Esophageal lung associated with VACTERL anomaly: a case report

Esophageal lung is an extremely rare type of bronchopulmonary foregut malformation in which the main stem bronchus is anomalously connected to the esophagus instead of the trachea and is supplied by branches of pulmonary artery. Less than 25 cases have been reported so far in literature. We hereby report first case of esophageal lung associated with VACTREL anomaly. An 8-month-old female child with weight of 4.7 kg presented with recurrent lower respiratory infections. She was diagnosed to have esophageal lung on basis of clinical examination, chest X-ray f/b computed tomogram of chest and esophagobronchoscopy. There was a bifid vertebra at D9 level with scoliosis, an ectopic left kidney and dextrocardia with patent foramen ovale. Thus, this case was classified as having VACTREL association. Patient was successfully operated for excision of the hypoplastic lung via thoracotomy. She recovered well and gaining weight at 3 months f/u without any respiratory infection since surgery. High index of suspicion is necessary for the diagnosis of esophageal lung when common causes of recurrent respiratory infections are ruled out.

Direct Comparison of HPV16 Viral Genomic Integration, Copy Loss, and Structural Variants in Oropharyngeal and Uterine Cervical Cancers Reveal Distinct Relationships to E2 Disruption and Somatic Alteration

Squamous cell carcinoma of the oropharynx caused by HPV type 16 (HPV16+ OPSCC) is the most common HPV-associated malignancy in the USA and has many molecular differences from uterine cervical squamous cell carcinoma (UCSCC). Our understanding of HPV oncogenesis relied on studies of UCSCC revealing a consensus model reliant on HPV integration with a loss of E2. Here, we compare patterns of HPV integration in UCSCC and OPSCC by analysis of affinity capture sequencing of the HPV16 genome in 104 OPSCC and 44 UCSCC tumors. These cohorts were contemporaneously sequenced using an identical strategy. Integration was identified using discordant read pair clustering and assembly-based approaches. Viral integration sites, structural variants, and copy losses were examined. While large-scale deep losses of HPV16 genes were common in UCSCC and were associated with E2 loss, deep copy losses of the HPV16 genome were infrequent in HPV16+ OPSCC. Similarly, structural variants within HPV16 favored E2 loss in UCSCC but not OPSCC. HPV16 integration sites were non-random, with recurrent integration hot-spots identified. OPSCC tumors had many more integration sites per tumor when compared to UCSCC and had more integration sites in genomic regions with high gene density. These data show that viral integration and E2 disruption are distinct in UCSCC and OPSCC. Our findings also add to growing literature suggesting that HPV tumorigenesis in OPSCC does not follow the model developed based on UCSCC

Effect of Dapagliflozin in Patients with Heart Failure: A Systematic Review and Meta-Analysis

Background: Heart failure (HF) is a major cause of recurrent hospitalization and death worldwide. Sodium-glucose cotransporter-2 inhibitors including Dapagliflozin are anti-diabetic drugs with promising cardiovascular (CV) effects. We performed systematic review and meta-analysis of randomized controlled trials investigating the effects of Dapagliflozin in heart failure patients. Methods: We searched PubMed, Scopus and ScienceDirect databases. A total of 1,567 studies from January 2017 to September 10, 2022, were screened. After applying exclusion criteria, 22 studies were retrieved for full-text screening, and 9 of them were eligible for this meta-analysis. Effect estimates for dichotomous variables were expressed as risk ratio (RR) and 95% CI. The primary outcomes were the incidence of all-cause mortality, hospitalization due to HF and CV death. This review was registered on PROSPERO with ID CRD42022347793. Results: A total of 14,032 patients were included. The overall risk ratio of all-cause mortality favored the dapagliflozin group over the placebo/standard therapy group (RR= 0.89, 95% CI: 0.82 - 0.97, P=0.006) and the pooled studies were not heterogenous (I2= 0%). Additionally, Dapagliflozin significantly reduced the hospitalization due to heart failure (RR= 0.76, 95% CI: 0.70 – 0.84, P> 0.00001, I2= 0%), cardiovascular death (RR= 0.87, 95% CI: 0.78 – 0.97, P= 0.01, I2= 0%) and their composite outcomes. Conclusion: Dapagliflozin reduces the risk of all-cause mortality, heart failure hospitalizations and cardiovascular death in a wide range of heart failure patients

PARP inhibitor efficacy depends on CD8+ T cell recruitment via intratumoral STING pathway activation in BRCA-deficient models of triple-negative breast cancer.

Combinatorial clinical trials of PARP inhibitors with immunotherapies are ongoing, yet the immunomodulatory effects of PARP inhibition have been incompletely studied. Here, we sought to dissect the mechanisms underlying PARP inhibitor-induced changes in the tumor microenvironment of BRCA1-deficient triple-negative breast cancer (TNBC). We demonstrate that the PARP inhibitor olaparib induces CD8+ T cell infiltration and activation in vivo, and that CD8+ T cell depletion severely compromises anti-tumor efficacy. Olaparib-induced T cell recruitment is mediated through activation of the cGAS/STING pathway in tumor cells with paracrine activation of dendritic cells and is more pronounced in HR-deficient compared to HR-proficient TNBC cells and in vivo models. CRISPR-knockout of STING in cancer cells prevents proinflammatory signaling and is sufficient to abolish olaparib-induced T cell infiltration in vivo. These findings elucidate an additional mechanism of action of PARP inhibitors and provide rationale for combining PARP inhibition with immunotherapies for the treatment of TNBC

Coagulation Signaling through PAR1 as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with a 5-year survival rate of less than 10% following diagnosis. The aggressive and invasive properties of pancreatic cancer tumors coupled with poor diagnostic options contribute to the high mortality rate since most patients present with late-stage disease. Accordingly, PDAC is linked to the highest rate of cancer-associated venous thromboembolic disease of all solid tumor malignancies. However, in addition to promoting clot formation, recent studies suggest that the coagulation system in PDAC mediates a reciprocal relationship, whereby coagulation proteases and receptors promote PDAC tumor progression and dissemination. Here, upregulation of tissue factor (TF) by tumor cells can drive local generation of the central coagulation protease thrombin that promotes cell signaling activity through protease-activated receptors (PARs) expressed by both tumor cells and multiple stromal cell subsets. Moreover, the TF-thrombin-PAR1 signaling axis appears to be a major mechanism of cancer progression in general and PDAC in particular. Here, we summarize the current literature regarding the role of PAR1 in PDAC and review possibilities for pharmacologically targeting PAR1 as a PDAC therapeutic approach

Facial Scar Management by Hair Transplant: A Case Report

Facial scars in hair-bearing areas are a difficult problem to deal with owing to the nature of the scar tissue and the poor survivability of the grafts. A 26-year-old male presented with a scar on the right cheek area. The patient complained of recurrence and widening of scar and resultant facial asymmetry after serial excision in another hospital. The scar was the result of a burn injury sustained 15 years back. The scar was managed by using 2,642 hair grafts harvested from the scalp area. The patient had excellent hair growth at the end of 1 year with a high satisfaction level. There was a visible improvement in the lip deviation. Restoration of hair in the hair-bearing region of the face may be considered a permanent single-stage solution in such patients

Blockchain-based Healthcare Portal – A Bibliometric Analysis

User privacy has been a topmost priority and one such domain where this is neglected is the area of healthcare. Our solution focuses on the idea of using blockchain to provide a platform for healthcare experts and patients, giving patients full control over the data that will be shared. This paper focuses on identifying current research that has been conducted in this area in the form of a bibliometric analysis. A bibliometric study on a research area involves a detailed analysis of citations and papers across a domain of study. The purpose of this study is a statistical analysis of publications which is so complex that it is close to impossible to understand trends merely based on knowledge and experience. There are specific tools required to recognize these trends based on the bibliometric data. This paper will give an outlook on the areas of blockchain that were explored by various papers, the criteria and pattern followed by the combination of papers, and a cumulative statistical analysis of the papers that were fetched for the purpose of our study from the Scopus database. The most popular visualization software tool VOSviewer was taken into use

Optimization of Agrobacterium Mediated Genetic Transformation in Paspalum scrobiculatum L. (Kodo Millet)

An efficient and reproducible protocol for Agrobacterium tumefaciens mediated genetic transformation was developed for kodo millet (Paspalum scrobiculatum L.) by optimizing various parameters. Agrobacterium strains EHA 105 and LBA 4404 harboring plasmids pCNL 56 and pCAMBIA 2300, respectively, provided the highest transformation efficiency. Addition of acetosyringone (AS) in infection medium (200 µM-EHA 105, 250 µM-LBA 4404) and co-cultivation medium (50 µM) increased the transformation efficiency. Transient and stable expression of gus gene was confirmed with histochemical assay of infected embryos and leaves of transformed plants, respectively. The best GUS response was obtained by pretreatment of callus with an antinecrotic mixture (10 mg/L Cys + 5 mg/L Ag + 2.5 mg/L As) at infection time of 20 min followed by co-cultivation for 3 days (EHA 105) and 5 days (LBA 4404) in dark. Regenerated transgenic plants were obtained after 8 to 10 weeks of selection on callus induction medium (NAA 0.5 mg/L, BAP 1 mg/L) containing 50 mg/L Kan + 250 mg/L Cef and were rooted for 2 weeks on MS medium containing PAA (1 mg/L) and phytagel. The plantlets established in greenhouse showed normal growth. Therefore, the protocol developed in the present study can be used for development of improved varieties of kodo millet

Management of tubular oesophageal duplication - A novel approach

Background and aim: Oesophageal duplication is a rare congenital malformation which occurs due to embryogenesis errors. It accounts for 15% of all digestive tract duplications, most common being ileal duplications. Here we report a case of tubular Oesophageal duplication and a novel surgical approach for its management.6 year male child, 11 kgs, presented with progressive dysphagia to solids > liquids since birth. He had stunted growth, height and weight were less than 50th percentile. On investigations, Barium swallow and CECT neck with thorax was done to diagnose the pathology and define anatomy. It reported that the child had a congenital partial duplication of the proximal and mid esophagus with midline fold/membrane approximately 6 cm from C5 to D7 level with a dilated lower esophagus and a large hiatal hernia with focal stricture in the right lumen of proximal end. Surgical management was done by excision of oesophageal septum by endoscopic staplers via a gastrotomy under endoscopic guidance per orally and via gastrotomy. Results: Gradually diet started and well tolerated, to be kept on endoscopic surveillance. Conclusions: This is a novel approach to manage oesophageal tubular duplication with minimal risk of mediastinal complications that would occur otherwise by a thoracic approach