Outcomes after radioscapholunate arthrodesis for intra-articular malunion of distal radius fractures.

PURPOSE: To study the clinical, radiological, and functional outcomes after of radioscapholunate (RSL) fusion for intra-articular malunion of the distal radius. METHODS: This retrospective study included 26 patients (17 males and 9 females) with intra-articular malunion of distal radius fractures who underwent RSL arthrodesis using locked miniplates (without distal scaphoid excision) between 2012 and 2020. Their mean age was 43 years (range, 32-56). Patients were assessed radiographically for union and clinically for range of motion, grip strength, and pain (assessed by Visual Analogue Scale (VAS) for pain). Functional evaluation was performed by using the Mayo modified wrist score (MMWS) and the Disabilities for the Arm, Shoulder, and Hand (DASH) questionnaire. RESULTS: All patients showed complete healing at the fusion site after a mean of 8.7 weeks (range, 8-12). The mean follow-up period was 72 months (range, 60-84). The pinch strength improved from a mean of 6.2 kg (range, 3-12) to a mean of 9.8 kg (range, 5-18) which represents 80% of the contralateral side. The mean pinch strength was 7 kg (range, 5-18) which presents 80% of the other side. VAS for pain showed a mean improvement of 72.6%. The DASH score improved to a mean of 19.2 (range, 14-24). The MMWS improved to a mean of 68 (range, 45-86). At the final follow-up period, no degenerative changes were detected in the midcarpal joint. CONCLUSION: RSL arthrodesis (using locked miniplates without distal scaphoid excision) is a reliable surgical procedure to manage cases of radiocarpal OA after intra-articular malunion of distal radius fractures with good clinical and radiological outcomes. LEVEL OF EVIDENCE: Level IV- therapeutic.

A novel homozygous nonsense mutation in CCDC88A gene cause PEHO-like syndrome in consanguineous Saudi family.

Progressive encephalopathy, edema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an unusual Mendelian phenotype of unidentified origin that causes profound intellectual disability, optic nerve/cerebellar atrophy, epileptic seizures, developmental progress, pedal edema, and early death. Uncharacteristic affected individuals are often classified as having PEHO-like syndrome, although they may be misdiagnosed as having epileptic encephalopathy, a potential result of early birth. In this study, we report a consanguineous Saudi family with a novel homozygous nonsense mutation of the CCDC88A gene causing PEHO-like syndrome. The children were suffering from developmental delay, epilepsy, mental disability, optic nerve/cerebellar atrophy, and pedal edema. Whole exome sequencing was conducted for the members of the family who have the disorder to study the novel mutation. Whole exome sequencing data analysis, confirmed by subsequent Sanger sequencing validation, identified a novel homozygous nonsense mutation c. 1292G > A, which was caused by p.Trp431* stop gain. This mutation was ruled out in 100 unrelated healthy controls. The nonsense homozygous mutation detected in this study has not yet been reported as pathogenic in the literature or various databases. In conclusion, a complete loss of protein function due to premature stop gain was caused by a mutation in exon 12 of CCDC88A. This loss may lead to PEHO phenotype. CCDC88A gene may therefore play an important and critical role for multiple aspects of normal human neurodevelopment.

Canalis basalis medianus with cerebrospinal fluid leak: rare presentation and literature review.

Canalis Basalis Medianus is a rare congenital normal anatomically variant of the clivus .We report a very rare case of cerebrospinal fluid leak from a canalis basilaris medianus in a 22-year-old male, who presented to our hospital with frontal headache and running nose two weeks after an elective septoplasty.

Glomerular mitochondrial changes in HIV associated renal injury.

HIV-associated nephropathy (HIVAN) is an AIDs-related disease of the kidney. HIVAN is characterized by severe proteinuria, podocyte hyperplasia, collapse, glomerular, and tubulointerstitial damage. HIV-1 transgenic (Tg26) mouse is the most popular model to study the HIV manifestations that develop similar renal presentations as HIVAN. Viral proteins, including Tat, Nef, and Vpr play a significant role in renal cell damage. It has been shown that mitochondrial changes are involved in several kidney diseases, and therefore, mitochondrial dysfunction may be implicated in the pathology of HIVAN. In the present study, we investigated the changes of mitochondrial homeostasis, biogenesis, dynamics, mitophagy, and examined the role of reactive oxygen species (ROS) generation and apoptosis in the Tg26 mouse model. The Tg26 mice showed significant impairment of kidney function, which was accompanied by increased blood urea nitrogen (BUN), creatinine and protein urea level. In addition, histological, western blot and PCR analysis of the Tg26 mice kidneys showed a downregulation of NAMPT, SIRT1, and SIRT3 expressions levels. Furthermore, the kidney of the Tg26 mice showed a downregulation of PGC1α, MFN2, and PARKIN, which are coupled with decrease of mitochondrial biogenesis, imbalance of mitochondrial dynamics, and downregulation of mitophagy, respectively. Furthermore, our results indicate that mitochondrial dysfunction were associated with ER stress, ROS generation and apoptosis. These results strongly suggest that the impaired mitochondrial morphology, homeostasis, and function associated with HIVAN. These findings indicated that a new insight on pathological mechanism associated with mitochondrial changes in HIVAN and a potential therapeutic target.

Renal aquaporin-4 associated pathology in TG-26 mice.

Human immunodeficiency virus-associated nephropathy (HIVAN) is a leading cause of end-stage renal disease in HIV patients, which is characterized by glomerulosclerosis and renal tubular dysfunction. Aquaporin-4 (AQP-4) is a membrane bound water channel protein that plays a distinct role in water reabsorption from renal tubular fluid. It has been proven that failure of AQP-4 insertion into the renal tubular membrane leads to renal dysfunction. However, the role of AQP-4 in HIVAN is unclear. We hypothesize that impaired water reabsorption leads to renal injury in HIVAN, where AQP-4 plays a crucial role. Renal function is assessed by urinary protein and serum blood urea nitrogen (BUN). Kidneys from HIV Transgenic (TG26) mice (HIVAN animal model) were compared to wild type mice by immunostaining, immunoblotting and quantitative RT-PCR. TG26 mice had increased proteinuria and BUN. We found decreased AQP-4 levels in the renal medulla, increased endothelin-1, endothelin receptor A and reduced Sirtuin1 (SIRT-1) levels in TG26 mice. Also, oxidative and endoplasmic reticulum stress was enhanced in kidneys of TG26 mice. We provide the first evidence that AQP-4 is inhibited due to induction of HIV associated stress in the kidneys of TG26 mice which limits water reabsorption in the kidney which may be one of the cause associated with HIVAN, impairing kidney physiology. AQP-4 dysregulation in TG26 mice suggests that similar changes may occur in HIVAN patients. This work may identify new therapeutic targets to be evaluated in HIVAN.

Hydrochemical characterization and pollution assessment of groundwater in Jammu Siwaliks, India.

Physico-chemical groundwater (GW) parameters were evaluated to understand the hydrogeochemical processes in the Siwalik plains of Jammu and Kashmir, India. During the 2012-2013 post-monsoon (POM) and pre-monsoon (PRM) seasons, GW samples (n = 207) from deep bore wells and shallow open wells were chemically analysed. Cations (Ca2+, Mg2+, Na+, K+ and Fe2+) and anions (HCO3-, Cl-, SO42- and F-) showed a wide spatio-temporal variation. Results suggest that weathering and dissolution of carbonates and silicate rocks is the main source of water mineralization. The major hydrochemical facies is characterized by Ca-Mg-HCO3 and Ca-HCO3 during the PRM and POM seasons respectively. The presence of sulphate-bearing water in a large number of the samples indicates a significant role of gypsum dissolution and anthropogenic contamination of the GW. Factor analysis (FA) and hierarchical cluster analysis (HCA) revealed that the variability of hydrochemistry is mainly related to rock-water interaction, dissolution of carbonates and other lithological units as well as the influence of anthropogenic activities in the area. Overall, it was found that the GW quality is within the limits of human consumption. The higher concentration of a few chemicals indicates an increasing trend of industrial contamination of the GW. For sustainable development of the portable GW in Siwaliks, it is necessary to minimize the adverse impacts of the anthropogenic and industrial contamination on the GW resources through best management practices and prevent its further contamination to a level that could make GW unsuitable for human uses.

Psychiatric Manifestation of Patients with Epilepsy in Mosul, Iraq.

BACKGROUND: It has been proven that physical morbidity is related to psychiatric illness. Some physical illnesses are more related to psychiatric morbidity compared to others. Epilepsy is considered one of them, as patients who suffer from epilepsy has disturbances of consciousness and this leads to a variety of psychological disturbance in addition to the psychological and social impact of the illness. AIMS: To identify risk factors and psychiatric morbidity in epilepsy, in order to try to manage it and improve outcome of this illness and enhance quality of life. METHODS: Patients who were referred to the department of Neurology at Mosul Teaching hospital from primary care centres between October 2012 and February 2013 and consented to participate in the study, were checked and if they fulfilled the criteria for the diagnosis of epilepsy, they were interviewed and their sociodemographic data were recorded, the hospital anxiety and depression questionnaire (HAD) was administered. Results were input in a computer programme and software statistical programme Minitab version 14.1 was utilised to analyse these data. RESULTS: The whole sample was 100 patients. 55 females and 45 males were included. Mean age was 30 years. Mean duration of illness was 5.5 years. Mean HAD score was 17. Male patients were a little bit older but there was no statistically significant difference compared to females and they both scored similar HAD score. There was no difference between urban and rural population with regards to HAD score. The results showed statistically significant correlation between age and duration of the illness and HAD score. DISCUSSION: The present study showed that there is a correlation between epilepsy and psychiatric morbidity. It has confirmed that females are more affected compared to males, which is expected as compared to the general population. It has also confirmed that psychiatric morbidity is positively related to epilepsy as it showed that the duration of illness has increased the psychiatric morbidity. CONCLUSION: Psychiatric morbidity is a neglected area in the management and care of physical illnesses, especially, epilepsy, where patients may get stigmatised and traumatised in the society. They may live in constant fear of having a fit. Assessing and managing the psychiatric morbidity of such patients will be reflected on the outcome of the illness and improve the quality of life of patients.

Psychiatric Manifestation of Patients with Bronchial Asthma in Mosul, Iraq.

AIMS AND METHODS: To identify risk factors and psychiatric morbidity in bronchial Asthma. Patients who consented to participate in the study, were checked for bronchial asthma. They were interviewed and their sociodemographic data were recorded, the hospital anxiety and depression was administered. Results were inputted in a computer programme and software statistical programme Minitab version 14.1 was utilised to analyse these data. RESULTS: It showed statistically significant correlation between age, duration of asthma and HAD score. IMPLICATIONS: Psychiatric morbidity is a neglected area in the management and care of physical illnesses, especially, bronchial asthma, where patients may get very worried and scared during acute attacks when they feel that they may suffocate. Assessing and managing the psychiatric morbidity of such patients will be reflected on the outcome of the illness and improve the quality of life of such patients.

Massive land system changes impact water quality of the Jhelum River in Kashmir Himalaya.

The pristine aquatic ecosystems in the Himalayas are facing an ever increasing threat from various anthropogenic pressures which necessitate better understanding of the spatial and temporal variability of pollutants, their sources, and possible remedies. This study demonstrates the multi-disciplinary approach utilizing the multivariate statistical techniques, data from remote sensing, lab, and field-based observations for assessing the impact of massive land system changes on water quality of the river Jhelum. Land system changes over a period of 38 years have been quantified using multi-spectral satellite data to delineate the extent of different anthropogenically driven land use types that are the main non-point sources of pollution. Fifteen water quality parameters, at 12 sampling sites distributed uniformly along the length of the Jhelum, have been assessed to identify the possible sources of pollution. Our analysis indicated that 18% of the forested area has degraded into sparse forest or scrublands from 1972 to 2010, and the areas under croplands have decreased by 24% as people shifted from irrigation-intensive agriculture to orchard farming while as settlements showed a 397% increase during the observation period. One-way ANOVA revealed that all the water quality parameters had significant spatio-temporal differences (p < 0.01). Cluster analysis (CA) helped us to classify all the sampling sites into three groups. Factor analysis revealed that 91.84% of the total variance was mainly explained by five factors. Drastic changes in water quality of the Jhelum since the past three decades are manifested by increases in nitrate-nitrogen, TDS, and electric conductivity. The especially high levels of nitrogen (858 ± 405 µgL(-1)) and phosphorus (273 ± 18 µgL(-1)) in the Jhelum could be attributed to the reckless application of fertilizers, pesticides, and unplanned urbanization in the area.

Discovery of consensus gene signature and intermodular connectivity defining self-renewal of human embryonic stem cells.

Molecular markers defining self-renewing pluripotent embryonic stem cells (ESCs) have been identified by relative comparisons between undifferentiated and differentiated cells. Most of analysis has been done under a specific differentiation condition that may present significantly different molecular changes over others. Therefore, it is currently unclear if there are true consensus markers defining undifferentiated human ESCs (hESCs). To identify a set of key genes consistently altered during differentiation of hESCs regardless of differentiation conditions, we have performed microarray analysis on undifferentiated hESCs (H1 and H9) and differentiated EBs and validated our results using publicly available expression array datasets. We constructed consensus modules by Weighted Gene Coexpression Network Analysis and discovered novel markers that are consistently present in undifferentiated hESCs under various differentiation conditions. We have validated top markers (downregulated: LCK, KLKB1, and SLC7A3; upregulated: RhoJ, Zeb2, and Adam12) upon differentiation. Functional validation analysis of LCK in self-renewal of hESCs using LCK inhibitor or gene silencing with siLCK resulted in a loss of undifferentiation characteristics-morphological change, reduced alkaline phosphatase activity, and pluripotency gene expression, demonstrating a potential functional role of LCK in self-renewal of hESCs. We have designated hESC markers to interactive networks in the genome, identifying possible interacting partners and showing how new markers relate to each other. Furthermore, comparison of these datasets with available datasets from induced pluripotent stem cells (iPSCs) revealed that the level of these newly identified markers was correlated to the establishment of iPSCs, which may imply a potential role of these markers in gaining of cellular potency.

Synthesis and evaluation of the biostability and cell compatibility of novel conjugates of nucleobase, peptidic epitope, and saccharide.

This article reports the synthesis of a new class of conjugates containing a nucleobase, a peptidic epitope, and a saccharide and the evalution of their gelation, biostability, and cell compatibility. We demonstrate a facile synthetic process, based on solid-phase peptide synthesis of nucleopeptides, to connect a saccharide with the nucleopeptides for producing the target conjugates. All the conjugates themselves (1-8) display excellent solubility in water without forming hydrogels. However, a mixture of 5 and 8 self-assembles to form nanofibers and results in a supramolecular hydrogel. The proteolytic stabilities of the conjugates depend on the functional peptidic epitopes. We found that TTPV is proteolytic resistant and LGFNI is susceptible to proteolysis. In addition, all the conjugates are compatible to the mammalian cells tested.

Progression from Prediabetes to Diabetes in a Diverse U.S. Population: A Machine Learning Model.

Objective: To date, there are no widely implemented machine learning (ML) models that predict progression from prediabetes to diabetes. Addressing this knowledge gap would aid in identifying at-risk patients within this heterogeneous population who may benefit from targeted treatment and management in order to preserve glucose metabolism and prevent adverse outcomes. The objective of this study was to utilize readily available laboratory data to train and test the performance of ML-based predictive risk models for progression from prediabetes to diabetes. Methods: The study population was composed of laboratory information services data procured from a large U.S. outpatient laboratory network. The retrospective dataset was composed of 15,029 adults over a 5-year period with initial hemoglobin A1C (A1C) values between 5.0% and 6.4%. ML models were developed using random forest survival methods. The ground truth outcome was progression to A1C values indicative of diabetes (i.e., ≥6.5%) within 5 years. Results: The prediabetes risk classifier model accurately predicted A1C ≥6.5% within 5 years and achieved an area under the receiver-operator characteristic curve of 0.87. The most important predictors of progression from prediabetes to diabetes were initial A1C, initial serum glucose, A1C slope, serum glucose slope, initial HDL, HDL slope, age, and sex. Conclusions: Leveraging readily obtainable laboratory data, our ML risk classifier accurately predicts elevation in A1C associated with progression from prediabetes to diabetes. Although prospective studies are warranted, the results support the clinical utility of the model to improve timely recognition, risk stratification, and optimal management for patients with prediabetes.

Pancreatic Cancer Action Network's SPARK: A Cloud-Based Patient Health Data and Analytics Platform for Pancreatic Cancer.

PURPOSE: Pancreatic cancer currently holds the position of third deadliest cancer in the United States and the 5-year survival rate is among the lowest for major cancers at just 12%. Thus, continued research efforts to better understand the clinical and molecular underpinnings of pancreatic cancer are critical to developing both early detection methodologies as well as improved therapeutic options. This study introduces Pancreatic Cancer Action Network's (PanCAN's) SPARK, a cloud-based data and analytics platform that integrates patient health data from the PanCAN's research initiatives and aims to accelerate pancreatic cancer research by making real-world patient health data and analysis tools easier to access and use. MATERIALS AND METHODS: The SPARK platform integrates clinical, molecular, multiomic, imaging, and patient-reported data generated from PanCAN's research initiatives. The platform is built on a cloud-based infrastructure powered by Velsera. Cohort exploration and browser capabilities are built using Velsera ARIA, a specialized product for leveraging clinicogenomic data to build cohorts, query variant information, and drive downstream association analyses. Data science and analytic capabilities are also built into the platform allowing researchers to perform simple to complex analysis. RESULTS: Version 1 of the SPARK platform was released to pilot users, who represented diverse end users, including molecular biologists, clinicians, and bioinformaticians. Included in the pilot release of SPARK are deidentified clinical (including treatment and outcomes data), molecular, multiomic, and whole-slide pathology images for over 600 patients enrolled in PanCAN's Know Your Tumor molecular profiling service. CONCLUSION: The pilot release of the SPARK platform introduces qualified researchers to PanCAN real-world patient health data and analytical resources in a centralized location.

A novel regulatory factor recruits the nucleosome remodeling complex to wingless integrated (Wnt) signaling gene promoters in mouse embryonic stem cells.

The nucleosome remodeling and deacetylation (NuRD) complex is required for modulating the transcription of essential pluripotency genes in ESC self-renewal. MBD3 is considered a key player in the formation of a functional NuRD complex. The recruitment of MBD3 to methylated promoters may require other prerequisite factors. We show that cyclin-dependent kinase 2-associated protein 1 (CDK2AP1), an essential gene for early embryonic development, plays a role in pluripotency of ESC by engaging MBD3 to the promoter region of Wnt signaling genes. The occupancy of MBD3 on several promoters of Wnt genes was significantly lost in the absence of CDK2AP1, resulting in hyperactivation of Wnt. We propose that the transcriptional modulation of the Wnt pathway mediated by NuRD requires the presence of essential auxiliary components such as CDK2AP1, which may aid the association of the complex with specific focal regions of the target promoters.

Two-stage PCR assay for detection of human brucellosis in endemic areas.

BACKGROUND: Brucellosis is a common zoonosis that can cause a severe febrile illness in humans. It constitutes a persistent health problem in many developing countries around the world. It is one of the most frequently reported diseases in Saudi Arabia and incidence is particularly high in the Central region, and around the city of Riyadh. The aim of this study was to evaluate a two-stage PCR assay for detection of human brucellosis particularly in endemic areas. METHODS: A total of 101 serum samples were collected from patients with acute febrile illness (AFI) of unknown cause from two different locations in the Western region of Saudi Arabia. The first location (Northern) is characterized by a nomadic rural population while the second (Central) is a modern urban city. All samples were subjected to DNA extraction and Brucella genus-specific PCR amplification using B4/B5 primers of the bcsp31 gene. Positive B4/B5 samples were subjected to multiplex species-specific Brucella PCR amplification. RESULTS: In the Northern location, 81.9% of the AFI samples were confirmed Brucella positive, while all the samples collected from the Central region proved to be Brucella negative. Samples positive for Brucella were subjected to multiplex species-specific Brucella amplification. B. abortus was detected in 10% and B. melitensis in 8% of the samples, while the majority (82%) of samples showed both B. abortus and B. melitensis. As expected, B. suis was not detected in any of the samples. CONCLUSIONS: This study concluded that a two-stage PCR assay could be useful as a rapid diagnostic tool to allow the consideration of brucellosis as a possible cause of AFI, particularly in non-urban locations. It also recommends the collection of epidemiological data for such patients to obtain further information that may help in rapid diagnosis.

CKD Progression Prediction in a Diverse US Population: A Machine-Learning Model.

Rationale & Objective: Chronic kidney disease (CKD) is a major cause of morbidity and mortality. To date, there are no widely used machine-learning models that can predict progressive CKD across the entire disease spectrum, including the earliest stages. The objective of this study was to use readily available demographic and laboratory data from Sonic Healthcare USA laboratories to train and test the performance of machine learning-based predictive risk models for CKD progression. Study Design: Retrospective observational study. Setting & Participants: The study population was composed of deidentified laboratory information services data procured from a large US outpatient laboratory network. The retrospective data set included 110,264 adult patients over a 5-year period with initial estimated glomerular filtration rate (eGFR) values between 15-89 mL/min/1.73 m2. Predictors: Patient demographic and laboratory characteristics. Outcomes: Accelerated (ie, >30%) eGFR decline associated with CKD progression within 5 years. Analytical Approach: Machine-learning models were developed using random forest survival methods, with laboratory-based risk factors analyzed as potential predictors of significant eGFR decline. Results: The 7-variable risk classifier model accurately predicted an eGFR decline of >30% within 5 years and achieved an area under the curve receiver-operator characteristic of 0.85. The most important predictor of progressive decline in kidney function was the eGFR slope. Other key contributors to the model included initial eGFR, urine albumin-creatinine ratio, serum albumin (initial and slope), age, and sex. Limitations: The cohort study did not evaluate the role of clinical variables (eg, blood pressure) on the performance of the model. Conclusions: Our progressive CKD classifier accurately predicts significant eGFR decline in patients with early, mid, and advanced disease using readily obtainable laboratory data. Although prospective studies are warranted, our results support the clinical utility of the model to improve timely recognition and optimal management for patients at risk for CKD progression. Plain-Language Summary: Defined by a significant decrease in estimated glomerular filtration rate (eGFR), chronic kidney disease (CKD) progression is strongly associated with kidney failure. However, to date, there are no broadly used resources that can predict this clinically significant event. Using machine-learning techniques on a diverse US population, this cohort study aimed to address this deficiency and found that a 5-year risk prediction model for CKD progression was accurate. The most important predictor of progressive decline in kidney function was the eGFR slope, followed by the urine albumin-creatinine ratio and serum albumin slope. Although further study is warranted, the results showed that a machine-learning model using readily obtainable laboratory information accurately predicts CKD progression, which may inform clinical diagnosis and management for this at-risk population.

Structural Racism, Social Determinants of Health, and Provider Bias: Impact on Brain Development in Critical Congenital Heart Disease.

Critical congenital heart disease (cCHD) has neurodevelopmental sequelae that can carry into adulthood, which may be due to aberrant brain development or brain injury in the prenatal and perinatal/neonatal periods and beyond. Health disparities based on the intersection of sex, geography, race, and ethnicity have been identified for poorer pre- and postnatal outcomes in the general population, as well as those with cCHD. These disparities are likely driven by structural racism, disparities in social determinants of health, and provider bias, which further compound negative brain development outcomes. This review discusses how aberrant brain development in cCHD early in life is affected by reduced access to quality care (ie, prenatal care and testing, postnatal care) due to divestment in non-White neighbourhoods (eg, redlining) and food insecurity, differences in insurance status, location of residence, and perceived interpersonal racism and bias that disproportionately affects pregnant people of colour who have fewer economic resources. Suggestions are discussed for moving forward with implementing strategies in medical education, clinical care, research, and gaining insight into the communities served to combat disparities and bias while promoting cultural humility.

Understanding the linkages between spatio-temporal urban land system changes and land surface temperature in Srinagar City, India, using image archives from Google Earth Engine.

Land-use and land-cover (LULC) is an important component for sustainable natural resource management, and there are considerable impacts of the rapid anthropogenic LULC changes on environment, ecosystem services, and land surface processes. One of the significant adverse implications of the rapidly changing urban LULC is the increase in the Land Surface Temperature (LST) resulting in the urban heat island effect. In this study, we used a time series of Landsat satellite images from 1992 to 2020 in the Srinagar city of the Kashmir valley, North-western Himalaya, India to understand the linkages between LULC dynamics and LST, derived from the archived images using the Google Earth Engine (GEE). Furthermore, the relationship between LST, urban heat island (UHI), and biophysical indices, i.e., Normalized Difference Vegetation Index (NDVI) and Normalized Difference Water Index (NDWI), was also analysed. LULC change detection analysis from 1992 to 2020 revealed that the built-up area has increased significantly from 12% in 1992 to 40% in 2020, while the extent of water bodies has decreased from 6% in 1992 to 4% in 2020. The area under plantations has decreased from 26% in 1992 to 17% in 2020, and forests have decreased from 4 to 2% during the same period. Urban sprawl of Srinagar city has resulted in the depletion of natural land covers, modification of natural drainage, and loss of green and blue spaces over the past four decades. The study revealed that the maximum LST in the city has increased by 11°C between 1992 and 2020. During the same period of time, the minimum LST in the city has increased by 5°C, indicating the impact of urbanization on the city environment, which is reflected by the observed changes in various environmental indices. UHI impact in the city is quite evident with the maximum LST at the city centre having increased from 13.03°C in 1992 to 22.01°C in 2020. The findings shall serve as a vital source of knowledge for urban planners and decision-makers in developing sustainable urban environmental management strategies for Srinagar city.