Uncovering the role of aquaporin and chromobox family members as potential biomarkers in head and neck squamous cell carcinoma via integrative multiomics and in silico approach.

Head and neck squamous cell carcinoma (HNSC) is a diverse group of tumors arising from oral cavity, oropharynx, larynx, and hypopharynx squamous epithelium, posing significant morbidity. Aquaporins (AQPs) are membrane proteins forming water channels, some associated with carcinomas. Chromobox (CBX) family is known to modulate physiological and oncological processes. In our study, we analyzed AQPs and CBXs having significant expression followed by their prognostic and mutational assessment. Next, we performed enrichment and tumor infiltration analysis followed by HPA validation. Lastly, we established a 3-node miRNA-TF-mRNA regulatory network and performed protein-protein docking of the highest-degree subnetwork motif between TF and mRNA. Significant upregulation of CBX3/2 and downregulation of AQP3/5/7 correlated with poor overall survival (OS) in HNSC patients. The most significant pathway, GO-BP, GO-MF, and GO-CC terms associated with AQP3 and CBX3 were passive transport by aquaporins, response to vitamin, glycerol channel activity, and condensed chromosome, centromeric region. AQP3 negatively correlated with [Formula: see text] T cells, positively with [Formula: see text] T cells and B cells, and negatively with tumor purity, whereas CBX3 positively correlated with [Formula: see text] T cells, negatively with [Formula: see text] T cells and B cells, and positively with tumor purity. Three-node miRNA-TF-mRNA regulatory network revealed a highest-degree subnetwork motif comprising one TF (SMAD3), one miRNA (miR-423-5p), and one mRNA (AQP3). Protein-protein interaction studies suggested a direct interaction between AQP3 and Smad3 proteins. We concluded that AQP3 and CBX3 hold potential as treatment strategies and individual prognostic biomarkers, while further protein-protein interaction studies of AQP3 could offer insights into its interactions with Smad3 proteins.

Venovenous extracorporeal membrane oxygenation after cardiac arrest for acute respiratory distress syndrome caused by Legionella: a case report.

BACKGROUND: Legionella remains underdiagnosed in the intensive care unit and can progress to acute respiratory distress syndrome (ARDS), multiorgan failure and death. In severe cases, venovenous extracorporeal membrane oxygenation (VV-ECMO) allows time for resolution of disease with Legionella-targeted therapy. VV-ECMO outcomes for Legionella are favorable with reported survival greater than 70%. Rapid molecular polymerase chain reaction (PCR) testing of the lower respiratory tract aids in diagnosing Legionella with high sensitivity and specificity. We present a unique case of a patient with a positive COVID-19 test and ARDS who suffered a cardiac arrest. The patient was subsequently cannulated for VV-ECMO, and after lower respiratory tract PCR testing, Legionella was determined to be the cause. She was successfully treated and decannulated from VV-ECMO after eight days. CASE PRESENTATION: A 53-year-old female presented with one week of dyspnea and a positive COVID-19 test. She was hypoxemic, hypotensive and had bilateral infiltrates on imaging. She received supplemental oxygen, intravenous fluids, vasopressors, broad spectrum antibiotics, and was transferred to a tertiary care center. She developed progressive hypoxemia and suffered a cardiac arrest, requiring ten minutes of CPR and endotracheal intubation to achieve return of spontaneous circulation. Despite mechanical ventilation and paralysis, she developed refractory hypoxemia and was cannulated for VV-ECMO. Dexamethasone and remdesivir were given for presumed COVID-19. Bronchoscopy with bronchoalveolar lavage (BAL) performed with PCR testing was positive for Legionella pneumophila and negative for COVID-19. Steroids and remdesivir were discontinued and she was treated with azithromycin. Her lung compliance improved, and she was decannulated after eight days on VV-ECMO. She was discharged home on hospital day 16 breathing room air and neurologically intact. CONCLUSIONS: This case illustrates the utility of rapid PCR testing to diagnose Legionella in patients with respiratory failure and the early use of VV-ECMO in patients with refractory hypoxemia secondary to Legionella infection. Moreover, many patients encountered in the ICU may have prior COVID-19 immunity, and though a positive COVID-19 test may be present, further investigation with lower respiratory tract PCR testing may provide alternative diagnoses. Patients with ARDS should undergo Legionella-specific testing, and if Legionella is determined to be the causative organism, early VV-ECMO should be considered in patients with refractory hypoxemia given reported high survival rates.

Nitric oxide as a double-edged sword in pulmonary viral infections: Mechanistic insights and potential therapeutic implications.

In the face of the global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), researchers are tirelessly exploring novel therapeutic approaches to combat coronavirus disease 2019 (COVID-19) and its associated complications. Nitric oxide (NO) has appeared as a multifaceted signaling mediator with diverse and often contrasting biological activities. Its intricate biochemistry renders it a crucial regulator of cardiovascular and pulmonary functions, immunity, and neurotransmission. Perturbations in NO production, whether excessive or insufficient, contribute to the pathogenesis of various diseases, encompassing cardiovascular disease, pulmonary hypertension, asthma, diabetes, and cancer. Recent investigations have unveiled the potential of NO donors to impede SARS-CoV- 2 replication, while inhaled NO demonstrates promise as a therapeutic avenue for improving oxygenation in COVID-19-related hypoxic pulmonary conditions. Interestingly, NO's association with the inflammatory response in asthma suggests a potential protective role against SARS-CoV-2 infection. Furthermore, compelling evidence indicates the benefits of inhaled NO in optimizing ventilation-perfusion ratios and mitigating the need for mechanical ventilation in COVID-19 patients. In this review, we delve into the molecular targets of NO, its utility as a diagnostic marker, the mechanisms underlying its action in COVID-19, and the potential of inhaled NO as a therapeutic intervention against viral infections. The topmost significant pathway, gene ontology (GO)-biological process (BP), GO-molecular function (MF) and GO-cellular compartment (CC) terms associated with Nitric Oxide Synthase (NOS)1, NOS2, NOS3 were arginine biosynthesis (p-value = 1.15 x 10-9) regulation of guanylate cyclase activity (p-value = 7.5 x 10-12), arginine binding (p-value = 2.62 x 10-11), vesicle membrane (p-value = 3.93 x 10-8). Transcriptomics analysis further validates the significant presence of NOS1, NOS2, NOS3 in independent COVID-19 and pulmonary hypertension cohorts with respect to controls. This review investigates NO's molecular targets, diagnostic potentials, and therapeutic role in COVID-19, employing bioinformatics to identify key pathways and NOS isoforms' significance.

Long non-coding RNA: An immune cells perspective.

Long non-coding RNAs (lncRNAs) were considered as accumulated genetic waste until they were found to be gene expression regulators by highly sensitive modern genomics platforms. It is a huge class of non-coding transcripts with an arbitrary length of >200 nucleotides, which has gained much attention in the past few years. Increasing evidence from several experimental studies unraveled the expression of lncRNA linked to immune response and disease progression. However, only a small number of lncRNAs have robust evidence of their function. Differential expression of lncRNAs in different immune cells is also evident. In this review, we focused on how lncRNAs expression assist in shaping immune cells (Macrophages, Dendritic cells, NK cells, T cells, B cells, eosinophils, neutrophils, and microglial cells) function and their response to the diseased conditions. Emerging evidence revealed lncRNAs may serve as key regulators in the innate and adaptive immune response system. So, the molecular mechanism insight into the function of lncRNAs in immune response may contribute to the development of potential therapeutic targets for various disease treatments. Therefore, it is imperative to explore the expression of lncRNAs and understand its relevance associated with the immune system.

Spontaneous uterine rupture at 22 weeks' gestation in a multipara with previous hysteroscopic resection of fibroid.

A 34-year-old multiparous woman presented at 22(+6) weeks' gestation with severe abdominal pain which preceded a mechanical fall down the stairs. On admission, fetal movements were felt and fetal heart rate was detected by Doppler ultrasound. Over the course of 12 h, although she maintained her vital signs, repeat laboratory and radiological investigations suggested sinister intra-abdominal pathology. Subsequently, fetal movements and heart rate ceased and the patient began to decompensate. A CT scan confirmed uterine rupture. Subsequent emergency laparotomy revealed a 2 l haemoperitoneum and lifeless fetoplacental unit in the abdominal cavity. It is postulated that this rupture occurred as a rare yet life-threatening complication of a hysteroscopic resection of fibroid that the patient underwent 1 year previously. There are no known published cases of a spontaneous uterine rupture following a hysteroscopic procedure at such an early gestation. The patient made a full physical recovery.

Etiology, functional status and short term outcome of patients with pituitary lesions. An experience from a developing country.

OBJECTIVE: To describe the etiology, functional status and short term outcome of patients with pituitary lesions (PL). METHODS: Brain or pituitary MRI reports of 3753 patients were analyzed for PL over the period of 2000 to 2007, done at the Aga Khan University Hospital (AKUH), Karachi, Pakistan. MRIs with reported PL and all those ordered by Endocrinologists with or without pituitary abnormalities, were included in the analysis. This made a total of 338 (9%) MRI reports. PL were defined as pituitary tumors, cysts, haemorrhage, hypoplasia; and empty sella. Patients with these PL, were analyzed for symptoms, hormonal profile and short term outcome in the hospital retrospectively. RESULTS: In the analysis of 338 MRI reports, 23% had normal pituitary gland on MRI examination. Hypogonadotrophic hypogonadism was the commonest (38.5%) endocrine abnormality seen with normal pituitary MRI, followed by hypopituitarism (5.1%). Most common PL identified were macroadenoma (38.7%), empty sella (16.5%) and microadenoma (12.7%). Patients with macroadenoma had 58% of non-functional tumours while 19.1% had hypopituitrism, 17.6% had acromegaly and 17.5% had prolactinoma. Majority of these lesions were causing headache and visual symptoms (42.7%) and were treated with surgery (75.5%). Patients with microadenoma included 39.5% prolactinomas, 18.6% cushing disease, 14% acromegaly, 4.7% hypogonadotrophic hypogonadism and 2.3% hypopituitrism. Majority of these lesions were treated with drugs and 37.3% were treated with surgery. In empty sella patients, 32% patients had endocrine abnormalities among which 21.4% had hypopituitrism, 2% had hypogonadotrophic hypogonadism, and only 6% patients had normal endocrine workup. A significant number of patients (62.5%) never had endocrine hormonal checkup. CONCLUSION: Although PL are less common entities (9% in 3,753 reports) but they are associated with significant endocrinal abnormalities and need prompt treatment. Empty sella, which is not considered as a distinct abnormality, is also associated with significant endocrine deficiencies.

Long-term patient satisfaction with prolapse surgery in general gynecology.

This retrospective cohort study aimed to explore the factors associated with long-term success of prolapse surgery in a general gynecology setting. A chart review was performed of 528 women who had had a total of 535 operations for prolapse at least 4 years earlier. Those who had not had further pelvic floor surgery were sent a questionnaire exploring their satisfaction with surgery. The outcome could be determined for 406 (75%) of the women, of whom 238 (59%) were improved. In multivariate analyses, women were more likely to be satisfied with surgery if they were older, did not have a prior or concurrent colposuspension, if the prolapse operation included a hysterectomy and if they were operated on by one particular team. Selection of the right operation for the correct patient by the correct surgeon could improve the success of prolapse surgery.

Comparison of clinico-radiological features of patients with positive cultures of nontuberculous mycobacteria and patients with tuberculosis.

OBJECTIVE: To identify the clinico-radiological features of patients with positive cultures for nontuberculous mycobacteria (NTM) and compare those to a sample of patients with tuberculosis (MTB). METHODS: A laboratory database was used to retrieve all specimens submitted to King Khalid University Hospital, Riyadh, mycobacteriology laboratory for mycobacterial smears and cultures during the period from October 1999-April 2002. Using this database, the original records of the mycobacteriology laboratory and a review of the patient's health records, a standard proforma was completed that included demographic, clinical, radiological and laboratory information on patients included in this study. The patients were divided into 2 groups; the NTM group, which included all patients with positive cultures for NTM and the MTB group, which included a sample of patients with documented tuberculosis. RESULTS: During the study period, 286 patients had positive mycobacterial cultures. Seventy patients (24.5%) grew NTM and 216 (75.5%) grew MTB. For patients with MTB, 54 patients were included as per the selection protocol of the study. There was no difference between the 2 groups in all measured demographic variables. The presence of weight loss and fever was significantly more in the MTB group. Radiologically, the presence of hilar adenopathy was more significant among patients with MTB than those with NTM (17% versus 4%, p=0.02). However, bronchiectatic changes were seen significantly more among NTM patients compared to patients with MTB (26% versus 11%, p=0.03). CONCLUSION: The isolation of NTM in the mycobacteriology laboratory is high. The clinico-radiological features were not sufficiently specific to differentiate patients with NTM from patients with MTB. Local studies are needed to explore NTM disease in various developing countries and identify the NTM species causing infections in non-immunosuppressed patients in each locality.