L-Proline-catalysed synthesis of chromeno[2,3-b]chromene from 4-hydroxy-2H-chromene-2-thione and an anti-proliferative study.

The reactivity of 4-hydroxy-2H-chromene-2-thione is investigated with aryl aldehydes and 5,5-dimethylcylohexane-1,3-dione (dimedone) in the presence of 20 mol% L-proline in toluene at 90 °C. Instead of the expected linear product with a sulphur atom in the ring provided by 4-hydroxydithiocoumarin or an angular product obtained from 4-hydroxycoumarin, the hitherto unreported products, 12-aryl substituted chromeno[2,3-b]chromenes (4), were obtained in good to excellent yields. The reaction proceeds through a three-component reaction via Knoevenagel condensation between dimedone with an aromatic aldehyde followed by Michael addition with 4-hydroxy-2H-chromene-2-thione. In addition, a molecular docking study of all the derivatives was performed and among them, four compounds exhibited anti-proliferative activity and elevated ROS generation in breast cancer (MCF7) cell lines.

Scrub Typhus Presenting as Unilateral Abducens Nerve Palsy.

Scrub typhus, an acute febrile infectious disease prevalent in the "Tsutsugamushi Triangle", is a mite-born rickettsial zoonosis, caused by Orientia tsutsugamushi. Although the clinical presentation is protean, it rarely causes abducens nerve palsy. We report a 14-year-old previously healthy Indian girl who presented with a recent onset right abducens nerve palsy and headache, but without fever and without the classic dermatological manifestation ("eschar") of the disease. After exclusion of common infectious, autoimmune, and neoplastic causes, she was finally diagnosed with scrub typhus associated with an abducens nerve palsy, which responded to doxycycline therapy.

An unconventional route to an ambipolar azaheterocycle and its in situ generated radical anion.

Herein we report the synthesis, characterization and application of an azaheterocycle 4 obtained via an unprecedented C-N coupling. The neutral azaheterocycle undergoes one-electron reduction to form an air-stable radical anion in situ, which provides added benefit towards operational stability of the device during n-type charge transport. The unusual stability of this radical anion is due to the fact that the fused cyclopentane ring upon reduction forms aromatic cyclopentadienyl anion, and the negative charge delocalizes over the nearly planar azaheterocycle core. The present azaheterocycle can be considered as a mimic of a fullerene fragment, which shows balanced ambipolar charge transport in space charge limited current (SCLC) devices with moderate hole (µh) and electron (µe) mobilities (µh = 2.96 × 10-3 cm2 V-1 s-1 and µe = 1.11 × 10-4 cm2 V-1 s-1). Theoretical studies such as nucleus independent chemical shifts (NICS) calculations, anisotropy of the induced current density (ACID) plots, spin density mapping and anisotropic mobility calculations were performed to corroborate the experimental findings.

Association of Germline Variants in Natural Killer Cells With Tumor Immune Microenvironment Subtypes, Tumor-Infiltrating Lymphocytes, Immunotherapy Response, Clinical Outcomes, and Cancer Risk.

Importance: Only a small fraction of patients with cancer receiving immune checkpoint therapy (ICT) respond, which is associated with tumor immune microenvironment (TIME) subtypes and tumor-infiltrating lymphocytes (TILs). Objective: To examine whether germline variants of natural killer (NK) cells, a key component of the immune system, are associated with TIME subtypes, the abundance of TILs, response to ICT, clinical outcomes, and cancer risk. Design, Setting, and Participants: This genetic association study explored TIME subtypes and examined the association of the germline genomic information of patients with cancer with TIME subtypes, abundance of TILs, response to ICT, prognosis, and cancer risk. Clinical information, tumor RNA sequencing, and whole-exome sequencing (WES) data of paired normal samples of patients with 13 common cancers (n = 5883) were obtained from the Cancer Genome Atlas. The WES data of individuals with no cancer (n = 4500) were obtained from the database of Genotypes and Phenotypes. Data collection and analysis took place in March 2017. Main Outcomes and Measures: Associations between the number of germline defective genes in NK cells and survival time and the abundance of TILs. Results: Based on tumor RNA sequencing data, tumors were stratified into TIME-rich, TIME-intermediate, and TIME-poor subtypes. Tumors of TIME-rich subtype had more TILs (TIL-NK cells in TIME-rich head and neck squamous cell carcinoma [HNSC] tumors: t = 4.85; 95% CI of the difference, 0.01-0.03; P = 2.19 × 10-6) compared with TIME-intermediate HNSC tumors (t = 3.70; 95% CI of the difference, 0.01-0.03; P < .001), better prognosis (patients with HNSC: hazard ratio, 0.65; 95% CI, 0.41-1.02; P = .054) compared with TIME-intermediate and TIME-poor subtypes, and better ICT response (patients with melanoma: odds ratio [OR], 4.45; 95% CI, 0.99-27.08; P = .04). Patients with TIME-rich tumors had significantly fewer inherited defective genes in NK cells than patients with TIME-intermediate and TIME-poor tumors (patients with HNSC: OR, 0.49; 95% CI, 0.26-1.07; P = .005). Similarly, patients with cancer had significantly more inherited defective genes in NK cells than individuals with no cancer (patients with HNSC: OR, 19.09; 95% CI, 4.30-315.96; P = 6.21 × 10-4). Among 11 of 13 common cancers, the number of heritable defective genes in NK cells was significantly negatively associated with survival (patients with HNSC: hazard ratio, 1.77; 95% CI, 1.18-2.66; P = .005), abundance of TILs (patients with HNSC: R = -0.25; 95% CI, -0.65-2.17; P = 0.02), and response to ICT (patients with melanoma: OR, 4.45; 95% CI, 0.99-27.08; P = .04). Conclusions and Relevance: These results suggest that individuals who have more inherited defective genes in NK cells had a higher risk of developing cancer and that these inherited defects were associated with TIME subtypes, recruitment of TILs, ICT response, and clinical outcomes. The findings have implications for identifying individuals at risk for developing cancer of many types based on germline variants of NK cells and for improving existing ICT and chimeric antigen receptor-T cell therapy by adoptive transfer of healthy NK cells to patients with TIME-intermediate and TIME-poor tumors.

Comparative Evaluation of Antiplaque Efficacy between Essential Oils with Alcohol-Based and Chlorhexidine with Nonalcohol-Based Mouthrinses.

AIM AND OBJECTIVES: The aim of this study is to compare the antiplaque efficacy of alcohol-based mouthwash with essential oils and nonalcohol-based chlorhexidine mouthrinse in 4 days plaque re-formation study. MATERIALS AND METHODS: The current research paper is double-blinded, parallel designed clinical trial that was conducted in the Department of Periodontics and Oral Implantology, Kalinga Institute of Dental Sciences, Bhubaneswar. This included ninety dental students of Bachelor of Dental Surgery curriculum (in the age range from 20 to 24 years) Professional cleaning with scaling and polishing was carried out to acquire a zero plaque and gingival index (GI) for all ninety patients at baseline. Ninety patients were randomly divided into three groups with thirty patients in each group named as Group A, B, and C, respectively. Two commercially available mouthrinses, one containing alcohol (labeled as Solution (A) and one without alcohol (labeled as Solution (B) were placed in identical bottles and distributed to Group A and Group B patients. Whereas, the Group C patientswere instructed to use warm saline mouth rinse. The statistical analysis was performed using the Statistical Package for the Social Sciences software (Version 18). RESULTS: Essential oils with an alcohol-based and chlorhexidine (CHX) alcohol-free mouthrinse (0.2%) groups compared to normal saline showed significant reductions in GI and PI scores.(P < 0.0001). CONCLUSION: The antiplaque efficacy of both alcohol-based mouthwash with essential oils and nonalcohol based CHX mouthwash were found to be equally effective in 4 days of plaque re-formation.

Ventral herniation due to tuberculosis at space of Retzius: a rare presentation.

Tuberculosis may involve any organ in the body and extra-pulmonary tuberculosis is commonly seen in immuno-compromised patients mostly in developing countries. Here we report an unusual case of tuberculosis of space of retzius (pre-peritoneal space) forming a lump, this lump caused weakness of anterior abdominal wall which later developed ventral hernia, corrected by surgery in a 62-year immuno-competent person. This type of presentation of extra-pulmonary tuberculosis at space of Retzius has been rarely reported.

Small Bowel Obstruction in a Neurofibromatosis Patient-A Rare Presentation of Gastro-Intestinal Stromal Tumors (GISTs): Case Report and Literature Review.

Gastrointestinal stromal tumours (GISTs) are infrequently encountered, mesenchymal tumours of the gastrointestinal tract of varying malignant potential. Multiple (in hundreds) small intestinal GISTs have been reported to occur only very occasionally in patients with type 1 neurofibromatosis (NF1). They are mostly silent, often detected incidentally or when complicated by bleeding or other symptoms. Such a case of multiple jejunal GISTs causing small bowel obstruction in a patient with NF1 is described and relevant literatures are briefly discussed.