Gating machinery of InsP3R channels revealed by electron cryomicroscopy.

Inositol-1,4,5-trisphosphate receptors (InsP3Rs) are ubiquitous ion channels responsible for cytosolic Ca(2+) signalling and essential for a broad array of cellular processes ranging from contraction to secretion, and from proliferation to cell death. Despite decades of research on InsP3Rs, a mechanistic understanding of their structure-function relationship is lacking. Here we present the first, to our knowledge, near-atomic (4.7 Å) resolution electron cryomicroscopy structure of the tetrameric mammalian type 1 InsP3R channel in its apo-state. At this resolution, we are able to trace unambiguously ∼85% of the protein backbone, allowing us to identify the structural elements involved in gating and modulation of this 1.3-megadalton channel. Although the central Ca(2+)-conduction pathway is similar to other ion channels, including the closely related ryanodine receptor, the cytosolic carboxy termini are uniquely arranged in a left-handed α-helical bundle, directly interacting with the amino-terminal domains of adjacent subunits. This configuration suggests a molecular mechanism for allosteric regulation of channel gating by intracellular signals.

Urinothorax: A Rare Cause of Pleural Effusion.

Urinothorax is a rare cause of pleural effusion, which is seen in patients with obstructive uropathy, blunt trauma, or ureteric injury during abdominal surgical procedures. Clinical symptoms may include dyspnea, chest pain, cough, fever, abdominal pain, and decreased urine output. Diagnosis is made by thoracentesis, which would reveal fluid with a urine-like odor, and pleural fluid analysis, which would show if fluid is transudative in nature with a pH lower than 7.30. Pleural fluid to serum creatine ratio of more than 1 is diagnostic for this condition. In our case, the patient underwent percutaneous nephrolithotripsy with a stent placement three days before presentation to the hospital. She was diagnosed with urinothorax, which led to further investigations, and she was found to have persistent hydronephrosis. Her condition improved after her underlying hydronephrosis was addressed with stent placement. She was discharged home in stable condition.

Association of care by a non-medical intensive care unit provider team with outcomes of medically critically ill patients.

OBJECTIVE: To determine the association of boarding of critically ill medical patients on non-medical intensive care unit (ICU) provider teams with outcomes. DESIGN: A retrospective cohort study. SETTING: ICUs in a tertiary academic medical center. PATIENTS: Patients with medical critical illness. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We compared outcomes for critically ill medical patients admitted to a non-medical specialty ICU team (April 1 - August 30, 2020) with those admitted to the medical ICU team (January 1, 2018 - March 31, 2020). The primary outcome was hospital mortality; secondary outcomes were hospital length of stay (LOS) and hospital disposition for survivors. Our cohort consisted of 1241 patients admitted to the medical ICU team and 230 admitted to non-medical ICU teams. Unadjusted hospital mortality (medical ICU, 38.8% vs non-medical ICU, 42.2%, p = 0.33) and hospital LOS (7.4 vs 7.4 days, p = 0.96) were similar between teams. Among survivors, more non-medical ICU team patients were discharged home (72.6% vs 82.0%, p = 0.024). After multivariable adjustment, we found no difference in mortality, LOS, or home discharge between teams. However, among hospital survivors, admission to a non-medical ICU team was associated with a longer LOS (regression coefficient [95% CI] for log-transformed hospital LOS: 0.23 [0.05,0.40], p = 0.022). Certain subgroups-patients aged 50-64 years (odds-ratio [95% CI]: 4.22 [1.84,9.65], p = 0.001), with ≤10 comorbidities (0-5: 2.78 (1.11,6.95], p = 0.029; 6-10: 6.61 [1.38,31.71], p = 0.018), without acute respiratory failure (1.97 [1.20,3.23], p = 0.008)-had higher mortality when admitted to non-medical ICU teams. CONCLUSIONS: We found no association between admission to non-medical ICU team and mortality for medically critically ill patients. However, survivors experienced longer hospital LOS when admitted to non-medical ICU teams. Middle-aged patients, those with low comorbidity burden, and those without respiratory failure had higher mortality when admitted to non-medical ICU teams.

Spontaneous rupture of thymoma.

We report a case of patient who presented to the hospital due to shoulder pain and was later diagnosed with ruptured thymoma. Shortly after being admitted to the hospital for the work up patient developed respiratory distress and underwent emergent endotracheal intubation. CT scan of the chest showed anterior mediastinal mass with associated right sided hemothorax. He subsequently underwent medial sternotomy with resection of the mass which turned out to be thymoma.

Pulmonary strongyloidiasis causing septic shock in a patient with Crohn's disease.

A 58 years old male who was admitted to the intensive care unit for septic shock secondary to pneumonia, he has Crohn's disease currently treated with Vedolizumab and previously with infliximab. He was started on broad spectrum antibiotics and vasopressors for treatment of septic shock without improvement in the following days, sputum & blood cultures were negative. Bronchoscopy was done for non-resolving pneumonia work up, broncheoalveolar lavage smears and cultures were negative for bacteria, tuberculosis and Fungi. Bronchial washings cytology showed filariform larvae and serology was positive for Strongyloides, He was started on ivermectin and his condition improved significantly.

A Rare Case of Pulmonary Mucoepidermoid Carcinoma in an 81-Year-Old Male.

BACKGROUND Lung mucoepidermoid carcinoma is a form of non-small cell lung carcinoma that originates from the submucosal glands of the tracheobronchial tree; it is rare and causes 0.1% to 0.2% of lung malignancies. In this article, we report on an occurrence of this condition in an 81-year-old male, which is rare occurrence in this age group. In this case, we found a history of smoking and asbestos exposure which might suggest that exposure to both of these factors can possibly increase the risk for this malignancy. CASE REPORT An 81-year-old male presented with chronic cough and yellow sputum, associated with right upper back pain. The patient was a smoker of 30 packs per year and reported a history of asbestos exposure. He had past medical history of rectal cancer, but no previous history of salivary glands tumors. Physical examination was normal, laboratory investigations were unremarkable. Computed tomography chest showed endobronchial mass with post-obstructive atelectasis. Bronchoscopic evaluation revealed a whitish, endobronchial mass occluding the posterior segment of the right lower lobe. Biopsy showed benign squamous papilloma and malignancy was not excluded as only superficial parts of the mass were obtained. The decision was made to remove the lesion. A right lower lobectomy was done, and histopathology revealed a low grade mucoepidermoid carcinoma; immunohistochemical staining showed tumor cells positive for p40 and p63 supporting the diagnosis. No further adjuvant treatment was recommended, and follow-up imaging was planned for surveillance. CONCLUSIONS Mucoepidermoid carcinoma of the lung is a rare form of non-small cell lung carcinoma. Appropriate diagnosis requires correctly interpreted biopsy results along with immunohistochemical staining results.