Identification of circulatory microRNA based biomarkers for early pregnancy diagnosis in buffalo.

Introduction: The most crucial factor in improving animal reproduction efficiency is early pregnancy diagnosis. Early diagnosis not only reduces the time interval between two calvings but also aids farmers in identifying open animals, thereby preventing significant milk production losses. Therefore, the objective of this study was to discover circulatory miRNAs that would be useful for early pregnancy diagnosis in buffalo. Material and methods: Blood samples were taken on 0, 6th, 12th, and 18th day after artificial insemination from pregnant animals (n = 30) and non-pregnant animals (n = 20). During these stages of pregnancy, total RNA was extracted, and a small RNA library was subsequently generated and sequenced on the Illumina platform. Subsequently, Real-time PCR was used to validate the findings. Results and discussion: There were 4,022 miRNAs found during the pregnancy, with 15 of those lacking sequences and 4,007 having sequences already in the database. From the beginning of pregnancy until the 18th day, 25 of these miRNAs showed a substantial shift in expression levels in the maternal blood, with a change more than two logs. Furthermore, based on qPCR results, 19 miRNAs were found to be more abundant in pregnant animals than in non-pregnant animals. We used target prediction analysis to learn how maternally expressed miRNAs relate to fetal-maternal communication. In conclusion, miRNA based biomarkers that could be associated with the diagnosis of pregnancy were identified including miR-181a and miR-486 highly upregulated on the 18th day of pregnancy. This study also provides a comprehensive profile of the entire miRNA population in maternal buffalo blood during the early stages of pregnancy.

Celastrol-loaded polymeric mixed micelles shows improved antitumor efficacy in 4 T1 bearing xenograft mouse model through spatial targeting.

In this study, we have proposed a novel approach that combines hyaluronic acid (HA), folic acid (FA), and celastrol (CLS) within a polymeric micelle system (CLS-HF/MLs), offering a dual-action strategy against breast cancer. Polymeric mixed micelles were prepared through the thin-film hydration method, and comprehensive quality control parameters were established, encompassing particle size, polydispersity index, zeta potential, surface morphology, encapsulation efficiency, drug content, in vitro drug release, and storage stability assessment. The average particle size of CLS-HF/MLs micelles was found to be 120 nm and their drug loading and encapsulation efficiencies were 15.9 % and 89.52 %, respectively. The in vitro release data showed that the CLS-HF/MLs targeted mixed micelles displayed a prolonged release profile compared to the free drug. Additionally, the stability of the developed polymeric mixed micelles was maintained for up to 8 weeks of storage in terms of particle size and drug content. Furthermore, both flow cytometry and confocal laser scanning microscopy studies indicated a significant enhancement in the cellular uptake efficiency and cytotoxicity of CLS-HF/MLs mixed micelles against MCF-7 cell line. In terms of pharmacokinetic analysis, the half-life and AUC values of CLS-HF/MLs mixed micelles were found to be approximately 4.71- and 7.36-folds higher than the values of free drug (CLS), respectively. The CLS-HF/MLs micelles exhibited remarkable antitumor efficacy (almost complete ablation of the 4 T1-cell bearing tumor xenografts mouse model) due to the dual receptor (CD44 and folate) targeting effects with minimal side effects. When considering the cumulative findings of our present research, it becomes evident that mixed micelles designed for chemotherapy offer a promising and potentially effective therapeutic avenue for the treatment of breast cancer.

Breast lymphomas: Clinical and pathological insights from a tertiary cancer care center in India.

BACKGROUND: Breast lymphomas are a rare group of malignancies that are further subdivided into primary and secondary. AIMS: To study the pathological and clinical course of breast lymphomas. MATERIALS AND METHODS: This is a retrospective analysis of patients treated at our institute over a period of 4.5 years from September 2018 to February 2023. The details of all the patients diagnosed with breast lymphoma were reviewed and analysed for the histomorphological, immunohistochemical, clinical, and treatment details. Appropriate statistical analysis including Kaplan-Meier methods was used. RESULTS: Out of 11 cases of breast lymphoma, five were primary and six were secondary. It was seen predominantly in females (82%) and the age range was 31 to 73 years. Diffuse large B cell lymphoma (DLBCL) was the predominant morphology (73%), along with single rare cases of ALK-negative anaplastic large cell lymphoma, Burkitt lymphoma, and small lymphocytic lymphoma. The treatment details were analyzed for 7 patients. The median follow-up was 28 months. Rituximab along with CHOP regimen or its variants was commonly used as first-line treatment with initial response rates of 71%. The median progression-free survival was 5 months. The median overall survival was 15 months. CONCLUSION: Lymphomas of the breast are rare but it is crucial to differentiate them from the commoner breast carcinomas as the treatment and prognosis vary vastly.

Ultrasound-guided selective peripheral nerve block for the snakebite pain management in the emergency department: Our experience.

Envenomation from snakebites (SBs) is a significant public health hazard globally. The venomous SB is associated with moderate-to-severe pain. Weak opioids such as tramadol or acetaminophen are commonly used for pain management but often provide inadequate analgesia. We hereby report our experience of using ultrasound-guided selective superficial peroneal, sural, and saphenous nerve blocks for pain management following SBs in nine patients. The selective peripheral nerve blocks are achieved with a small amount of local anesthesia and without loss of motor functions.

Clofarabine Has a Superior Therapeutic Window as compared to Gemcitabine in Preclinical Bladder Cancer Models.

Current standard-of-care systemic therapy options for locally advanced and metastatic bladder cancer (BC), which are predominantly based on cisplatin-gemcitabine combinations, are limited by significant treatment failure rates and frailty-based patient ineligibility. We previously addressed the urgent clinical need for better-tolerated BC therapeutic strategies using a drug screening approach, which identified outstanding antineoplastic activity of clofarabine in preclinical models of BC. To further assess clofarabine as a potential BC therapy component, we conducted head-to-head comparisons of responses to clofarabine versus gemcitabine in preclinical in vitro and in vivo models of BC, complemented by in silico analyses. In vitro data suggest a distinct correlation between the two antimetabolites, with higher cytotoxicity of gemcitabine, especially against several nonmalignant cell types, including keratinocytes and endothelial cells. Accordingly, tolerance of clofarabine (oral or intraperitoneal application) was distinctly better than for gemcitabine (intraperitoneal) in patient-derived xenograft models of BC. Clofarabine also exhibited distinctly superior anticancer efficacy, even at dosing regimens optimized for gemcitabine. Neither complete remission nor cure, both of which were observed with clofarabine, were achieved with any tolerable gemcitabine regimen. Taken together, our findings demonstrate that clofarabine has a better therapeutic window than gemcitabine, further emphasizing its potential as a candidate for drug repurposing in BC. PATIENT SUMMARY: We compared the anticancer activity of clofarabine, a drug used for treatment of leukemia but not bladder cancer, and gemcitabine, a drug currently used for chemotherapy against bladder cancer. Using cell cultures and mouse models, we found that clofarabine was better tolerated and more efficacious than gemcitabine, and even cured implanted tumors in mouse models. Our results suggest that clofarabine, alone or in combination schemes, might be superior to gemcitabine for the treatment of bladder cancer.

Lead optimization based design, synthesis, and pharmacological evaluation of quinazoline derivatives as multi-targeting agents for Alzheimer's disease treatment.

The complexity and multifaceted nature of Alzheimer's disease (AD) have driven us to further explore quinazoline scaffolds as multi-targeting agents for AD treatment. The lead optimization strategy was utilized in designing of new series of derivatives (AK-1 to AK-14) followed by synthesis, characterization, and pharmacological evaluation against human cholinesterase's (hChE) and ß-secretase (hBACE-1) enzymes. Amongst them, compounds AK-1, AK-2, and AK-3 showed good and significant inhibitory activity against both hAChE and hBACE-1 enzymes with favorable permeation across the blood-brain barrier. The most active compound AK-2 revealed significant propidium iodide (PI) displacement from the AChE-PAS region and was non-neurotoxic against SH-SY5Y cell lines. The lead molecule (AK-2) also showed Aß aggregation inhibition in a self- and AChE-induced Aß aggregation, Thioflavin-T assay. Further, compound AK-2 significantly ameliorated Aß-induced cognitive deficits in the Aß-induced Morris water maze rat model and demonstrated a significant rescue in eye phenotype in the Aꞵ-phenotypic drosophila model of AD. Ex-vivo immunohistochemistry (IHC) analysis on hippocampal rat brains showed reduced Aß and BACE-1 protein levels. Compound AK-2 suggested good oral absorption via pharmacokinetic studies and displayed a good and stable ligand-protein interaction in in-silico molecular modeling analysis. Thus, the compound AK-2 can be regarded as a lead molecule and should be investigated further for the treatment of AD.

Enhancing biomethanation performance through co-digestion of diverse organic wastes: a comprehensive study on substrate optimization, inoculum selection, and microbial community analysis.

A blend of organic municipal solid waste, slaughterhouse waste, fecal sludge, and landfill leachate was selected in different mixing ratios to formulate the best substrate mixture for biomethanation. Individual substrates were characterized, and the mixing ratio was optimized with the help of a response surface methodology tool to a value of 1:1:1:1 (with a C/N ratio of 28±0.769 and total volatile fatty acid (VFA) concentration of 2500±10.53 mg/L) to improve the overall biomethanation. The optimized blend (C/N ratio: 28.6, VFA: 2538 mg/L) was characterized for physicochemical, biological, and microbial properties and subjected to anaerobic digestion in lab-scale reactors of 1000 mL capacity with and without the addition of inoculum. The biogas yield of individual substrates and blends was ascertained separately. The observed cumulative biogas yield over 21 days from the non-inoculated substrates varied between 142±1.95 mL (24.6±0.3 ml/gVS) and 1974.5±21.72 mL (270.4±3.1 ml/gVS). In comparison, the addition of external inoculation at a 5% rate (w/w) of the substrate uplifted the minimum and maximum cumulative gas yield values to 203±9.9 mL (35.0±1.6 mL/gVS) and 3394±13.4 mL (315.3±1.2 mL/gVS), respectively. The inoculum procured from the Defence Research and Development Organisation (DRDO) was screened in advance, considering factors such as maximizing VFA production and consumption rate, biogas yield, and digestate quality. A similar outcome regarding biogas yield and digestate quality was observed for the equivalent blend. The cumulative gas yield increased from 2673±14.5 mL (373.7±2.2 mL/gVS) to 4284±111.02 mL (391.47±20.02 mL/gVS) over 21 days post-application of a similar dosage of DRDO inoculum. The 16S rRNA genomic analysis revealed that the predominant bacterial population belonged to the phylum Firmicutes, with the majority falling within the orders Clostridiales and Lactobacillales. Ultimately, the study advocates the potential of the blend mentioned above for biomethanation and concomitant enrichment of both biogas yield and digestate quality.

Comparison of McCoy, Macintosh, and Truview laryngoscope for bougie-aided naso-tracheal intubation: A randomized controlled study.

Background: Video laryngoscopes are commonly used along with Macintosh and McCoy laryngoscopes for Nasotracheal intubation (NTI). The purpose of this study was to evaluate the performance of McCoy, Macintosh, and Truview laryngoscopes during bougie-aided NTI with respect to intubation time, success rate, and hemodynamic changes during the procedure. Methods: Forty-five American Society of Anesthesiologists (ASA) I-II adult patients, with Mallampati grade 1-4, requiring NTI, were enrolled after taking written informed consent. ASA III/IV, restricted mouth opening, and body mass index >30 were excluded from the study. Patients were randomly allocated to intubate with one of the three laryngoscopes (McCoy, Macintosh, and Truview) and the anesthesiologists were well experienced with all of them. The primary outcome was intubation time and secondary outcomes included first attempt success rate, external laryngeal manipulation, Cormack-Lehane (CL) grade, and hemodynamic responses. Results: The intubation time of McCoy, Macintosh, and Truview, was 86.87 ± 15.92, 82.87 ± 16.46, and 79.93 ± 14.53 (mean ± standard deviation) seconds, respectively, which is comparable with Truview being the shortest. CL grade 1 was obtained more in the Truview group (53.3%) compared to the other two groups, while CL grade 3 was obtained in 20% each in McCoy and Macintosh groups. Conclusions: McCoy, Macintosh, and Truview laryngoscopes were comparable in performance during bougie-aided NTI, with Truview having the shortest intubation time and better visualization.

A comparative study of perioperative pain, blood loss, and hospital stay in an Indian population undergoing mini-open oblique lumbar interbody fusion versus open transforaminal lumbar interbody fusion.

Background: There are several approaches for lumbar fusion, although there is yet to be a consensus on which approach is the best. This study aimed to evaluate the intraoperative blood loss and acute postoperative pain in single-level mini-open oblique lumbar interbody fusion (OLIF) versus open transforaminal lumbar interbody fusion (TLIF) surgeries for the degenerative spine. Methods: Thirty-two patients were assigned by the surgeon to OLIF or TLIF groups - 16 in mini-open OLIF and 16 in open TLIF groups. The intraoperative blood loss and postoperative hemoglobin, numerical rating scale (NRS) at proposed time intervals for 24 h postoperative, and rescue analgesics used were compared among the groups. The operative duration and hospital stay in both groups were also compared. Results: The OLIF group showed significantly higher postoperative hemoglobin (11.5 vs. 10.5 g %, P = 0.04), lower 24-h postoperative pain scores on movement, (NRS 4 vs. 5.5, P = 0.0001), and shorter hospital stay (4.5 vs. 7 days, P = 0.003) than TLIF group. However, the surgery duration was significantly longer in OLIF than in TLIF (190 vs. 150 min, P = 0.005). Intraoperative hemodynamics, other postoperative pain scores at variable time points, and rescue analgesics given were comparable among groups (P > 0.05). Intraoperative blood loss was lower in OLIF than TLIF (275 vs. 500 mL) but was not statistically significant (P > 0.05). Conclusion: Mini-open OLIF has favorable perioperative outcomes compared to open TLIF. Patients have higher postoperative hemoglobin and lesser pain on movement on the first postoperative day, leading to earlier mobilization and a shorter hospital stay.

A comparative assessment of biomethane potential of fresh fecal matter and fecal sludge and its correlation with malodor.

Comprehensive and proper management of fecal sludge (FS) is an ongoing concern in many nations. Decentralized fecal sludge treatment plants (FSTPs) are effective in this regard; however, many have experienced strong public opposition based partly on suspicion of malodor. Fecal sludge and freshly generated fecal matter (FM) samples from various FSTPs were collected, characterized, and investigated for biomethane potential. The homogenized samples were anaerobically digested for 28 days. Digestion successfully reduced total suspended solids, biochemical oxygen demand, and threshold odor number values of 97,350-97,420 mg/l, 43,230-43,260 mg/l, and 130-150 for FM, to 49,500-49,650 mg/l, 23,760-23,850 mg/l, and 3338, respectively, for FS samples. The comprehensive gas yield from Bhongir, Boduppal, and Shadnagar FS samples was 40, 55, and 31 ml, respectively. In contrast, cumulative gas generation from the FM was 26,361 ml. Digestion of FS samples also reduced concentrations of volatile solids and coliforms by 66-72% and 99%, respectively. Characterization of gas samples revealed methane and carbon dioxide concentrations as 56% and 22% for FM, and 0.4% and 61% for FS samples, respectively. Hydrogen sulfide and ammonia gas were absent in FS samples, dispelling common societal misconceptions of FSTPs being associated with malodor.

Trends in avascular necrosis and related arthroplasties in hospitalized patients with systemic lupus erythematosus and rheumatoid arthritis.

OBJECTIVE: Avascular necrosis (AVN) is a devastating complication often necessitating arthroplasty, particularly common in systemic lupus erythematosus (SLE). Limited research exists on arthroplasty trends since new steroid-sparing agents. We analyzed trends and characteristics associated with AVN and AVN-related arthroplasties among SLE and RA hospitalizations using two decades of data from the U.S. National Inpatient Sample (NIS). METHODS: This cross-sectional study used NIS (2000-2019) to identify hospitalized adults with SLE and RA, with or without AVN, using ICD codes. AVN was further grouped by arthroplasty status. Primary outcomes were AVN and AVN-related arthroplasty rates and time trends in SLE and RA. Baseline sociodemographics and comorbidities were compared. Analyses used STATA and Joinpoint regression to calculate annual percent change (APC). RESULTS: Overall, 42,728 (1.3 %) SLE and 43,600 (0.5 %) RA hospitalizations had concomitant AVN (SLE-AVN and RA-AVN). Of these, 16,724 (39 %) and 25,210 (58 %) underwent arthroplasties, respectively. RA-AVN increased (APC: 0.98*), with a decrease in arthroplasties (APC: -0.82*). In contrast, SLE-AVN initially increased with a breakpoint in 2011 (APC 2000-2011: 1.94* APC 2011-2019 -2.03), with declining arthroplasties (APC -2.03*). AVN hospitalizations consisted of individuals who were younger and of Black race; while arthroplasties were less likely in individuals of Black race or Medicaid coverage. CONCLUSION: We report a breakpoint in rising SLE-AVN after 2011, which may relate to newer steroid-sparing therapies (i.e., belimumab). AVN-associated arthroplasties decreased in SLE and RA. Fewer AVN-associated arthroplasties were noted for Black patients and those with Medicaid, indicating potential disparities. Further research should examine treatment differences impacting AVN and arthroplasty rates.

An Innovative Technique for Assessment of Bone Change, Bite Force, and Retention of the Single-Implant-Supported Mandibular Overdenture: A Clinical Study.

This study is the first study to incorporate a novel approach to single-implant-retained mandibular overdenture with a bar attachment on a single implant in the symphysis region. The use of a single-implant-retained bar overdenture significantly improved patients' chewing efficiency, indicating enhanced overdenture retention and stability. Materials and Methods: Ten maxillary and mandibular completely edentulous patients were enrolled in the study. A complete denture was fabricated for them. On completion, bite force, retention force, and bone change were recorded. Bite force was recorded with the strain gauge, retention force with the force measurement gauge, and bone changes with radiographs. Conclusion: Single-implant-supported bar mandibular overdenture (SISBOD) can be a suitable standard economic option for edentulous mandible and can greatly improve the quality of life of patients.

Prevalence of Periodontal Disease among Patients Reporting to Tertiary Care Hospital in Ranchi.

Background: Despite a huge number of advancements in the medical field, periodontitis still remains one of the most prevalent oral diseases worldwide. Aim: Thus, the primary aim of our study was to evaluate the prevalence of periodontal diseases in patients reporting to the tertiary healthcare setup in Ranchi. Materials and Methods: Based on inclusion criteria, subjects aged 18-60 years were selected and a per forma was filled by the observer. The prevalence of periodontal disease was measured using the community periodontal index, simplified oral hygiene index, and stage of periodontitis. Results: Descriptive variables were assessed using frequency, percentage, mean, and standard deviations, while the categorical analysis was performed using the Chi-square tests. Conclusion: General awareness about periodontal health and regular dental visits should be given utmost importance among the rural populations of every developing country.

Clinical Utility of Tectal Plate Measurements on Magnetic Resonance Imaging in Progressive Supranuclear Palsy.

BACKGROUND: Midbrain atrophy is a characteristic feature of progressive supranuclear palsy (PSP), observed in PSP-Richardson's syndrome (PSP-RS) and to a lesser extent PSP-parkinsonism (PSP-P). OBJECTIVE: Our aim was to critically evaluate the utility of manual magnetic resonance imaging measurements of the midbrain tectal plate as a diagnostic biomarker in PSP. METHODS: Length of the tectal plate and width of the superior and inferior colliculi were measured in 40 PSP (20 PSP-RS and 20 PSP-P) patients and compared with 20 Parkinson's disease and 20 healthy control subjects. RESULTS: Tectal plate length was reduced in both PSP groups compared with Parkinson's disease and control subjects and was most abnormal in PSP-RS followed by PSP-P. Reduced tectal plate length was associated with worse PSP Rating Scale scores. CONCLUSIONS: Simple manual measurements of tectal plate length show utility as a diagnostic biomarker in PSP, particularly for PSP-RS. © 2024 International Parkinson and Movement Disorder Society.

Altered structural and functional connectivity in Posterior Cortical Atrophy and Dementia with Lewy bodies.

Posterior cortical atrophy (PCA) and dementia with Lewy bodies (DLB) show distinct atrophy and overlapping hypometabolism profiles, but it is unknown how disruptions in structural and functional connectivity compare between these disorders and whether breakdowns in connectivity relate to either atrophy or hypometabolism. Thirty amyloid-positive PCA patients, 24 amyloid-negative DLB patients and 30 amyloid-negative cognitively unimpaired (CU) healthy individuals were recruited at Mayo Clinic, Rochester, MN, and underwent a 3T head MRI, including structural MRI, resting state functional MRI (rsfMRI) and diffusion tensor imaging (DTI) sequences, as well as [18F] fluorodeoxyglucose (FDG) PET. We assessed functional connectivity within and between 12 brain networks using rsfMRI and the CONN functional connectivity toolbox and calculated regional DTI metrics using the Johns Hopkins atlas. Multivariate linear-regression models corrected for multiple comparisons and adjusted for age and sex compared DTI metrics and within-network and between-network functional connectivity across groups. Regional gray-matter volumes and FDG-PET standard uptake value ratios (SUVRs) were calculated and analyzed at the voxel-level using SPM12. We used univariate linear-regression models to investigate the relationship between connectivity measures, gray-matter volume, and FDG-PET SUVR. On DTI, PCA showed degeneration in occipito-parietal white matter, posterior thalamic radiations, splenium of the corpus collosum and sagittal stratum compared to DLB and CU, with greater degeneration in the temporal white matter and the fornix compared to CU. We observed no white-matter degeneration in DLB compared to CU. On rsfMRI, reduced within-network connectivity was present in dorsal and ventral default mode networks (DMN) and the dorsal-attention network in PCA compared to DLB and CU, with reduced within-network connectivity in the visual and sensorimotor networks compared to CU. DLB showed reduced connectivity in the cerebellar network compared to CU. Between-network analysis showed increased connectivity in both cerebellar-to-sensorimotor and cerebellar-to-dorsal attention network connectivity in PCA and DLB. PCA showed reduced anterior DMN-to-cerebellar and dorsal attention-to-sensorimotor connectivity, while DLB showed reduced posterior DMN-to-sensorimotor connectivity compared to CU. PCA showed reduced dorsal DMN-to-visual connectivity compared to DLB. The multimodal analysis revealed weak associations between functional connectivity and volume in PCA, and between functional connectivity and metabolism in DLB. These findings suggest that PCA and DLB have unique connectivity alterations, with PCA showing more widespread disruptions in both structural and functional connectivity; yet some overlap was observed with both disorders showing increased connectivity from the cerebellum.

Guidance on sexual, reproductive, maternal, newborn, child and adolescent health in humanitarian and fragile settings: a scoping review.

INTRODUCTION: Progress related to sexual, reproductive, maternal, newborn, child and adolescent health (SRMNCAH) has stalled. COVID-19, conflict and climate change threaten to reverse decades of progress and to ensure the health and well-being of vulnerable populations in humanitarian and fragile settings (HFS) going forward, there is a need for tailored guidance for women, children and adolescents (WCA). This review seeks to map and appraise current resources on SRMNCAH in HFS. METHODS: In line with the updated Joanna Briggs Institute guidance and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews framework, a manual literature review was conducted of global and regional guidance published between January 2008 and May 2023 from members of the Global Health Cluster, the Global Nutrition Cluster and the Inter-Agency Working Group on Reproductive Health in Crises. A content analysis was conducted. Scores were then calculated according to the Appraisal of Guidelines for Research and Evaluation II scoring tool and subsequently categorised as high quality or low quality. RESULTS: A total of 730 documents were identified. Of these, 141 met the selection criteria and were analysed. Available guidance for delivering SRMNCH services exists, which can inform policy and programming for the general population and WCA. Important gaps related to beneficiaries, health services and health system strengthening strategies were identified. CONCLUSION: The review revealed there is evidence-based guidance available to support interventions targeting WCA in HFS, including: pregnant and lactating women, women of reproductive age, adolescents, newborns, small vulnerable newborns, stillbirths, refugees and internally displaced persons and WCA with disabilities. However, gaps related to beneficiaries, health services and health system strengthening strategies must be addressed in updated guidance that is created, disseminated and monitored in a standardised way that is mindful of the need to respond rapidly in HFS.