Dermatomyositis: Practical Guidance and Unmet Needs.

Dermatomyositis is a heterogeneous idiopathic inflammatory myopathy associated with various cutaneous manifestations and variable presence of myositis, interstitial lung disease, and other visceral organ involvement. An accurate diagnosis of dermatomyositis requires correlating clinical examination findings with serological and histological findings. Familiarity with pathognomonic and common cutaneous manifestations of dermatomyositis, which are highlighted here, can be especially helpful in making an accurate diagnosis. Additionally, evaluating patients for presence of myositis-specific autoantibodies can further support or refute a dermatomyositis diagnosis. When present, myositis-specific autoantibodies can also help guide workups for various dermatomyositis-associated manifestations, as each is associated with relatively distinct clinical characteristics. Evaluating patients for various systemic manifestations often relies on expert opinion recommendations; however, societal guideline statements concerning the evaluation of some manifestations have recently been described. Although malignancy-associated dermatomyositis is a well-accepted subtype, there is limited evidence to support extensive malignancy screening has a favorable benefit-risk ratio in most dermatomyositis patients. However, recent research has uncovered novel associations between dermatomyositis and malignancy, suggesting the possibility of identifying high-risk subsets of dermatomyositis patients in whom malignancy screening may have a high value. Treatment for dermatomyositis has remained largely unchanged over the past several decades. Although many dermatomyositis patients can be effectively treated with current options, either as monotherapy or with combination regimens, there is a need for more targeted and effective DM therapies, in general, and for MDA5(+) dermatomyositis-associated rapidly progressive interstitial lung disease. Fortunately, significant current and emerging research activities evaluating various novel medications for dermatomyositis provide hope for exciting future advances in patients with this intriguing immune-mediated disease.

Link between individual resilience and aggressiveness in dental students and the mediating effect of spirituality: A path analysis.

BACKGROUND: The role of spirituality in people's lives, particularly the lives of health professionals, as well as its impact on mental health issues like anger and aggressiveness and resilience, are particularly significant. Therefore, the purpose of this study was to examine the link between the propensity for violence and personal resilience in dental students by taking into account the function of spirituality as a mediator. MATERIALS AND METHODS: In this cross-sectional questionnaire survey, 211 volunteer dentistry students participated from a government institute in Jammu and Kashmir, India using a stratified sample procedure. The Spiritual Orientation Scale, Buss and Perry Aggression Questionnaire, and Connor-Davidson Resilience Scale were used to gather the data. SPSS version 20.0 was used for conducting a bivariate analysis to ascertain the directionality connection between the research variables. In addition; structural equation modelling analysis was conducted by Smart PLS. RESULTS: According to the findings, resilience and spirituality have a substantial and positive link (r = 0.468 r = 0.023). Aggressiveness and resilience revealed a statistically significant inverse link (r = 0.325, P = 0.04), but aggression and spirituality had no significant correlation. Spirituality played a substantial mediation influence in the indirect pathway of violence on resilience (P = 0.001). CONCLUSION: According to the study's findings, spirituality can help pupils become more resilient as individuals and can act as a helpful intermediary between aggressiveness and resilience.

Unravelling the role of Silibinin in targeting CD44+ cancer stem cells: Therapeutic implications, effective strategies and approaches.

CD44+ cancer stem cells (CSCs) are believed to account for drug resistance and tumour recurrence due to their potential to self-renew and differentiate into heterogeneous lineages. Therefore, efficient treatment strategies targeting and eliminating these CSCs are required. The flavonolignan, Silibinin, has gained immense attention in targeting CD44+ CSCs as it alters functional properties like cell cycle arrest, apoptosis, inhibition of invasion and metastasis and also inhibits a range of molecular pathways. However, its limited bioavailability is a major hurdle in asserting Silibinin as a translational therapeutic agent. Combinatorial therapy of Silibinin with conventional chemotherapeutic drugs is an alternative approach in targeting CD44+ CSCs as it increases the efficacy and reduces the cytotoxicity of chemotherapeutic drugs, thus preventing drug resistance. Certain Silibinin-conjugated nano-formulations have also been successfully developed, through which there is improved absorptivity/bioavailability of Silibinin and a decrease in the concentration of therapeutic drugs leading to reduced cytotoxicity. In this review, we summarise the effectiveness of the synergistic therapeutic approach for Silibinin in targeting the molecular mechanisms of CD44+ CSCs and emphasise the potential role of Silibinin as a novel therapeutic agent.

Intra-abdominal Venous Thromboses and Their Management.

While a plethora of articles discuss management of deep venous thromboses in extremities, there is a relative scarcity of literature comprehensively describing intra-abdominal venous thromboses, and their management. Intra-abdominal venous thromboses include iliocaval venous obstruction (ICVO), hepatic venous thrombosis (HVT), portal venous thrombosis (PVT), renal vein thrombosis (RVT), splenic vein thrombosis (SVT), and gonadal vein thrombosis (GVT); each of which provides unique microenvironmental challenges to management. Doppler ultrasound is the first line imaging modality for diagnosis, and computed tomography and magnetic resonance imaging can help define the extent of thrombus burden and aid with interventional planning. Systemic anticoagulation remains the common medical treatment for intra-abdominal venous thrombosis, however, catheter directed thrombolysis and thrombectomy show positive outcomes in ICVO, HVT, PVT, and RVT, with transjugular intrahepatic portosystemic shunt (TIPS) creation especially beneficial in HVT and PVT. In this review article, we describe pathophysiology, clinical features, imaging findings, and current management options for intra-abdominal venous thromboses.

Navigating the Diagnostic Challenge of Aspergillus Spinal Epidural Abscess in an Immunocompetent Patient: A Case Report and Literature Review.

Aspergillus spinal epidural abscess (ASEA) is a rare, life-threatening condition that can cause spinal cord compression with neurologic deficits. The diagnosis of ASEA can be challenging due to the atypical clinical presentation and low prevalence. We describe the successful management of a rare, immunocompetent, 85-year-old male with ASEA at the T12-L1 and L1-L2 levels and present a review of the literature. Based on most case reports and our knowledge, this is a rare presentation of ASEA in a patient without systemic symptoms, leukocytosis, or a history of immunosuppressive status due to chronic steroid use. The patient presented with multiple falls and lower extremity paraparesis with near-complete paralysis of the right lower extremity for a duration of three months. Systemic symptoms of infection were absent and standard lab evaluations were unremarkable. CT imaging identified cord signal changes at the level of T10-T11 and a contrast block at L1 suspicious for spinal stenosis and impingement. During lumbar spine exploration, purulent fluid consistent with an abscess was found in the epidural space. Cultures were forwarded to microbiology and returned with Aspergillus. Postoperatively, Infectious Disease (ID) recommended treatment with voriconazole, cefepime, and vancomycin, which yielded gradual symptom improvement. The successful management of ASEA requires a multidisciplinary approach involving neurosurgeons, infectious disease specialists, radiologists, and physical therapists. Clinicians should be aware of the possibility of ASEA regardless of systemic symptoms, and early diagnosis and prompt treatment with surgical decompression and appropriate antifungal therapy are imperative for successful management.

COVID-19-Induced Encephalopathy: A Case Report.

While COVID-19 is known to cause common neurological manifestations such as loss of taste and smell, headaches, and myalgias, rare and severe neurological complications can also occur. We describe the hospitalization of a middle-aged Caucasian woman who presented with altered mental status and an absence of moderate-severe pulmonary symptoms. The patient tested positive for COVID-19 and experienced a tonic-clonic seizure six days after admission. Diagnostic testing, including cerebrospinal fluid analysis, blood cultures, urine cultures, brain imaging, and electroencephalograms were unremarkable, indicating a global encephalopathic state. This case highlights the need for clinicians to anticipate neurological complications when managing patients with COVID-19, especially when respiratory symptoms are minimal or absent. Moreover, further research on COVID-19-induced encephalopathy is crucial to improve patient outcomes and inform clinical practice.

A novel 3-miRNA network regulates tumour progression in oral squamous cell carcinoma.

BACKGROUND: Late diagnosis is one of the major confounders in oral squamous cell carcinoma (OSCC). Despite recent advances in molecular diagnostics, no disease-specific biomarkers are clinically available for early risk prediction of OSCC. Therefore, it is important to identify robust biomarkers that are detectable using non-invasive liquid biopsy techniques to facilitate the early diagnosis of oral cancer. This study identified potential salivary exosome-derived miRNA biomarkers and crucial miRNA-mRNA networks/underlying mechanisms responsible for OSCC progression. METHODS: Small RNASeq (n = 23) was performed in order to identify potential miRNA biomarkers in both tissue and salivary exosomes derived from OSCC patients. Further, integrated analysis of The Cancer Genome Atlas (TCGA) datasets (n = 114), qPCR validation on larger patient cohorts (n = 70) and statistical analysis with various clinicopathological parameters was conducted to assess the effectiveness of the identified miRNA signature. miRNA-mRNA networks and pathway analysis was conducted by integrating the transcriptome sequencing and TCGA data. The OECM-1 cell line was transfected with the identified miRNA signature in order to observe its effect on various functional mechanisms such as cell proliferation, cell cycle, apoptosis, invasive as well as migratory potential and the downstream signaling pathways regulated by these miRNA-mRNA networks. RESULTS: Small RNASeq and TCGA data identified 12 differentially expressed miRNAs in OSCC patients compared to controls. On validating these findings in a larger cohort of patients, miR-140-5p, miR-143-5p, and miR-145-5p were found to be significantly downregulated. This 3-miRNA signature demonstrated higher efficacy in predicting disease progression and clinically correlated with poor prognosis (p < 0.05). Transcriptome, TCGA, and miRNA-mRNA network analysis identified HIF1a, CDH1, CD44, EGFR, and CCND1 as hub genes regulated by the miRNA signature. Further, transfection-mediated upregulation of the 3-miRNA signature significantly decreased cell proliferation, induced apoptosis, resulted in G2/M phase cell cycle arrest and reduced the invasive and migratory potential by reversing the EMT process in the OECM-1 cell line. CONCLUSIONS: Thus, this study identifies a 3-miRNA signature that can be utilized as a potential biomarker for predicting disease progression of OSCC and uncovers the underlying mechanisms responsible for converting a normal epithelial cell into a malignant phenotype.

Grassroots Approach to Forming a Diversity, Equity, and Inclusion Committee in an Academic Radiology Department.

Radiology is among the medical specialties that have made the fewest gains in closing the gap in underrepresented minorities and women. Diversity, equity, and inclusion (DEI) initiatives are important for promoting healthy learning environments for trainees, health equity for patients, and equitable career development opportunities for employees, all of which contribute to innovation in today's competitive health care environment. DEI committees can self-organize or form from institutional directives. These committees can implement impactful projects in multiple domains in education, recruitment and retention, department culture, and health equity research. This article describes the formation of a grassroots DEI committee, key initiatives and strategies, and structures for accountability. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Human CD4 cytotoxic T lymphocytes mediate potent tumor control in humanized immune system mice.

Efficacy of immune checkpoint inhibitors in cancers can be limited by CD8 T cell dysfunction or HLA-I down-regulation. Tumor control mechanisms independent of CD8/HLA-I axis would overcome these limitations. Here, we report potent CD4 T cell-mediated tumor regression and memory responses in humanized immune system (HIS) mice implanted with HT-29 colorectal tumors. The regressing tumors showed increased CD4 cytotoxic T lymphocyte (CTL) infiltration and enhanced tumor HLA-II expression compared to progressing tumors. The intratumoral CD4 T cell subset associated with tumor regression expressed multiple cytotoxic markers and exhibited clonal expansion. Notably, tumor control was abrogated by depletion of CD4 but not CD8 T cells. CD4 T cells derived from tumor-regressing mice exhibited HLA-II-dependent and tumor-specific killing ex vivo. Taken together, our study demonstrates a critical role of human CD4 CTLs in mediating tumor clearance independent of CD8 T cells and provides a platform to study human anti-tumor immunity in vivo.

An unusual arrangement between the highest denticulate ligament and posterior inferior cerebellar artery.

The posterior inferior cerebellar artery (PICA) is often involved in pathologies of the posterior cranial fossa. Therefore, a good understanding of the vessel's normal and variant courses is important to the neurosurgeon or neurointerventionalist. During the routine microdissection of the craniocervical junction, an unusual arrangement between the highest denticulate ligament and PICA was observed. On the right side, the PICA was given rise to by the V4 segment of the vertebral artery 9 mm after the artery entered the dura mater of the posterior cranial fossa. The artery made an acute turn around the lateral edge of the highest denticulate ligament to then recur 180 degrees and travel medially toward the brainstem. Invasive procedures that target the PICA should be aware of the variant as described herein.

IL-6-GP130 signaling protects human hepatocytes against lipid droplet accumulation in humanized liver models.

Liver steatosis is an increasing health issue with few therapeutic options, partly because of a paucity of experimental models. In humanized liver rodent models, abnormal lipid accumulation in transplanted human hepatocytes occurs spontaneously. Here, we demonstrate that this abnormality is associated with compromised interleukin-6 (IL-6)-glycoprotein 130 (GP130) signaling in human hepatocytes because of incompatibility between host rodent IL-6 and human IL-6 receptor (IL-6R) on donor hepatocytes. Restoration of hepatic IL-6-GP130 signaling, through ectopic expression of rodent IL-6R, constitutive activation of GP130 in human hepatocytes, or humanization of an Il6 allele in recipient mice, substantially reduced hepatosteatosis. Notably, providing human Kupffer cells via hematopoietic stem cell engraftment in humanized liver mice also corrected the abnormality. Our observations suggest an important role of IL-6-GP130 pathway in regulating lipid accumulation in hepatocytes and not only provide a method to improve humanized liver models but also suggest therapeutic potential for manipulating GP130 signaling in human liver steatosis.

Post-COVID Multisystem Inflammatory Syndrome-Adult Leading to Cardiomyopathy and Autoimmune Thyroiditis: A Case Report.

The Coronavirus disease pandemic is an evolving disease with myriad presentations and sequelae. Multisystem inflammatory syndrome in adults (MIS-A) can affect various organ systems, including cardiovascular, gastrointestinal, and neurologic systems, with fever and abnormally increased inflammatory markers without significant respiratory affection. This is a well-known complication in children (MIS-C). Validated clinical criteria are used to diagnose this condition. Long-term sequelae of MIS-A are unclear and underreported. Here, we describe a case of Post-COVID-19 MIS-A who presented with cardiac dysfunction, hepatitis, and acute kidney injury and recovered well with steroids. He was left with persistent cardiomyopathy and thyroiditis with hypothyroidism which to date has not fully recovered. This case emphasizes that the sequelae of COVID-19 and its pathophysiology are not fully understood, and more research is needed to predict and prevent the same.

A masquerade: An uncommon presentation of a dual infection of leprosy and human immunodeficiency virus.

Leprosy and human immunodeficiency virus (HIV) often mimic clinical features of connective tissue disease (CTD). They can present such as lupus, rheumatoid arthritis, scleroderma, or overlap syndromes and it sometimes creates confusion about the diagnosis. Serology may not be enough to differentiate the two and effective tissue biopsies are often the answer. We report the case of a 38-year-old female, who presented clinically with features of multisystem involvement suspected to be CTD, but was found to have dual infection: HIV and borderline tuberculoid leprosy.

A study of clinical, radiological features and HLA-B27 serology of axial spondyloarthropathy with comparison of radiographic and non-radiographic disease.

Background: Axial spondyloarthropathy is a type of disease which affects the axial skeleton affecting productive years. Methods: This was a cross-sectional, observational study in which 28 consecutive patients more than 16 years of age, fulfilling the Assessment of SpondyloArthritis International Society (ASAS) criteria for axial spondyloarthropathy were included. They were further sub-grouped into radiographic and non-radiographic axial spondyloarthropathy. Clinical features, joint involvement, measurements, HLA-B27 serology, and disease activity were evaluated. Data was entered into Microsoft Excel, and SPSS (Statistical Package for Social Sciences) software 2.0 was used for analyzing the data. Results: Mean age was 28.5 ± 6.3 years. 85.7% were males. Inflammatory low back pain was the most common clinical feature at presentation (89.2%). Enthesitis was the most common extra-articular feature seen in 35.7% of patients. 42.8% were non-radiographic axial spondyloarthritis. 85.7% of patients were HLA-B27 positive. 50% of patients had bone marrow edema on MRI, and only one patient had ankylosis indicating predominantly early disease. 50%-70% of our patients had high disease activity and 89.3% were responding well to non-steroidal anti-inflammatory drugs (NSAIDs). There was no significant difference between the radiographic axial spondyloarthritis group and the non-radiographic group except for elevated C-reactive protein (CRP). Conclusion: Ankylosing spondylitis in western India occurs mostly in the age group of 20-30 years, suggesting affection of productive age group. There was a delay of diagnosis for approximately three years from the onset of symptoms. There was a positive association with HLA-B27 in majority of the patients. Most of our patients had early disease based on radiological findings, suggesting that there was room for therapeutic intervention before irreversible ankylosis had set in.

Quantification of Genome Editing and Transcriptional Control Capabilities Reveals Hierarchies among Diverse CRISPR/Cas Systems in Human Cells.

CRISPR/Cas technologies have revolutionized the ability to redesign genomic information and tailor endogenous gene expression. Nevertheless, the discovery and development of new CRISPR/Cas systems has resulted in a lack of clarity surrounding the relative efficacies among these technologies in human cells. This deficit makes the optimal selection of CRISPR/Cas technologies in human cells unnecessarily challenging, which in turn hampers their adoption, and thus ultimately limits their utility. Here, we designed a series of endogenous testbed systems to methodically quantify and compare the genome editing, CRISPRi, and CRISPRa capabilities among 10 different natural and engineered Cas protein variants spanning Type II and Type V CRISPR/Cas families. We show that although all Cas protein variants are capable of genome editing and transcriptional control in human cells, hierarchies exist, particularly for genome editing and CRISPRa applications, wherein Cas9 ≥ Cas12a > Cas12e/Cas12j. Our findings also highlight the utility of our modular testbed platforms to rapidly and systematically quantify the functionality of practically any natural or engineered genomic-targeting Cas protein in human cells.

Salivary Exosomal miRNA-1307-5p Predicts Disease Aggressiveness and Poor Prognosis in Oral Squamous Cell Carcinoma Patients.

Background: Salivary exosomal miRNAs as biomarkers facilitate repeated sampling, real-time disease monitoring and assessment of therapeutic response. This study identifies a single salivary exosomal miRNA prognosticator that will aid in improved patient outcome using a liquid biopsy approach. Method: Small RNA and transcriptome sequencing profiles of tumour tissues (n = 12) and salivary exosomes (n = 8) from oral cancer patients were compared to their non-cancerous counterparts. We validated these results using The Cancer Genome Atlas database and performing Real-time PCR on a large patient cohort (n = 19 tissue samples; n = 12 salivary exosomes). Potential target genes and the miRNA-mRNA networks and enriched biological pathways regulated by this microRNA were identified using computational tools. Results: Salivary exosomes (size: 30-50 nm) demonstrated a strong expression of CD47 and detectable expression of tetraspanins CD63, CD81 and CD9 by flow cytometry. miR-1307-5p was exclusively overexpressed in tissues and salivary exosomes of oral cancer patients compared to their non-cancerous counterparts. Enhanced expression of miR-1307-5p clinically correlated with poor patient survival, disease progression, aggressiveness and chemo-resistance. Transcriptome analysis suggested that miRNA-1307-5p could promote oral cancer progression by suppressing THOP1, EHF, RNF4, GET4 and RNF114. Conclusions: Salivary exosomal miRNA-1307-5p is a potential prognosticator for predicting poor survival and poor patient outcome in oral cancers.

Evaluating satisfaction with pharmacist-provided MTM services in a Medicaid population.

OBJECTIVES: Optimizing patient outcomes is a goal for medication therapy management (MTM) programs, with patient satisfaction representing a valuable measure to provide information about pharmacist-delivered services and the overall effectiveness of the program. The objective of this study was to assess patient satisfaction after engaging in a telephonic comprehensive medication review (CMR) with a pharmacist in a Medicaid population. STUDY DESIGN: This was a retrospective cohort study. METHODS: A quality assurance component of the MTM program was incorporated as a survey evaluating patient satisfaction. Three questions were administered at the conclusion of the CMR, with 2 questions conducted during a follow-up review. Of the 5 total questions, 2 were open response, 1 used a 5-point Likert scale, and 2 were yes/no questions. RESULTS: Response rates of 93.0% and 53.5% for the first and second halves of the survey, respectively, were achieved. Seventy-eight percent of patients indicated satisfaction with the MTM program, 63.5% reported that the medication review was helpful, and 80% reported experiencing a very good level of care. In addition, 59% found the patient takeaway documents received after the CMR to be helpful and 81% felt they had a better understanding of their medications. A subgroup analysis found that of the patients who reported feeling that the CMR was helpful, 66% were taking 7 or more medications. CONCLUSIONS: Overall, Medicaid patients in this study were very satisfied with the telephonic MTM services provided and found the information relayed during the conversation with the pharmacist to be helpful. Further studies are recommended to confirm these findings.

A Study of Haematological Profile in Newly Diagnosed Rheumatoid Arthritis and its Correlation with Disease Activity.

Rheumatoid Arthritis is a chronic inflammatory disease of unknown etiology characterised by presence of symmetric involvement of multiple joints, mainly small joints that rapidly progresses to multisystem inflammation. Common haematological abnormalities observed are anemia,leucocytosis, neutropenia, thrombocytosis, thrombocytopenia, eosinophilia and haematological malignancies. This study is aimed at the various haematological parameters observed in newly diagnosed patients of rheumatoid arthritis and correlating it with disease activity measured by indices like DAS 28 CRP and HAQDI. MATERIAL: Patients more than 16 years of age and newly diagnosed cases of rheumatoid arthritis according to the ACR EULAR 2010 criteria who presented in the rheumatology opd were included in the study. A total of 20 patients fulfilling the inclusion criteria were studied.Any patient with active blood loss from any site, infection,chronic liver or kidney disease, malignancies,hematological diseases,those already on disease modifying drugs,other autoimuune diseases were excluded from the study. OBSERVATION: Out of 20 patients of rheumatoid arthritis studied,55%(11) had anemia of chronic disease and 27.5%(5) had iron deficiency anemia,3%(1) had eosinophilia. The disease activity was measured using DAS 28 CRP and HAQ DI. A negative correlation was observed between Hb level and disease activity whereas a positive correlation was observed between platelet count and disease activity. CONCLUSION: In our study it was observed that Hb is significantly lower in patients with high disease activity whereas platelet count and MPV are significantly higher with high disease activity compared to patients with low to moderate disease activity.So, from Hb level, platelet count and MPV, we can predict disease activity in RA patients which can guide us for proper and aggressive management to prevent further disease progression.

Saliva Based Liquid Biopsies in Head and Neck Cancer: How Far Are We From the Clinic?

Head and neck cancer (HNC) remains to be a major cause of mortality worldwide because of confounding factors such as late-stage tumor diagnosis, loco-regional aggressiveness and distant metastasis. The current standardized diagnostic regime for HNC is tissue biopsy which fails to determine the thorough tumor dynamics. Therefore, due to the ease of collection, recent studies have focused on the utility of saliva based liquid biopsy approach for serial sampling, early diagnosis, prognosis, longitudinal monitoring of disease progression and treatment response in HNC patients. Saliva collection is convenient, non-invasive, and pain-free and offers repetitive sampling along with real time monitoring of the disease. Moreover, the detection, isolation and analysis of tumor-derived components such as Circulating Tumor Nucleic Acids (CTNAs), Extracellular Vesicles (EVs), Circulating Tumor Cells (CTCs) and metabolites from saliva can be used for genomic and proteomic examination of HNC patients. Although, these circulatory biomarkers have a wide range of applications in clinical settings, no validated data has yet been established for their usage in clinical practice for HNC. Improvements in isolation and detection technologies and next-generation sequencing analysis have resolved many technological hurdles, allowing a wide range of saliva based liquid biopsy application in clinical backgrounds. Thus, in this review, we discussed the rationality of saliva as plausible biofluid and clinical sample for diagnosis, prognosis and therapeutics of HNC. We have described the molecular components of saliva that could mirror the disease status, recent outcomes of salivaomics associated with HNC and current technologies which have the potential to improve the clinical value of saliva in HNC.