The Curious Case of a Painful Leg Ulcer.

Sickle cell disease is a condition that can involve numerous organ systems secondary to vascular occlusion. Herein, we present a case of a 21-year-old male with sickle cell disease requiring long-term hydroxyurea therapy. Upon migrating to the United States from Yemen, the patient developed a rapidly progressive, exquisitely painful ulcer on his right lower extremity. Given his country of origin, a broad differential, including select infectious diseases, was essential. Moreover, establishing the unequivocally correct diagnosis was crucial to determine proper and safe therapy. Ultimately, a lesional biopsy demonstrated numerous sickled red blood cells occluding blood vessels, leading to the diagnosis of sickle cell disease-related leg ulceration.

Single-Cell RNA Sequencing Reveals Dysregulated POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis.

Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. We performed single-cell transcriptomic profiling of 28,695 lesional and nonlesional PN cells. Lesional PN has increased dysregulated fibroblasts (FBs) and myofibroblasts. FBs in lesional PN were shifted toward a cancer-associated FB-like phenotype, with POSTN+WNT5A+ cancer-associated FBs increased in PN and similarly so in squamous cell carcinoma. A multicenter cohort study revealed an increased risk of squamous cell carcinoma and cancer-associated FB-associated malignancies (breast and colorectal) in patients with PN. Systemic fibroproliferative diseases (renal sclerosis and idiopathic pulmonary fibrosis) were upregulated in patients with PN. Ligand-receptor analyses demonstrated an FB neuronal axis with FB-derived WNT5A and periostin interactions with neuronal receptors melanoma cell adhesion molecule and ITGAV. These findings identify a pathogenic and targetable POSTN+WNT5A+ FB subpopulation that may predispose cancer-associated FB-associated malignancies in patients with PN.

Single-cell RNA sequencing reveals dysregulated fibroblast subclusters in prurigo nodularis.

Prurigo nodularis (PN) is an intensely pruritic, chronic inflammatory skin disease that disproportionately affects black patients. However, the pathogenesis of PN is poorly understood. We performed single-cell transcriptomic profiling, ligand receptor analysis and cell trajectory analysis of 28,695 lesional and non-lesional PN skin cells to uncover disease-identifying cell compositions and genetic characteristics. We uncovered a dysregulated role for fibroblasts (FBs) and myofibroblasts as a key pathogenic element in PN, which were significantly increased in PN lesional skin. We defined seven unique subclusters of FBs in PN skin and observed a shift of PN lesional FBs towards a cancer-associated fibroblast (CAF)-like phenotype, with WNT5A+ CAFs increased in the skin of PN patients and similarly so in squamous cell carcinoma (SCC). A multicenter PN cohort study subsequently revealed an increased risk of SCC as well as additional CAF-associated malignancies in PN patients, including breast and colorectal cancers. Systemic fibroproliferative diseases were also upregulated in PN patients, including renal sclerosis and idiopathic pulmonary fibrosis. Ligand receptor analyses demonstrated increased FB1-derived WNT5A and periostin interactions with neuronal receptors MCAM and ITGAV, suggesting a fibroblast-neuronal axis in PN. Type I IFN responses in immune cells and increased angiogenesis/permeability in endothelial cells were also observed. As compared to atopic dermatitis (AD) and psoriasis (PSO) patients, increased mesenchymal dysregulation is unique to PN with an intermediate Th2/Th17 phenotype between atopic dermatitis and psoriasis. These findings identify a pathogenic role for CAFs in PN, including a novel targetable WNT5A+ fibroblast subpopulation and CAF-associated malignancies in PN patients.

Pd single-atom-site stabilized by supported phosphomolybdic acid: design, characterizations and tandem Suzuki-Miyaura cross coupling/nitro hydrogenation reaction.

Herein, a single-metal (Pd) site with high surface energy was stabilized and dispersed on a support (zirconia) via a stabilizing agent (phosphomolybdic acid) using a wet chemistry method. HRTEM and HAADF-STEM showed a highly uniform dispersion of Pd SASc on PMA/ZrO2. The Pd SASc showed superior catalytic activity (>99% conversion) for the Suzuki-Miyaura cross-coupling reaction, which was further feasible for catalyzing mechanistically different nitro hydrogenation reactions in tandem fusion under mild reaction conditions. This catalyst showed outstanding activity (100% conversion and 99% selectivity) with a substrate/catalyst ratio of 927 and TON of 918 using a very low amount of Pd (0.94 × 10-3 mmol) for the tandem Suzuki-Miyaura cross-coupling/nitro hydrogenation reaction. It also exhibited superior stability and reusability for up to three cycles without any change in its activity.

Role of Citrullinated Collagen in Autoimmune Arthritis.

Citrullination of proteins plays an important role in protein function and it has recently become clear that citrullinated proteins play a role in immune responses. In this study we examined how citrullinated collagen, an extracellular matrix protein, affects T-cell function during the development of autoimmune arthritis. Using an HLA-DR1 transgenic mouse model of rheumatoid arthritis, mice were treated intraperitoneally with either native type I collagen (CI), citrullinated CI (cit-CI), or phosphate buffered saline (PBS) prior to induction of autoimmune arthritis. While the mice given native CI had significantly less severe arthritis than controls administered PBS, mice receiving cit-CI had no decrease in the severity of autoimmune arthritis. Using Jurkat cells expressing the inhibitory receptor leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), Western blot analysis indicated that while CI and cit-CI bound to LAIR-1 with similar affinity, only CI induced phosphorylation of the LAIR ITIM tyrosines; cit-CI was ineffective. These data suggest that cit-CI acts as an antagonist of LAIR-1 signaling, and that the severity of autoimmune arthritis can effectively be altered by targeting T cells with citrullinated collagen.

Complications associated with peripherally inserted central catheters in paediatric cardiac patients.

OBJECTIVES: To characterise the use of peripherally inserted central catheters in paediatric cardiac patients and to identify risk factors associated with their complications. MATERIALS AND METHODS: Observational retrospective cohort study in paediatric cardiac patients who underwent peripherally inserted central catheter placement in a tertiary children's hospital from January 2000 to June 2018. RESULTS: 1822 cardiac patients underwent 2952 peripherally inserted central catheter placements in the study period. Median age was 29 days, with survival to hospital discharge of 96.4%. Successful placement achieved 94.5% of attempts, with a median line duration of 12 days. Factors associated with successful placement were the use of general anaesthesia (odds ratio 7.52, p < 0.001) and year of placement (odds ratio 1.08, p < 0.001). The incidence of complications was 28.6%, with thrombosis/occlusion being the most frequent (33%). Thrombosis/occlusion were associated with two and three lumens (odds ratio 1.96, p < 0.001 and 4.63, p = 0.037, respectively). Lines placed by interventional radiology had decreased infiltration (odds ratio 0.20, p = 0.002) and lower migration/malposition (odds ratio 0.36, p < 0.001). The use of maintenance intravenous fluids (odds ratio 3.98, p = 0.008) and peripheral tip position (odds ratio 3.82, p = 0.001) were associated with increased infiltration. The probability of infection decreased over time (odds ratio 0.79, p < 0.001). CONCLUSION: Peripherally inserted central catheters in paediatric cardiac patients have complication rates similar to other paediatric populations. A prospective assessment of the factors associated with their complications in this patient population may be beneficial in improving outcomes.

Cardiovascular Events After Partner Bereavement, What is the Role of Low Dose Aspirin and Beta-Blockers?

Bereavement due to loss of a partner is one of the most stressful life events, often leading to adverse physiological responses. Spousal loss has been associated with an increased morbidity and mortality, particularly from cardiovascular disease. Use of aspirin and/or beta adrenergic blockers have previously been suggested to play a role in cardiovascular risk associated with early bereavement. However, the available literature regarding this topic is limited. In this review article, we explore the potential beneficial role of aspirin and beta blockers in early bereavement. Our systematic review suggests that most studies have found aspirin and beta blockers to be beneficial in preventing adverse cardiovascular outcomes associated with early bereavement. Further randomized controlled long-term studies are warranted with adequate sample size to clearly establish the role of these medications on cardiovascular disease in late bereavement.

Mind-Body Connection: Cardiovascular Sequelae of Psychiatric Illness.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the world. Mental health disorders are associated with the onset and progression of cardiac disease. The adverse sequelae of this association include worsened quality of life, adverse cardiovascular outcomes, and heightened mortality. The increased prevalence of CVD is partly explained by increased rates of traditional cardiovascular risk factors including hypertension, hyperlipidemia, diabetes mellitus, obesity, and smoking, but mental illness is an independent risk factor for CVD and mortality. Given the association between mental health disorders and poor cardiovascular health, it is vital to have an early and accurate identification and treatment of these disorders. Our review article shares the current literature on the adverse cardiovascular events associated with psychiatric disorders. We present a review on depression, anxiety, bipolar disorder, schizophrenia, type A and D personality disorders, obsessive-compulsive disorder, and stress.

Costs incurred by patients with oral potentially malignant disorders: is there a public health need for financial protection in India?

OBJECTIVES: Financial protection mechanisms are in place to overcome the costs of a few diseases in India. Our objective was to estimate the costs incurred due to Oral Potentially Malignant Disorders (OPMD) and to determine predictors of such costs. RESULTS: We found that the median (Interquartile range IQR) total costs of OPMD was Indian Rupees (INR) 500 (350-750), direct medical costs was INR 0 (0-50), direct non-medical costs was INR 150 (40-200) and indirect costs was INR 350 (250-500). The travel cost to attend the health facilities [INR 100 (40-150)] and the patient's loss of wages [INR 200 (150-400)] mainly accounted for the direct non-medical and indirect costs respectively. The median expenditure on smokeless and smoking forms of tobacco was INR 6000 (5400-7200) and INR 2400 (1800-3600) respectively. On multiple linear regression analysis, rural residence, belonging to below poverty line family, being a sole earner in the family, number of months since diagnosis and first visit at a private provider were found to be the significant predictors of total costs of OPMD. Financial protection mechanisms are needed for covering the direct non-medical and indirect costs. Early management of OPMD might mitigate the costs of OPMD.

Chronic Systemic Inflammatory Skin Disease as a Risk Factor for Cardiovascular Disease.

Chronic systemic skin disease and cardiovascular disease are multisystem disorders which have been associated with each other for centuries. Recent research has strengthened this association, particularly in systemic inflammatory disease. Here we explore the current literature on psoriasis, hidradenitis suppurativa, lupus erythematosus, acanthosis nigricans, atopic dermatitis, and bullous pemphigoid. Psoriasis is a chronic inflammatory disorder that has been labeled as a risk-modifier for hyperlipidemia and coronary artery disease by the American College of Cardiology ACC lipid guidelines. Cardiovascular disease is also found at a significantly higher rate in patients with hidradenitis suppurativa and lupus erythematosus. Some associations have even been noted between cardiovascular disease and acanthosis nigricans, atopic dermatitis, and bullous pemphigoid. While many of these associations have been attributed to a shared underlying disease process such as chronic systemic inflammation and shared underlying risk factors, these dermatologic manifestations can help to identify patients at higher risk for cardiovascular disease.

Efficacy and safety of supplemental intravenous lidocaine for sedation in gastrointestinal endoscopic procedures: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Some studies have shown that intravenous (IV) lidocaine reduces the dose requirement of propofol in GI endoscopic procedures. We conducted this study to evaluate the efficacy and safety of the combination of IV lidocaine and propofol compared with propofol alone in GI endoscopic procedures. METHODS: We reviewed several databases from inception to October 13, 2020, to identify randomized controlled trials (RCTs) that compared the role of IV propofol and lidocaine with IV propofol plus placebo for sedation in endoscopic procedures. Our outcomes of interest were the differences in total dose of propofol administered, procedure time, and intraoperative adverse events. For categorical variables, we calculated pooled risk ratios with 95% confidence intervals (CI); for continuous variables, we calculated standardized mean difference (SMD) with 95% CI. Data were analyzed using a random effect model. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework to ascertain the quality of evidence. RESULTS: We included 5 randomized controlled trials with 318 patients. We found that the total dose of propofol administered was significantly lower in the lidocaine group than the control group (SMD, -0.76; 95% CI, -1.09 to -0.42). We found no significant difference in procedure time (SMD, 0.16; 95% CI, -0.26 to 0.57) or adverse events (risk ratio, 0.60; 95% CI, 0.35-1.03) between the groups. There was moderate to substantial heterogeneity in the data. Quality of evidence based on the GRADE framework ranged from low to moderate. CONCLUSIONS: Moderate quality of evidence suggests that IV lidocaine decreases the dose of propofol administered for GI endoscopic procedures.

Knowledge and perceptions about COVID-19 among the medical and allied health science students in India: An online cross-sectional survey.

BACKGROUND: An infection (COVID-19) without any specific cure makes the people more vulnerable to get affected due to insufficient knowledge and unhealthy practices. In this scenario, healthcare students can act as reliable information providers. This study aimed to assess the knowledge and perception about COVID-19 among medical and allied health science students. METHODS: A web-based cross sectional survey was conducted during February and March 2020. A 24-item survey was developed and randomly distributed among the study population. Descriptive statistics was applied to represent participant characteristics and Chi-square test was used to evaluate the level of association among variables with a significance level of p < 0.01. RESULTS: Total, 97.95% (715/730) participants completed the survey. High proportion of students were from pharmacy (45.73%) followed by medical (22.52%), physiotherapy, nursing and dental background. Majority of participants were having adequate knowledge while about 18% had partial knowledge about the symptoms of severe COVID-19 cases. Students have shown a positive perception of COVID-19 prevention and control while few invalid responses related to the use of herbal medicines or garlic were noted. About 50% had rightly stated that, the antibiotics and vaccine are not effective in COVID-19 infection at present. CONCLUSION: As the COVID-19 cases are rapidly increasing worldwide, it is essential to improve the knowledge and beliefs among general public to prevent its spread. Health care students with their education background and basic understanding about COVID-19 can play a significant role by making community people aware about the seriousness of this pandemic situation.

Evaluation of efficacy of an inactivated vaccine against bovine respiratory syncytial virus in calves with maternal antibodies.

OBJECTIVE: To assess short- and long-term efficacy of an inactivated bovine respiratory syncytial virus (BRSV) vaccine administered i.m. to calves with maternally derived antibodies. ANIMALS: 28 two-week-old calves with neutralizing, maternally derived antibodies against BRSV. PROCEDURE: For evaluation of short-term efficacy, 6 calves were vaccinated i.m. at 2 and 6 weeks of age and challenged intranasally and intratracheally along with a matched group of 4 unvaccinated control calves at 10 weeks of age. For evaluation of long-term efficacy, 2 groups of 6 calves each were vaccinated i.m. at 2, 6, and 18 weeks of age or 14 and 18 weeks of age; these calves were challenged intranasally and intratracheally along with 6 matched unvaccinated control calves at 43 weeks of age. Serum virus neutralizing antibody titer, clinical reactions, and virus shedding in nasal mucus and lung washings were assessed. RESULTS: None of the vaccination regimens resulted in a significant increase in serum virus neutralizing antibody titer. As judged by virus shedding in nasal mucus and lung washings, vaccinated calves were protected against challenge, compared with unvaccinated control groups. Clinical signs attributable to challenge were coughing (short-term efficacy study) and tachypnea and dyspnea (long-term efficacy study). The severity and incidence of disease were significantly lower in the vaccinated groups, compared with that in the unvaccinated groups. CONCLUSIONS AND CLINICAL RELEVANCE: Through vaccination, it is possible to protect vulnerable calves with maternal antibodies against BRSV infection and reduce respiratory tract disease.