Comparison of patch test positivity after 24 and 48 hours of occlusion time in patients of allergic contact dermatitis: A prospective study.

BACKGROUND: Patch test is the gold standard for diagnosing allergic contact dermatitis. Conventionally, the patches are applied for 48 h, which in tropical weather conditions causes excessive sweating, leading to irritation, and sometimes the patches come off, making the test inconclusive. OBJECTIVE: To compare the patch test positivity after 24 and 48 h of occlusion time in patients of allergic contact dermatitis, using standard allergen concentration. MATERIALS AND METHODS: Clinically suspected patients of allergic contact dermatitis were enrolled and patch tested using the Indian Standard Series, parthenium acetone extracts (1:50, 1:100 and 1:200 dilutions) and patient material. Patches were applied in duplicate on either side of the back, using a random number table. One set of patches was removed after 24-h of occlusion, while the other set after 48-h. Readings were performed at 48- and 96-h by two independent dermatologists, blinded to the duration of occlusion. RESULTS: The study had 97 adult patients (58 males and 39 females; mean age: 48.12 ± 13.07 years). A total of 133 and 142 positive reactions were observed after 48 h occlusion at 48 and 96 h reading, respectively. Of these 117 (87.9%) and 132 (92.9%) patches were positive and concordant and noted at 24 h occlusion time. The Cohen's kappa coefficient were 0.94 for 48 h and 0.97 for 96 h reading, hence showing an almost complete agreement (ⱪ > 0.81) between patches occluded for 24 and 48 h. CONCLUSION: Though there is no significant difference in patch test positivity among ISS allergens after either occlusion time, 48 h occlusion performs significantly better compared with 24 h, when reactions of all allergens (ISS, patient material and parthenium acetone extract) are analysed together.

Report of a collaborative study to establish the first Indian Pharmacopoeia reference standard for teriparatide.

A collaborative study was conducted to establish the first Indian Pharmacopoeia Reference Standard (IPRS) for teriparatide to be used in quality control testing of marketed products in compliance with the Indian Pharmacopoeia (IP) monograph. The study objective was to evaluate the candidate standard in terms of the WHO International Standard (IS) to assign its content in mg per vial terms. This study involved four laboratories from India and the candidate standard was calibrated against the WHO IS by each participant laboratory using high-performance liquid chromatography (HPLC) assay method per IP monograph. Direct calibration of the candidate standard resulted in an assigned content of 1.02 mg per vial. Based on the study results the candidate standard was judged suitable to serve as the first IPRS for teriparatide for identification and assay by HPLC.

Nutrition morbidity interactions in pre-school children.

Background & objectives: Research studies in the 1970s reported that in pre-school children, undernutrition increased the risk of infections and infections aggravated undernutrition. Over decades, there has been a reduction in prevalence of undernutrition and improvement in access to healthcare for treatment of infections. A mixed longitudinal study was undertaken to assess whether over time there were any changes from the earlier reported effect of undernutrition prior to infection on the risk of morbidity and effect of morbidity on nutritional status in pre-school children. Methods: Pre-school (0-59 months of age) children from urban low- and middle-income families whose parents were willing to allow their participation in the study were enrolled. Information on sociodemographic profile of the families was collected at enrolment. Weight of all children and length in infants were recorded every month; length/height in children 12-59 months of age was recorded once in three months. Morbidity information was collected through fortnightly visits. Results: 3888 pre-school children were followed up in 74636 home visits. Among these children, underweight and wasting were associated with a small increase in risk of infections. The odds ratio for risk of infection for underweight children was 1.09 (95% CI: 1.02 to 1.16) and for wasting was 1.18 (95% CI: 1.08 to 1.29). The deterioration in Z scores for weight-for-age and body mass index-for-age in children during illness and convalescence was small but significant (P<0.001). Interpretation & conclusions: The increased risk of infections in undernourished children living in overcrowded tenements in areas with poor environmental hygiene was not significant, perhaps because the risk of infection in normally nourished children was also high. The deterioration in nutritional status following infection was small because of the ready access to and utilization of health and nutrition care.

Comprehensive chemo-profiling of coumarins enriched extract derived from Aegle marmelos (L.) Correa fruit pulp, as an anti-diabetic and anti-inflammatory agent.

Aegle marmelos (L.) Correa is an Indian medicinal plant known for its vast therapeutic activities. In Ayurveda, the plant is known to balance "vata," "pitta," and "kapha" dosh. Recent studies suggest anti-inflammatory, anti-microbial, and anti-diabetic potential but lack in defining the dosage over the therapeutic activities. This study aims to determine the chemical profile of Aegle marmelos fruit extract; identification, enrichment, and characterization of the principal active component(s) having anti-inflammatory and anti-diabetic potential. Targeted enrichment of total coumarins, focusing on marmelosin, marmesin, aegeline, psoralen, scopoletin, and umbelliferone, was done from Aegle marmelos fruit pulp, and characterized using advanced high-throughput techniques. In vitro and in silico anti-diabetic and anti-inflammatory activities were assessed to confirm their efficacy and affinity as anti-diabetic and anti-inflammatory agents. The target compounds were also analysed for toxicity by in silico ADMET study and in vitro MTT assay on THP-1 and A549 cell lines. The coumarins enrichment process designed, was found specific for coumarins isolation as it resulted into 48.61% of total coumarins enrichment, which includes 31.2% marmelosin, 8.9% marmesin, 4% psoralen, 2% scopoletin, 1.7% umbelliferone, and 0.72% aegeline. The quantification with HPTLC and qNMR was found to be correlated with the HPLC assay results. The present study validates the potential use of Aegle marmelos as an anti-inflammatory and anti-diabetic agent. Coumarins enriched from the plant fruit have good therapeutic activity and can be used for Phytopharmaceutical ingredient development. The study is novel, in which coumarins were enriched and characterized by a simple and sophisticated methodology.

Evaluation of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) as an early diagnostic marker of acute kidney injury (AKI) in critically ill trauma patients.

Background and Aims: Acute kidney injury (AKI) is a frequent complication of severe trauma associated with high mortality. The aim of this study was to evaluate the diagnostic ability of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of AKI assessed by RIFLE criteria as reference in trauma patients in intensive care unit (ICU). Material and Methods: This was a prospective observational study. Four hundred and eighteen patients admitted in the trauma ICU with age ≥18 years without known renal diseases were followed-up (serum creatinine, urine output, and estimated glomerular filtration rate) for 5 consecutive days. As per RIFLE criteria, 70 patients were broadly classified as AKI and rest of the patients (n = 348) as non-AKI. Plasma and urine samples of AKI (n = 70) and non-AKI (n = 70) patients were further assessed for 3 consecutive days following admission. Results: Mean plasma NGAL (pNGAL) was significantly elevated in AKI patients as compared with non-AKI patients; on admission: 204.08 versus 93.74 ng/mL (P = 0.01); at 24 h: 216.73 versus 94.63 ng/mL (P = 0.01); and 48 h: 212.77 versus 86.32 ng/mL (P = 0.01). Mean urine NGAL (uNGAL) at 48 h was also significantly elevated: 15.45 ng/mL in AKI patients as compared with 13.48 ng/mL in non-AKI patients (P = 0.01). Plasma and urine NGAL levels were significantly associated with increased mortality. Conclusion: pNGAL had good predictive value on admission (area under the receiver operative characteristic [AUROC] 0.84), at 24 h (AUROC 0.88) and 48 h (AUROC 0.87), while uNGAL had moderate performance at 24 h (AUROC 0.61) and 48 h (AUROC 0.71). pNGAL can be used as an early and potent diagnostic and predictive marker of AKI and mortality in critically ill trauma patients.

3Rs implementation in veterinary vaccine batch-release testing: Current state-of-the-art and future opportunities. A webinar and workshop report.

Regulatory authorities require veterinary batch-release testing to confirm vaccine potency and safety, but these tests have traditionally relied on large numbers of laboratory animals. Advances in vaccine research and development offer increasing opportunities to replace in vivo testing, and some stakeholders have made significant progress in incorporating 3Rs elements in quality control strategies. A three-part event series entitled "3Rs Implementation in Veterinary Vaccine Batch-Release Testing: Current state-of-the-art and future opportunities" was jointly organized by the Animal-Free Safety Assessment Collaboration, HealthforAnimals, and the International Alliance of Biological Standardization. Two webinars and a workshop aimed to outline the state-of-the-art non-animal approaches for veterinary batch-release testing. The events included information on the state of the deletion of obsolete safety testing and the current initiatives implemented by European, North American, and Asian-Pacific stakeholders on 3Rs implementation and regulatory acceptance. The events contributed to a better understanding of the barriers to 3Rs implementation. Participants highlighted the need for open communication, continued collaboration between stakeholders, and international harmonization of regulatory requirements to help accelerate acceptance. Despite the challenges, the countries represented at this three-part event have shared their commitments to advancing the acceptance of alternative methods.

Future of TABST and LABST in the Indian Pharmacopoeia Monographs A Humane Society International/India Workshop Report.

Humane Society International India (HSI India) organized and facilitated a workshop on the 'Future of Target Animal Batch Safety Test (TABST) and Laboratory Animal Batch Safety Test (LABST) in the Indian Pharmacopoeia (IP) Monographs'. The workshop hosted key Indian regulators from the Indian Pharmacopoeia Commission (IPC) and the Central Drugs Standard Control Organization (CDSCO), industry representatives from the Indian Federation of Animal Health Companies (INFAH), Asian Animal Health Association (AAHA), and international experts representing the European Directorate for the Quality of Medicines (EDQM), the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), and multinational veterinary products manufacturers. The workshop was organized to encourage a bidirectional flow of information and to discuss the deletion of TABST and LABST from the veterinary vaccine monographs in the IP. This workshop was built from the symposium held by Humane Society International on the 'Global Harmonization of Vaccine Testing Requirements' held in 2019. This report details the outcomes of the workshop with proposed activities to be taken up as part of the next steps for the elimination or waiving of these tests.

Discovery of Novel Dimeric Pyridinium Bromide Analogues Inhibits Cancer Cell Growth by Activating Caspases and Downregulating Bcl-2 Protein.

Flexible dimeric substituted pyridinium bromides with primary and tertiary amines are prepared by conventional and solvent-free methods. The formation of compounds 2 and 4 is much easier than that of compounds 1 and 3 because of the benzyl carbon which is more electropositive than the primary alkyl carbon. The newly synthesized dimeric pyridinium compounds are optimized using DFT and B3LYP 6-31 g(d,p). The in vitro antiproliferative activity is studied in lung (A549) and breast cancer cell lines (MDA-MB 231). Among the four compounds, 1,1'-(1,3-phenylene bis(methylene)bis 2-aminopyridinium bromide 4 showed potent anticancer activity when compared to the standard drug 5-fluorouracil. 1,1'-(1,3-Phenylene bis(methylene)bis 2-aminopyridinium bromide 4 is not toxic to normal cell lines 3T3-L1 and MRC-5 cell lines. Also, 1,1'-(1,3-phenylene bis(methylene)bis 2-aminopyridinium bromide 4-induced apoptosis in cancer cell lines is examined using AO/EB and Hoechst staining, which is further supported by cell cycle analysis. Western blot analysis showed that 1,1'-(1,3-phenylene bis(methylene)bis 2-aminopyridinium bromide 4 induces apoptosis through the extrinsic apoptotic pathway by upregulating caspase 3 and caspase 9. This compound also downregulates intrinsic apoptotic proteins, including Bcl-2, Bcl-x, and Bad. From the present study results, it is confirmed that 1,1'-(1,3-phenylene bis(methylene)bis 2-aminopyridinium bromide 4 has potent anticancer activity when compared to other compounds.

Prevalence and Correlates of Vitamin D Deficiency Among Children and Adolescents From a Nationally Representative Survey in India.

OBJECTIVE: To evaluate the prevalence of vitamin D deficiency (VDD) and its correlates among apparently healthy children and adolescents. METHODS: We carried out a secondary analysis of data of Comprehensive National Nutrition Survey 2016-18 to analyze the pre-valence and predictors of VDD among Indian children and adolescents. RESULTS: The over-all prevalence of VDD in preschool children (1-4 years), school age (5-9 years) children, and adolescents (10-19 years) was 13.7%, 18.2%, and 23.9%, respectively. Age, living in urban area, and winter season were significantly associated with VDD. Vegetarian diet and high-income households were the main risk factors observed in 5-19 years age category. Female sex and less than three hour of physical activity/week were independent risk factors among adolescents. CONCLUSION: The prevalence and determinants of VDD across different age-groups are reported, and these should be interpreted and addressed to decrease the burden of VDD in India.

Effect of Age, Stage, and Type of Surgical Revascularization on Clinical and Angiographic Outcome in Moyamoya Disease - Experience from a Case Series of 175 Revascularization Procedures.

Background: There is dearth of literature on impact of age - pediatric versus adult, Suzuki staging - early versus late, and revascularization type - indirect versus direct on clinical and angiographic outcome in moyamoya disease (MMD). Hence, we intend to comprehensively evaluate factors influencing outcome in MMD following surgical revascularization. Methods: MMD patients operated at our institute from January 2011 to August 2018 were followed for an average 24 months. Primary outcomes were modified Rankin score (mRS) and stroke risk reduction. Secondary outcome was angiographic outcome score (AOS). Results: A total of 133 patients including 37.6% adults (>18 years; n = 50) underwent 175 revascularizations - 89 direct (DR) and 86 indirect (IR) subgroups. Mean mRS scores improved in pediatric DR (P < 0.001), IR (P < 0.001), adult IR (P = 0.10), and DR (P = 0.25) subgroups. Recurrent stroke rate was similar in pediatric-DR (2.7%) and IR (7.6%, P = 0.61), and adult-DR (0%) and IR (4.1%) subgroups (P = 1.00). AOS scores improved in pediatric DR (P = 0.002) and IR (P = 0.01), and adult-DR (P = 0.02) and IR (P = 0.06) subgroups. Late-stage MMD (Suzuki IV-VI) showed better improvement in mRS scores than early-stage-Suzuki (I-III; P < 0.001). Recurrent stroke rates were similar (P = 0.26) and AOS scores improved significantly in early- and late-stage MMD (P < 0.001). Conclusions: In pediatrics, clinical and angiographic outcome significantly improved after revascularization procedure, and in adults, angiographic improvement was more evident than clinical recovery. Late-stage Suzuki MMD patients demonstrated significantly better clinical improvement than early stage. The angiographic improvement was equivalent to early stage, irrespective of age and type of revascularization.

Association between D-dimer levels and post-acute sequelae of SARS-CoV-2 in patients from a tertiary care center.

Background: Post-acute sequelae of SARS-CoV-2 (PASC) is becoming an important concern in SARS-CoV-infected people. The pathophysiology behind PASC is unknown, and much study should be carried out to check the D-dimer levels in the PASC population. Methodology: In COVID-19 patients, the D-dimer level was checked during admission and discharge, and a follow-up study was carried out after 3 and 6 months of discharge. The results were compared with the appropriate statistical tests. Results: Patients had a high D-dimer value than the normal range, and the elevated D-dimer value continued to increase up to 6 months. Conclusion: Persistence of PASC has a direct correlation with increased D-dimer values. D-dimer can be used as biomarker in PASC patients.

Outcomes of surgical interventions for the treatment of limbal stem cell deficiency.

Background & objectives: In the current scenario, with availability of different surgical procedures for limbal stem cell deficiency (LSCD), there exists no common consensus as to the standardization of the management protocol for the same. In addition, there also exists diversity in the views about the clinical diagnosis, ancillary investigations and clinical parameters. The objective of the present study was to evaluate the reported outcomes of surgical interventions for the management of LSCD. Methods: A systematic review of published literature on limbal stem cell transplantation (LSCT) was performed using Ovid Medline, Embase and PubMed for a duration of 2009 to 2019. Original studies including prospective, retrospective case series and randomized controlled trials, articles in English language, articles with access to full text and studies with more than or at least 10 patients were included in this review. Data related to clinical and visual outcomes were evaluated, and pool estimates of different surgeries were calculated using random-effects model and individually using Pearson's Chi-square test. Results: A total of 1133 abstracts were evaluated. Finally, 17 studies were included for the analysis. Among these 17 studies, direct limbal lenticule transplantation was performed in five studies, of which autologous tissue from the fellow eye [conjunctival limbal autograft (CLAU)], allograft from a cadaver/live donor [keratolimbal allograft (KLAL)/conjunctival limbal allograft (CLAL)] and combination of CLAU plus KLAL were done in one, three and one studies, respectively. The ex vivo expanded cultivated limbal epithelial transplantation (CLET) was reported in six studies and simple limbal epithelial transplantation (SLET) in four studies. Two were comparative studies comparing CLET and CLAL (living-related CLAL) with cadaveric KLAL, respectively. Outcome analysis of the included studies showed significant heterogeneity. Calculated pool rate for various types of surgeries was calculated. The pool estimate for CLAL was 67.56 per cent [95% confidence interval (CI), 41.75-93.36; I2=83.5%, P=0.002]. For KLAL, this value was 63.65 per cent (95% CI, 31.38-95.91; I2=92.4%, P=0.000). Pool estimate for CLET was 78.90 per cent (95% CI, 70.51-87.28; I2=73.6%, P=0.001). Corresponding values for SLET were 79.08 per cent (95% CI, 74.10-84.07; I2=0.0%, P=0.619). CLAU and combination of CLAU plus KLAL were done in one study each; hence, statistical analysis could not be done. The functional outcome in terms of gain in visual acuity post-operatively was better in KLAL (P<0.005) and SLET group as compared to CLET group. Interpretation & conclusions: The present analysis suggests that though the anatomical success rates were almost identical between SLET, CLET, CLAL, and KLAL procedures, the functional success rates were better following KLAL and SLET procedures as compared to CLET. Decision for LSCT for cases of ocular burns based on either clinical judgement of the surgeon or individual diagnosis remains a suitable option.

Azathioprine weekly pulse versus methotrexate for the treatment of chronic plaque psoriasis: A randomized controlled trial.

BACKGROUND: Methotrexate is the most commonly used drug in the treatment of psoriasis with good efficacy and safety. Recently, weekly azathioprine pulse has been shown to be effective in this disease. AIM: The aim of this study is to compare the effectiveness and safety of weekly pulse doses of azathioprine and methotrexate for the treatment of chronic plaque psoriasis. METHODS: In this randomized controlled trial, 80 patients with chronic plaque psoriasis were recruited. After detailed clinical and laboratory evaluation, patients were randomized to 2 groups to receive either weekly 300 mg azathioprine (n = 40) or 15 mg methotrexate every week (n = 40) for 20 weeks, following which the response to treatment and adverse effects were assessed. The patients were then followed up every 4 weeks for 3 months to determine any relapse. RESULTS: Overall, 48 (60%) patients achieved PASI 75, while 36 (45%) and 59 (73.8%) patients achieved PASI 100 and 50, respectively. On intention to treat analysis, PASI ≥ 75 was achieved in 47.5% (19/40) patients in group 1 compared to 85% (34/40) patients in group 2 (p < 0.001). However, on per protocol analysis, PASI ≥ 75 was achieved in 86% (19/22) patients in group 1 and 92% (34/37) patients in group 2 (p = 0.497). Minor clinical and biochemical adverse effects were noted in both the groups, which were comparable. One (7.7%) patient in group 1 and 4 (17.4%) in group 2 relapsed during follow-up. LIMITATIONS: Limitations of study include small sample size and short follow-up. CONCLUSION: Weekly azathioprine pulse appears to be beneficial in the management of chronic plaque psoriasis. However, it is less effective than weekly methotrexate. It can thus be of use as a therapeutic option in patients with contraindication to methotrexate or other similar agents in this disease.

Frontal lobe metabolic alterations characterizing Parkinson's disease cognitive impairment.

BACKGROUND AND PURPOSE: Diagnosis of Parkinson's disease (PD) cognitive impairment at early stages is challenging compared to the stage of PD dementia where functional impairment is apparent and easily diagnosed. Hence, to evaluate potential early stage cognitive biomarkers, we assessed frontal lobe metabolic alterations using in vivo multi-voxel proton magnetic resonance spectroscopic imaging (1H-MRSI). METHOD: Frontal metabolism was studied in patients with PD with normal cognition (PD-CN) (n = 26), with cognitive impairment (PD-CI) (n = 27), and healthy controls (HC) (n = 30) using a single slice (two-dimensional) 1H-MRSI at 3 T. The acquired spectra were post-processed distinctly for voxels corresponding to the bilateral middle/superior frontal gray matter (GM) and frontal white matter (WM) regions (delineated employing neuromorphometrics atlas) using the LC-Model software. RESULT: Significant (post hoc p < 0.016) reduction in the concentration of N-acetyl aspartate (NAA) in the middle and superior frontal GMs and total choline (tCho) and total creatine (tCr) in the frontal WM was observed in PD-CI compared to PD-CN and HC, while that in HC and PD-CN groups were comparable. The NAA and tCr/tCho metabolite concentrations showed significant (p < 0.05) positive correlations with cognitive test scores in the frontal GM and WM, respectively. The receiver operating curve (ROC) analysis revealed significant (p < 0.05) "area under curve" for NAA/tNAA in the frontal GM and tCho in the frontal WM. CONCLUSION: The frontal metabolic profile is altered in cognitively impaired PD compared with cognitively normal PD. Neuronal function loss (NAA), altered energy metabolism (Cr), and cholinergic (Cho) neural transmission are implicated in PD cognitive pathology. Frontal neuro-metabolism may promisingly serve as PD cognitive biomarker.

Association between concentration of active MMP-9 in pulpal blood and pulpotomy outcome in permanent mature teeth with irreversible pulpitis - a preliminary study.

AIM: To investigate the correlation between the concentration of active-matrix metalloproteinases-9 (aMMP-9) in pulpal blood and the outcome of pulpotomy in mature permanent teeth with symptomatic irreversible pulpitis (SIP). METHODOLOGY: Forty permanent molar teeth with a clinical diagnosis of SIP and normal apical tissues with periapical index (PAI) score ≤ 2 and ten permanent teeth (8 molars and two premolars) with a diagnosis of normal pulp that required root canal treatment for prosthetic reasons from patients between the ages of 15-35 years were recruited. All clinical procedures were performed under local anaesthesia and rubber dam isolation. After access opening, the coronal pulp tissue was amputated up to the canal orifice. A 100 µL volume of the pulpal blood was collected using a micropipette and transported to the laboratory. Sodium hypochlorite (2.5 %) was used as a haemostatic agent, and mineral trioxide aggregate (MTA) was used as the pulp capping material. The tooth was restored with composite at the same visit. Teeth with normal pulps were treated with single-visit root canal treatment. Patients with pulpotomy were recalled at 6 and 12 months. Outcome assessment of teeth with pulpotomy was carried out at 12 months and was categorized as success (asymptomatic patients with PAI score ≤ 2) or failure (symptomatic patients or PAI score ≥ 3). Quantification of aMMP-9 in pulpal blood was achieved using a fluorometric assay. The following statistical analyses were performed to assess the data: t-test, Fisher's exact test, kappa coefficient, non-parametric test, Wilcoxon rank-sum test, Spearman rank correlation test and receiver operating characteristic curve (ROC). RESULT: The success rate of pulpotomy was 88 % at 12-months. There was a significant difference between the median concentrations of aMMP-9 in pulpal blood of teeth with normal pulps (52 (12-96) ng mL-1 :) and SIP (193.3 (25.8-607.7) ng mL-1 :) (P = 0.0003) and successful (132.3 (25.8-548.3) ng mL-1 :) and failed cases (512.4 (334.8-607.7 ng mL-1 :) (P = 0.0015) of MTA pulpotomy. A significant association was established between aMMP-9 concentration and outcome of pulpotomy. The area under the receiver operating characteristics curve (0.9484, 95%CI) suggested excellent discriminatory power of aMMP-9 concentration in pulpal blood to predict the pulpotomy outcome. CONCLUSION: The pulpal blood concentration of aMMP-9 was significantly associated with the outcome of pulpotomy in teeth with symptomatic irreversible pulpitis, where it may be used as a potential prognostic biomarker.

Cortical thickness and gyrification index measuring cognition in Parkinson's disease.

OBJECTIVE: Cortical dynamics is driven by cortico-cortical connectivity and it characterizes cortical morphological features. These brain surface features complement volumetric changes and may offer improved understanding of disease pathophysiology. Hence, present study aims to investigate surface features; cortical thickness (CT) and gyrification index (GI) in Parkinson's disease (PD) patients of normal cognition (PD-CN), cognitively impaired patients with PD (PD-CI) in comparison with cognitively normal healthy controls (HC) to better elucidate cognition linked features in PD. METHOD: Anatomical MRI (3DT1) was carried out in 30 HC (56.53 ± 8.42 years), 30 PD-CN (58.8 ± 6.07 years), and 30 PD-CI (60.3 ± 6.43 years) subjects. Whole brain ROI based parcellation using Desikan-Killiany (DK-40) atlas followed by regional CT and GI differentiation [with 'age' and 'total intracranial volume' (TIV) correction], multiple linear regression (with 'age', 'TIV', and 'education' correction) with clinical variables, ROC analysis, and CT-GI correlation across the groups was used for data analysis. RESULTS: Widespread cortical thinning with regional GI reduction was evident in PD-CI with respect to other two groups (HC and PD-CN), and with absence of such alterations in PD-CN compared to HC. Frontal, parietal, and temporal CT/GI significantly correlated with cognition and presented classification abilities for cognitive state in PD. Mean regional CT and GI were found negatively correlated across groups with heterogeneous regions. CONCLUSION: Fronto-parietal and temporal regions suffer cognition associated cortical thinning and GI reduction. CT may serve better discriminator properties and may be more consistent than GI in studying cognition in PD. Heterogeneous surface dynamics across the groups may signify neuro-developmental alterations in PD.

The effect of anaesthetic exposure in presurgical period on delayed cerebral ischaemia and neurological outcome in patients with aneurysmal subarachnoid haemorrhage undergoing clipping of aneurysm: A retrospective analysis.

BACKGROUND AND AIMS: Delayed cerebral ischaemia is one of the major contributors to morbidity in aneurysmal subarachnoid haemorrhage (aSAH). General anaesthesia (GA) in the presurgical period may have a preconditioning effect. The primary aim was to assess the effect of preoperative exposure to GA during digital subtraction angiography (DSA) on neurological outcome in patients presenting with aSAH. METHODS: After Ethical Committee approval, we conducted a retrospective analysis of the data of patients with aSAH treated surgically. Patients, admitted to neurosurgical ICU (June 2014 and December 2017) with a computed tomography (CT) diagnosis of aSAH and underwent DSA, were included. DSA, done with or without exposure to a general anaesthetic, was classified to GA group and LA group, respectively. Propensity score matching was done on the baseline variables. Appropriate statistical methods were applied. RESULTS: Of the 278 patients, 116 (41.7%) patients had received GA during DSA. Propensity matching yielded 114 (57 in each group) matched patients. In a logistic regression model, the odds ratio (OR) for poor outcome at discharge in GA group as compared to LA group was 4.4 (CI: 2.7-7.4), P = 0.001, whereas, in the matched data, the OR for poor outcome at discharge in GA group as compared to LA group was 1.2 (CI: 0.6-2.6), P = 0.57. CONCLUSION: The presurgical exposure to GA did not offer any neuroprotection and the odds of poor outcome were higher compare to non-exposure to GA group.

Ultrasound liver elastography for the detection of liver fibrosis in patients with psoriasis and reactive arthritis on long-term methotrexate therapy: A cross-sectional study.

BACKGROUND: Long-term low-dose methotrexate therapy is associated with liver fibrosis. Although liver biopsy is the gold standard for detecting fibrosis, it is an invasive procedure associated with morbidity and mortality risks. Hence noninvasive imaging techniques such as transient elastography (TE) and shear wave elastography (SWE) have been studied to measure liver stiffness. AIMS: To assess the utility of TE and SWE in detecting fibrosis in patients with psoriasis and reactive arthritis on long-term methotrexate therapy. METHODS: A cross-sectional prospective study was undertaken on 54 patients with psoriasis and reactive arthritis who had received ≥1.5 g of methotrexate. Various clinical and biochemical [fibrosis 4 index (FIB4), aspartate-transaminase-to-platelet ratio index (APRI)] parameters were calculated and liver stiffness measurement (LSM) was done with TE and SWE. The degree of steatosis was measured using controlled attenuation parameter (CAP). Liver biopsy was done when indicated and was interpreted by a pathologist blinded to clinical and imaging results. RESULTS: Fifty four patients with a mean age of 40.3 years and a male-to-female ratio of 5:1 were included. The mean cumulative methotrexate dose was 3.04 g. The median FIB4, APRI, and gamma-glutamyl transpeptidase-to-platelet ratio values were 0.75, 0.23, and 0.15, respectively. The median LSM for TE and SWE was 5.3 and 7.32 kPa, respectively. SWE and TE showed a weak positive correlation (r = 0.26, P = 0.053). The mean CAP was 217 dB/m (area under the receiver operating characteristic = 0.70). In the 19 of 26 cases whose liver biopsies could be assessed, only 4 (21%) showed F1 fibrosis (Ishak staging). The median LSM on SWE was significantly higher in patients with a cumulative methotrexate dose ≥ 4 g when compared with those with a dose <4 g (9.85 vs 7.1, P = 0.02). Other parameters did not correlate with TE and SWE. LIMITATIONS: The small sample size and the low number of cases with significant fibrosis on histopathology were the major limitations of this study. CONCLUSION: Histologically detectable LF is uncommon in patients with psoriasis and reactive arthritis on long-term methotrexate therapy. Both TE and SWE are good at detecting the absence of fibrosis in these patients. In our study, SWE and TE values did not correlate with clinical, biochemical, or histopathological parameters.

Increase in concentration of patch test allergen reduces patch test occlusion time to 12 hours without affecting patch test reactivity in patients with parthenium dermatitis.

BACKGROUND: Patch testing is the standard method to diagnose contact allergy. Patches are applied for 48 hours, which is inconvenient to patients in tropical weather. Therefore, we evaluated different patch test occlusion times with increased concentrations of an allergen to determine if occlusion time can be reduced without compromising patch test reactivity. METHODS: Patch test positive patients with parthenium dermatitis were enrolled and patch tested using five different concentrations (10%, 4%, 2%, 1%, and 0.5%) of parthenium extract. The patches were applied in triplicate. The first set was removed after 12 hours, whereas the second and third sets were removed after 24 and 48 hours, respectively. Readings were performed at 24, 48, and 96 hours. RESULTS: Fifty patients with parthenium dermatitis were included. The positive patch test reaction rates were comparable in all three sets at 24- and 48-hour readings irrespective of the occlusion time. All were positive, with 10%, 4%, and 2% concentrations at 96-hour reading with an occlusion time of 12 hours. CONCLUSION: An occlusion time of 12 hours seems adequate to elicit positive patch test reaction at a 96-hour reading if the concentration of patch test allergen can be increased, that is, from 1% to 2% in these patients.

Domain specific cognitive impairment in Parkinson's patients with mild cognitive impairment.

Mild cognitive impairment (MCI) affects nearly 20-50% patients with Parkinson's disease (PD). It may be the prodromal stage of dementia and impacts quality of life of the patient and caregiver. Characterizing PD cognition at the stage of MCI may help in understanding of cognitive pathophysiology. This study assessed and compared cognition in patients with PD and mild cognitive impairment (PD-MCI, n = 32, age = 61.09 ± 5.97 years), PD patients with normal cognition (PD-NC, n = 32, age = 58.81 ± 6.15 years) and healthy controls (HC, n = 38, age = 57.39 ± 7.14 years). Montreal Cognitive Assessment Test (MoCA) was used for categorization of subjects. Cognitive assessment of five domains: executive function, attention, visuospatial function, memory and language (using two tests in each domain) were performed. The effect of PD clinical scores on cognition and cognitive domain specificity in diagnosing PD-MCI were assessed by correlation and receiver operating curve (ROC) analyses, respectively. All the analyses followed removal of potential confounds (age, education and clinical scores). Attention, memory, executive and visuospatial functions were impaired in PD-MCI on comparison with HC and PD-NC groups. Performance in digit span forward and trail making tests for attention and memory (immediate recall) were comparable in both the PD groups. Both the PD groups revealed impairment in attention, memory and language with respect to HC, suggesting the fronto-striatal and posterior cortical syndrome in PD. Highly significant Visual-N-back correlation with UPDRS-III may implicate the shared motor-visuospatial neural pathways. Visual-N-back/PGI delayed recall domains are promising in characterizing PD-MCI stage.