Valvular heart disease in Antiphospholipid antibody syndrome: Isolated Tricuspid stenosis

Antiphospholipid antibody syndrome (APLS) is a rare disorder characterized by a hypercoagulable state. Manifestations include arterial or venous thrombosis, recurrent fetal wastage, coronary artery disease, valvular heart disease, dilated cardiomyopathy, pulmonary artery hypertension, and intracardiac thrombus. Most commonly mitral valve is affected followed by aortic and then tricuspid valve. In this report, a rare case of spontaneous aortic thrombosis with tricuspid stenosis uncomplicated by other valve lesions is presented with clinical and echocardiographic studies and computed tomographic images.     

Malignant progression of B16 melanoma cells induced in vitro by growth factors produced by highly malignant cells

Four mouse B16 melanoma subclones (G3.15, G3.5, G3.12 and G3.26) exhibit progressively greater growth capacity in vitro and in vivo. Previously, non-metastatic G3.15 cells were sequentially converted, in monolayer cultures, to the moderately-metastatic G3.5 cells, and then to a highly-metastatic G3.5^* phenotype. Both conversions were induced by hypoxia followed by confluence, and also occurred in tumors. G3.5^* cells were comparable with, yet distinguishable from, G3.12 cells in being growth-autonomous in culture. In this study, the presumption that rapidly-growing G3.26 cells represented the ultimate progression step in this clonal system was examined. Both G3.12 and G3.5^* cells converted in vitro to the G3.26 phenotype during growth in serum-free medium conditioned by G3.26 cell growth. By selective filtration of conditioned medium and characterization of the stability of growth- and conversion-promoting activities, three distinct activities were found to promote a two-step G3.12 to G3.26 phenotype conversion: (1) a < 10 kDa filtrate stimulated slight attachment and proliferation of G3.12 cells, effects that were reversible, partly attributable to accumulated lactate, and fully mimicked by medium acidification to pH 6.5; (2) medium acidification, together with a heat- and acid-stable but partially trypsin-sensitive > 10 kDa activity, induced G3.12 G3.5^* conversion that resulted in acquisition of growth autonomy; and (3) a heat-, acid- and trypsin-sensitive > l0 kDa activity induced G3.5^* G3.26 conversion, characterized by anchorage-independent growth in soft agar, and potent lung colonization following intravenous injection. Phenotype analysis of G3.12 tumors and lung metastases revealed that G3.5^*-like cells were regularly present in tumors and metastases, whereas G3.26-like cells occurred almost exclusively in large lung metastases. While G3.12 cells might convert to G3.5^* cells in order to disseminate, G3.26 cells are apparently not involved in metastatic spread but probably account for the rapid growth of established metastases.     

Kinetics of the nitrogen dioxide initiated polymerization of acrylic acid

Acrylic acid (AA) was polymerized with NO₂ in tetrahydrofuran (THF) and in 1,4-dioxane. The effects of monomer and initiator concentration and of temperature on polymer conversion, initial rate of polymerization, and molecular weight were studied. The overall activation energy of polymerization was found to be 16,3 kcal mol^?1 (68,23 kJ · mol^?1) and 15,54 kcal · mol^?1 (65,05 kJ · mol^?1) in THF and in 1,4-dioxane, respectively. High molecular weight polymers (M ca. 10⁵) were obtained. The polymerization appears to be initiated by free radicals.     

Association of obesity with illness severity in hospitalized patients with COVID-19: A retrospective cohort study

BackgroundAlthough recent studies have shown an association between obesity and adverse coronavirus disease 2019 (COVID-19) patient outcomes, there is a paucity in large studies focusing on hospitalized patients. We aimed to analyze outcomes associated with obesity in a large cohort of hospitalized COVID-19 patients.MethodsWe performed a retrospective study at a tertiary care health system of adult patients with COVID-19 who were admitted between March 1 and April 30, 2020. Patients were stratified by body mass index (BMI) into obese (BMI ≥ 30 kg/m 2) and non-obese (BMI < 30 kg/m 2) cohorts. Primary outcomes were mortality, intensive care unit (ICU) admission, intubation, and 30-day readmission.ResultsA total of 1983 patients were included of whom 1031 (51.9%) had obesity and 952 (48.9%) did not have obesity. Patients with obesity were younger (P < 0.001), more likely to be female (P < 0.001) and African American (P < 0.001) compared to patients without obesity. Multivariable logistic models adjusting for differences in age, sex, race, medical comorbidities, and treatment modalities revealed no difference in 60-day mortality and 30-day readmission between obese and non-obese groups. In these models, patients with obesity had increased odds of ICU admission (adjusted OR, 1.37; 95% CI, 1.07?1.76; P = 0.012) and intubation (adjusted OR, 1.37; 95% CI, 1.04?1.80; P = 0.026).ConclusionsObesity in patients with COVID-19 is independently associated with increased risk for ICU admission and intubation. Recognizing that obesity impacts morbidity in this manner is crucial for appropriate management of COVID-19 patients.     

Pyridine: the scaffolds with significant clinical diversity

The nitrogen-bearing heterocycle pyridine in its several analogous forms occupies an important position as a precious source of clinically useful agents in the field of medicinal chemistry research. This privileged scaffold has been consistently incorporated in a diverse range of drug candidates approved by the FDA (Food and Drug Administration). This moiety has attracted increasing attention from several disease states owing to its ease of parallelization and testing potential pertaining to the chemical space. In the next few years, a larger share of novel pyridine-based drug candidates is expected. This review unifies the current advances in novel pyridine-based molecular frameworks and their unique clinical relevance as reported over the last two decades. It highlights an inclination to the use of pyridine-based molecules in drug crafting and the subsequent emergence of several potent and eligible candidates against a range of diversified diseases.

The nitrogen-bearing heterocycle pyridine in its several analogous forms occupies an important position as a precious source of clinically useful agents in the field of medicinal chemistry research.     

Pure Sertoli cell tumor of the ovary: A case report

Pure Sertoli cell tumors are an uncommon variant of rare ovarian Sertoli‐Leydig cell tumors. Due to nonspecific clinical and imaging features, diagnosis is often made after histopathological examination. The prognosis is excellent as most are detected in the early stages and surgical resection is often curative in most cases.     

Reverse Swiss Roll technique for diabetic vitreous membranes

Background:Diabetic membranes are always a challenge for a surgeon because of sticky nature and chances of iatrogenic break while removing.Purpose:To demonstrate a safe reverse swiss roll technique to dissect diabetic vitreous membranes.Synposis:Approaches and techniques for membrane dissection are segmentation, delamination and en-bloc dissection using various types of instruments and illumination. With vitreous cutte, picks and scissors, surgical steps are traditionallu performed by using classic lift and shave technique. After identifying the plane, tissue is lifted and then cut, which puts the retina at risk of break because of traction and active suction. Such a threat can be reduced by placing the cutter above the membrane thereby having the membrane itseld acting as a protective cushion to the retina. Port here, unlike lift and shave technique, doesn’t face the edge of membrane but is exactly 180 degree opposite and membrane curls into port because of suction. Also, hemostasis is maintained by continuous aspiration and cutting as the instrument is moved side to side, retracting from the edge.Highlights:Reverse swiss roll technique is safer compared to lift and shave because of the safety cushion of the membrane between the port and the retina. There is inherently less chances of retinal break because the active suction from the port is directed away from the retina. The technique also minimises traction and localised pull on the atrophic macula.Video link: https://youtu.be/WNnSsP69ZLw     

The ALK inhibitor ASP3026 eradicates NPM-ALK+ T-cell anaplastic large-cell lymphoma in vitro and in a systemic xenograft lymphoma model

NPM-ALK⁺ T-cell anaplastic large-cell lymphoma (ALCL) is an aggressive type of cancer. Standard treatment of NPM-ALK⁺ ALCL is CHOP polychemotherapy. Although patients initially respond favorably to CHOP, resistance, relapse, and death frequently occur. Recently, selective targeting of ALK has emerged as an alternative therapeutic strategy. ASP3026 is a second-generation ALK inhibitor that can overcome crizotinib resistance in non-small cell lung cancer, and is currently being evaluated in clinical trials of patients with ALK⁺ solid tumors. However, NPM-ALK⁺ ALCL patients are not included in these trials. We studied the effects of ASP3026 on NPM-ALK⁺ ALCL cell lines in vitro and on systemic lymphoma growth in vivo. ASP3026 decreased the viability, proliferation, and colony formation, as well as induced apoptotic cell death of NPM-ALK⁺ ALCL cells. In addition, ASP3026 significantly reduced the proliferation of 293T cells transfected with NPM-ALK mutants that are resistant to crizotinib and downregulated tyrosine phosphorylation of these mutants. Moreover, ASP3026 abrogated systemic NPM-ALK⁺ ALCL growth in mice. Importantly, the survival of ASP3026-treated mice was superior to that of control and CHOP-treated mice. Our data suggest that ASP3026 is an effective treatment for NPM-ALK⁺ ALCL, and support the enrollment of patients with this lymphoma in the ongoing clinical trials.