Search

AIDS is one of the world's most serious public health challenges. Protease inhibitors are key components of AIDS treatment regimen. Ritonavir is a well-known protease inhibitor with low aqueous solubility belonging to BCS class II category. Some of the severe adverse effects associated with this drug restricted its use in the treatment of AIDS. However, several attempts were made by researchers in the past to enhance the oral bioavailability of Ritonavir.The current review mainly focuses on the adverse effects of Ritonavir and recent approaches followed by researchers on the development of nanoformulations of Ritonavir. Further, various patents filed on Ritonavir have also been discussed in the current review.Most research on nanoformulation development for Ritonavir is mainly focused on enhancing the solubility and oral bioavailability of the drug. Some of the researchers focused on the lymphatic targeting of the drug in order to bypass the hepatic metabolism of the drug. However, most of the research topics did not cover the toxicity evaluation of the developed formulation. Since the major issue of Ritonavir is not only oral bioavailability but also drug-induced toxicity, this area needs to be considered during the formulation development.

Autologous stem cell transplant (ASCT) is a standard therapy for transplant eligible patients of multiple myeloma (MM). To evaluate impact of time to transplant on subsequent outcomes, we analyzed data on consecutive MM patients who received novel agents-based induction prior to transplant.Between 2006 and 2019, 363 MM patients underwent ASCT. Patients' median age was 52 years, ranging from 20 to 72 years, 233 (64.2%) were males. Median interval from diagnosis to transplant was 11.5 months (range, 4-67.5); 201 (55.4%) patients underwent ASCT within 12 months (early) and 162 (44.6%) beyond 12 months since diagnosis (delayed ASCT). Primary objective was progression-free survival. Secondary objectives were-response rate to transplant, overall survival (OS), and transplant-related mortality (TRM).Post-ASCT complete response (CR) (77.1% vs. 64.8%; P.025) and CR+ very good partial response rate (89% vs. 81.5%; P.03) was higher for early ASCT cohort. Engraftment characteristics, regimen-related toxicities, and day +100 TRM (3.5% vs 3.7%; P = .564) were similar in 2 cohorts. Median OS for early versus late cohort from date of diagnosis is 127.0 (95% CI, 98.9-155.1) versus 104.5 months (95% CI, 79.3-129.6; P = .356) and from date of transplant is 119.0 (95% CI, 93.4-144.6) versus 89.5 months (95% CI, 57.4-121.6), P.02. Median PFS is better for early transplant cohort; 69.5 (95% CI, 56.7-82.3) versus 50.0 months (95% CI, 35.6-64.4), P.05, respectively.Early transplant for myeloma is associated with higher response rate and better progression-free survival.

Cancer is a most common cause of mortality globally. Available medicines possess severe side effects owing to their non-specific targeting. Hence, there is a need of an alternative in the healthcare system that should have high efficacy with the least side effects, also having the ability to achieve site-specific targeting and be reproducible. This is possible with the help of fullerenes. Fullerenes are having the unique physicochemical and photosensitizer properties. This article discusses the synthesis, functionalization, mechanism, various properties, and applications of C60 fullerenes in the treatment of cancer. The review article also addresses the various factors influencing the activity of fullerenes including the environmental conditions, toxicity profile, and future prospective. Graphical abstract

The evaluation of plasma cell (PC) compartment is influenced by the quality of bone marrow aspirate (BMA). Herein, we evaluated the impact of sequence of pull on quality of clinical assessment in plasma cell proliferative disorders (PCPDs).Histomorphology along with smears from first pull and second pull BMA and flow cytometric immunophenotyping (FCMI) data from second pull aspirate were evaluated for cellularity and PC%.Of the 484 samples, BMA smears were adequate in 87.4% of first pull (median PC = 7%; IQR = 2-25%) and 51.2% of second pull samples (median PC = 2%; IQR = 0.5-12%; p 0.001). Recovery of PC was least on FCMI (median PC = 0.59%; IQR = 0.14-3.07%), however, sample adequacy was met in 42.6% of samples with acquisition of ≥3 million events. Second pull smears under-reported PC% in 34% of newly diagnosed multiple myeloma (NDMM) (10% PC) and 46% of MM on therapy (5% PC), resulting in suboptimal assessment. Bone marrow biopsy (BMBx) was evaluated in a total of 309 cases (median PC = 10.0%; IQR 4.0-40.0%) with significantly higher numbers of BMPC% on BMBx compared with first pull smears (Mean ± 2SD: 25.9% ± 30.54 vs. 20.77% ± 20.20; p = 0.001).First pull BMA smears were of superior quality but inadequate in one-tenth of samples. Second pull smears underreported PC% and recovery of PC compartment was poorest on FCMI. Concurrent bone marrow biopsy and use of the first pull sample for FCMI along with acquisition of a higher number of cells on FCMI may enhance the quality of assessment in PCPDs.

Treatment of patients with resistant/refractory multiple myeloma (MM) is an unmet need. In this phase II study, we evaluated the role of bendamustine, pomalidomide and dexamethasone combination in this setting. Between February 2020 and December 2021, 28 patients were recruited. Patients received bendamustine 120 mg/m

The expression pattern of common antigens including cytoplasmic kappa/lambda ratio (cyKLR) was evaluated by flow cytometric immunophenotyping (FCMI) to explore their relevance in discriminating normal and aberrant plasma cells (NPC and APC, respectively) across spectrum of plasma cell proliferative disorders (PCPD).In this prospective analysis, 791 samples from PCPD (treatment naive = 455; partially treated = 336) were evaluated for expression of CD38, CD138, CD45, CD19, CD56, CD27, CD81, CD117, Cy-kappa, and Cy-lambda using FCMI.Amongst the entire cohort, 20.7% (n = 164) samples displayed only APC, 21% (n = 165) only NPC and 58% (n = 462) showed coexistence of NPC and APC. Using pattern-based recognition (PBR) for three common patterns (CD19 vs. CD56; CD27 vs. CD56 and CD19 vs. CD27), APC was separable from NPC in 93% samples. In 6.5% samples, the gating markers contributed in APC-NPC differentiation and in the remaining 0.5% CD117 and CD81 proved useful. Clonality assessment was found to be crucial to label plasma cell compartment as completely normal or aberrant in 42% cases with either all NPC or all APC. Sixty one out of 462 cases (13%) revealed cyKLR within normal reference range and in these cases; abnormal cyKLR was demonstrable only after gating APC separately based on PBR.Fair discrimination between NPC and APC is achievable in all PCPD samples using eight markers (Gating: CD38, CD138, CD45; PBR:CD19, CD56, CD27; clonality: Cy-kappa and Cy-lambda). Thus, combined assessment of clonality and immunophenotypic aberrancies is required for accurate, reliable and precise assessment of NPC and APC compartments in PCPD.

Primary surgical management is successful as the sole therapeutic modality in the majority of women with early-stage cervical, vaginal and vulvar cancer, but the presence of certain risk factors in the surgico-pathological specimen indicates a poorer prognosis. Adjuvant treatment can improve overall survival in such cases. Important risk factors in cervical cancer include intermediate-risk factors (large tumor size, deep cervical stromal invasion, lymph-vascular space invasion) and high-risk factors (positive or close margins, lymph nodes, or parametrial involvement). In vulvar cancer, positive margins and lymph nodes are the two most important factors for adjuvant therapy. Radiation therapy has been the mainstay of adjuvant therapy in these cancers, supplemented by chemotherapy. Recent advances have witnessed the inclusion of newer therapeutic modalities such as immunotherapy. This review addresses the current status of various adjuvant therapeutic modalities for these gynecological cancers.

BackgroundThe COVID-19 pandemic has changed the healthcare landscape drastically. Stricken by sharp surges in morbidity and mortality with resource and manpower shortages confounding their efforts, the medical community has witnessed high rates of burnout and post-traumatic stress amongst themselves. Whilst the prevailing literature has offered glimpses into their professional war, no review thus far has collated the deeply personal reflections of physicians and ascertained how their self-concept, self-esteem and perceived self-worth has altered during this crisis. Without adequate intervention, this may have profound effects on their mental and physical health, personal relationships and professional efficacy.MethodsWith mentions of the coronavirus pervading social media by the millions, this paper set out to collate and thematically analyse social media posts containing first-person physician reflections on how COVID-19 affected their lives and their coping mechanisms. A consistent search strategy was employed and a PRISMA flowchart was used to map out the inclusion/exclusion criteria.ResultsA total of 590 social media posts were screened, 511 evaluated, and 108 included for analysis. Salient themes identified include Disruptions to Personal Psycho-Emotional State, Disruptions to Professional Care Delivery, Concern for Family, Response from Institution, Response from Society and Coping Mechanisms.ConclusionIt is evident that the distress experienced by physicians during this time has been manifold, multi-faceted and dominantly negative. Self-concepts were distorted with weakened self-esteem and perceived self-worth observed. The Ring Theory of Personhood (RToP) was adopted to explain COVID-19’s impact on physician personhood as it considers existential, individual, relational and social concepts of the self. These entwined self-concepts serve as ‘compensatory’ to one another, with coping mechanisms buffering and fortifying the physician’s overall personhood. With healthcare institutions playing a vital role in providing timely and targeted support, it was further proposed that a comprehensive assessment tool based on the RToP could be developed to detect at-risk physicians and evaluate the presence and effectiveness of established support structures.

To date, although the microscopic alterations present in Alzheimer's disease (AD) have been well known for over a century only a handful of symptomatic treatments have been developed which are a far cry from a full cure providing volatile benefits. In this context, the intervention of stem cell therapy (SCT) has been proposed as an auxiliary treatment for AD as suggested by the rising number of pre-clinical studies that stem cell engraftment could provide an exciting future treatment regimen against neurodegeneration. Although, most of the primary enthusiasm about this approach was based on replacing deteriorating neurons, the latest studies have implied that the positive modulations fostered by stem cells are fuelled by bystander effects. Present review provides a detailed update on stem cell therapy for AD along with meticulous discussion regarding challenges in developing different stem cells from an aspect of experiment to clinical research and their potential in the milieu of AD hallmarks. Specifically, we focus and provide in depth view on recent advancements in the discipline of SCT aiming to repopulate or regenerate the degenerating neuronal circuitry in AD using stem-cell-on-a-chip and 3D bioprinting techniques. The focus is specifically on the successful restoration of cognitive functions upon engraftment of stem cells on in vivo models for the benefit of the current researchers and their understanding about the status of SCT in AD and finally summarizing on what future holds for SCT in the treatment of AD.

Ensuring medical students are equipped with essential knowledge and portable skills to face complex ethical issues underlines the need for ethics education in medical school. Yet such training remains variable amidst evolving contextual, sociocultural, legal and financial considerations that inform training across different healthcare systems. This review aims to map how undergraduate medical schools teach and assess ethics.Guided by the Systematic Evidence-Based Approach (SEBA), two concurrent systematic scoping reviews were carried out, one on ethics teaching and another on their assessment. Searches were conducted on PubMed, Embase, PsycINFO and ERIC between 1 January 1990 and 31 December 2020. Data was independently analysed using thematic and content analysis.Upon scrutinising the two sets of full-text articles, we identified 141 articles on ethics teaching and 102 articles on their assessments. 83 overlapped resulting in 160 distinct articles. Similar themes and categories were identified, these include teaching modalities, curriculum content, enablers and barriers to teaching, assessment methods, and their pros and cons.This review reveals the importance of adopting an interactive, multimodal and interdisciplinary team-teaching approach to ethics education, involving community resource partners and faculty trained in ethics, law, communication, professionalism, and other intertwining healthcare professions. Conscientious effort should also be put into vertically and horizontally integrating ethics into formal medical curricula to ensure contextualisation and application of ethics knowledge, skills and attitudes, as well as protected time and adequate resources. A stage-based multimodal assessment approach should be used to appropriately evaluate knowledge acquisition, application and reflection across various practice settings. To scaffold personalised development plans and remediation efforts, multisource evaluations may be stored in a centralised portfolio. Whilst standardisation of curricula content ensures cross-speciality ethical proficiency, deliberative curriculum inquiry performed by faculty members using a Delphi approach may help to facilitate the narrowing of relevant topics.

The number of patients for carcinoma cervix with implanted hip prostheses has been increasing worldwide during the past several decades. Technological advancements are useful for delivering higher doses, i.e., dose escalation to the target, but the presence of high-density implanted hip prosthesis creates challenges for the planner.A population of 25 patients was selected for the study. Plans were generated using the MONACO treatment planning system keeping the isocenter same. The parameters evaluated for planning target volume (PTV) were DDRadiotherapy is standard care of practice for known cases of cervical malignancies. As per our investigations, VMAT has generated comparable plans in terms of target coverage (DVMAT has an edge over other techniques in terms of target coverage and sparing of critical organs in the presence of metallic prosthesis. Information about the geometry and density of prosthesis will be beneficial for treatment planning.

High mortality has been observed in the cancer population affected with COVID-19 during this pandemic. We undertook this study to determine the characteristics and outcomes of cancer patients with COVID-19 and assessed the factors predicting outcome.Patients of all age groups with a proven history of malignancy and a recent diagnosis of SARS-CoV-2 infection based on nasal/nasopharyngeal reverse transcriptase (RT)-PCR tests were included. Demographic, clinical and laboratory variables were compared between survivors and non-survivors groups, with respect to observed mortality.Between May 11 and August 10, 2020, 134 patients were included from the three centres and observed mortality was 17.1 per cent. The median age was 53 yr (interquartile range 39-61 yr) and thirty four patients (25%) were asymptomatic. Solid tumours accounted for 69.1 per cent and breast cancer was the most common tumour type (20%). One hundred and five patients (70.5%) had received chemotherapy within the past four weeks and 25 patients (19.3%) had neutropenia at presentation. On multivariate analysis, age [odds ratio (OR) 7.99 (95% confidence interval [CI] 1.18-54.00); P=0.033], haemoglobin [OR 6.28 (95% CI 1.07-37.04); P=0.042] neutrophil-lymphocyte ratio [OR 12.02 (95% CI 2.08-69.51); P=0.005] and baseline serum albumin [OR 18.52 (95% CI 2.80-122.27); P=0.002], were associated with higher mortality. Recent chemotherapy, haematological tumours type and baseline neutropenia did not affect the outcome.Higher mortality in moderate and severe infections was associated with baseline organ dysfunction and elderly age. Significant proportion of patients were asymptomatic and might remain undetected.

Background Treatment of patients with platinum resistant/refractory epithelial ovarian cancer (EOC) is an unmet need. We evaluated the role of oral metronomic therapy in this setting. Patients and methods Between October 2017 and September 2019 seventy five patients with platinum resistant/refractory EOC were enrolled. Patients received oral etoposide (50 mg, day 1 to 14, cyclophosphamide 50 mg, day 1 to 28, every 4 weeks (Arm A, n = 38). Patients in Arm- B (n = 37) received Pazopanib (400 mg once daily) in addition to etoposide and cyclophosphamide. Quality of life (QoL) was evaluated using the EORTC questionnaire. Serum VEGF and PDGF were estimated at baseline, after 3rd and 6th cycle. The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and QoL. Results Patients characteristics were well matched. Median PFS was higher in arm B, 5.1 months (95% CI 3.13 to10.33) compared to 3.4 months (95% CI 3.0 to 6.53) in arm A, p = 0.045. Median OS has ‘not reached’ in Arm B compared to 11.2 months (95% CI, 5.66 - not reached) in arm A, p = 0.032. Therapy was tolerated well; oral mucositis (p = 0.36) and fatigue (p = 0.08) being more in arm B. QoL assessment revealed modest improvement in ‘symptom scales’ in Arm B. Serum VEGF and PDGF levels decreased with therapy in both arms (Arm A-p Conclusion Addition of pazopanib to etoposide and cyclophosphamide could be a novel oral combination for metronomic therapy for platinum resistant/refractory EOC. Trial registration CTRI/2017/10/010219.

Background Professional identity formation (PIF) in medical students is a multifactorial phenomenon, shaped by ways that clinical and non-clinical experiences, expectations and environmental factors merge with individual values, beliefs and obligations. The relationship between students’ evolving professional identity and self-identity or personhood remains ill-defined, making it challenging for medical schools to support PIF systematically and strategically. Primarily, to capture prevailing literature on PIF in medical school education, and secondarily, to ascertain how PIF influences on medical students may be viewed through the lens of the ring theory of personhood (RToP) and to identify ways that medical schools support PIF. Methods A systematic scoping review was conducted using the systematic evidence-based approach. Articles published between 1 January 2000 and 1 July 2020 related to PIF in medical students were searched using PubMed, Embase, PsycINFO, ERIC and Scopus. Articles of all study designs (quantitative and qualitative), published or translated into English, were included. Concurrent thematic and directed content analyses were used to evaluate the data. Results A total of 10443 abstracts were identified, 272 full-text articles evaluated, and 76 articles included. Thematic and directed content analyses revealed similar themes and categories as follows: characteristics of PIF in relation to professionalism, role of socialization in PIF, PIF enablers and barriers, and medical school approaches to supporting PIF. Discussion PIF involves iterative construction, deconstruction and inculcation of professional beliefs, values and behaviours into a pre-existent identity. Through the lens of RToP, factors were elucidated that promote or hinder students’ identity development on individual, relational or societal levels. If inadequately or inappropriately supported, enabling factors become barriers to PIF. Medical schools employ an all-encompassing approach to support PIF, illuminating the need for distinct and deliberate longitudinal monitoring and mentoring to foster students’ balanced integration of personal and professional identities over time.

Regardless of progress in therapy management which are developed for colon cancer (CC), it remains the third most common cause of mortality due to cancers around the world. Conventional medicines pose side effects due to untoward action on non-target cells. Their inability to deliver drugs to the affected regions of the colon locally, in a reproducible manner raises a concern towards the efficacy of therapy. In this regard, nanoparticles emerged as a promising drug delivery system due to their flexibility in designing, drug release modulation and cancer cell targeting. Not only are nanoparticles making their way into colon cancer research in the revolution of conventional onco-therapeutics, but they also offer promising scope in the development of colon cancer vaccines and theranostic tools. However, there are challenges with respect to drug delivery using nanoparticles, which may hamper the delivery of these novel carriers to the colon. The present review addresses recent advents in nanotechnology for colon-specific drug delivery (CDDS) which may help to overcome the existing challenges and intends to recognize futuristic potentials in the treatment of CC with CDDS.

Ovarian cancer is the most lethal gynecological malignancy in women. The phenotype is characterized by delayed diagnosis, recurrence and drug resistance. Inherent immunogenicity potential, oncogenic function and expression of cancer-testis/germline antigen (CTA) in ovarian cancer render them a potential candidate for immunotherapy. Revolutionary clinical findings indicate that tumor antigen-mediated T-cell and dendritic cell-based immunotherapeutic approaches provide an excellent strategy for targeting tumors. Currently, dendritic cell vaccination for the treatment of B-cell lymphoma and CTA-based T-cell receptor transduced T-cell therapy involving MAGE-A4 and NY-ESO-1 are well documented and shown to be effective. This review highlighted the mechanical aspects of epigenetic drugs that can elicit a CTA-based humoral and cellular immune response and implicate T-cell and dendritic cell-based immunotherapeutic approaches.Despite substantial advancements in prognosis and diagnostic approaches, epithelial ovarian cancer is still the most lethal gynecological malignancy worldwide. In addition to radiotherapy, chemotherapy, hormonal therapy, and surgery, immunotherapy in the clinical setting is promising. Tumor-restricted expression and strong immunogenic potential make cancer-testis/germline antigen (CTA) a potential candidate for efficient T-cell and dendritic cell-mediated cancer immunotherapy. The expression of CTAs is shown to be modulated by a specific epigenetic fine-tuning mechanism. However, the expression and role of CTA in epithelial ovarian cancer immunotherapy are poorly understood. Therefore, in the current work, the authors thoroughly highlight and explore the possible epigenetic mechanisms associated with CTA expression and their implication in T-cell and dendritic cell-based immunotherapy approaches to ovarian cancer. Understanding such a paradigm is essential to adopting a precision medicine approach for better therapeutic options.

Communication skills training (CST) remains poorly represented and prioritised in medical schools despite its importance. A systematic scoping review (SSR) of CST is proposed to better appreciate current variability in their structure, content, and assessment. This is to guide their future design in medical school curricula.The Systematic Evidence-Based Approach (SEBA) was used to guide concurrent SSRs of teaching and assessment in CST. After independent database searches, concurrent thematic and content analysis of included articles were conducted separately. Resultant themes/categories were combined via the jigsaw perspective to provide a more holistic view of the data. These were then compared to tabulated summaries of the included articles to create funnelled domains.52,300 papers were identified, 150 full-text articles included, and four funnelled domains were identified: Indications, Design, Assessment, and Barriers and Enablers of CST. CSTs confer numerous benefits to physicians and patients. It saw increased confidence, improved diagnostic capabilities and better clinical management, as well as greater patient satisfaction and treatment compliance. Skills may be divided into core, prerequisite competencies, and advanced skills pertinent to more challenging and nuanced scenarios - such as population or setting-specific situations. CST teaching and assessment modalities were found to align with Miller's Pyramid, with didactic teaching gradually infused with experiential approaches to enhance their understanding and integration. A plethora of CST frameworks, teaching and assessment methods were identified and are presented together.While variable in approach, content and assessment, CST in medical schools often employ stage-based curricula to instil competency-based topics of increasing complexity throughout medical school education. This process builds on the application of prior knowledge and skills, influencing practice and, potentially, the students' professional identity formation. In addition, the institution plays a critical role in overseeing training, ensuring longitudinal guidance and holistic assessments of the students' progress.

PURPOSE Patients with advanced and metastatic cervical cancer have a poor prognosis with a 1-year survival rate of 10%-15%. Recently, an antiangiogenic humanized monoclonal antibody bevacizumab has shown to improve the survival of these patients. This study was designed to assess the cost effectiveness of incorporating bevacizumab with standard chemotherapy for the treatment of patients with advanced and metastatic cervical cancer in India. METHODS Using a disaggregated societal perspective and lifetime horizon, a Markov model was developed for estimating the costs and health outcomes in a hypothetical cohort of 1,000 patients with advanced and metastatic cervical cancer treated with either standard chemotherapy alone or in combination with bevacizumab. Effectiveness data for each of the treatment regimen were assessed using estimates from Gynecologic Oncology Group 240 trial. Data on disease-specific mortality in metastatic cervical cancer, health system cost, and out-of-pocket expenditure were derived from Indian literature. Multivariable probabilistic sensitivity analysis was undertaken to account for parameter uncertainty. RESULTS Over the lifetime of one patient with advanced and metastatic cervical cancer, bevacizumab along with standard chemotherapy results in a gain of 0.275 (0.052-0.469) life-years (LY) and 0.129 (0.032-0.218) quality-adjusted life-years (QALY), at an additional cost of $3,816 US dollars (USD; 2,513-5,571) compared with standard chemotherapy alone. This resulted in an incremental cost of $19,080 USD (7,230-52,434) per LY gained and $34,744 USD (15,782-94,914) per QALY gained with the use of bevacizumab plus standard chemotherapy. CONCLUSION Addition of bevacizumab to the standard chemotherapy is not cost effective for the treatment of advanced and metastatic cervical cancer in India at a threshold of 1-time per-capita gross domestic product.

Precise identification of Plasmodium species is critical in malaria control and elimination. Despite several shortcomings, microscopy and rapid diagnostic test (RDT) continue to be the leading diagnostic methods. Polymerase chain reaction (PCR) is the most sensitive method but its dependency on advanced laboratory and skilled workers limits its use. Here, we compared the diagnostic performance of microscopy, RDT, and PCR in clinically suspected patients from a high malaria burden state (Odisha) of India. The diagnostic performance (sensitivity, specificity, positive predictive value, and negative predictive value) of all three methods was compared using microscopy and PCR as the gold standard. PCR identified 323 (76.5 %) positive cases out of 422 samples, whereas microscopy and RDT identified only 272 (64.4 %) and 266 (63.0 %) positive cases, respectively. The sensitivity of RDT and microscopy for detecting malaria and P. falciparum cases was >80% compared to that by PCR. However, the sensitivity in identifying P. vivax (57.0 %) and a mixture of P. falciparum and P. vivax (18.0 %) was poor. We highlight application of PCR in malaria diagnosis and its benefits in reducing the transmission. This emphasizes the need for incorporation of molecular diagnostic approaches for effective elimination strategies.

Purpose: Trauma is the leading cause of mortality in people below the age of 45 years. Abdominal trauma constitutes one-fourth of the trauma burden. Scoring systems in trauma are necessary for grading the severity of the injury and prior mobilization of resources in anticipation. The aim of this study was to evaluate RTS, ISS, CASS and TRISS scoring systems in blunt trauma abdomen. Materials and methods: A prospective single-center study was conducted on 43 patients of blunt trauma abdomen. Revised trauma score (RTS), Injury Severity Score (ISS), Clinical Abdominal Scoring System (CASS) and Trauma and Injury Severity Score (TRISS) were calculated and compared with the outcomes such as need for surgical intervention, post-operative complications and mortality. Results: The majority of the study subjects were males (83.7%). The most common etiology for blunt trauma abdomen as per this study was road traffic accident (72.1%). Spleen was the most commonly injured organ as per the study. CASS and TRISS were significant in predicting the need for operative intervention. Only ISS significantly predicted post-operative complications. All scores except CASS significantly predicted mortality. Conclusions: Among the scoring systems studied CASS and TRISS predicted the need for operative intervention with good accuracy. For the prediction of post-operative complications, only the ISS score showed statistical significance. ISS, RTS and TRISS predicted mortality with good accuracy but the superiority of one score over the other couldn’t be proved.

Background: Before the approval of first-line immune checkpoint inhibitors, platinum doublets were the standard of care in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. Pemetrexed-platinum combinations are preferred in non-squamous NSCLC. However, there has been no direct comparison to paclitaxel-carboplatin. Methods: This open-label randomized trial was designed to compare pemetrexed-carboplatin with (weekly) paclitaxel-carboplatin in treatment-naïve advanced/metastatic non-squamous NSCLC without driver mutations. Patients received either pemetrexed 500 mg/m2 and carboplatin AUC 5 every 3 weeks, or paclitaxel 80 mg/m2 on day 1, day 8, and day 15 with carboplatin AUC 5 every 4 weeks for 4 cycles. Patients in both arms were allowed to receive pemetrexed maintenance. Results: A total of 180 patients were enrolled. The study was terminated early; however, at the time of analysis 75.8% of the required events had occurred. Finally, 164 patients were evaluable, 83 in the pemetrexed arm and 81 in the paclitaxel arm. After a median follow-up of 17 months, progression-free survival (PFS) rates at 6 months were not different in the two treatment arms (47.45 vs. 48.64%, p = 0.88). The median PFS values were 5.67 months (95% CI 3.73–7.3) and 5.03 months (95% CI 2.63–7.43) in each arm, respectively (HR 1.13, 95% CI 0.81–1.59, p = 0.44). The median overall survival was also not different: 14.83 months (95% CI 9.5–18.73) and 11.3 (95% CI 8.3–19.7; HR 1.19, 95% CI 0.8–1.78, p = 0.37). All grade toxicities were similar except for alopecia and peripheral neuropathy, which were higher in the paclitaxel arm. Conclusion: Pemetrexed-carboplatin is not superior to (weekly) paclitaxel-carboplatin as the first-line regimen in advanced non-squamous NSCLC in terms of PFS.

Interprofessional mentoring in palliative care sees different members of the interprofessional team providing holistic, personalised andlongitudinal mentoring support, skills training and knowledge transfer as they mentor trainees at different points along their mentoring journeys. However, gaps in practice and their risk of potential mentoring malpractice even as interprofessional mentoring use continues to grow in palliative medicine underlines the need for careful scrutiny of its characteristics and constituents in order to enhance the design, evaluation and oversight of interprofessional mentoring programmes. Hence, a systematic scoping review on prevailing accounts of interprofessional mentoring in medicine is conducted to address this gap. Using Arksey and O'Malley's (2005) methodological framework for conducting scoping reviews and identical search strategies, 6 reviewers performed independent literature reviews of accounts of interprofessional mentoring published in 10 databases. Braun and Clarke's (2006) thematic analysis approach was adopted to evaluate across different mentoring settings. A total of 11111 abstracts were identified from 10 databases, 103 full-text articles reviewed and 14 full-text articles were thematically analysed to reveal 4 themes: characterizing, implementing, evaluating and obstacles to interprofessional mentoring. Interprofessional mentoring is founded upon a respectful and collaborative mentoring relationship that thrives despite inevitable differences in individual values, ethical perspectives at different career stages within diverse working environments. This warrants effective mentor-mentee trainings, alignment of expectations, roles and responsibilities, goals and timelines, and effective oversight of the programmes. Drawing upon the data provided, an interprofessional mentoring framework is forwarded to guide the design, evaluation and oversight of the programmes.

Prostate cancer (PC) is the most prevalent male urogenital cancer worldwide. PC patients presenting an advanced or metastatic cancer succumb to the disease, even after therapeutic interventions including radiotherapy, surgery, androgen deprivation therapy (ADT), and chemotherapy. One of the hallmarks of PC is evading immune surveillance and chronic inflammation, which is a major challenge towards designing effective therapeutic formulations against PC. Chronic inflammation in PC is often characterized by tumor microenvironment alterations, epithelial-mesenchymal transition and extracellular matrix modifications. The inflammatory events are modulated by reactive nitrogen and oxygen species, inflammatory cytokines and chemokines. Major signaling pathways in PC includes androgen receptor, PI3K and NF-κB pathways and targeting these inter-linked pathways poses a major therapeutic challenge. Notably, many conventional treatments are clinically unsuccessful, due to lack of targetability and poor bioavailability of the therapeutics, untoward toxicity and multidrug resistance. The past decade witnessed an advancement of nanotechnology as an excellent therapeutic paradigm for PC therapy. Modern nanovectorization strategies such as stimuli-responsive and active PC targeting carriers offer controlled release patterns and superior anti-cancer effects. The current review initially describes the classification, inflammatory triggers and major inflammatory pathways of PC, various PC treatment strategies and their limitations. Subsequently, recent advancement in combinatorial nanotherapeutic approaches, which target PC inflammatory pathways, and the mechanism of action are discussed. Besides, the current clinical status and prospects of PC homing nanovectorization, and major challenges to be addressed towards the advancement PC therapy are also addressed.

Introduction The redeployment of mentors and restrictions on in-person face-to-face mentoring meetings during the COVID-19 pandemic has compromised mentoring efforts in Palliative Medicine (PM). Seeking to address these gaps, we evaluate the notion of a combined novice, peer-, near-peer and e-mentoring (CNEP) and interprofessional team-based mentoring (IPT) program. Methods A Systematic Evidence Based Approach (SEBA) guided systematic scoping review was carried out to study accounts of CNEP and IPT from articles published between 1st January 2000 and 28th February 2021. To enhance trustworthiness, concurrent thematic and content analysis of articles identified from structured database search using terms relating to interprofessional, virtual and peer or near-peer mentoring in medical education were employed to bring together the key elements within included articles. Results Fifteen thousand one hundred twenty one abstracts were reviewed, 557 full text articles were evaluated, and 92 articles were included. Four themes and categories were identified and combined using the SEBA’s Jigsaw and Funnelling Process to reveal 4 domains - characteristics, mentoring stages, assessment methods, and host organizations. These domains suggest that CNEP’s structured virtual and near-peer mentoring process complement IPT’s accessible and non-hierarchical approach under the oversight of the host organizations to create a robust mentoring program. Conclusion This systematic scoping review forwards an evidence-based framework to guide a CNEP-IPT program. At the same time, more research into the training and assessment methods of mentors, near peers and mentees, the dynamics of mentoring interactions and the longitudinal support of the mentoring relationships and programs should be carried out.

The lymphatic system plays a crucial role in mounting immune response against intracellular pathogens, and recent studies have documented its role in facilitating tumor dissemination linked largely with cancer cells. However, in mucocutaneous leishmaniasis (MCL) caused by

Background Recognizing that physicians may struggle to achieve knowledge, skills, attitudes and or conduct at one or more stages during their training has highlighted the importance of the ‘deliberate practice of improving performance through practising beyond one’s comfort level under guidance’. However, variations in physician, program, contextual and healthcare and educational systems complicate efforts to create a consistent approach to remediation. Balancing the inevitable disparities in approaches and settings with the need for continuity and effective oversight of the remediation process, as well as the context and population specific nature of remediation, this review will scrutinise the remediation of physicians in training to better guide the design, structuring and oversight of new remediation programs. Methods Krishna’s Systematic Evidence Based Approach is adopted to guide this Systematic Scoping Review (SSR in SEBA) to enhance the transparency and reproducibility of this review. A structured search for articles on remediation programs for licenced physicians who have completed their pre-registration postings and who are in training positions published between 1st January 1990 and 31st December 2021 in PubMed, Scopus, ERIC, Google Scholar, PsycINFO, ASSIA, HMIC, DARE and Web of Science databases was carried out. The included articles were concurrently thematically and content analysed using SEBA’s Split Approach. Similarities in the identified themes and categories were combined in the Jigsaw Perspective and compared with the tabulated summaries of included articles in the Funnelling Process to create the domains that will guide discussions. Results The research team retrieved 5512 abstracts, reviewed 304 full-text articles and included 101 articles. The domains identified were characteristics, indications, frameworks, domains, enablers and barriers and unique features of remediation in licenced physicians in training programs. Conclusion Building upon our findings and guided by Hauer et al. approach to remediation and Taylor and Hamdy’s Multi-theories Model, we proffer a theoretically grounded 7-stage evidence-based remediation framework to enhance understanding of remediation in licenced physicians in training programs. We believe this framework can guide program design and reframe remediation’s role as an integral part of training programs and a source of support and professional, academic, research, interprofessional and personal development.

The injuries or wounds caused by various means will impact human lives severely. An increase in the demand for wounds or burns was observed. For better wound healing and to combat the free radical effect on the healing process, wounds must be treated with multifunctional or multipurpose dressing or gel or any other type of biomaterial.The study aimed to develop, optimize, and evaluate the naringin-loaded proposomal gel (PPG) for quick wound healing.The central composite design was employed for the optimization of proposomes. Naringin-loaded proposomes were evaluated for percentage entrapment efficiency (EE), the particle size of proposomes (PsP), and the zeta potential of proposomes (ZpP). The change in drug release profile was studied by dissolution. Furthermore, naringin and naringin-loaded proposomes, antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) reagent and ascorbic acid as a reference standard. Different gel bases were prepared, and based on various parameters, the G2 (0.6% Carbopol 974) gel base was selected for naringin proposomes loading. The naringin-loaded PPG was evaluated for various in vitro and in vivo wound-healing properties.The optimized naringin-loaded proposomes showed extended drug release (90.78 ± 2.19%) for 72 h. The naringin-loaded PPG improved the permeability of naringin, which showed 28.91 ± 2.81% of drug release after 96 h, and the drug solution showed 9.05 ± 0.92%. IC50 values of antioxidant activity of naringin and naringin proposomes were found to be 337.31 μg/ml and 201.86 μg/ml, respectively. The naringin-loaded PPG showed better wound closure on the 15th day (3.32%) compared with proposomal solution (4.75%) or naringin topical gel (4.2%).Based on the obtained results, we conclude naringin-loaded PPG can be an alternative strategic approach to deliver the naringin for quick wound healing.

In this study, we evaluate the cost and outcomes of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus fulvestrant, fulvestrant alone, and conventional chemotherapy as the second-line therapy for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) in India.Using a Markov model, the clinical effectiveness of managing HR+, HER2- MBC in postmenopausal women with either a CDK4/6i (either ribociclib or palbociclib) and fulvestrant, fulvestrant alone, and chemotherapy (single-agent paclitaxel or capecitabine) was measured in terms of quality-adjusted life-years (QALYs). The costs were estimated from two different points of view: scenario I, as per the prevailing market prices of the drugs; and scenario II, as per the reimbursement rates set up by the publicly financed national health insurance scheme. Incremental cost per QALY gained with a given treatment option was compared against the next best alternative and was assessed for cost effectiveness using a threshold of 1-time the per capita gross domestic product (GDP) in India from a societal perspective.In scenario I, an MBC patient was found to incur a lifetime cost of Indian Rupees (₹) 2.54 million ($34,644), ₹2.53 million ($34,496), ₹512,598 ($6,984), ₹326,026 ($4,442) and ₹237,115 ($3,230) for the ribociclib and palbociclib combination arms, fulvestrant monotherapy, single-agent paclitaxel and the single-agent capecitabine treatment arms, respectively. The lifetime cost for CDK4/6i (ribociclib and palbociclib) combination therapy, fulvestrant monotherapy, paclitaxel, and capecitabine arms was estimated to be ₹1.94 million ($26,459), ₹1.92 million ($26,220), ₹315,387 ($4,296), ₹187,392 ($2,553) and ₹153,263 ($2,088), respectively, in scenario II. The mean QALYs lived per MBC patient with CDK4/6i (either ribociclib or palbociclib) combination therapy, fulvestrant, paclitaxel and capecitabine were estimated to be 1.4, 1.0, 0.9 and 0.7, respectively. None of the treatment arms are cost effective at current prices and reimbursement rates at a threshold of 1-time the per capita GDP of India. However, a 78% reduction in the current market price or a 72% reduction in the reimbursement rate of fulvestrant in the government-funded insurance program will make it a cost-effective treatment option for HR+, HER2- MBC patients in India.CDK4/6i (ribociclib and palbociclib) therapy is not a cost-effective treatment option for MBC patients. A 72% reduction in the reimbursement rate for fulvestrant monotherapy will make it a cost-effective treatment option in the Indian context.

Imaging has been added to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system of cervical carcinoma. This study was performed to assess the impact of imaging in staging and to ascertain the prevalence and pattern of nodal metastasis on contrast-enhanced computed tomography (CECT) in patients with cervical carcinoma who were treated based on FIGO 2009 staging system.This retrospective study was conducted to evaluate all patients with biopsy-proven cervical carcinoma who underwent CECT of abdomen at a tertiary cancer centre in north India from April 2017 to April 2019 and for whom either baseline or follow up scans were available. In patients with enlarged or necrotic lymph nodes, the location, size and pattern of infiltration of adjacent organs were recorded.A total of 602 patients of cervical carcinoma had undergone CT during the study period, of whom 138 (22.9%) underwent CT at baseline and 464 (77.1%) patients during follow up. The FIGO (2009) stage distribution at the time of presentation was stage IB: 109 (18.1%); stage IIA: 14 (2.3%), stage IIB: 118 (19.6%), stage IIIA: 12 (2%), stage IIIB: 277 (46%), stage IVA: 20 (3.3%) and stage IVB: 52 (8.6%). Ninety of the 138 (65.22%) patients underwent a stage shift according to the FIGO 2018 because of the presence of enlarged lymph nodes at baseline scan. Sixteen (2.7%) patients had infiltrative nodal masses most commonly involving the blood vessels (n=14) followed by ureter (n=8), bones (n=5), muscle and bowel (n=3, each). The majority (14/16) of these patients presented with vague abdominal pain, discomfort and vomiting, while two had bone pain.CECT at baseline helps in accurately assessing the stage in cervical carcinoma. It helps in the identification of lymph node metastasis in cervical carcinoma, which is crucial for guiding accurate management.

Acquired immunodeficiency syndrome (AIDS) is a condition caused by the infection of a retrovirus namely, human immunodeficiency virus (HIV). Currently, highly active anti-retroviral therapy (HAART), a combination of anti-viral drugs belonging to different classes is considered to be effective in the management of HIV. Ritonavir, a protease inhibitor (PI), is one of the most important components of the HAART regimen. Because of its lower bioavailability and severe side effects, presently, ritonavir is not being used as a PI. However, this drug is being used as a pharmacokinetic boosting agent for other PIs such as lopinavir and in lower doses. The current study aimed to develop nanostructured lipid carriers (NLCs) encapsulating ritonavir to reduce its side effects and enhance oral bioavailability. Ritonavir-loaded NLCs were developed using a combination of two different solid lipids and liquid lipids. Alpha-tocopherol, a well-known anti-oxidant, was used as an excipient (liquid lipid) in the development of NLCs which were prepared using a simple hot-emulsion and ultrasonication method. Drug-excipient studies were performed using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). QbD approach was followed for the screening and optimization of different variables. The developed NLCs were characterized for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). Furthermore, NLCs were studied for their in vitro drug release profile, and finally, pharmacokinetic parameters were determined using in vivo pharmacokinetic studies. The optimized NLC size was in the range of 273.9 to 458.7 nm, PDI of 0.314 to 0.480, ZP of −52.2 to − 40.9 mV, and EE in the range of 47.37 to 74.51%. From in vitro drug release, it was found that the release of drug in acidic medium was higher than phosphate buffer pH 6.8. Finally, in vivo pharmacokinetic studies revealed a 7-fold enhancement in the area under the curve (AUC) and more than 10-fold higher Cmax with the optimized formulation in comparison to pure drug suspension.

Immunophenotypic profile and post-therapy alteration in antigenic expression were evaluated in normal, reactive, and aberrant plasma cells (NPC, RPC, and APC) for impact on measurable residual disease (MRD) assessment in multiple myeloma (MM).Samples from non-MM staging marrow (n = 30), Hodgkin's lymphoma (n = 30) and MM (n = 724) were prospectively evaluated for expression profiles of NPC, RPC, and APC using antigens recommended in consensus guidelines.Polyclonal NPC-RPC demonstrated aberrations for all antigens evaluated with a higher frequency of aberrancies in post-therapy samples compared to treatment naïve samples (p 0.001%). Immunomodulation in APC was observed in 79% of post-therapy samples with a change in expression of 1, 2, and ≥3 antigens in 19.9%, 15.6%, and 43.5% samples, respectively. In 13.4% of samples, APC showed no aberrancy and aberrant status was assigned based on cytoplasmic light chain restriction (cyLCR) alone. 9% samples with an admixture of NPC and APC displayed normal cytoplasmic kappa to lambda ratio (cyKLR) when the percentage of APC of total PC (neoplastic plasma cell index, NPCI), was below 25% and 50% for kappa and lambda restricted cases, respectively.The panorama and high frequency of antigenic aberrations on polyclonal PC signify the importance of MRD assay validation on a large cohort under normal and reactive conditions. Frequent Immunophenotypic shifts in APC re-confirm the redundancy of baseline immunophenotype for MRD evaluation. Small clones of APC may be missed by assessment of cyKLR alone and therefore, surface marker aberrancy supported by cyLCR is required for definitive assignment of residual APC.

Female urethral defects are rare, congenital defects being more uncommon than acquired, and difficult to manage. Most female urethral defects are associated with incontinence or acute urinary retention. There is a lack of standard protocol-based management of female urethral defects because of limited experience. In this study, we describe our results of using anterior or posterior bladder wall flaps in the management of a variety of female urethral defects. We reviewed the case records of 22 patients who had undergone either anterior or posterior bladder wall-based flap procedures for complex urethral defects at our institute. Patients were assessed by taking a comprehensive history including aetiological factors and details of prior surgical intervention, thorough physical and pelvic examination, cysto-urethroscopy and relevant imaging. These factors, along with availability and status of tissue available for reconstruction affected the selection of procedure for reconstruction. Out of 22 patients, anterior and posterior bladder flaps were used in 16 and 6 patients respectively. A total of 18 patients became socially dry and 15 achieved complete continence after removal of the catheter and were voiding satisfactorily, whereas the remaining 4 patients had incontinence postoperatively. An additional 3 out of 18 patients had minimal stress incontinence requiring conservative treatment and 2 patients developed voiding difficulty requiring self-calibration. Female urethral defects with bladder neck involvement are complex and challenging to manage. Bladder wall-based flaps offer a good chance of successful repair of these complex urethral defects.

BACKGROUND Interprofessional communication (IPC) improves patient care, cost efficiency and improves teamwork among healthcare professionals. For medical students IPC training is crucial to navigating complex healthcare practices yet there is little consistency to IPC training. This scoping review looks at IPC training approaches for medical students to improve preparedness for clinical practice.METHODS Arksey and O’Malley (2005) framework for scoping review was used to guide this review of articles on IPC training for medical students published between 1 January 2000 to 31 December 2017 in PubMed, ScienceDirect, JSTOR, Google Scholar, ERIC, Embase, Scopus, PsycINFO, Mednar and OpenGrey. A ‘split approach’ that sees concurrent independent use of a directed content analysis and Braun and Clarke’s approach to thematic approach was employed by different members of the research team to scrutinize the data.RESULTS 17,493 titles and abstracts were found, 250 full-text articles were reviewed and 70 full text articles were included. The ‘split approach’ to analysis forwarded similar themes that corresponded with the different levels of Miller’s Pyramid. These were “Knows”, “Knows How”, “Shows how” and “Does”. Each stage involves particular training modalities and context appropriate modes of assessments to measure medical students’ competency levels. IPC training was found to be well received, positive, increased students’ understanding and practice of communication. Obstacles to IPC training include scheduling constraints, inexperienced and untrained teachers, and initial anxiety and adjustment for students.CONCLUSIONS This scoping review reveals IPC training to be competency and assessment based, and dependent upon learning objectives and a clear alignment of expectations. Faculty training, a conducive learning environment tailored to the learner, and effective assessment methods at each training stage are crucial to the success of IPC training. Further evaluations are recommended to ensure the translatability of these findings to other medical specialities and other healthcare professions.

CD123 is overexpressed in many hematologic malignancies and found to be useful in characterizing leukemic blasts of both acute myeloid leukemia (AML) and B-acute lymphoblastic leukemia (B-ALL). CD123 has been recently found to be a marker of leukemic stem cells, and its utility to measure residual disease and potential role in disease relapse is under evaluation.Herein, we have evaluated the expression of CD123 in 757 samples of acute leukemia including 479 treatment-naive and 278 follow-up samples and compared with post-induction morphologic complete remission and measurable residual disease (MRD) status. Multiparametric flow cytometry was used for assessment of CD123 expression and immunophenotypic characterization of leukemic blasts at diagnostic and MRD assessment time points.Using variable cutoffs of 5%, 10%, and 20% to define a case as CD123-positive, expression of CD123 was observed in 75.6%, 66.2%, and 50% of AML and 88.6%, 81.8%, and 75% of B-ALL, respectively. Of 11 patients, 7 (63.63%) had mixed phenotype acute leukemia, but none of the 12 patients with T-acute lymphoblastic leukemia showed positivity for CD123. CD123 expression at diagnosis was associated with post-induction MRD-positive status in both B-ALL (P .001) and AML (P = .001). We also evaluated the utility of CD123 as a leukemia-associated aberrant immunophenotype and found it to be useful in both patients with AML (baseline, 50.6%; follow-up, 53%) and B-ALL (baseline, 75%; follow-up, 73.07%).In conclusion, CD123 may be considered as a cardinal marker for residual disease assessment and response evaluation in AML and B-ALL.

YPEL3 that induces cellular senescence in both normal and tumour cells of humans may show altered expression under the influence of incidental mutations. In this study, we proposed the first structure of Native YPEL3 protein and its five possible deleterious mutants—V40M, C61Y, G98R, G108S, and A131T and predicted their deleterious effects to alter stability, flexibility and conformational changes in the protein. The MD simulation (RMSD, RMSF, Rg, h-bond and SASA) analysis revealed that the variants V40M, G98R and G108S increased the flexibility in protein, and variant V40M imparted more compactness to the protein.. In general, variants attributed changes in the native conformation and structure of the YPEL3 protein which might affect the native function of cellular senescence. The study provides opportunities for health professionals and practitioners in formulating précised medicines to effectively cure various cancers. We propose in-vitro or in-vivo studies should consider these reported nsSNPs while examining any malfunction in the YPEL3 protein.

Introduction:Caring for terminally ill children influences nurses’ and allied health provider’s quality of life, ability to provide personalized, dignified and empathetic care and even their concepts of personhood. In the absence of data this review utilizes the Ring Theory of Personhood (RToP) to evaluate how a physician’s concept of personhood is affected caring for terminally ill children in order to better support them holistically.Methods:Using PRISMA Guidelines, 14 researchers carried out independent searches of PubMed, CINAHL, PsycINFO, Cochrane Library and gray literature databases for articles published between 2000 to 2019. Concurrent and independent employment of content and thematic analysis (Split Approach) was used to enhance the trustworthiness of the analysis.Results:13,424 titles and abstracts were retrieved, 188 full texts were evaluated, and 39 articles were included and analyzed. Identical categories and themes identified using the Split Approach suggest that caring for dying children in PPC impacts the physician’s professional identity, clinical decision making, personal well-being and relationships. The data also suggests that the magnitude of these effects depends on the presence of protective and risk factors.Conclusion:Aside from providing a novel insight into the upon the physician, this review proffers a unique approach to accounting for the presence, magnitude and influence of incoming catalysts, resultant conflicts, and protective and risk factors upon the physician’s personhood. Further studies into the changes in personhood are required. Design of a personalized assessment tool based on the RToP will help direct timely, appropriate and personalized support to these physicians.

Introduction: Professionalism is an evolving, socioculturally informed multidimensional construct that influences doctor-patient relationships, patient satisfaction and care outcomes. However, despite its clinical significance there is little consistency in how professionalism is nurtured amongst medical students. To address this gap a systemic scoping review of nurturing professionalism in medical schools, is proposed.Methods: Levac's framework and the PRISMA-P 2015 checklist underpinned a 6-stage systematic review protocol. Concurrent use of Braun and Clarke's approach to thematic analysis and directed content analysis was used to identify the key elements in nurturing professionalism.Results: 13921 abstracts were identified from six databases, 854 full-text articles reviewed, and 162 full-text included articles were included. The 4 themes identified through thematic analysis are consistent with findings of the directed content analysis. These were the definition of professionalism, the approaches, content, barriers and enablers to teaching professionalism.Conclusion: Informed by a viable definition of professionalism and clear milestones nurturing professionalism nurturing professionalism begins with culturally appropriate training in clinical competence, humanistic qualities and reflective capacity. This process requires effective evaluations of professional identity formation, and the impact of the learning environment underlining the need for longitudinal assessments of the training process.

Introduction Interprofessional communication (IPC) enhances patient experiences and outcomes and improves well-being and satisfaction among health care professionals. This scoping review seeks to guide design of IPC training in internal medicine. Methods The framework of Arksey and O'Malley (2005) guided this systematic scoping review in internal medicine across PubMed, Embase, CINAHL, Scopus, PsycINFO, ERIC, JSTOR, and Google Scholar databases for publications from the years 2000 to 2018. Results Twenty-two thousand eight hundred seventy-four abstracts were retrieved, 326 full-text articles were reviewed, and 32 articles were included. The themes identified using directed content analysis were indications for an IPC program, training stages, and obstacles. The rationale for IPC programs was to improve interprofessional teamwork and enhance patient care. IPC training occurs in five stages beginning with instilling the role, value, and skills behind IPC and gradually practicing these skills within the clinical setting. The challenges to IPC highlight the need to confront workplace hierarchies and the lack of resources. Discussion The findings of this systematic scoping review also serve to underscore the importance of understanding, evaluating, and influencing the clinical environment and the work environment and the need for new assessment tools that will guide the individualized, longitudinal, competency-based learning process that underpins IPC training.

Abnormal expression patterns of regulatory small non-coding RNA (sncRNA) molecules such as microRNAs (miRs), piwi-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs) play an important role in the development and progression of cancer. Identification of clinically relevant sncRNA signatures could, therefore, be of tremendous translational value. In the present study, genome-wide small RNA sequencing identified a unique pattern of differential regulation of eight miRs in Chronic Lymphocytic Leukemia (CLL). Among these, three were up-regulated (miR-1295a, miR-155, miR-4524a) and five were down-regulated (miR-30a, miR-423, miR-486*, let-7e, and miR-744) in CLL. Altered expression of all these eight differentially expressed miRs (DEMs) was validated by RQ-PCR. Besides, seven novel sequences identified to have elevated expression levels in CLL turned out to be transfer RNA (tRNA)/piRNAs (piRNA-30799, piRNA-36225)/snoRNA (SNORD43) related. Multivariate analysis showed that miR-4524a (HR: 1.916, 95% CI: 1.080–3.4, p value: 0.026) and miR-744 (HR: 0.415, 95% CI: 0.224–0.769, p value: 0.005) were significantly associated with risk and time to first treatment. Further investigations could help establish the scope of integration of these DEM markers into risk stratification designs and prognostication approaches for CLL.

Management of locally advanced cervix cancer underwent major change 2 decades back when concurrent chemotherapy (CCRT) (with cisplatin alone or in combination) along with definite radiation therapy (external + brachytherapy) was found to be superior compared to radiation alone in a series of randomized trials. Since then CCRT has been the standard treatment approach; this has resulted in 5-year overall survival rate of 66% and disease-free survival (DFS) of 58%. About 30% to 40% of patients with locally advanced cervical cancer continue to have treatment failure. Also, some patients experience early and late side effects of treatment with negative impact on quality of life. To improve the outcome further - recent approaches have explored use of weekly paclitaxel and carboplatin for 4 to 6 weeks as dose dense chemotherapy prior to CCRT, adjuvant chemotherapy after CCRT in high risk patients. For patients with early stage disease (IA2-IIA), short course chemotherapy prior to surgery is associated with improved outcome in many studies. Bevacizumab- an inhibitor of vascular endothelial growth factor - is associated with improved survival. More recently, addition of treatment with immune check inhibitors (to boost the ability of T cells to destroy cancer cells) have improved responses and survival in the treatment of recurrent and metastatic cervical cancer. Whether these and other similar novel agents targeting molecular pathways could be brought in front line treatment along with cytotoxic chemotherapy along with bevacizumab are potential areas of current research.

Introduction: Blunt trauma chest contributes to significant number of trauma admissions globally and is a cause of major morbidity and mortality. Many scoring systems and risk factors have been defined in past for prognosticating blunt trauma chest but, none is considered to be gold standard. Aim: This study was conducted to reassess the significance of available scoring systems and others indicators of severity in prognosticating blunt trauma chest patients. Materials and Methods: In this prospective observational study from November 2016 till March 2018, 50 patients with age more than 12 years with blunt chest trauma who required hospitalization were included. Nine risk factors were assessed namely- age of the patient, duration of presentation after trauma, number of ribs fractured, bilateral thoracic injury, evidence of lung contusion, associated extra thoracic injury, need for mechanical ventilation, Revised trauma Score (RTS) and Modified Early Warning Sign Score (MEWS). Severity of blunt thoracic trauma was assessed on following outcomes-SIRS, ARDS and Death. The inferences were drawn with the use of statistical software package SPSS v22.0. Results: The age of 50 patients included in our study with a range of 15 to 76 years, the median age was 35.5 years. Statistically significant association was observed between occurrence of SIRS and multiple ribs fractured (p-value- 0.049), associated extra-thoracic injury (p-value-0.016) and higher MEWS score (p-value-0.025). ARDS occurrence was statistically significantly associated with all the risk factors except age.Death occurred more in patients with delayed duration of presentation to hospital (p-value Conclusion: High MEWS, associated extra-thoracic injuries and multiple rib fractured can very well predict poor outcome in terms of SIRS, ARDS and death. Aggressive treatment protocols should be established for better outcome in these patients with blunt trauma chest.

Background Mentoring’s pivotal role in nurturing professional identity formation (PIF) owes much to its combined use with supervision, coaching, tutoring, instruction, and teaching. However the effects of this combination called the ‘mentoring umbrella’ remains poorly understood. This systematic scoping review thus aims to map current understanding. Methods A Systematic Evidence-Based Approach guided systematic scoping review seeks to map current understanding of the ‘mentoring umbrella’ and its effects on PIF on medical students and physicians in training. It is hoped that insights provided will guide structuring, support and oversight of the ‘mentoring umbrella’ in nurturing PIF. Articles published between 2000 and 2021 in PubMed, Scopus, ERIC and the Cochrane databases were scrutinised. The included articles were concurrently summarised and tabulated and concurrently analysed using content and thematic analysis and tabulated. The themes and categories identified were compared with the summaries of the included articles to create accountable and reproducible domains that guide the discussion. Results A total of 12201 abstracts were reviewed, 657 full text articles evaluated, and 207 articles included. The three domains identified were definitions; impact on PIF; and enablers and barriers. The mentoring umbrella shapes PIF in 3 stages and builds a cognitive base of essential knowledge, skills and professional attitudes. The cognitive base informs thinking, conduct and opinions in early supervised clinical exposure in Communities of practice (COP). The COPs’ individualised approach to the inculcation of desired professional characteristics, goals, values, principles and beliefs reshapes the individual’s identity whilst the socialisation process sees to their integration into current identities. Conclusion The mentoring umbrella’s provides personalised longitudinal support in the COP and socialisation process. Understanding it is key to addressing difficulties faced and ensuring holistic and timely support.

Background Characterised by feelings of helplessness in the face of clinical, organization and societal demands, medical students are especially prone to moral distress (MD). Despite risks of disillusionment and burnout, efforts to support them have been limited by a dearth of data and understanding of MD in medical students. Yet, new data on how healthcare professionals confront difficult care situations suggest that MD could be better understood through the lens of the Ring Theory of Personhood (RToP). A systematic scoping review (SSR) guided by the RToP is proposed to evaluate the present understanding of MD amongst medical students. Methods The Systematic Evidence-Based Approach (SEBA) is adopted to map prevailing accounts of MD in medical students. To enhance the transparency and reproducibility, the SEBA methodology employs a structured search approach, concurrent and independent thematic analysis and directed content analysis (Split Approach), the Jigsaw Perspective that combines complementary themes and categories, and the Funnelling Process that compares the results of the Jigsaw Perspective with tabulated summaries to ensure the accountability of these findings. The domains created guide the discussion. Results Two thousand six hundred seventy-one abstracts were identified from eight databases, 316 articles were reviewed, and 20 articles were included. The four domains identified include definitions, sources, recognition and, interventions for MD. Conclusions MD in medical students may be explained as conflicts between the values, duties, and principles contained within the different aspects of their identity. These conflicts which are characterised as disharmony (within) and dyssynchrony (between) the rings of RToP underline the need for personalised and longitudinal evaluations and support of medical students throughout their training. This longitudinal oversight and support should be supported by the host organization that must also ensure access to trained faculty, a nurturing and safe environment for medical students to facilitate speak-up culture, anonymous reporting, feedback opportunities and supplementing positive role modelling and mentoring within the training program.

Context : There are few international studies about the continuous use of sedatives (CUS) in the last days of life. Objectives : We aim to describe the experiences and opinions regarding CUS of physicians caring for terminally ill patients in seven countries. Methods : Questionnaire study about practices and experiences with CUS in the last days of life among physicians caring for terminally ill patients in Belgium (N=175), Germany (N=546), Italy (N=214), Japan (N=513), the Netherlands (N=829), United Kingdom (N=114) and Singapore (N=21). Results : The overall response rate was 22%. Of the respondents, 88-99% reported that they had clinical experience of CUS in the last 12 months. More than 90% of respondents indicated that they mostly used midazolam for sedation. The use of sedatives to relieve suffering in the last days of life was considered acceptable in cases of physical suffering (87-99%). This percentage was lower but still substantial in cases of psycho-existential suffering in the absence of physical symptoms (45-88%). These percentages were lower when the prognosis was at least several weeks (22- 66% for physical suffering and 5-42% for psycho-existential suffering). Of the respondents, 10% or less agreed with the statement that CUS is unnecessary because suffering can be alleviated with other measures. A substantial proportion (41-95%) agreed with the statement that a competent patient with severe suffering has the right to demand the use of sedatives in the last days of life. Conclusion : Many respondents in our study considered CUS acceptable for the relief of physical and psycho-existential suffering in the last days of life. The acceptability was lower regarding CUS for psycho-existential suffering and regarding CUS for patients with a longer life expectancy. Funding : Ministry of Education, Culture, Sports, Science and Technology, Japan Key message : This questionnaire study among physicians caring for terminally ill patients showed that many considered the continuous use of sedatives acceptable to relieve physical and psycho-existential suffering in the last days of life. Respondents’ regarded the practice as less acceptable in patients with a longer life expectancy.

POEMS syndrome, a rare plasma cell disorder, is challenging both in the diagnostic and therapeutic management. We present real word retrospective analysis of 108 cases analyzing clinical features and therapeutic modes. We compare our results with the available literature. This is the first description with such wide use of proteasome inhibitors in first line treatment. POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome is a rare and challenging plasma cell disorder, both in the diagnostic and therapeutic management of the disease. Currently, the literature on POEMS is sparse with most evidence being case reports and small case studies. We present a retrospective real world experience of 108 patients with POEMS. We analyzed the clinical features and therapeutic interventions. Regarding clinical features, our findings demonstrated that skin lesions, thrombocythemia and polycythemia were present less frequently than reported previously. Regarding clinical interventions, this is one of the largest analyses of front line treatment in POEMS and the first one to include frequent utilization of proteasome inhibitors (37%). Bortezomib monotherapy was the most effective therapy achieving complete remission/very good partial remissions (CR/VGPR) in 69% of patients. Thirty percent of patients proceeded to planned autologous stem cell transplant (ASCT) as part of the front-line treatment resulting in statistically superior progression-free (PFS) and overall survival (OS) compared to non-ASCT treated patients (P= .003). In multivariate analysis, anemia, thrombocytopenia, and as age over 60 were associated with a negative impact on patient outcomes.

Earlier research from our laboratory demonstrated the presence of stimulatory activity of different growth factors in the fetal liver (FL) extracts when collected in a medium known as fetal liver conditioned medium (FLCM) using Enzyme-linked Immunosorbent Assay (ELISA). In the present study, we have assessed two other cytokines viz. IL-6 and FMS like tyrosine kinase-3 (Flt-3) with the help of bioneutralization assay. FLCM was prepared by incubating fetal liver cells with Iscove's Modified Dulbecco's Medium (IMDM) containing 10% fetal bovine serum (FBS) and 10% Phytohemagglutinin and collected after 24hrs, 48hrs, 72 hrs. and on the 7th day of incubation. Clonal cultures were established for 1 X 10

To validate the AcurosA Clinac-iX (2300CD) linear accelerator and Eclipse TPS (Varian Medical System, Inc., Palo Alto, USA) was used for commissioning of AXB algorithm using a 6 megavolts photon beam. Percentage depth dose (PDD) and profiles for field size 2 cm × 2 cm, 4 cm × 4 cm, 6 cm × 6 cm, 10 cm × 10 cm, 20 cm × 20 cm, 30 cm × 30 cm to 40 cm × 40 cm were taken. AXB calculated PDDs and profiles were evaluated against the measured and analytical anisotropic algorithm (AAA)-calculated PDDs and profiles. Test sites recommended by American Association of Physicists in Medicine task group (AAPM TG)-119 recommendation were used for RA planning and delivery verification using AXB algorithm.Dosimetric analysis of AXB calculated data showed that difference between calculated and measured data for PDD curves were maximum1% beyond the depth of dose maximum and computed profiles in central region matches with maximum1% for all considered field sizes. Ion-chamber measurements showed that the average confidence limit (CLs) was 0.034 and 0.020 in high-gradient and 0.047 and 0.042 in low-gradient regions, respectively, for AAA and AXB calculated RA plans. Portal measurements show the average CLs were 2.48 and 2.58 for AAA and AXB-calculated RA plans, with gamma passing criteria of 3%/3 mm.AXB shows excellent agreement with measurements and AAA calculated data. The CLs were consistent with the baseline values published by TG-119. AXB algorithm has the potential to perform photon dose calculation with comparable fast calculation speed without negotiating the accuracy. AAPM TG-119 was successfully implemented to access the proper configuration of AXB algorithm following the TPS upgrade.

Large forested landscapes often harbour significant amount of biodiversity and support mankind by rendering various livelihood opportunities and ecosystem services. Their periodic assessment for health and ecological integrity is essential for timely mitigation of any negative impact of human use due to over harvesting of natural resources or unsustainable developmental activities. In this context, monitoring of mega fauna may provide reasonable insights about the connectivity and quality of forested habitats. In the present study, we conducted a largest non-invasive genetic survey to explore mammalian diversity and genetically characterized 13 mammals from the Indian Himalayan Region (IHR). We analyzed 4806 faecal samples using 103 autosomal microsatellites and with three mitochondrial genes, we identified 37 species of mammal. We observed low to moderate level of genetic variability and most species exhibited stable demographic history. We estimated an unbiased population genetic account (PGA

In order to maintain cellular homeostasis and a healthy state, aberrant and aggregated proteins are to be recognized and rapidly cleared from cells. Parkinson's disease, known to be associated with multiple factors; presents with impaired clearance of aggregated alpha synuclein as a key factor. We endeavored to study microRNA molecules with potential role on regulating multiple checkpoints of protein quality control within cells. Carrying out global miRNA profiling in a transgenic C. elegans model that expresses human alpha synuclein, we identified novel miRNA, miR-4813-3p, as a significantly downregulated molecule. Further studying its putative downstream target genes, we were able to mechanistically characterize six genes gbf-1, vha-5, cup-5, cpd-2, acs-1 and C27A12.7, which relate to endpoints associated with alpha synuclein expression, oxidative stress, locomotory behavior, autophagy and apoptotic pathways. Our study reveals the novel role of miR-4813-3p and provides potential functional characterization of its putative target genes, in regulating the various pathways associated with PQC network. miR-4813-3p modulates ER

Depth of invasion (DOI) has been incorporated in the new AJCC 8th classification. However, even with this new AJCC classification stage III oral tongue squamous cell carcinoma (OTSCC) remains a heterogenous group. The study aims at finding a discreet group within stage III using DOI as a cut-off of 10 mm.The institutional database was reviewed from 2012 to 2018 for postoperative stage III OTSCC patients who subsequently received postoperative radiotherapy. Ninety-six patients matched the inclusion criteria. Two groups were created using a DOI cut-off of 10 mm (superficial and deep groups). The groups were analyzed for overall survival (OS) and relapse-free survival (RFS).The baseline and treatment characteristics were comparable between the groups except for the higher number of extensive surgeries, endophytic configuration, pT3 and, DOI in the deep group. For a median follow-up of 40.5 (range: 4-139) months, the median OS and RFS for the superficial group were not reached. The median OS and RFS for the deep group were 101 (range: 73.7-128.3) and 60 (range: 46.6-73.4) months, respectively. The difference was statistically significant for median RFS (P = .008) and trended toward significance for median OS (P = .066) for the superficial group. Multivariate Cox regression analysis showed DOI cut-off as a significant predictor for RFS but not for OS.DOI significantly predicts poor RFS. However, showed a trend toward poor OS. This study hints toward a possibility of sub-dividing stage III OTSCC based on DOI cut-off.3 (Retrospective cohort study) Laryngoscope, 132:1594-1599, 2022.