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Background: Ultrasound has become the standard of care for the insertion of central venous catheters (CVCs) in the intensive care unit. With the introduction of ultrasonography in CVC insertion, there has been an improvement in the success rate and a dramatic decrease in the rate of complications. Aims and Objectives: The aim of this study was to compare the safety and ease of insertion of ultrasonically guided cannulation of the internal jugular vein (IJV) with that of the supraclavicular subclavian vein (SCV) in adult patients undergoing various surgical procedures. Materials and Methods: All the patients in whom central venous cannulation was planned were assigned to two groups. Group I underwent ultrasound-guided IJV while as Group II underwent cannulation ultrasound-guided SCV cannulation. A comparison was made between the two groups, of the success rates, durations of procedure, number of attempts at needle redirections, difficulties if any during insertion of guidewires, and the complications encountered. Results: The IJV group had a higher proportion of first-attempt success (93.2% versus 62.7%). The IJV group had a lesser incidence (3.2%) of complications such as guidewire progression and needle redirections compared with SCV (15.2%). The frequency of adverse events did not differ between the two study groups with an incidence in 3.2% in IJV group and 9.6% in the subclavian group. Higher first-attempt success rates and fewer procedural complications were seen with ultrasound-guided IJV. Conclusion: IJV central venous catheterization is an easier and less invasive and less risky procedure for patients.

Given that radium-223 is a radiopharmaceutical that induces DNA damage, and olaparib is a PARP inhibitor that interferes with DNA repair mechanisms, we hypothesized their synergy in metastatic castration-resistant prostate cancer (mCRPC). We sought to demonstrate the safety and efficacy of olaparib + radium-223. We conducted a multicenter phase I 3+3 dose escalation study of olaparib with fixed dose radium-223 in patients with mCRPC with bone metastases. The primary objective was to establish the RP2D of olaparib, with secondary objectives of safety, PSA response, alkaline phosphatase response, radiographic progression-free survival (rPFS), overall survival, and efficacy by homologous recombination repair (HRR) gene status. Twelve patients were enrolled; all patients received a prior androgen receptor signaling inhibitor (ARSI; 100%) and 3 patients (25%) prior docetaxel. Dose-limiting toxicities (DLT) included cytopenias, fatigue, and nausea. No DLTs were seen in the observation period however delayed toxicities guided the RP2D. The RP2D of olaparib was 200 mg orally twice daily with radium-223. The most common treatment-related adverse events were fatigue (92%) and anemia (58%). The rPFS at 6 months was 58% (95% confidence interval, 27%-80%). Nine patients were evaluable for HRR gene status; 1 had a BRCA2 alteration (rPFS 11.8 months) and 1 had a CDK12 alteration (rPFS 3.1 months). Olaparib can be safely combined with radium-223 at the RP2D 200 mg orally twice daily with fixed dose radium-223. Early clinical benefit was observed and will be investigated in a phase II study.

Abstract Background A ventriculoperitoneal (VP) shunt is a cerebral shunt that diverts excess cerebrospinal fluid (CSF).Obstruction in the normal outflow or decreased absorption of the fluid is the usual cause. Hydrocephalus is treated by cerebral shunts.In paediatric patients, untreated hydrocephalus can be lethal and leads to many adverse effects including increase irritabilities, chronic headaches, learning difficulties, visual disturbances, and, in more advanced cases, severe mental retardation. Malfunction of the shunt with excess CSF accumulated can increase the intracranial pressure resulting in cerebral oedema and ultimately herniation. Objective To study and evaluate the mechanical causes of shunt failure and their surgical remedies and reduce the preventable morbidity, cost and mortality associated with shunt failure. Methods We conducted a prospective observational study including 70 patients who developed pure mechanical shunt failure for the first time from 2017 to 2020 in the Department of Neurosurgery Sher-i-kashmir Institute of Medical Sciences. Patients with previous shunt surgeries which include VP shunting and shunt revision or failure and shunt infections were excluded. Identity of all the patients has been kept anonymus. Written informed consent was obtained from all patients or their guardians in case of minors. Shunt malfunction was in the form of catheter misplacement, kinking, displacement from the ventricle or peritoneal cavity, disconnection, migration,inadvertent suturing of the catheter, air in shunt bulb. Results We found kinking at the proximal end in 25 (35%) patients as the most common cause of shunt failure. It was mostly as a result of inadequate and less spacious tunnelling made for the reservoir. Inadvertant suturing of shunt while closing abdomen in 7 (10%), shunt disconnection in 6 (8.5%), air in shunt bulb in 2 (2.8%), wrong placement at ventricular end in 10 (14.2%), shunt migration into the brain parenchyma in 5 (7.1%), shunt migration through the anal canal in 1(1.4%), pseudomeningocele around catheter valve in 3 (4.2%), placement of lower end into the preperitoneal space in 4 (5.7%) patients. Conclusions Shunt surgery is seemingly a straightforward operation for neurosurgeons. But considering the incidence of shunt failure and its associated morbidity and mortality, it should always be done with trepidation and extreme caution. Exclusive mechanical shunt malfunction is a major concern and leads to great deal of morbidity in the shunt operations. However, there are trivial remedies and technical nuances which needs to be followed during surgery to avoid these complications.

Abstract Background Epidural hematomas have been treated with urgent surgical evacuation to prevent catastrophic neurological sequelae and death. Brain Trauma Foundation recommends EDH volume greater than 30 cm3 and warrants surgical evacuation irrespective of GCS. However, due to increase in number of patients undergoing brain CTs following head injuries, more patients have been detected with EDH causing minimal symptoms. Aims and objectives To study factors influencing patients being treated conservatively for head injury with supratentorial epidural hematomas. Material and methods Our study is a retrospective analysis of supratentorial epidural hematoma treated conservatively from august 2018 to July 2020 at Sher-i-Kashmir institute of medical sciences, Srinagar, Jammu and Kashmir. Results A total of 19 patients with EDH were treated conservatively and fulfilled the inclusion criteria.(GCS of 13–15 with no neurological deficit, mild signs of elevated ICP, EDH thickness 13 on admission. 8 patients were hospitalised for a week, whilst 2 patients stayed in the hospital for 20 and 25 days, respectively, due to problems not related to EDH. One patient in whom conservative treatment had to be changed to surgical evacuation after 6 days of observation because of worsening headache, impaired alertness repeated imaging showed slight increase in EDH. Conclusions EDH can be managed conservatively in carefully selected patients of minor head injury with radiological surveillance and close neurological monitoring. Patients with GCS on admission more than 13, midline shift of less than 5 mm, location and volume of EDH less than 30 ml. Thus, leading to optimal utilisation of hospital resources. So, we conclude that even a dreaded entity like extradural haemorrhage can be managed conservatively in selected cases with strict clinical and radiological surveillance. We have called them ‘’Benign extradural haemorrhages’’.

Rapid industrialization has led to an increase in cadmium pollution, a dangerously toxic heavy metal. Cadmium (Cd) is released into the environment through industrial processes and can contaminate air, water, and soil. This pollution poses a significant risk to human health and has become a pressing concern in many industrialized areas. Due to its extended half-life, it leads to a range of health problems, including hepato-nephritic toxicity, brain damage, and degenerative bone disorders. Intoxication alters various intracellular parameters, leading to inflammation, tissue injury, and oxidative stress within cells, which disrupts normal cellular functions and can eventually result in cell death. It has also been linked to the development of bone diseases such as osteoporosis. These adverse effects highlight the urgent need to address cadmium pollution and find effective solutions to mitigate its impact on human health. This article highlights the Cd-induced risks and the role of Catharanthus roseus (C. roseus) extract as a source of alternative medicine in alleviating the symptoms. Numerous herbal remedies often contain certain bioactive substances, such as polyphenols and alkaloids, which have the power to mitigate these adverse effects by acting as antioxidants and lowering oxidative cell damage. Research conducted in the field of alternative medicine has revealed its enormous potential to meet demands that may be effectively used in safeguarding humans and their environment. The point of this review is to investigate whether C. roseus extract, known for its bioactive substances, is being investigated for its potential to mitigate the harmful effects of cadmium on health. Further investigation is needed to fully understand its effectiveness. Moreover, it is important to explore the potential environmental benefits of using C. roseus extract to reduce the negative effects of Cd. This review conducted in the field of alternative medicine has revealed its enormous potential to meet demands that could have significant implications for both human health and environmental sustainability.

PurposeAfrican Americans experience greater prostate cancer risk and mortality than do Caucasians. An analysis of pooled phase III data suggested differences in overall survival (OS) between African American and Caucasian men receiving sipuleucel-T. We explored this in PROCEED (NCT01306890), an FDA-requested registry in over 1900 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with sipuleucel-T.Patients and methodsOS for patients who received ≥1 sipuleucel-T infusion was compared between African American and Caucasian men using an all patient set and a baseline prostate-specific antigen (PSA)-matched set (two Caucasians to every one African American with baseline PSAs within 10% of each other). Univariable and multivariable analyses were conducted. Survival data were examined using Kaplan-Meier and Cox proportional hazard methodologies.ResultsMedian follow-up was 46.6 months. Overall survival differed between African American and Caucasian men with hazard ratios (HR) of 0.81 (95% confidence interval [CI]: 0.68-0.97, P = 0.03) in the all patient set and 0.70 (95% CI: 0.57-0.86, P

Purpose: Previous phases of trachoma mapping in Pakistan completed baseline surveys in 38 districts. To help guide national trachoma elimination planning, we set out to estimate trachoma prevalence in 43 suspected-endemic evaluation units (EUs) of 15 further districts.Methods: We planned a population-based trachoma prevalence survey in each EU. Two-stage cluster sampling was employed, using the systems and approaches of the Global Trachoma Mapping Project. In each EU, residents aged ≥1 year living in 30 households in each of 26 villages were invited to be examined by trained, certified trachoma graders. Questionnaires and direct observation were used to evaluate household-level access to water and sanitation.Results: One EU was not completed due to insecurity. Of the remaining 42, three EUs had trichiasis prevalence estimates in ≥15-year-olds ≥0.2%, and six (different) EUs had prevalence estimates of trachomatous inflammation-follicular (TF) in 1-9-year-olds ≥5%; each EU requires trichiasis and TF prevalence estimates below these thresholds to achieve elimination of trachoma as a public health problem. All six EUs with TF prevalences ≥5% were in Khyber Pakhtunkhwa Province. Household-level access to improved sanitation ranged by EU from 6% to 100%. Household-level access to an improved source of water for face and hand washing ranged by EU from 37% to 100%.Conclusion: Trachoma was a public health problem in 21% (9/42) of the EUs. Because the current outbreak of extremely drug-resistant typhoid in Pakistan limits domestic use of azithromycin mass drug administration, other interventions against active trachoma should be considered here.

The temporal switching of serotypes from serotype Ogawa to Inaba and back to Ogawa was identified in Vibrio cholerae O1, which was responsible for seasonal outbreaks of cholera in Dhaka during the period 2015 to 2018. In order to delineate the factors responsible for this serotype transition, we performed whole-genome sequencing (WGS) of V. cholerae O1 multidrug-resistant strains belonging to both the serotypes that were isolated during this interval where the emergence and subsequent reduction of the Inaba serotype occurred. The whole-genome-based phylogenetic analysis revealed clonal expansion of the Inaba isolates mainly responsible for the peaks of infection during 2016 to 2017 and that they might have evolved from the prevailing Ogawa strains in 2015 which coclustered with them. Furthermore, the wbeT gene in these Inaba serotype isolates was inactivated due to insertion of a transposable element at the same position signifying the clonal expansion. Also, V. cholerae isolates in the Inaba serotype dominant clade mainly contained classical ctxB allele and revealed differences in the genetic composition of Vibrioseventh pandemic island II (VSP-II) and the SXT integrative and conjugative element (SXT-ICE) compared to those of Ogawa serotype strains which remerged in 2018. The variable presence of phage-inducible chromosomal island-like element 1 (PLE1) was also noted in the isolates of the Inaba serotype dominant clade. The detailed genomic characterization of the sequenced isolates has shed light on the forces which could be responsible for the periodic changes in serotypes of V. cholerae and has also highlighted the need to analyze the mobilome in greater detail to obtain insights into the mechanisms behind serotype switching.IMPORTANCE The switching of serotype from Ogawa to Inaba and back to Ogawa has been observed temporally in Vibrio cholerae O1, which is responsible for endemic cholera in Bangladesh. The serospecificity is key for effective intervention and for preventing cholera, a deadly disease that continues to cause significant morbidity and mortality worldwide. In the present study, WGS of V. cholerae allowed us to better understand the factors associated with the serotype switching events observed during 2015 to 2018. Genomic data analysis of strains isolated during this interval highlighted variations in the genes ctxB, tcpA, and rtxA and also identified significant differences in the genetic content of the mobilome, which included key elements such as SXT ICE, VSP-II, and PLE. Our results indicate that selective forces such as antibiotic resistance and phage resistance might contribute to the clonal expansion and predominance of a particular V. cholerae serotype responsible for an outbreak.

Cervical cancer (CC) is themost common cancer in women and poses a serious threat to health. Despite familiaritywith the factors affecting its etiology, initiation, progression, treatment strategies, and even resistance to therapy, it is considered a significant problem for women. However, several factors have greatly affected the previous aspects of CC progression and treatment in recent decades. miRNAs are short noncoding RNA sequences that regulate gene expression by inhibiting translation of the targetmRNA. miRNAs play a crucial role in CCpathogenesis by promoting cancer stem cell (CSC) proliferation, postponing apoptosis, continuing the cell cycle, and promoting invasion, angiogenesis, and metastasis. Similarly, miRNAs influence important CCrelated molecular pathways, such as the PI3K/AKT/mTOR signaling pathway, Wnt/ß-catenin system, JAK/STAT signaling pathway, and MAPK signaling pathway. Moreover, miRNAs affect the response of CC patients to chemotherapy and radiotherapy. Consequently, this review aims to provide an acquainted summary of onco miRNAs and tumor suppressor (TS) miRNAs and their potential role in CC pathogenesis and therapy responses by focusing on the molecular pathways that drive them. [ABSTRACT FROM AUTHOR]

Introduction: Among the various potential health risks, self-medication and inappropriate storage of medicines at home are found to be very important. Inappropriate storage conditions and irrational use of medication without medical consultation may result in serious health problems. Worldwide there has been an increase in the self-medication rate, which can lead to waste of resources and serious adverse reactions. Aim: To assess the practice of self-medication and household storage of medicines amongst the study population. Materials and Methods: This was a cross-sectional and questionnaire based study conducted in the southern district of Kashmir, India from 1st September 2021 to 28th February 2022. A total of 471 households were included and interviewed to determine the practice of home storage of medicines and self-medication pattern. Quantitative data was presented as means and standard deviation (mean±SD) and qualitative data as frequency and 95% Confidence Interval (CI). Results: Almost three quarters of the households were having monthly income of less than 20,000 INR whereas 219 (46.50%) of them were illiterate. Proton pump inhibitors, minerals and vitamins, antibiotics and analgesics were the most common medicines stored at home. Drawer was the most common place used for storage of medicines whereas the refrigerator was used in less than 1% of cases for the same. Solid dosage forms were mostly used by the householders and the injectables were least used for household storage purposes. Conclusion: The study revealed that the studied householders stored large amount of medicines in homes, often under inappropriate storage conditions. There is a need for better public knowledge and information about the risks of reuse of prescribed medications.

With the emergence of day-by-day increasing distance learning institutions worldwide, the question of quality assurance (QA) in distance education (DE) needs to be addressed at appropriate level. The objective of this paper was to examine various QA practices undertaken by several QA regulatory bodies and existing models in distance and online education being followed globally. The researcher undertook extensive review of related literature pertaining to QA practices worldwide to reach at a common ground that how a DE institution be dealt in relation to its QA needs. The paper highlighted that prevailing QA models in distance and online learning have been developed in response to specific demands of stakeholders to ensure transparency and improved attention towards learning outcomes, that means a single model is not likely to fulfil the needs of all stakeholders. The paper also emphasised that it will neither be appropriate nor admissible to prefer and recommend one system of QA to another since the selection mostly depends on the efficacy and relevance of model to the specific needs, aims and maturity of educational institutions. In addition, the paper provided a comparative review of research on the effectiveness of QA practices in DE. Some recent studies reviewed in this paper highlighted the similar nature of benchmarks or dimensions for an external QA system for distance and online programs with minor variations on account of institutional local needs. However, due to technological developments external QA instruments may need revision to deal current standards and best practices.

Background and Importance: Spinal Subdural Hematoma (SSH) is a rare condition with an unknown incidence in the general population. Iatrogenic spinal subdural hematoma radiologically mimicking a prolapsed dorsolumbar disc has not been published in the literature. Case Presentation: A 65-year-old female presented with altered sensorium and generalized weakness for 3 days evaluated by a neurologist who diagnosed it as a metabolic encephalopathy with Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) with severe anemia and hypothyroidism. She underwent a diagnostic lumbar puncture and following which, within 24 hours, she developed weakness of both the lower limbs. MRI of dorsolumbar spine was done which revealed D12-L1 extruded disc causing severe compression to the conus medullaris with D12-L2 subarachnoid lesion and cord edema. On opening the dura, a large organized hematoma on the anterior aspect of the conus was seen and evacuated. Conclusion: Spinal subdural hematoma presents with a spectrum of signs and symptoms. Although MRI is the investigation of choice but SSH presenting like a prolapsed intervertebral disc on MRI is one of its kinds and should be kept in mind since it carries a grave prognosis if not treated early with emergency decompression.

Androgen receptor (AR) is a main driver for castration-resistant prostate cancer (CRPC). c-Myc is an oncogene underlying prostate tumorigenesis. Here, we find that the deubiquitinase USP11 targets both AR and c-Myc in prostate cancer (PCa). USP11 expression was up-regulated in metastatic PCa and CRPC. USP11 knockdown (KD) significantly inhibited PCa cell growth. Our RNA-seq studies revealed AR and c-Myc as the top transcription factors altered after USP11 KD. ChIP-seq analysis showed that either USP11 KD or replacement of endogenous USP11 with a catalytic-inactive USP11 mutant significantly decreased chromatin binding by AR and c-Myc. We find that USP11 employs two mechanisms to up-regulate AR and c-Myc levels: namely, deubiquitination of AR and c-Myc proteins to increase their stability and deubiquitination of H2A-K119Ub, a repressive histone mark, on promoters of AR and c-Myc genes to increase their transcription. AR and c-Myc reexpression in USP11-KD PCa cells partly rescued cell growth defects. Thus, our studies reveal a tumor-promoting role for USP11 in aggressive PCa through upregulation of AR and c-Myc activities and support USP11 as a potential target against PCa. [ABSTRACT FROM AUTHOR]

Peristaltic movement of fluid flows has significant applications in biomedical engineering, medicine, human physiology, etc. Specifically, it is very useful to understand and cure the very common intestinal diseases in human beings. A number of theoretical and empirical models are used to analyze peristaltic movement. In this work, the peristaltic movement of nanofluid is modeled with a non-Newtonian Ellis fluid model in a curved channel with compliant wall properties. The effects of Brownian motion, thermophoresis, and nonlinear radiations are considered in the heat transfer for better thermal analysis. The mathematical modeling of the physical problem yields the nonlinear partial differential equations with boundary conditions. First, the governing partial differential equations are non-dimensionalized, and then the resultant system is simplified by using the assumptions of a small Reynolds number and long wavelength. Then the obtained boundary value problem of differential equations is solved with the built-in Mathematica command NDSolve. The accuracy and reliability of the adopted procedure are verified by comparing the computed results with the reported literature. The impacts of the pertinent parameters (Brownian motion, thermal radiation, mixed convection, and thermophoresis phenomenon) on thermal energy, velocity, concentration, heat transfer rate, and stress at the lower wall are analyzed both in qualitative and quantitative manners. This study revealed some interesting facts, such as the peristaltic-driven motion of nanoliquid is strongly influenced by wall properties (i.e., wall elasticity, mass density, and wall damping). In addition, the flow experienced more resistance in the case of larger wall damping, but larger wall elasticity and mass density provide favorable movement for fluid motion. In addition, mixed convection plays a vital role in heat transfer and nanoparticle concentration in the curved domain. In addition, the curved channel walls have a higher stress factor than straight-plane channels. The results of the current study are very useful to understand many biological phenomena, such as the peristaltic movement of liquid during dialysis, food movement through the intestine, etc. [ABSTRACT FROM AUTHOR]