BackgroundHypoxia causes remodeling and contractile responses in both pulmonary artery (PA) and pulmonary vein (PV). Here we explore the effect of hypoxia on PV and pulmonary venous smooth muscle cells (PVSMCs).MethodsChronic hypoxic pulmonary hypertension (CHPH) model was established by exposing rats to 10% O2 for 21 days. Rat distal PVSMCs were isolated and cultured for in vitro experiments. The fura-2 based fluorescence calcium imaging was used to measure the basal intracellular Ca2+ concentration ([Ca2+]i) and store-operated Ca2+ entry (SOCE). Quantitative RT-PCR and western blotting were performed to measure the expression of mRNA and levels of canonical transient receptor potential (TRPC) protein respectively.ResultsHypoxia increased the basal [Ca2+]i and SOCE in both freshly dissociated and serum cultured distal PVSMCs. Moreover, hypoxia increased TRPC6 expression at mRNA and protein levels in both cultured PVSMCs exposed to prolonged hypoxia (4% O2, 60 h) and distal PV isolated from CHPH rats. Hypoxia also enhanced proliferation and migration of rat distal PVSMCs.ConclusionsHypoxia induces elevation of SOCE in distal PVSMCs, leading to enhancement of basal [Ca2+]i in PVSMCs. This enhancement is potentially correlated with the increased expression of TRPC6. Hypoxia triggered intracellular calcium contributes to promoted proliferation and migration of PVSMCs.
As the first Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines passed United Kingdom and United States regulatory milestones in late 2020 and early 2021, multiple professional societies offered recommendations to assist pregnant and breastfeeding people as they choose whether to undergo vaccination. Despite such guidance, the lack of data describing vaccine safety, immunogenicity, and efficacy in pregnant and breastfeeding people has made this decision challenging for many. However, even considering the paucity of data, the known risks of Coronavirus Disease 2019 (COVID-19) during pregnancy likely outweigh the not yet fully elucidated risks of SARS-CoV-2 vaccines, which have reassuring safety and efficacy profiles among non-pregnant people.
Prosthetic joint infections are a serious complication of joint replacement surgery due to the significant morbidity and financial burden that is associated with conventional treatments. When patients fail the gold standard two-stage revision surgery, very limited, well-defined standardized approaches are available. Herein, we discuss the case of a sixty-four-year-old woman who had a recalcitrant MRSA prosthetic joint infection of her knee and hip that failed repeated conventional surgical and medical treatments. Only after receiving intraoperative and intravenous bacteriophage therapy was the patient able to achieve cure of her prosthetic joint infections, as demonstrated by the lack of clinical recurrence and sterility of intraoperative cultures while off antibiotics. This case reinforces that bacteriophage therapy holds promise in the treatment of prosthetic joint infections and more specifically in complicated cases who have failed conventional surgical and medical interventions.
Background: Chronic respiratory disease-associated pulmonary hypertension (PH) is an important subtype of PH, which lacks clinical epidemiological data in China. Methods: Six hundred and ninety three patients hospitalized from 2010 to 2013 were classified by echocardiography according to pulmonary arterial systolic pressure (PASP): mild (36≤ PASP <50 mmHg); moderate (50≤ PASP <70 mmHg) and severe (PASP ≥70 mmHg). Results: Dyspnea (93.51%) was the most common symptom. Hemoptysis observed in the severe group (6.42%) was significantly higher than the other two groups (P<0.05). COPD (78.35%), lung bullae (44.16%), tuberculosis (including obsolete pulmonary tuberculosis) (38.82%), and bronchiectasis (30.45%) were frequently present. Mild group occupied the highest proportion (84.7%) in COPD, while severe group occupied the highest proportion (19.3%) in pulmonary embolism (P<0.01). Age, partial pressure of oxygen (PaO 2 ), hematocrit (HCT), partial pressure of carbon dioxide (PaCO 2 ), increase of N-terminal pro brain natriuretic peptide (NT-proBNP) and right ventricular (RV) diameter (>20 mm) were associated with moderate-to-severe PH, while RV [odds ratio (OR) =3.53, 95% CI, 2.17-5.74], NT-proBNP (OR=2.44, 95% CI, 1.51-3.95), HCT (OR=1.03, 95% CI, 1.00-1.07) and PaCO 2 (OR=1.01, 95% CI, 1.00-1.03) were independent risk factors. Conclusions: PH related to respiratory diseases is mostly mild to moderate, and the severity is associated with the category of respiratory disease. Increased HCT can be an independent risk factor for PH related to chronic respiratory diseases.
AimsWhile the SARS-CoV-2 pandemic may be contained through vaccination, transfusion of convalescent plasma (CCP) from individuals who recovered from COVID-19 (CCP) is considered an alternative treatment. We investigate if CCP transfusion in patients with severe respiratory failure increases plasma titres of SARS-CoV-2 antibodies and improves clinical outcomes.MethodsPatients with COVID-19 (n=34) were consented for CCP transfusion and serial blood draws pretransfusion and post-transfusion. Plasma SARS-CoV-2 antireceptor binding domain (RBD) IgG and IgM titres were measured by ELISA serially, and compared with serial plasma titre levels from control patients (n=68). The primary outcome was survival at 30 days, and secondary outcomes were length of ventilator and/or extracorporeal membrane oxygenation (ECMO) support, length of stay (LOS) in the hospital and in the intensive care unit (ICU). Outcomes were compared with matched control patients (n=34). Kinetics of antibodies and clinical outcomes were compared using LOess regression and ORs, respectively.ResultsPrior to CCP transfusion, 74% of patients were anti-RBD seropositive for IgG (median 1:3200), and 81% were anti-RBD IgM seropositive (median 1:320), while 16% were seronegative. The kinetics of antibody titres in CCP recipients were similar to controls. CCP recipients presented with similar survival, duration on ventilatory and/or ECMO support, as well as ICU and hospital LOS compared with controls.ConclusionsCCP transfusion did not increase the kinetics of SARS-CoV2 antibodies and did not result in improved clinical outcomes in patients with COVID-19 with severe respiratory failure, suggesting that CCP may not be indicated in this category of patients.
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