Coverage and evaluation survey of post-mass drug administration for lymphatic filariasis in four endemic districts of Uttar Pradesh: are we on the track?

BACKGROUND OBJECTIVES: There is a persistent high microfilaria rate and variable reporting of coverage of Mass Drug Administration (MDA). The study aims to estimate the coverage, effective coverage, and compliance of drugs administered under MDA and to determine the predictors affecting the effective coverage. METHODS: A community-based cross-sectional study was conducted in Amethi, Lucknow, Raebareli and Sultanpur districts of Uttar Pradesh, India. The study participants were selected using multi-stage random sampling using Probability Proportional to Estimated Size (PPES). The coverage, effective coverage and compliance of drugs were presented as proportion. The multivariable logistic regression model was applied to identify the significant predictors for effective coverage. RESULTS: Of 4151 participants, 997 (24.0%), 340 (8.2%), 1158 (27.9%) and 1656 (39.9%) belonged to Amethi, Lucknow, Raebareli and Sultanpur districts respectively. The coverage ranged from 49.8% to 87.9% and effective coverage ranged from 51.8% to 73.2% across districts. The compliance was the poorest (70.7%) in Sultanpur. The source of information about MDA, the sex of the study participants and the area of residence emerged as predictors for effective coverage in the districts. INTERPRETATION CONCLUSION: The effective coverage was poor with good drug complianceacross the districts. There is a need for a well-designed pre-MDA campaign addressing the fear of side effects of drugs and emphasising the presence of the community during the MDA round along with monitoring and evaluation of the round.

Peroxisome proliferator-activated receptor agonists: A new hope towards the management of alcoholic liver disease.

In this editorial, we examine a paper by Koizumi et al, on the role of peroxisome proliferator-activated receptor (PPAR) agonists in alcoholic liver disease (ALD). The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD. The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis, which are both affected by ALD. Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide. This editorial analyzes the possibility of PPAR agonists as treatments for ALD. As key factors of inflammation and metabolism, PPARs offer multiple methods for managing the complex etiology of ALD. We assess the abilities of PPARα, PPARγ, and PPARß/δ agonists to prevent steatosis, inflammation, and fibrosis due to liver diseases. Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease. This editorial discusses the data analyzed and the obstacles, advantages, and mechanisms of action of PPAR agonists for ALD. Further research is needed to understand the efficacy, safety, and mechanisms of PPAR agonists for treating ALD.

Association between myeloid disorders and adult onset-inflammatory syndromes, successful treatment with JAK-inhibitors: Case series and literature review.

Approximately one-third of patients with myeloid disorders like myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) exhibit inflammatory and autoimmune disorders (IADs). These IADs often include atypical and incomplete forms of common autoimmune conditions, and exhibit resistance to conventional immunosuppressive therapies. There is growing interest in molecular relationships between IADs and MDS/CMML to find potential targeted therapies. Recently, patients with somatic mutations in the UBA1 gene were identified as having VEXAS syndrome. Herein, we present a concise case-series illustrating concurrent elderly-onset inflammatory manifestations and myeloid disorders (MDS, CMML, and idiopathic cytopenia of undetermined significance). These patients manifested inflammatory or autoimmune symptoms, including erythema nodosum, Raynaud's phenomenon, Sjogren syndrome, and refractory pruritus, having onset after 60-years of age. The inflammatory manifestations were largely refractory to traditional immunosuppressive regimens. Remarkably, treatment with a JAK-1 inhibitor, upadacitinib, in two cases yielded marked resolution of inflammatory symptoms, facilitating the gradual tapering of corticosteroids, improvement of hemoglobin levels, and reduction in serum C-reactive protein levels. Upon loss of response to upadacitinib, JAK-2 inhibitor ruxolitinib provided clinical benefit in one of the cases, facilitating further tapering of glucocorticoids. This arena warrants further exploration through prospective studies of larger cohorts to delineate optimal management strategies.

Evaluation of C-Reactive Proteins Levels in Peri-Implantitis Patients.

Background: To evaluate C-reactive protein (CRP) levels in peri-implantitis patients. Material and Methods: This study comprised a total of 100 participants. Fifty participants with a confirmed clinical and radiological diagnosis of peri-implantitis formed one group. Another group of 50 volunteers who came in for a normal health checkup served as healthy controls. All the patients were recalled in the morning. Fasting venous blood samples were collected. CRP concentrations in the laboratory were determined using an auto-analyzer. Results: In this study, there were 40 females and 60 males. Mean CRP levels among subjects of the peri-implantitis group and the control group were 0.615 and 0.201 mg/dL, respectively. Conclusion: It was observed that mean CRP levels were higher among subjects having peri-implantitis as compared to the controls.

The Role of Silver Diamine Fluoride in Contemporary Dental Practice: A Comprehensive Review.

Silver diamine fluoride (SDF) has garnered increasing attention in contemporary dental practice due to its unique properties and clinical applications. The minimally invasive nature, antimicrobial efficacy, and desensitization capabilities of SDF position it as a valuable tool in preventive and restorative dentistry. However, esthetic concerns associated with tooth discoloration and the need for further research to understand long-term outcomes underscore the importance of ongoing investigation and clinical integration. This article underscores the transformative potential of SDF in modern dental care and emphasizes the necessity of continued research and education to maximize its benefits.

Intensification mechanisms and moisture dynamics of super cyclonic storm 'Amphan' over the Bay of Bengal: Implications for aerosol re-distribution.

The present research investigates the dynamics and underlying causes contributing to the exceptional intensity of Super Cyclonic Storm (SuCS) Amphan (16th to 21st May 2020) over the Bay of Bengal (BoB), as well as its impact on aerosol redistribution along the four cities of eastern coast and north-eastern India. Notably, the SuCS was formed during the first phase of the COVID-19 lockdown in India, giving it a unique aspect of study and analysis. Our analysis based on 30 years of climatology data from Modern-Era Retrospective Analysis for Research and Applications, Version 2 (MERRA-2) reanalysis reveals 'positive' monthly anomalous winds (0.8 to 1.6 m/s) prevailed over the central BoB for May 2020. The present study further found the evolution of 'barrier layer thickness'(BLT) leading up to landfall, noting a thickening trend from 8 to 3 days before landfall, contributing to maintaining warmer sea surface temperatures near the coast. Additionally, utilizing European Centre for Medium-Range Weather Forecasts (ECMWF), reanalysis version-5 (ERA-5) data, a mean positive sea surface temperature (SST) anomaly of 0.8 to 1 °C was observed 'before' cyclone period (10-15 May 2020) near the cyclogenesis point. A detailed examination of Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) vertical cross-section plots during the cyclone's intensification stage reveals the presence of high-altitude clouds composed primarily of ice crystals. Further, analysis also indicates that the cyclone transported Sea-salt PM2.5 aerosols from the ocean, dispersing them in the landfall region.The aerosol optical Depth (AOD) data obtained from the National Aeronautics and Space Administration's (NASA) 'Clouds and the Earth's Radiant Energy System (CERES)' mission and MERRA-2 were also analysed, revealing that the cyclone redistributed aerosols over the Bengal basin region (mainly over 'Kolkata') and three other nearby cities along the track of the cyclone (i.e., Bhubaneswar (Odisha) Agartala (Tripura) and Shillong (Meghalaya) respectively).

Synthesis and characterization of cis and trans cobalt(II) nalidixate complexes having a 1-(4-chlorophenyl)-3-(pyridin-4-ylmethyl)urea ligand.

The synthesis and characterization of specific cis- and trans-isomers of a cobalt(II) bis-nalidixate complex with a pyridine-based urea, 1-(4-chlorophenyl)-3-(pyridin-4-ylmethyl)urea (L), ligand are reported. The two isomers, cis-[Co(L)2(NALD)2]·0.5DMF·H2O and trans-[Co(L)2(NALD)2]·2DMF·2H2O (the nalidixate anion is abbreviated to NALD) were prepared by anion-guided synthesis. When cobalt(II) chloride was used as one of the reactants, the reaction yielded the trans-isomer under ambient reaction conditions. Whereas a reaction using cobalt(II) nitrate provided only the cis-isomer when the reaction was continued for a prolonged time. On the other hand, the cis-isomer was converted to the trans-isomer in solution upon treatment with chloride ions. The chloride-assisted formation of the trans-isomer was investigated by a UV-visible study, and it passed through a bond reorganization by forming a tetrahedral intermediate complex. A DFT calculation was carried out to show the difference in energy between the isomers as well as the energy of a plausible tetrahedral cobalt complex. The aggregation behavior of the cis-isomer in different solvents was investigated, and solvent-dependent aggregation and a solvent-dependent Cotton effect were observed.

Vulnerability assessment of aerosol and climate variability for rice and maize yield using EO datasets for sustainable agriculture over India.

Human-generated aerosol pollution gradually modifies the atmospheric chemical and physical attributes, resulting in significant changes in weather patterns and detrimental effects on agricultural yields. The current study assesses the loss in agricultural productivity due to weather and anthropogenic aerosol variations for rice and maize crops through the analysis of time series data of India spanning from 1998 to 2019. The average values of meteorological variables like maximum temperature (TMAX), minimum temperature (TMIN), rainfall, and relative humidity, as well as aerosol optical depth (AOD), have also shown an increasing tendency, while the average values of soil moisture and fraction of absorbed photosynthetically active radiation (FAPAR) have followed a decreasing trend over that period. This study's primary finding is that unusual variations in weather variables like maximum and minimum temperature, rainfall, relative humidity, soil moisture, and FAPAR resulted in a reduction in rice and maize yield of approximately (2.55%, 2.92%, 2.778%, 4.84%, 2.90%, and 2.82%) and (5.12%, 6.57%, 6.93%, 6.54%, 4.97%, and 5.84%), respectively. However, the increase in aerosol pollution is also responsible for the reduction of rice and maize yield by 7.9% and 8.8%, respectively. In summary, the study presents definitive proof of the detrimental effect of weather, FAPAR, and AOD variability on the yield of rice and maize in India during the study period. Meanwhile, a time series analysis of rice and maize yields revealed an increasing trend, with rates of 0.888 million tons/year and 0.561 million tons/year, respectively, due to the adoption of increasingly advanced agricultural techniques, the best fertilizer and irrigation, climate-resilient varieties, and other factors. Looking ahead, the ongoing challenge is to devise effective long-term strategies to combat air pollution caused by aerosols and to address its adverse effects on agricultural production and food security.

Risk Prediction for Clonal Cytopenia: Multicenter Real-World Evidence.

Clonal cytopenia of undetermined significance (CCUS) represents a distinct disease entity characterized by myeloid-related somatic mutations with a variant allele fraction of ≥2% in individuals with unexplained cytopenia(s) but without a myeloid neoplasm (MN). Notably, CCUS carries a risk of progressing to MN, particularly in cases featuring high-risk mutations. Understanding CCUS requires dedicated studies to elucidate its risk factors and natural history. Our analysis of 357 CCUS patients investigated the interplay between clonality, cytopenia, and prognosis. Multivariate analysis identified 3 key adverse prognostic factors: the presence of splicing mutation(s) (score = 2 points), platelet count <100×109/L (score = 2.5), and ≥2 mutations (score = 3). Variable scores were based on the coefficients from the Cox proportional hazards model. This led to the development of the Clonal Cytopenia Risk Score (CCRS), which stratified patients into low- (score <2.5 points), intermediate- (score 2.5-<5), and high-risk (score ≥5) groups. The CCRS effectively predicted 2-year cumulative incidence of MN for low- (6.4%), intermediate- (14.1%), and high- (37.2%) risk groups, respectively, by Gray's test (P <.0001). We further validated the CCRS by applying it to an independent CCUS cohort of 104 patients, demonstrating a c-index of 0.64 (P =.005) in stratifying the cumulative incidence of MN. Our study underscores the importance of integrating clinical and molecular data to assess the risk of CCUS progression, making the CCRS a valuable tool that is practical and easily calculable. These findings are clinically relevant, shaping the management strategies for CCUS and informing future clinical trial designs.

Microenvironment shapes small-cell lung cancer neuroendocrine states and presents therapeutic opportunities.

Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intratumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the cell-extrinsic drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the TME exhibit substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAFs) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting exceptionally poor prognosis. Our work provides a comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLC's adaptable nature, opening possibilities for reprogramming the TME-tumor communications that shape SCLC tumor states.

A rare case of Philadelphia-positive (P210BCR-ABL1) T-cell acute lymphoblastic leukemia/lymphoma associated with minimal residual disease persistence after intensive chemotherapeutic approaches.

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is a rare and aggressive leukemia. Philadelphia chromosome-positive cytogenetic abnormality is most common in CML. It is difficult to differentiate between de novo Ph+ T-ALL/LBL and T-cell lymphoblastic crises of CML. We present a case of adult Ph+ T-ALL/LBL with a likely history of antecedent CML. Initially thought to be a case of chronic-phase CML, a diagnostic quandary led to the pursuit of a lymph node biopsy that established the diagnosis of Ph+ T-LBL or T lymphoblastic blast crisis of CML, a clinical presentation extremely rare and only the second of its kind from our review of the literature. The patient was treated with an intensive chemotherapy regimen for over a year due to persistent minimal residual disease (MRD) positivity indicating aggressive disease.

Isolation and Detection of Pathological Tau Species in a Tauopathy Mouse Model.

Tau protein in Alzheimer's disease (AD) and tauopathies becomes insoluble due to hyperphosphorylation, conformational alterations, and aggregation. To analyze insoluble tau and pathological tau species, this study employs a methodology that utilizes wild-type and transgenic tau mice (P310S Tau) tissue extraction using 1% Sarkosyl or N-Lauroylsarcosine sodium salt and the radio immunoprecipitation assay (RIPA) buffer. However, the commonly used methods to study the insoluble tau fraction using detergents like Sarkosyl and RIPA require a large amount of homogenate, which can pose challenges when dealing with small tissue samples. Additionally, the study employs immunohistochemistry to visualize and quantify the pathological tau species in the brain tissue of transgenic mice, aiming to identify and analyze pathological tau species such as hyperphosphorylated tau to further our understanding of tauopathies such as Alzheimer's disease.

Efficacy and safety of mitoxantrone, etoposide, and cytarabine for treatment of relapsed or refractory acute myeloid leukemia.

BACKGROUND/RATIONALE: Most patients with acute myeloid leukemia (AML) develop relapsed or refractory (R/R) disease after receiving initial induction chemotherapy. Salvage chemotherapy followed by allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative therapy for R/R AML. Mitoxantrone, etoposide, and cytarabine (MEC) is the current standard of care salvage regimen for R/R AML at Cleveland Clinic. The primary objective was to determine the overall remission rate (ORR: defined as patients achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi)) in R/R AML patients who received MEC. METHODS: Adult patients with R/R AML treated with MEC between July 1, 2014 and September 30, 2022 were included. ORR and its association with baseline characteristics were determined. Secondary outcomes included overall survival (OS), event-free survival (EFS), relapse-free survival (RFS), and safety. RESULTS: Sixty patients were evaluated. The ORR was 51.7% (33.3% CR and 18.3% CRi). The median time from receipt of MEC to CR/CRi was 7.7 weeks. Patients with bone marrow blasts ≤20% and peripheral blood blasts ≤30% at MEC initiation were more than twice as likely to achieve CR/CRi compared to those with a higher blast burden. The median OS was 6.3 months. Twenty-four (40.0%) patients proceeded to alloHSCT. Twenty-one (35.0%) patients were transferred to the intensive care unit (ICU) during their admission. CONCLUSIONS: MEC is an effective salvage regimen for patients with R/R AML, especially among those with low disease burden at initiation. Febrile neutropenia, infections, and severe oral mucositis were common with MEC administration.

The crossroads of cancer therapies and clonal hematopoiesis.

The intricate interplay between Clonal Hematopoiesis (CH) and the repercussions of cancer therapies has garnered significant research focus in recent years. Previously perceived as an age-related phenomenon, CH is now closely linked to inflammation ("Inflammaging") and cancer, impacting leukemogenesis, cancer progression, and treatment responses. This review explores the complex interplay between CH and diverse cancer therapies, including chemotherapy, targeted treatments, radiation, stem cell transplants, CAR-T cell therapy, and immunotherapy, like immune checkpoint inhibitors. Notably, knowledge about post-chemotherapy CH mutation/acquisition has evolved from a de novo incident to more of a clonal selection process. Chemotherapy and radiation exposure, whether therapeutic or environmental, increases CH risk, particularly in genes like TP53 and PPM1D. Environmental toxins, especially in high-risk environments like post-disaster sites or space exploration, are associated with CH. CH affects clinical outcomes in stem cell transplant scenarios, including engraftment, survival, and t-MN development. The presence of CH also alters CAR-T cell therapy responses and impacts the efficacy and toxicity of immunotherapies. Furthermore, specific mutations like DNMT3A and TET2 thrive under inflammatory stress, influencing therapy outcomes and justifying the ongoing tailored interventions in clinical trials. This review underscores the critical need to integrate CH analysis into personalized medicine, enhancing risk assessments and refining treatment strategies. As we progress, multidisciplinary collaboration and comprehensive studies are imperative. Understanding CH's impact, especially concerning genotoxic stressors, will inform screening, surveillance, and early detection strategies, decreasing the risk of therapy-related myeloid neoplasms and revolutionizing cancer treatment paradigms.

Role of Single Port Rigid Thoracoscopy in Undiagnosed Pleural Effusion.

BACKGROUND: In recent years, medical thoracoscopy has been well established to play an important role in undiagnosed pleural effusion; however, this procedure is underutilized due to limited availability of the instruments it requires. This study analysed the outcome of single port rigid thoracoscopy in patients with undiagnosed pleural effusions. METHODS: This study retrospectively analysed the outcomes of all patients with undiagnosed pleural effusion presenting to our centre between 2016 to 2020 who underwent single port rigid medical thoracoscopy as a diagnostic procedure. RESULTS: In total, 92 patients underwent single port rigid medical thoracoscopy. The most common presenting symptom was shortness of breath. A majority of the patients had lymphocytic exudative pleural effusion. The average biopsy sample size was 18 mm, and no major complication was reported in any of the patients. CONCLUSION: Single port rigid thoracoscopy is a safe and well-tolerated procedure that yields a biopsy of a larger size with high diagnostic yield. Moreover, the low cost of the instruments required by this procedure makes it particularly suited for use in developing countries.

Heavy metal geochemistry and toxicity assessment of water environment from Ib valley coalfield, India: Implications to contaminant source apportionment and human health risks.

The present study aims to investigate the hydrogeochemical evolution of heavy metals and assesses impacts of mining activities on the groundwater resources and potential human health risks in the coal mining areas of Ib valley coalfield. In this perspective, a total of one hundred and two mine water and groundwater samples were collected from different locations. The water samples were analysed for some selected heavy metals i.e. Mn, Cu, Pb, Zn, Ni, Co, As, Se, Al, Sr, Ba, Cd, Cr, V and Fe using ICP-MS. In addition, pH and SO42- concentration were also measured following APHA procedure. The water pH in the Ib valley coalfields ranged from 3.26 to 8.18 for mine water and 5.23 to 8.52 for groundwater, indicating acidic to alkaline nature of water. Mn in mine water and Zn in groundwater environment were observed as the most dominant metals. The water hazard index (WHI) reflects that around 80% of mine water are non-toxic (WHI<5), 5% slightly toxic (510) and 15% extremely toxic (WHI>15). Relatively high pH and low concentration of dissolved metals and SO42- in groundwater as compared to mine water indicate lesser impact of mining activities. The calculated drinking water quality index (DWQI) suggests that Mn, Al, Ni and Fe in mine water and Mn, Fe, Ni and Pb in groundwater were the major objectionable metals which caused the water quality deterioration for drinking uses. Further, the non-carcinogenic health risk assessment for adult male, female and child populations identifies Co, Mn, Ni as the key elements making the water hazardous for human health. Comparatively higher ratio of ingestion rate and body weight in child population might be causing higher health risks in child population as compared to adult male and adult female population.

Development of a [89Zr]Zr-labeled Human Antibody using a Novel Phage-displayed Human scFv Library.

PURPOSE: Tax-interacting protein 1 (TIP1) is a cancer-specific radiation-inducible cell surface antigen that plays a role in cancer progression and resistance to therapy. This study aimed to develop a novel anti-TIP1 human antibody for noninvasive PET imaging in patients with cancer. EXPERIMENTAL DESIGN: A phage-displayed single-chain variable fragment (scFv) library was created from healthy donors' blood. High-affinity anti-TIP1 scFvs were selected from the library and engineered to human IgG1. Purified Abs were characterized by size exclusion chromatography high-performance liquid chromatography (SEC-HPLC), native mass spectrometry (native MS), ELISA, BIAcore, and flow cytometry. The labeling of positron emitter [89Zr]Zr to the lead Ab, L111, was optimized using deferoxamine (DFO) chelator. The stability of [89Zr]Zr-DFO-L111 was assessed in human serum. Small animal PET studies were performed in lung cancer tumor models (A549 and H460). RESULTS: We obtained 95% pure L111 by SEC-HPLC. Native MS confirmed the intact mass and glycosylation pattern of L111. Conjugation of three molar equivalents of DFO led to the optimal DFO-to-L111 ratio of 1.05. Radiochemical purity of 99.9% and specific activity of 0.37 MBq/µg was obtained for [89Zr]Zr-DFO-L111. [89Zr]Zr-DFO-L111 was stable in human serum over 7 days. The immunoreactive fraction in cell surface binding studies was 96%. In PET, preinjection with 4 mg/kg cold L111 before [89Zr]Zr-DFO-L111 (7.4 MBq; 20 µg) significantly (P < 0.01) enhanced the tumor-to-muscle standard uptake values (SUVmax) ratios on day 5 compared with day 2 postinjection. CONCLUSIONS: L111 Ab targets lung cancer cells in vitro and in vivo. [89Zr]Zr-DFO-L111 is a human antibody that will be evaluated in the first in-human study of safety and PET imaging.

Snow Cover Response to Climatological Factors at the Beas River Basin of W. Himalayas from MODIS and ERA5 Datasets.

Glaciers and snow are critical components of the hydrological cycle in the Himalayan region, and they play a vital role in river runoff. Therefore, it is crucial to monitor the glaciers and snow cover on a spatiotemporal basis to better understand the changes in their dynamics and their impact on river runoff. A significant amount of data is necessary to comprehend the dynamics of snow. Yet, the absence of weather stations in inaccessible locations and high elevation present multiple challenges for researchers through field surveys. However, the advancements made in remote sensing have become an effective tool for studying snow. In this article, the snow cover area (SCA) was analysed over the Beas River basin, Western Himalayas for the period 2003 to 2018. Moreover, its sensitivity towards temperature and precipitation was also analysed. To perform the analysis, two datasets, i.e., MODIS-based MOYDGL06 products for SCA estimation and the European Centre for Medium-Range Weather Forecasts (ECMWF) Atmospheric Reanalysis of the Global Climate (ERA5) for climate data were utilized. Results showed an average SCA of ~56% of its total area, with the highest annual SCA recorded in 2014 at ~61.84%. Conversely, the lowest annual SCA occurred in 2016, reaching ~49.2%. Notably, fluctuations in SCA are highly influenced by temperature, as evidenced by the strong connection between annual and seasonal SCA and temperature. The present study findings can have significant applications in fields such as water resource management, climate studies, and disaster management.

Suprascapular Nerve Block (SSNB) improves the outcome in exercise based management of Primary Adhesive Capsulitis (PAC): A prospective randomized comparative study.

Background and Aims: Increased pain and associated stiffness hinders the advantages of exercise and process of recovery in primary adhesive capsulitis. We hypothesized that suprascapular nerve block may positively affect the outcome due to its role in pain relief of acute or chronic shoulder pain. We compared the effect of suprascapular nerve block and exercise with only exercise on the recovery of primary adhesive capsulitis. Material and Methods: A total of 96 patients of both sexes presenting with primary adhesive capsulitis were divided by computer randomization in two equal groups (n = 48). Group A received exercise only and Group B received suprascapular nerve block followed by exercise. Oral paracetamol was given for analgesia as desired. Patients were followed up at 4, 8, 16, and 24 weeks. Pain was assessed by visual analog scale; functional outcome by Shoulder Pain and Disability Index and range of movement by goniometer. Results: The pain scores and Shoulder Pain and Disability Index scores were significantly lower at all observation points of 4, 8,16, and 24 weeks in Group B than Group A (P < 0.05). The range of movement in all the ranges of forward flexion, extension, internal and external rotation, and abduction at all observation points was significantly higher in Group-B (P < 0.05) compared to Group A. The consumption of analgesics was significantly more in Group A than Group B at 4 and 8 weeks (P = 0.020 and P = 0.044) but comparable at 12 and 24 weeks (P = 0.145 and P = 0.237 respectively). Conclusion: Combining SSNB with exercise is more effective in treatment of primary adhesive capsulitis than exercise alone and reduces the use of analgesics. SSNB it is effective and safe to use in primary adhesive capsulitis.

Blocking the functional domain of TIP1 by antibodies sensitizes cancer to radiation therapy.

Non-small-cell lung cancer (NSCLC) and glioblastoma (GB) have poor prognoses. Discovery of new molecular targets is needed to improve therapy. Tax interacting protein 1 (TIP1), which plays a role in cancer progression, is overexpressed and radiation-inducible in NSCLC and GB. We evaluated the effect of an anti-TIP1 antibody alone and in combination with ionizing radiation (XRT) on NSCLC and GB in vitro and in vivo. NSCLC and GB cells were treated with anti-TIP1 antibodies and evaluated for proliferation, colony formation, endocytosis, and cell death. The efficacy of anti-TIP1 antibodies in combination with XRT on tumor growth was measured in mouse models of NSCLC and GB. mRNA sequencing was performed to understand the molecular mechanisms involved in the action of anti-TIP1 antibodies. We found that targeting the functional domain of TIP1 leads to endocytosis of the anti-TIP1 antibody followed by reduced proliferation and increased apoptosis-mediated cell death. Anti-TIP1 antibodies bound specifically (with high affinity) to cancer cells and synergized with XRT to significantly increase cytotoxicity in vitro and reduce tumor growth in mouse models of NSCLC and GB. Importantly, downregulation of cancer survival signaling pathways was found in vitro and in vivo following treatment with anti-TIP1 antibodies. TIP1 is a new therapeutic target for cancer treatment. Antibodies targeting the functional domain of TIP1 exhibited antitumor activity and enhanced the efficacy of radiation both in vitro and in vivo. Anti-TIP1 antibodies interrupt TIP1 function and are effective cancer therapy alone or in combination with XRT in mouse models of human cancer.