An overview of benefits and risks of chronic melanocortin-1 receptor activation.

The melanocortin-1 receptor (MC1R) is a G protein-coupled receptor that plays a pivotal role in human skin pigmentation, melanin synthesis, redox homeostasis and inflammation. Loss-of-function MC1R variants suppress G protein-coupled receptor coupling or cell surface expression leading to a decrease in adenyl cyclase activation and intracellular levels of cyclic adenosine monophosphate. Chronic activation of MC1R can occur in certain medical conditions such as Addison's disease and physiologic states such as pregnancy melasma. MC1R activation is more commonly caused by environmental exposure to ultraviolet (UV) radiation. Approved pharmacologic melanocortin agonists that activate MC1R signalling in a targeted manner or as a bystander effect have recently become available for erythropoietic protoporphyria, sexual desire disorders, monogenic obesity and syndromic obesity. Further, small peptide analogues of α-melanocortin-stimulating hormone, human MC1R selective agonists, are photoprotective, decreasing the adverse impact of UV radiation (a primary risk factor for skin cancer) and are being investigated as potential chemoprevention strategies. MC1R activation through induction of UV-protective skin pigmentation increased DNA repair, and control of aberrant cell growth may reduce the risk of melanoma but importantly does not prevent melanoma particularly in individuals with risk factors and regular skin examination remains critical in high-risk individuals.

Acceptability, feasibility, and likelihood of stakeholders implementing the novel BPaL regimen to treat extensively drug-resistant tuberculosis patients.

BACKGROUND: BPaL, a 6 month oral regimen composed of bedaquiline, pretomanid, and linezolid for treating extensively drug-resistant tuberculosis (XDR-TB) is a potential alternative for at least 20 months of individualized treatment regimens (ITR). The ITR has low tolerability, treatment adherence, and success rates, and hence to limit patient burden, loss to follow-up and the emergence of resistance it is essential to implement new DR-TB regimens. The objective of this study was to assess the acceptability, feasibility, and likelihood of implementing BPaL in Indonesia, Kyrgyzstan, and Nigeria. METHODS: We conducted a concurrent mixed-methods study among a cross-section of health care workers, programmatic and laboratory stakeholders between May 2018 and May 2019. We conducted semi-structured interviews and focus group discussions to assess perceptions on acceptability and feasibility of implementing BPaL. We determined the proportions of a recoded 3-point Likert scale (acceptable; neutral; unacceptable), as well as the overall likelihood of implementing BPaL (likely; neutral; unlikely) that participants graded per regimen, pre-defined aspect and country. We analysed the qualitative results using a deductive framework analysis. RESULTS: In total 188 stakeholders participated in this study: 63 from Kyrgyzstan, 51 from Indonesia, and 74 from Nigeria The majority were health care workers (110). Overall, 88% (146/166) of the stakeholders would likely implement BPaL once available. Overall acceptability for BPaL was high, especially patient friendliness was often rated as acceptable (93%, 124/133). In contrast, patient friendliness of the ITR was rated as acceptable by 45%. Stakeholders appreciated that BPaL would reduce workload and financial burden on the health care system. However, several stakeholders expressed concerns regarding BPaL safety (monitoring), long-term efficacy, and national regulatory requirements regarding introduction of the regimen. Stakeholders stressed the importance of addressing current health systems constraints as well, especially in treatment and safety monitoring systems. CONCLUSIONS: Acceptability and feasibility of the BPaL regimen is high among TB stakeholders in Indonesia, Kyrgyzstan, and Nigeria. The majority is willing to start using BPaL as the standard of care for eligible patients despite country-specific health system constraints.

Corticosteroid-associated lupus pancreatitis: a case series and systematic review of the literature.

BACKGROUND: Acute pancreatitis is an uncommon complication that occurs in 0.85% to 4% of patients with systemic lupus erythematosus (SLE). In some patients, it occurs within days to weeks of starting medium-to-high dose corticosteroids. The authors have used the term 'corticosteroid-associated lupus pancreatitis' for these patients, and they report a case series and perform a systematic review of previously published reports. METHODS: For the purpose of this study, corticosteroid-associated lupus pancreatitis was defined as occurrence of acute pancreatitis in patients with SLE (fulfilling the 1997 ACR), within 3 weeks of starting therapy with medium-to-high dose corticosteroids - either newly initiated or escalated from a lower dose. All patients with SLE admitted in the last 2.5 years in a North Indian university hospital were reviewed, and those with pancreatitis who fulfilled the above criteria were included in the case series. For the systematic review, a PUBMED search using the keywords 'lupus' and 'pancreatitis' was performed, and reports in English were reviewed for an association with corticosteroids. RESULTS: Among 420 admissions of SLE patients, six patients (1.4%) fulfilled criteria for corticosteroid-associated lupus pancreatitis. All were female, with mean age and disease duration of 19.7 ± 3.3 and 3.8 ± 2.5 years respectively. All had active disease and developed acute pancreatitis within 48-72 hours of newly initiating medium-to-high dose corticosteroids (in three patients) or escalating them to medium-high dose (in three patients). After the development of pancreatitis, corticosteroids were continued in all except one patient. In addition, two patients received pulse methylprednisolone, two received pulse cyclophosphamide and one was started on azathioprine. Three patients died during hospitalization, all with severe pancreatitis. On systematic review, among 451 cases of lupus pancreatitis reported, 23 (5%) fulfilled criteria for 'corticosteroid-associated lupus pancreatitis'. A majority of them had pancreatitis within 3 days of starting treatment with medium-to-high dose corticosteroids. The mortality in these patients was 37.5%. CONCLUSION: In a small but substantial proportion of patients with lupus who develop pancreatitis, it occurs within days to weeks of starting medium-to-high dose corticosteroids. Many of these patients continue to receive corticosteroids, and some receive more aggressive immunosuppression. However, they have significant mortality, and further studies are required to identify appropriate treatment in this subgroup of patients.

Body temperature, cutaneous heat loss and skin blood flow during epidural anaesthesia for emergency caesarean section.

It is not clear how converting epidural analgesia for labour to epidural anaesthesia for emergency caesarean section affects either cutaneous vasomotor tone or mean body temperature. We hypothesised that topping up a labour epidural blocks active cutaneous vasodilation (cutaneous heat loss and skin blood flow decrease), and that as a result mean body temperature increases. Twenty women in established labour had body temperature, cutaneous heat loss and skin blood flow recorded before and after epidural top-up for emergency caesarean section. Changes over time were analysed with repeated measures ANOVA. Mean (SD) mean body temperature was 36.8 (0.5)°C at epidural top-up and 36.9 (0.6)°C at delivery. Between epidural top-up and delivery, the mean (SD) rate of increase in mean body temperature was 0.5 (0.5) °C.h-1 . Following epidural top-up, chest (p < 0.001) and forearm (p = 0.004) heat loss decreased, but head (p = 0.05), thigh (p = 0.79) and calf (p = 1.00) heat loss did not change. The mean (SD) decrease in heat loss was 15 (19) % (p < 0.001). Neither arm (p = 0.06) nor thigh (p = 0.10) skin blood flow changed following epidural top-up. Despite the lack of change in skin blood flow, the most plausible explanation for the reduction in heat loss and the increase in mean body temperature is blockade of active cutaneous vasodilation. It is possible that a similar mechanism is responsible for the hyperthermia associated with labour epidural analgesia.

Response to interferon-beta treatment in multiple sclerosis patients: a genome-wide association study.

Up to 50% of multiple sclerosis (MS) patients do not respond to interferon-beta (IFN-ß) treatment and determination of response requires lengthy clinical follow-up of up to 2 years. Response predictive genetic markers would significantly improve disease management. We aimed to identify IFN-ß treatment response genetic marker(s) by performing a two-stage genome-wide association study (GWAS). The GWAS was carried out using data from 151 Australian MS patients from the ANZgene/WTCCC2 MS susceptibility GWAS (responder (R)=51, intermediate responders=24 and non-responders (NR)=76). Of the single-nucleotide polymorphisms (SNP) that were validated in an independent group of 479 IFN-ß-treated MS patients from Australia, Spain and Italy (R=273 and NR=206), eight showed evidence of association with treatment response. Among the replicated associations, the strongest was observed for FHIT (Fragile Histidine Triad; combined P-value 6.74 × 10-6) and followed by variants in GAPVD1 (GTPase activating protein and VPS9 domains 1; combined P-value 5.83 × 10-5) and near ZNF697 (combined P-value 8.15 × 10-5).

Comparison of short-axis out-of-plane versus long-axis in-plane ultrasound-guided radial arterial cannulation in adult patients: a randomized controlled trial.

BACKGROUND: The current available literature is not unanimous in reporting the utility of short-axis and long-axis techniques for radial artery cannulation in both adults and children. This study was designed to compare short-axis out-of-plane (SA-OOP) and long-axis in-plane (LA-IP) techniques in ultrasound-guided radial artery cannulation in adults. METHODS: In this prospective randomized controlled trial, 150 adult patients of American Society of Anesthesiologists physical status I-III aged between 18 and 70 years were included. All patients were randomized into two groups (group SA-OOP) and (group LA-IP) of 75 each undergoing ultrasound-guided radial artery cannulation. The primary outcome was successful cannulation in the first attempt. Secondary outcomes included antero-posterior arterial diameter, skin-to-artery distance, ultrasonic localization time, cannulation time, no of attempts to cannulate artery, cannula insertion failure, and vascular complications. RESULTS: First-attempt arterial cannulation was successful in 80 % of patients in the SA-OOP group as opposed to 82.6 % patients in the LA-IP group (p = 0.67). The time to cannulate the artery was similar between the two groups, but the time to localize artery was significantly higher in the long-axis technique (p < 0.001). CONCLUSIONS: The first-attempt cannulation success rate and cannulation time in adult patients are similar in ultrasound-guided radial artery cannulation with both short-axis as well as long-axis techniques. Trial registration Clinical Trial Registry of India (CTRI/2015/02/005552).

Antibiotic stewardship in a tertiary care hospital of a developing country: establishment of a system and its application in a unit-GASP Initiative.

PURPOSE: Despite the proven benefits of antimicrobial stewardship, models for executing the same in the developing countries are sparse. The present study highlights the approaches undertaken by our group in initiating one such program in a public sector tertiary level health care setting of a developing country. METHODS: The study focussed on development of a system after evaluation of existing issues and case study of implementation of the program in a unit within the hospital. The system building exercise included (1) development of generic data capture form for prospective audit and feedback; (2) development of an electronic system for data capture; (3) identification of key intervention points for strategy decision for stewardship in a particular unit; (4) application of the stewardship method and (5) evaluation of outcomes. RESULTS: A digital system for prospective audit was constructed after a background study. In the study unit, there was a significant decline in double anaerobic coverage. There was a significant decline in the average number of antimicrobials used per patients and a decrease in Defined Daily Dose of designated antimicrobials was noted. Additionally, there was an increase in the use of optimized doses. CONCLUSION: A system for undertaking antimicrobial stewardship with a mechanism for prospective audit was put in place. The system may be adopted by other public sector hospitals of the developing country.

Clinico-radiological Correlation of Bone Changes in Leprosy Patients Presenting with Disabilities/Deformities.

Leprosy is a medical - social disease, it is associated with stigma in the society due to the resulting deformities in some persons. Although stigma has decreased after the widespread use of MDT, some disabilities do occur which are mostly due to late initiation of treatment and inappropriate care. Besides the nerve and skin involvement bone changes have been reported to be common in leprosy. These bony changes need to be understood in the present MDT era specially in the context of clinical spectrum and duration of disease/ deformities. Fifty clinically diagnosed and histologically classified leprosy patients with deformities/ disabilities of either hands/feet/face who attended the OPD of Department of Dermatology, Venereology and Leprosy, Government Medical College, Amritsar were examined and evaluated in the study. Radiological examination of hands, feet and skull was done in each case and the bone changes in hands and feet; and skull and paranasal sinus changes were correlated with clinical parameters. Bone changes were observed in 90% of cases radiologically. Specific bone changes in hands and feet, non-specific bone changes in hands, feet, skull and paranasal sinuses were seen in 66%, 82% and 32% of cases respectively. Common specific bone changes in hands and feet observed were primary periostitis (14%), honey combing (46%), bone cyst (36%), thinning and irregularity of cortex (28%) and area of bone destruction (20%); Among the non-specific bone changes observed were contracted fingers/claw hands/claw toes (64%) and absorption of terminal phalanges (40%). The maxillary sinus, and paranasal sinus changes were the most common radiological findings observed in skull. The study of the radiological changes may help the clinicians to understand the gravity of the situation and undertake steps for timely prevention of permanent loss of function and the occurrence of deformities and disabilities.

Effect of cryogenic grinding on volatile and fatty oil constituents of cumin (Cuminum cyminum L.) genotypes.

Effect of cryogenic grinding on recovery of volatile oil, fatty oil percentage and their constituents in two cumin (Cuminum cyminum L.) genotypes have been analyzed. Cryogenic grinding not only retains the volatiles but enhanced the recovery by 33.9 % in GC 4 and 43.5 % in RZ 209. A significant increase (29.9 %) over normal grinding in oil percentage was also observed in genotype RZ 209. This increase was, however, less (15.4 %) in genotype GC 4. Nineteen major compounds were identified in the essential oil of both genotypes. The two grinding techniques had significant effects on dependent variables, viz., volatile oil and monoterpenes. Cuminaldehyde was the main constituent in both genotypes, content of which increased from 48.2 to 56.1 % in GC 4 on cryo grinding. Content of terpines were found to decrease in cryo ground samples of GC 4 and either decrease or no change was found in RZ 209. Organoleptic test showed more pleasant aroma in cryo ground seeds of both the genotypes. Significant increase was also reported in fatty oil yield due to cryogenic grinding. Fatty acid methyl ester (FAME) analysis showed oleic acid as major FAME content of which increased from 88.1 to 94.9 % in RZ 209 and from 88.2 to 90.1 % in GC 4 on cryogenic grinding. Other prominent FAME were palmitic, palmitoleic and stearic acid. Results indicated commercial potential of cryogenic grinding technology for cumin in general and spices in particular for better retention of flavour and quality in spices.

An analysis of time utilization and cancellations of scheduled cases in the main operation theater complex of a tertiary care teaching institute of North India.

CONTEXT: Operation theater (OT) utilization. AIMS: To analyze the time utilization and to assess the stated causes of cancellations of scheduled cases in the OT complex of a tertiary care teaching institute. SETTINGS AND DESIGN: This prospective study was carried out from December 2010 to April 2011. MATERIALS AND METHODS: each of the 16 OT tables was observed for 6 days (total 96 days). The available resource hours were taken as 0800-1600 hrs. (480 min/day; 46,080 min in 96 days). The following parameters were recorded--time spent on supportive services, time spent on actual surgery, room turn over time, time spent for total procedure and time between entry and exit of patient. STATISTICAL ANALYSIS: Data were analyzed using the SPSS software version 15. RESULTS: Of the total 325 scheduled cases, 252 were operated and 73 (22.5%) were cancelled. There were delays on 15 days (15.63%) in starting the OT table at the scheduled time. Of the total resource hours (46,080 min), the mean "Raw utilization" was 37,573 min (81.54%) and the "Adjusted utilization" was 39,668 min (86.09%). The mean time spent on "supportive services" was 5539 min (12.02%) and on "actual surgery"' was 28,277 min (61.37%), and the "room turn over time" was 2095 min (5.39%). Among the stated reasons for cancellations, lack of operating time--57 cases (78.1%)--was the most common. CONCLUSION: Study of time utilization and cancellation are important tools in assessing the optimal utilization of available resource hours in an OT.

Pilot study of cytological testing for oesophageal squamous cell dysplasia in a high-risk area in Northern Iran.

BACKGROUND: Oesophageal squamous cell carcinoma (ESCC) is a fatal disease with 5-year survival rates of <5% in Northern Iran. Oesophageal squamous dysplasia (ESD) is the precursor histologic lesion of ESCC. This pilot study was conducted to assess the feasibility, safety, and acceptability of non-endoscopic cytological examination of the oesophagus and to provide initial data on the accuracy of cytological atypia for identifying patients with ESD in this very-high-risk area. METHODS: Randomly selected asymptomatic participants of the Golestan Cohort Study were recruited. A cytological specimen was taken using a capsule sponge device and evaluated for atypical cells. Sections of the cytological specimen were also stained for p53 protein. Patient acceptability was assessed using a visual analogue scale. The cytological diagnosis was compared with a chromoendoscopic examination using Lugol's solution. RESULTS: Three hundred and forty-four subjects (43% male, mean (s.d.) age 55.6 (7.9) years) were referred to the study clinic. Three hundred and twelve met eligibility criteria and consented, of which 301 subjects (96.5%) completed both cytological and endoscopic examinations. There were no complications. Most of the participants (279; 92.7%) were satisfied with the examination. The sensitivity and specificity of the cytological examination for identifying subjects with high-grade ESD were 100 and 97%, respectively. We found an accuracy of 100% (95% CI=99-100%) for a combination of cytological examination and p53 staining to detect high-grade ESD. CONCLUSIONS: The capsule sponge methodology seems to be a feasible, safe, and acceptable method for diagnosing precancerous lesions of the oesophagus in this population, with promising initial accuracy data for the detection of high-grade ESD.

Selection of aptamers for aflatoxin M1 and their characterization.

In the present work, aptamers against aflatoxin M1 and aflatoxin B1 were generated and tested for creating proof of principle of recognition of aflatoxin M1 by generated aptamers. The aptamers were selected through the process referred as systematic evolution of ligands by exponential enrichment. A total of 41 different aptamer (36 aptamers for aflatoxin M1 and 5 for aflatoxin B1) sequences were obtained. The determination of dissociation constant (Kd ) values revealed that aptamers generated against aflatoxin M1 exhibited Kd values in the range of 35-1515 nM. Selected aptamers were grouped on the basis of the presence of common motifs or G-quadruplex. We find it interesting that one aptamer with no conserved motif or G-quadruplex had lowest Kd value (Kd = 35 nM). This structural motif is very distinct from motifs present in other aptamers. The Kd values of selected aptamers for aflatoxin B1 were in the range of 96-221 nM. One aptamer from each group was further tested for its ability to be used in aptasensor. The aptamer recognized aflatoxin M1 as indicated by color change (red to purple or blue) of aptamer-coated gold nanoparticles in the presence of 250-500 nM aflatoxin M1. The aptamers can be used in developing methods for detection/estimation/separation of aflatoxin or antidote for aflatoxin toxicity.

Deciphering Intermediate Nugent scores: Utility of Real-time PCR for Bacterial Vaginosis diagnosis.

PURPOSE: To optimize real-time PCR assays for diagnosis of Bacterial Vaginosis (BV) and determine cut-off loads by ROC analysis for Gardnerella vaginalis, Atopobium vaginae and Lactobacillus spp. as compared to Nugent scoring (Gold standard) in clinical samples. RESULTS: Out of 125 women, 34 were positive, 26 intermediate and 65 negative for BV by Nugent scoring. All three real-time PCR assays were found to be highly sensitive & specific and AUC suggested excellent diagnostic accuracy. An optimal cut-off was >9.45 × 103 copies/ ml, >3.34 × 103 copies/ ml & ≤ 18.63 × 103 copies/ ml for G. vaginalis, A. vaginae and Lactobacillus spp. respectively, in BV positives. Gram staining and qPCR were discordant only in patients with intermediate scores (n = 26) where qPCR identified 15 (57.69%) as positive and 11 (42.3%) as negative. CONCLUSION: PCR-based molecular BV diagnosis is more accurate and can be used for deciphering intermediate Nugent scores.

Genetic diversity, morphological traits, quality traits and antioxidants potentiality of Coccinia grandis germplasm under rainfed semi-arid region.

The present study was conducted to evaluate the genetic variability for morphological and qualitative traits of Coccinia for development of trait specific lines at ICAR-Central Horticultural Experiment Station (CIAH-RS), Panchmahals (Godhra), Gujarat during 2020-2022. In this study, we evaluated 26 gynoecious accessions to assess the genetic divergence through principal component and cluster analysis. The experiment was carried out in a randomized complete block design with three replications under rainfed semi-arid conditions. High values of PCV and GCV were observed for variables such as NFFP (25.13 and 22.20), PL (23.14 and 20.69), FD (24.01 and 21.46), AFW (22.98 and 20.13), NFPY (26.38 and 24.40), FYP (37.57 and 31.29), FY (35.55 and 33.20), AsC (28.65 and 27.73), Ac (24.32 and 21.06), TSS (37.23 and 35.94), DPPHL (20.71 and 20.38), FRAPL (21.08 and 20.92), TPF(20.81 and 20.45) respectively. High heritability coupled with high genetic advance as per cent of mean was observed for vine length (VL), internodal length (IL), number of female flowers per plant (NFFP), fruit length (FL), peduncle length (PL), fruit diameter (FD), average fruit weight (AFW), number of fruit per plant per year (NFPY), fruit yield per plant (FYP), fruit yield (FY), ascorbic acid (AsC), acidity (Ac), total soluble solids (TSS), total phenols in leaves TPL), total flavonoids in leaves TFL, CUPRAC in leaves (CUPRACL), DPPH in leaves (DPPHL), FRAP in leaves (FRAPL), Total phenols in fruits (TPF), Total flavonoids in fruits (TFF), CUPRAC in fruits (CUPRACF) and DPPH in fruits (DPPHF). The FYP exhibited a significant positive correlation with variables like VL (0.6833), IL (0.2991), NFFP (0.8107), FD (0.5245), AFW (0.6766), NFPY (0.7659), ASC (0.4611), TSS (0.5004) and TPF (0.4281). The estimates of genetic parameters revealed scope for further improvement of fruit yield by selection. Of the eight principal components, PC-I through PC-VIII had eigen values greater than 1 and it accounts 85.02% of the total variation for 26 gynoecious accessions of Ivy gourd. The eigen values of PC-I comprised 5.775% of total variation followed by PC-II (4.250%), PC-III (3.175%), PC-IV (2.588%), PC-V (1.828%), PC-VI (1.447%), PC-VII (1.179%) and PC-VIII (1.013%).The cluster VI and cluster I having highest mean values for most of traits under study. Thus, genotypes from the distinct cluster like cluster VI and I for should be used for selection of parents and varietal improvement for further breeding programme in ivy gourd.

SIGLEC1 and SIGLEC7 expression in circulating monocytes of patients with multiple sclerosis.

BACKGROUND: Sialic acid binding immunoglobulin-like lectins (Siglecs) are cell surface receptors that recognize sialic acids and may attenuate immune responses and reduce inflammation. OBJECTIVE: The purpose of this study was to investigate the role of two members of the Siglec family, SIGLEC1 and SIGLEC7, in the clinical course and disease activity of patients with multiple sclerosis (MS). METHODS: SIGLEC1 and SIGLEC7 expression was determined by flow cytometry in the blood monocytes of 16 healthy controls and 55 untreated MS patients (13 primary progressive MS (PPMS) patients, 13 secondary progressive MS (SPMS) patients and 29 relapsing-remitting MS (RRMS) patients (18 during clinical remission and 11 during relapse)). RESULTS: SIGLEC1 expression by CD14+ monocytes was significantly increased in MS patients compared with controls (p=0.025 for percentage of positive cells; p=0.007 for mean fluorescence intensity (MFI)). Stratification of patients into different clinical forms revealed increased SIGLEC1 expression in patients with progressive forms of the disease, particularly in those with PPMS (p=0.003 for percentage of positive cells and p=0.001 for MFI when compared with controls; p=0.031 for percentage of positive cells when compared with RRMS patients). Both inflammatory and resident monocytes contributed to the increase in SIGLEC1 expression observed in PPMS patients. SIGLEC7 expression was significantly up-regulated in blood monocytes from RRMS during relapse compared with patients during clinical remission (p=0.001 for MFI). CONCLUSIONS: These findings suggest roles for SIGLEC1 in the chronic progressive phases of MS and for SIGLEC7 in acute disease activity.

Roles of the ubiquitin peptidase USP18 in multiple sclerosis and the response to interferon-ß treatment.

BACKGROUND AND PURPOSE: Ubiquitin specific peptidase 18 (USP18) is a deubiquitinating enzyme that functions as a negative regulator of the type I interferon (IFN) signalling pathway and is specifically induced by type I IFNs. In the present study, previous observations by our group were expanded suggesting an implication of USP18 in multiple sclerosis (MS) based on the finding of a deficient expression of the gene in peripheral blood mononuclear cells from MS patients compared with healthy controls. METHODS: Two polymorphisms, rs2542109 (intronic) and rs9618216 (promoter), were genotyped in a cohort of 691 relapse-onset MS patients and 1028 healthy controls and in 225 MS patients treated with IFNß and classified into responders and non-responders after 2 years of treatment according to clinical criteria. Correlations between genotypes and expression levels for USP18 and its target ISG15 were performed by real-time polymerase chain reaction. RESULTS: Two USP18 haplotypes were significantly associated with MS, TG and CG. Additional experiments revealed that CG carriers were characterized by lower USP18 gene expression levels in peripheral blood mononuclear cells and higher clinical disease activity. Finally, AA homozygosis for the intronic polymorphism rs2542109 was associated with the responder phenotype; however, USP18 expression levels induced by IFNß did not differ amongst MS patients carrying different rs2542109 genotypes. CONCLUSIONS: Altogether, these results point to a role of USP18 in MS pathogenesis and the therapeutic response to IFNß.

Risk factors for delirium and inpatient mortality with delirium.

BACKGROUND: There is limited on the risk factors and mortality in patients with delirium from India. AIM: This study aimed to evaluate the risk factors associated with delirium and inpatient mortality rates of patients diagnosed with delirium by psychiatry consultation liaison services. MATERIALS AND METHODS: Three hundred and thirty-one patients diagnosed as delirium by the psychiatry consultation liaison services were examined on standardized instruments: Delirium Rating Scale Revised 98 version (DRS-R-98), amended Delirium Motor Symptom Scale (DMSS), Delirium Etiology Checklist (DEC), Charlson Comorbidity index, and a checklist for assessment of risk factors. RESULTS: More than three medications as a risk factor and metabolic/endocrine disturbances as cause were observed to play largest role in development of delirium. The inpatient mortality rate was 12.4%. Compared to the survivor group, those who died were more likely to be young (<65 years), had significantly high rate of alcohol dependence and were more frequently restrained prior to development of delirium; of these only age <65 years and use of restraints emerged as the significant predictors of mortality in regression analysis. CONCLUSION: Age and use of restraints appears to be an important predictor mortality in patients with delirium.

G-weak contraction in ordered cone rectangular metric spaces.

We prove some common fixed-point theorems for the ordered g-weak contractions in cone rectangular metric spaces without assuming the normality of cone. Our results generalize some recent results from cone metric and cone rectangular metric spaces into ordered cone rectangular metric spaces. Examples are provided which illustrate the results.

Anti-tubercular therapy (ATT) induced thrombocytopenia: A systematic review.

INTRODUCTION: Drug-induced thrombocytopenia is a known adverse event of several drugs. Antitubercular therapy (ATT) is rarely reported but important cause of thrombocytopenia. The present review aimed to understand the profile of thrombocytopenia caused by first-line ATT i.e. isoniazid, rifampicin, pyrazinamide, and ethambutol. MATERIALS AND METHODS: We screened case reports, case series, and letter-to-editor from databases, like Pubmed/MEDLINE, Ovid, and EMBASE from 1970 to 2021. The PRISMA guidelines were followed in the present systematic review. RESULTS: Categorical data were expressed as n (%) and quantitative data were expressed as median (IQR). After applying the inclusion/exclusion criteria, 17 case reports and 7 letters to the editor were selected for the present review. Rifampicin was most frequently associated with thrombocytopenia (65%). A median (IQR) drop to 20,000 (49,500) platelets/mm3 was observed. Anti-rifampicin associated antibodies and anti-dsDNA positivity were found in six studies. Except for two, all patients responded to symptomatic treatment. DISCUSSION: ATT-induced thrombocytopenia can be life-threatening and require hospitalization. Clinicians should be aware of the association of ATT with thrombocytopenia and should take appropriate measures for patient management. CONCLUSION: This review provides clinicians a comprehensive picture of adverse effects and their management in ATT induced thrombocytopenia.