To describe the burden of osteoarthritis (OA) in India from 1990 to 2019.
Data from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used. The burden of OA –knee OA, hip ...OA, hand OA, and other OA– was estimated for India and its states from 1990 to 2019 through a systematic analysis of prevalence, incidence, years lived with disability (YLD), and disability-adjusted life years (DALY) using methods reported in GBD 2019 study.
Around 23.46 million individuals in India had OA in 1990; this increased to 62.35 million in 2019. The age-standardised prevalence of OA increased from 4,895 (95% uncertainty interval (UI):4,420–5,447) in 1990–5313 (95%UI:4,799–5,898) in 2019, per 100,000 persons. Similarly, DALYs due to OA increased from 0.79 million (95%UI:0.40–1.55) to 2.12 million (95%UI:1.07–4.23); while age-standardised DALYs increased from 164 (95%UI:83–325) to 180 (95%UI:91–361) per 100,000 persons from 1990 to 2019. OA was the 20th most common cause of YLDs in India in 2019, accounting for 1.48% (95%UI:0.88–2.78) of all YLDs; increasing from 23rd most common cause in 1990 (1.25%(95%UI:0.74–2.34)). Knee OA was the most common form of OA, followed by hand OA. The prevalence, incidence, and DALYs for OA and knee OA were consistently higher in females than males.
The burden and impact of OA in India are substantial and is increasing. Adopting suitable control and preventive community measures to reduce modifiable risk factors (obesity, injuries, occupational stress) are needed to reduce the current and future burden of OA in India.
We present new planetary nebulae (PNe) positions, radial velocities and magnitudes for six early-type galaxies obtained with the Planetary Nebulae Spectrograph (PNS), along with derived ...two-dimensional velocity and velocity dispersion fields, and the α parameters (i.e. the number of PNe per unit luminosity). We also present new deep absorption-line long-slit kinematics for three galaxies in the sample, obtained with the FOcal Reducer and low dispersion Spectrograph (FORS2) at the Very Large Telescope (VLT).
We extend this study to include additional 10 early-type galaxies with PNe radial velocity measurements available from the literature, including previous PNS studies, in order to obtain a broader description of the outer-halo kinematics in early-type galaxies. These data extend the information derived from stellar absorption-line kinematics to typically several and up to 8 effective radii.
The combination of photometry, absorption-line and PNe kinematics shows (i) a good agreement between the PNe number density distribution and the stellar surface brightness in the region where the two data sets overlap; (ii) a good agreement between PNe and absorption-line kinematics; (iii) that the mean rms velocity profiles fall into two groups, with part of the galaxies characterized by slowly decreasing profiles and the remainder having steeply falling profiles; (iv) a larger variety of velocity dispersion radial profiles; (v) that twists and misalignments in the velocity fields are more frequent at large radii, including some fast rotator galaxies; (vi) that outer haloes are characterized by more complex radial profiles of the specific angular momentum-related λR parameter than observed within 1 R
e; (vii) that many objects are more rotationally dominated at large radii than in their central parts and (viii) that the halo kinematics are correlated with other galaxy properties, such as total B band and X-ray luminosity, isophotal shape, total stellar mass, V/σ and α parameter, with a clear separation between fast and slow rotators.
Obtaining spectroscopic observations of the progenitors of core-collapse supernovae is often unfeasible, due to an inherent lack of knowledge as to what stars experience supernovae and when they will ...explode. In this Letter we present photometric and spectroscopic observations of the progenitor activity of SN 2023fyq before the He-rich progenitor explodes as a Type Ibn supernova. The progenitor of SN 2023fyq shows an exponential rise in flux prior to core collapse. Complex He I emission line features are observed in the progenitor spectra, with a P Cygni-like profile, as well as an evolving broad base with velocities of the order of 10 000 km s −1 . The luminosity and evolution of SN 2023fyq is consistent with a Type Ibn, reaching a peak r -band magnitude of −18.8 mag, although there is some uncertainty regarding the distance to the host, NGC 4388, which is located in the Virgo cluster. We present additional evidence of asymmetric He-rich material being present both prior to and after the explosion of SN 2023fyq, which suggests that this material survived the ejecta interaction. Broad O I , C I , and the Ca II triplet lines are observed at late phases, confirming that SN 2023fyq was a genuine supernova, rather than a non-terminal interacting transient. SN 2023fyq provides insight into the final moments of a massive star’s life, demonstrating that the progenitor is likely highly unstable before core collapse.
Rationale
Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is ...limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence.
Objectives
The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning.
Methods
In study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state.
Results
Cann-CBD reduced the likelihood of high-effort choices relative to placebo (
p
= 0.042) and increased sensitivity to expected value compared to both placebo (
p
= 0.014) and Cann + CBD (
p
= 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (
p
= 0.007).
Conclusions
Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC.
Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumour genomes to identify molecular markers at this lethal stage of disease. Previously, we ...characterized somatic alterations in metastatic tumours in the methylcytosine dioxygenase ten-eleven translocation 2 (TET2), which is altered in 5-15% of myeloid, kidney, colon and PCas. Genome-wide association studies previously identified non-coding risk variants associated with PCa and melanoma. We perform fine-mapping of PCa risk across TET2 using genotypes from the PEGASUS case-control cohort and identify six new risk variants in introns 1 and 2. Oligonucleotides containing two risk variants are bound by the transcription factor octamer-binding protein 1 (Oct1/POU2F1) and TET2 and Oct1 expression are positively correlated in prostate tumours. TET2 is expressed in normal prostate tissue and reduced in a subset of tumours from the Cancer Genome Atlas (TCGA). Small interfering RNA-mediated TET2 knockdown (KD) increases LNCaP cell proliferation, migration and wound healing, verifying loss drives a cancer phenotype. Endogenous TET2 bound the androgen receptor (AR) and AR-coactivator proteins in LNCaP cell extracts, and TET2 KD increases prostate-specific antigen (KLK3/PSA) expression. Published data reveal TET2 binding sites and hydroxymethylcytosine proximal to KLK3. A gene co-expression network identified using TCGA prostate tumour RNA-sequencing identifies co-regulated cancer genes associated with 2-oxoglutarate (2-OG) and succinate metabolism, including TET2, lysine demethylase (KDM) KDM6A, BRCA1-associated BAP1, and citric acid cycle enzymes IDH1/2, SDHA/B, and FH. The co-expression signature is conserved across 31 TCGA cancers suggesting a putative role for TET2 as an energy sensor (of 2-OG) that modifies aspects of androgen-AR signalling. Decreased TET2 mRNA expression in TCGA PCa tumours is strongly associated with reduced patient survival, indicating reduced expression in tumours may be an informative biomarker of disease progression and perhaps metastatic disease.
The susceptibility of the kidneys to fluoride toxicity can largely be attributed to its anatomy and function. As the filtrate moves along the complex tubular structure of each nephron, it is ...concentrated in the proximal and distal tubules and collecting duct. It has been frequently observed that the children suffering from renal impairments also have some symptoms of dental and skeletal fluorosis. The findings suggest that fluoride somehow interferes with renal anatomy and physiology, which may lead to renal pathogenesis. The aim of this study was to evaluate the fluoride-associated nephrotoxicity. A total of 156 patients with childhood nephrotic syndrome were screened and it was observed that 32 of them had significantly high levels (p ≤ 0.05) of fluoride in urine (4.01 ± 1.83 ppm) and serum (0.1 ± 0.013 ppm). On the basis of urinary fluoride concentration, patients were divided into two groups, namely group 1 (G-1) (n = 32) containing normal urine fluoride (0.61 ± 0.17 ppm) and group 2 (G-2) (n = 32) having high urine fluoride concentration (4.01 ± 1.83 ppm). Age-matched healthy subjects (n = 33) having normal levels of urinary fluoride (0.56 ± 0.15 ppm) were included in the study as control (group 0 (G-0)). Kidney biopsies were taken from G-1 and G-2 only, who were subjected to ultrastructural (transmission electron microscopy) and apoptotic (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling) analysis. Various subcellular ultrastructural changes including nuclear disintegration, chromosome condensation, cytoplasmic ground substance lysis, and endoplasmic reticulum blebbing were observed. Increased levels of apoptosis were observed in high fluoride group (G-2) compared to normal fluoride group (G-1). Various degrees of fluoride-associated damages to the architecture of tubular epithelia, such as cell swelling and lysis, cytoplasmic vacuolation, nuclear condensation, apoptosis, and necrosis, were observed.
InterPro (http://www.ebi.ac.uk/interpro/) is a database that integrates diverse information about protein families, domains and functional sites, and makes it freely available to the public via ...Web-based interfaces and services. Central to the database are diagnostic models, known as signatures, against which protein sequences can be searched to determine their potential function. InterPro has utility in the large-scale analysis of whole genomes and meta-genomes, as well as in characterizing individual protein sequences. Herein we give an overview of new developments in the database and its associated software since 2009, including updates to database content, curation processes and Web and programmatic interfaces.
Abstract Acute administration of the primary psychoactive constituent of cannabis, Δ-9-tetrahydrocannabinol (THC), impairs human facial affect recognition, implicating the endocannabinoid system in ...emotional processing. Another main constituent of cannabis, cannabidiol (CBD), has seemingly opposite functional effects on the brain. This study aimed to determine the effects of THC and CBD, both alone and in combination on emotional facial affect recognition. 48 volunteers, selected for high and low frequency of cannabis use and schizotypy, were administered, THC (8 mg), CBD (16 mg), THC+CBD (8 mg+16 mg) and placebo, by inhalation, in a 4-way, double-blind, placebo-controlled crossover design. They completed an emotional facial affect recognition task including fearful, angry, happy, sad, surprise and disgust faces varying in intensity from 20% to 100%. A visual analogue scale (VAS) of feeling ‘stoned’ was also completed. In comparison to placebo, CBD improved emotional facial affect recognition at 60% emotional intensity; THC was detrimental to the recognition of ambiguous faces of 40% intensity. The combination of THC+CBD produced no impairment. Relative to placebo, both THC alone and combined THC+CBD equally increased feelings of being ‘stoned’. CBD did not influence feelings of ‘stoned’. No effects of frequency of use or schizotypy were found. In conclusion, CBD improves recognition of emotional facial affect and attenuates the impairment induced by THC. This is the first human study examining the effects of different cannabinoids on emotional processing. It provides preliminary evidence that different pharmacological agents acting upon the endocannabinoid system can both improve and impair recognition of emotional faces.
Changes in cannabis regulation globally make it increasingly important to determine what predicts an individual's risk of experiencing adverse drug effects. Relevant studies have used diverse ...self-report measures of cannabis use, and few include multiple biological measures. Here we aimed to determine which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like symptoms.
In a naturalistic study, 410 young cannabis users were assessed once when intoxicated with their own cannabis and once when drug-free in counterbalanced order. Biological measures of cannabinoids (Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN) and their metabolites) were derived from three samples: each participant's own cannabis (THC, CBD), a sample of their hair (THC, THC-OH, THC-COOH, CBN, CBD) and their urine (THC-COOH/creatinine). Comprehensive self-report measures were also obtained. Self-reported and clinician-rated assessments were taken for cannabis dependency Severity of Dependence Scale (SDS), DSM-IV-TR and acute psychotic-like symptoms Psychotomimetic State Inventory (PSI) and Brief Psychiatric Rating Scale (BPRS).
Cannabis dependency was positively associated with days per month of cannabis use on both measures, and with urinary THC-COOH/creatinine for the SDS. Acute psychotic-like symptoms were positively associated with age of first cannabis use and negatively with urinary THC-COOH/creatinine; no predictors emerged for BPRS.
Levels of THC exposure are positively associated with both cannabis dependency and tolerance to the acute psychotic-like effects of cannabis. Combining urinary and self-report assessments (use frequency; age first used) enhances the measurement of cannabis use and its association with adverse outcomes.
Objective
The implementation of value‐based health care in inflammatory arthritis requires a standardized set of modifiable outcomes and risk‐adjustment variables that is feasible to implement ...worldwide.
Methods
The International Consortium for Health Outcomes Measurement (ICHOM) assembled a multidisciplinary working group that consisted of 24 experts from 6 continents, including 6 patient representatives, to develop a standard set of outcomes for inflammatory arthritis. The process followed a structured approach, using a modified Delphi process to reach consensus on the following decision areas: conditions covered by the set, outcome domains, outcome measures, and risk‐adjustment variables. Consensus in areas 2 to 4 were supported by systematic literature reviews and consultation of experts.
Results
The ICHOM Inflammatory Arthritis Standard Set covers patients with rheumatoid arthritis (RA), axial spondyloarthritis, psoriatic arthritis, and juvenile idiopathic arthritis (JIA). We recommend that outcomes regarding pain, fatigue, activity limitations, overall physical and mental health impact, work/school/housework ability and productivity, disease activity, and serious adverse events be collected at least annually. Validated measures for patient‐reported outcomes were endorsed and linked to common reporting metrics. Age, sex at birth, education level, smoking status, comorbidities, time since diagnosis, and rheumatoid factor and anti‐citrullinated protein antibody lab testing for RA and JIA should be collected as risk‐adjustment variables.
Conclusion
We present the ICHOM inflammatory arthritis Standard Set of outcomes, which enables health care providers to implement the value‐based health care framework and compare outcomes that are important to patients with inflammatory arthritis.
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