technique was used by trained nursing staff administering the Modified Morisky Adherence Scale (MMAS-9) questionnaire. Adherence was also measured on the basis of physician's assessment. JMP 13.0.0 was used for statistical analysis., Results: A total of 333 patients with a median age of 42 years were included in the study. The median BCR-ABL/ABL ratio (IS) was 0.175 (0.0 to 98.0). The mean MMAS-9 score was 11 ± 2. Adherence was seen in 54.95% on the basis of MMAS-9, whereas physician's assessment reported adherence in 90.39% of patients. Using the χ 2 test, no relationship was found between the two assessment techniques. There was a significant relationship between major molecular response status and adherence by physician's assessment and MMAS-9 ( P < .001). Bivariate analysis by logistic fit showed a good relation between the MMAS-9 score and the BCR-ABL/ABL ratio (IS), χ 2 (1,220) = 135.45 ( P < .001). On multivariate analysis, enrolment in the Novartis Oncology Access program (a patient assistance program) was significantly associated with adherence ( P = .012)., Conclusion: This study highlights the lack of adherence in real-world settings and the various factors responsible. Such studies are important from a public health services perspective in various settings around the world because they may lead to corrective action being taken at the institutional level.

Purpose: To investigate the independent impact of the incidence and progression of diabetic retinopathy (DR) on visual functioning (VF)., Design: Population-based cohort study., Participants: A total of 518 participants aged 40 to 80 years (baseline visit 2007-2009 and second visit 6 years later, 2013-2015), with diabetes, clinical data, and VF information at both visits., Main Outcome Measures: VF-7 scores, converted to interval-level person measures (in logits) using Rasch analysis., Methods: Incident DR was defined using the Modified Airlie House classification as "none or minimal" DR at baseline and at least mild nonproliferative DR at follow-up; incident vision-threatening DR (VTDR; severe nonproliferative DR, proliferative DR, and/or clinically significant macular edema) as no VTDR at baseline, and present at follow-up; and DR progression as at least a 1-step worsening in DR at follow-up from mild or worse status at baseline. The longitudinal associations between incident DR, VTDR, and DR progression, as well as change in composite and individual item scores of VF, were assessed using multivariable linear regression models., Results: Of the 518 participants (mean age ± standard deviation [SD] 59.8±9.0 years; 47.7% female), 42 (9.8%), 14 (2.8%), and 32 (42.7%) had incident DR, incident VTDR, and DR progression, respectively, at follow-up. In models adjusting for traditional confounders, persons with incident DR and VTDR had a 13.7% (β = -0.60; 95% confidence interval [CI], -0.96 to -0.24; P = 0.001) and 23% (β = -1.00; 95% CI, -1.61 to -0.38; P = 0.001) reduction in mean VF scores at follow-up. Furthermore, individuals with incident DR had similar independent reductions in scores for 7 individual items of the VF-7, whereas those with incident VTDR had the largest reductions for activities like cooking (31%; P = 0.003), reading the newspaper (29.6%; P < 0.001), and seeing street signs (28%, P = 0.001) at follow-up. Progression of DR was not independently associated with change in overall VF (β = -0.18; 95% CI, -1.00, 0.64; P = 0.660)., Conclusions: Incident DR, particularly vision-threatening stages, has a substantial negative impact on people's overall vision-dependent functioning and specific activities such as cooking, seeing street signs, and reading the newspaper. Our findings reinforce the need for strategies to prevent or delay the development of DR., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Osteopontin (OPN) is a proinflammatory cytokine with diverse functions. Increased levels of OPN in vitreous fluid have been reported in patients with diabetic retinopathy (DR); however, studies on circulating OPN levels in DR are limited. We aim to examine the association of plasma OPN levels with the presence and severity of DR in a multiethnic cohort with type 2 diabetes mellitus (type 2 diabetes) in Singapore., Methods: Plasma levels of OPN were measured using enzyme-linked immunosorbent assay. Digital color fundus photographs were assessed for DR. DR severity was categorized into non-proliferative DR (NPDR) and proliferative DR (PDR). Gradable fundus photographs and OPN measurements for 443 patients were used for analysis. A logistic regression model was used to evaluate the association of OPN with DR., Results: DR was diagnosed in 174 (39.3%) patients, including 132 (75.9%) with NPDR and 42 (24.1%) with PDR. The median of OPN was higher in the patients with DR (64.7 [49.7-89.5] ng/ml) than in the patients without DR (51.7 [38.9-66.9] ng/ml; p<0.001). After adjustment for clinical and biochemical factors, a 1-unit increase in nature logarithm (ln)-transformed OPN was associated with the presence of DR (2.770 [1.599-3.800], p<0.001). The area under the curve (AUC) increased statistically significantly after the addition of OPN (0.805[0.763-0.846] versus 0.825 [0.785-0.865], p=0.011). In the severity analyses, the median of OPN was statistically significantly higher in the patients with PDR (76.8 [55.0-103.6] ng/ml) than in the patients with NPDR (61.7 [47.7-87.3] ng/ml; p=0.017). After adjustment, the 1-unit increase in lnOPN remained associated with NPDR (2.673 [1.519-4.704], p=0.001) and PDR (3.389 [1.254-9.226], p=0.017), respectively (p-trend=0.001)., Conclusions: Plasma OPN levels were associated with the presence and severity of DR in patients with type 2 diabetes, suggesting OPN may be useful as a potential biomarker for DR.

Importance: Asian Indians are the fastest growing migration groups in the world. Studies evaluating the impact of migration on disease outcomes in this population are rare., Background: We describe the methodology of the Singapore Indian Eye Study-2 (SINDI-2) aimed to evaluate the impact of migration status on diabetic retinopathy and other major age-related eye diseases in Asian Indians living in an urban environment., Design: Population-based cohort study., Participants: A total of 2200 adults had participated in baseline SINDI (2007-2009, mean age [range] = 57.8 [42.7-84.1] years) and SINDI-2 (2013-2015, 56.5 [48.4-90.2] years)., Methods: Participants were classified as 'first generation' if they were Indian residents born outside of Singapore and as 'second-generation' immigrants (59.7% in SINDI vs. 63.6% in SINDI-2) if they were born in Singapore., Main Outcome Measures: Response rate, participant characteristics and prevalence of systemic diseases were stratified by migration status., Results: Of the 2914 eligible SINDI participants invited to participate, 2200 participated in SINDI-2 (response rate of 75.2%). In both SINDI and SINDI-2, compared with first-generation immigrants, second-generation immigrants were younger, less likely to have income <1000 SGD, had lower levels of pulse pressure, higher levels of high-density lipoprotein cholesterol, had lower prevalence of hypertension and chronic kidney disease and had higher prevalence of current smoking and obesity (all P < 0.05)., Conclusions and Relevance: In both SINDI and SINDI-2, second-generation immigrants had lower prevalence of cardiovascular risk factors except smoking and obesity compared with first-generation immigrants. The final report will confirm if these differences between generations are evident with regard to eye diseases., (© 2017 Royal Australian and New Zealand College of Ophthalmologists.)

We have synthesized six new congeners of acetamidobenzoxazolone for Translocator Protein [18 kDa, TSPO] imaging. The best in vitro binding affinity (10.8 ± 1.2 nm) for TSPO was found for N-methyl-2-(5-(naphthalen-1-yl)-2-oxobenzo[d]oxazol-3(2H)-yl)-N-phenylacetamide, (NBMP). NBMP was synthesised by Suzuki coupling reaction between 2-(5-bromo-2-oxo-1,3-benzoxazol-3(2H)-yl)-N-phenylacetamide and napthalene-1-boronic acid. Computational docking and simulation studies showed not much impact of intersubject variability on binding which is one of the major drawbacks of several TSPO ligands. These findings suggested that NBMP may become a promising marker for visualization of neuroinflammation via TSPO targeting., (© 2017 John Wiley & Sons A/S.)

Aims/hypothesis: We aimed to examine prospectively the association between a range of retinal vascular geometric variables measured from retinal photographs and the 6 year incidence and progression of diabetic retinopathy., Methods: We conducted a prospective, population-based cohort study of Asian Malay individuals aged 40-80 years at baseline (n = 3280) who returned for a 6 year follow-up. Retinal vascular geometric variables (tortuosity, branching, fractal dimension, calibre) were measured from baseline retinal photographs using a computer-assisted program (Singapore I Vessel Assessment). Diabetic retinopathy was graded from baseline and follow-up photographs using the modified Airlie House classification system. Incidence of diabetic retinopathy was defined as a severity of ≥15 at follow-up among those without diabetic retinopathy at baseline. Incidence of referable diabetic retinopathy was defined as moderate or severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy or diabetic macular oedema at follow-up in participants who had had no or mild non-proliferative diabetic retinopathy at baseline. Progression of diabetic retinopathy was defined as an increase in severity of ≥2 steps at follow-up. Log-binomial models with an expectation-maximisation algorithm were used to estimate RR adjusting for age, sex, diabetes duration, HbA 1c level, BP, BMI, estimated GFR and total and HDL-cholesterol at baseline., Results: A total of 427 individuals with diabetes participated in the baseline and 6 year follow-up examinations. Of these, 19.2%, 7.57% and 19.2% developed incidence of diabetic retinopathy, incidence of referable diabetic retinopathy and diabetic retinopathy progression, respectively. After multivariate adjustment, greater arteriolar simple tortuosity (mean RR [95% CI], 1.34 [1.04, 1.74]), larger venular branching angle (RR 1.26 [1.00, 1.59]) and larger venular branching coefficient (RR 1.26 [1.03, 1.56]) were associated with incidence of diabetic retinopathy. Greater arteriolar simple tortuosity (RR 1.82 [1.32, 2.52]), larger venular branching coefficient (RR 1.46 [1.03, 2.07]), higher arteriolar fractal dimension (RR 1.59 [1.08, 2.36]) and larger arteriolar calibre (RR 1.83 [1.15, 2.90]) were associated with incidence of referable diabetic retinopathy. Greater arteriolar simple tortuosity (RR 1.34 [1.12, 1.61]) was associated with diabetic retinopathy progression. Addition of retinal vascular variables improved discrimination (C-statistic 0.796 vs 0.733, p = 0.031) and overall reclassification (net reclassification improvement 18.8%, p = 0.025) of any diabetic retinopathy risk beyond established risk factors., Conclusions/interpretation: Retinal vascular geometry measured from fundus photographs predicted the incidence and progression of diabetic retinopathy in adults with diabetes, beyond established risk factors.

Diabetic retinopathy (DR) is a leading cause of vision-loss globally among type 2 diabetes (T2DM) patients. Information on the economic burden of DR in Singapore is limited. We aim to identify the total annual direct medical costs of DR at different stages, and to examine factors influencing the costs. Four hundreds and seventy T2DM patients who attended the Diabetes Centre in a secondary hospital in Singapore in 2011-2014 were included. Digital color fundus photographs were assessed for DR in a masked fashion. Retinopathy severity was further categorized into non-proliferative DR (NPDR), including mild, moderate and severe NPDR, and proliferative DR (PDR). Medical costs were assessed using hospital administrative data. DR was diagnosed in 172 (39.5%) patients, including 51 mild, 62 moderate and 18 severe NPDR, and 41 PDR. The median cost in DR [2012.0 (1111.2-4192.3)] was significantly higher than that in non-DR patients [1158.1 (724.1-1838.9)] (p<0.001). The corresponding costs for mild, moderate, severe NPDR and PDR were [1167.1 (895.4-2012.0)], [2212.0 (1215.5-3825.5)], [2717.5 (1444.0-6310.7)], and [3594.8.1 (1978.4-8427.7)], respectively. After adjustment, the corresponding cost ratios for mild, moderate, severe NPDR, and PDR relative to non-DR were 1.1 (p = 0.827), 1.8 (p = 0.003), 2.0 (p = 0.031) and 2.3 (p<0.001), respectively. The other factors affecting the total cost include smoking (ratio = 1.7, p = 0.019), neuropathy (ratio = 1.9, p = 0.001) and chronic kidney disease (CKD) (ratio = 1.4, p = 0.019). The presence and severity of DR was associated with increased direct medical costs in T2DM. Our results suggest that preventing progression of DR may reduce the economic burden of DR.

With the rising incidences of cancer cases, the quest for new metal based anticancer drugs has led to extensive research in cancer biology. Zinc complexes of amino acid residue side chains are well recognized for hydrolysis of phosphodiester bond in DNA at faster rate. In the presented work, a Zn(II) complex of cyclen substituted with two l-tryptophan units, Zn(II)-Cyclen-(Trp) 2 has been synthesized and evaluated for antiproliferative activity. Zn(II)-Cyclen-(Trp) 2 was synthesized in ∼70% yield and its DNA binding potential was evaluated through QM/MM study which suggested good binding (G=-9.426) with B-DNA. The decrease in intensity of the positive and negative bands of CT-DNA at 278nm and 240nm, respectively demonstrated an effective unwinding of the DNA helix with loss of helicity. The complex was identified as an antiproliferative agent against U-87MG cells with 5 fold increase in apoptosis with respect to control (2h post incubation, IC 50 25µM). Electrophoresis and comet assay studies exhibited an increase in DNA breakage after treatment with complex while caspase-3/β-actin cleavage established a caspase-3 dependent apoptosis pathway in U-87 MG cells after triggering DNA damage. In vivo tumor specificity of the developed ligand was validated after radiocomplexation with 99m Tc (>98% radiochemical yield and specific activity of 2.56GBq/µmol). Avid tumor/muscle ratio of >6 was depicted in biodistribution and SPECT imaging studies in U-87 MG xenograft model nude mice., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Oxidative stress, characterized by an excessive production of reactive oxygen intermediates has been suggested to play a role in the pathogenesis of age-related macular degeneration (AMD). We examined the association of urinary F2-isoprostanes (F2-IsoPs), a marker of lipid peroxidation and the most reliable marker of oxidative damage with AMD., Methods: We included 238 adults with AMD and 390 age- and sex-matched controls without AMD who participated in a population-based cross-sectional study in Singapore (Singapore Chinese Eye Study, 2009-2011). AMD was graded from retinal photographs using the Wisconsin Age-Related Maculopathy Grading System. Urinary-free F2-IsoPs (pmol/mmol of creatinine) were measured by gas chromatography mass spectrometry (GC-MS). The association between F2-IsoPs and AMD was examined using unconditional logistic regression models adjusted for potential confounders including smoking, body mass index (BMI), blood pressure, total and high-density lipoprotein cholesterol, and history of cardiovascular disease., Results: Higher levels of F2-IsoPs were associated with AMD independent of potential confounders. Compared to quartile 1 (Q1) of F2-IsoPs, the multivariable odds ratio (95% confidence interval) of AMD in quartiles 2, 3, and 4 were 2.05 (1.26-3.32), 1.80 (1.10-2.94), and 1.76 (1.06-2.94), respectively. In subgroup analyses comparing Q4 to Q1, this association was stronger in women, those with BMI less than 25 kg/m2 and those with hypertension, but no significant interaction was found (P interaction > 0.1 for each strata)., Conclusions: Higher levels of urinary F2-IsoPs levels were associated with AMD independent of potential confounders in Chinese adults.

Background: Genome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP., Methods and Results: We conducted genome-wide analysis among 18 422 East Asian participants (stage 1) followed by replication study of ≤46 629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a P <5.0×10 -8 and 2.5×10 - 6 , respectively, in joint analyses of stage-1 and stage-2 data. We identified 1 novel ARL3 variant, rs4919669 at 10q24.32, influencing LTA systolic BP (stage-1 P =5.03×10 - 8 , stage-2 P =8.64×10 - 3 , joint P =2.63×10 - 8 ) and mean arterial pressure (stage-1 P =3.59×10 - 9 , stage-2 P =2.35×10 - 2 , joint P =2.64×10 - 8 ). Three previously reported BP loci ( WBP1L , NT5C2 , and ATP2B1 ) were also identified for all BP phenotypes. Gene-based analysis provided the first robust evidence for association of KCNJ11 with LTA systolic BP (stage-1 P =8.55×10 - 6 , stage-2 P =1.62×10 - 5 , joint P =3.28×10 - 9 ) and mean arterial pressure (stage-1 P =9.19×10 - 7 , stage-2 P =9.69×10 - 5 , joint P =2.15×10 - 9 ) phenotypes. Fourteen genes ( TMEM180 , ACTR1A , SUFU , ARL3 , SFXN2 , WBP1L , CYP17A1 , C10orf32 , C10orf32 - ASMT , AS3MT , CNNM2 , and NT5C2 at 10q24.32; ATP2B1 at 12q21.33; and NCR3LG1 at 11p15.1) implicated by previous genome-wide association study meta-analyses were also identified. Among the loci identified by the previous genome-wide association study meta-analysis of LTA BP, we transethnically replicated associations of the KCNK3 marker rs1275988 at 2p23.3 with LTA systolic BP and mean arterial pressure phenotypes ( P =1.27×10 - 4 and 3.30×10 - 4 , respectively)., Conclusions: We identified 1 novel variant and 1 novel gene and present the first direct evidence of relevance of the KCNK3 locus for LTA BP among East Asians., (© 2017 American Heart Association, Inc.)

Background: Self-nanoemulsifying drug delivery system (SNEDDS) has immense potential in oral bioavailability enhancement of lipophilic drugs., Objective: This investigation involves the development of thermodynamically stable and dilutable SNEDDS for tolbutamide, for achieving higher water solubility and enhanced dissolution rate which in turn improves its oral bioavailability., Method: Preliminary solubility studies were carried out and pseudo-ternary phase diagrams were plotted for selection of best ratio of surfactant and co-surfactant. The drug loaded SNEDDS were prepared, characterized w.r.t. refractive index, viscocity, globule size, zeta potential, and TEM, and converted into solid self-nanoemulsifying granules (SSNEGs). These were further characterized and their antidiabetic efficacy in male Wistar rats was evaluated., Results: Solubility studies suggested the suitability of oleic acid as lipid phase; Tween 20 and PEG 400 as optimal surfactant and co-surfactant, respectively for formulation of SNEDDS formulations. The optimal SNEDDS formulation having mean globule diameter, viscosity, polydispersity 58.55 ± 0.2 nm, 26.18 ± 0.2 cps, 0.277 respectively, and infinite dilution capability displayed a highly significant increase in dissolution rate within 5 h compared to pure drug suspension. The SSNEGs showed 1.54 fold increase in drug dissolution rate compared to pure drug. Stability studies revealed no significant change in morphology and globule size. Anti-hyperglycemic activity of tolbutamide loaded SSNEGs in rats showed a significant reduction in elevated blood glucose level with absence of ketone and glucose in urine., Conclusion: The present study demonstrates a successful development of SNEDDS formulation with an overall potential of bioavailability enhancement for tolbutamide, a BCS-II drug., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Body mass index (BMI) is an established risk factor for diabetes. However, the association between BMI and diabetic retinopathy (DR) has been inconclusive. We aimed to assess the association between BMI and DR in a large population-based sample of multi-ethnic Asian adults in Singapore. We examined 2,278 adults aged ≥40 years with diabetes who participated in three population-based studies conducted from 2004 to 2011: the Singapore Malay Eye Study, the Singapore Indian Eye Study, and the Singapore Chinese Eye Study. Retinal photographs taken from both eyes were graded for any and vision-threatening (VTDR) using the modified Airlie House Classification. BMI (kg/m(2)) was categorized into normal/underweight (<25), overweight (25-29.9), and obese (≥30). The prevalence rates of any and VTDR in the study population were 35.1 % and 9.1 %, respectively. The prevalence of any and VTDR decreased with increasing categories of BMI (P trend <0.001 and 0.005). In multivariable models adjusted for potential confounders, compared to those with normal weight, the odds ratio (95 % confidence interval) of any DR was 0.71 (0.57-0.88) for overweight and 0.70 (0.53-0.92) for obese. Corresponding estimates for VTDR were 0.84 (0.59-1.21) for overweight and 0.58 (0.35-0.94) for obese. The inverse association between BMI and any DR was consistently present when BMI was analyzed as a continuous variable and in analyses stratified by ethnicity and age. In a population-based sample of multi-ethnic Asian adults, BMI levels were inversely associated with any DR and VTDR.