Exposure to secondhand smoke promotes sympathetic activity and cardiac muscle cachexia

Recent trials demonstrated that a single brief exposure to secondhand smoke (SHS) generates acute adverse health effects. We evaluated the acute (immediately after exposure) and short-term (0.5, 1, 2, 3 and 4?h after exposure) effects of SHS on cardiac autonomic control and myocardial integrity. Nineteen adult healthy never-smokers underwent a 1?h exposure to SHS at bar/restaurant levels and a 1?h control exposure. Heart rate variability (HRV), serum cotinine, and six cardiac protein markers were assessed before, during, and up to four hours following each exposure. SHS reduced the standard deviation of normal-to-normal intervals and increased cotinine levels, creatine kinase (CK)-MB, and myoglobin (p?相似文献   

Preferential production of IgG1, IL-4 and IL-10 in MuSK-immunized mice

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness associated with acetylcholine receptor (AChR), muscle-specific receptor kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4)-antibodies. MuSK-antibodies are predominantly of the non-complement fixing IgG4 isotype. The MuSK associated experimental autoimmune myasthenia gravis (EAMG) model was established in mice to investigate immunoglobulin (Ig) and cytokine responses related with MuSK immunity. C57BL/6 (B6) mice immunized with 30 μg of recombinant human MuSK in incomplete or complete Freund's adjuvant (CFA) showed significant EAMG susceptibility (> 80% incidence). Although mice immunized with 10 μg of MuSK had lower EAMG incidence (14.3%), serum MuSK-antibody levels were comparable to mice immunized with 30 μg MuSK. While MuSK immunization stimulated production of all antibody isotypes, non-complement fixing IgG1 was the dominant anti-MuSK Ig isotype in both sera and neuromuscular junctions. Moreover, MuSK immunized IgG1 knockout mice showed very low serum MuSK-antibody levels. Sera and MuSK-stimulated lymph node cell supernatants of MuSK immunized mice showed significantly higher levels of IL-4 and IL-10 (but not IFN-γ and IL-12), than those of CFA immunized mice. Our results suggest that through activation of Th2-type cells, anti-MuSK immunity promotes production of IL-4, which in turn activates anti-MuSK IgG1, the mouse analog of human IgG4. These findings might provide clues for the pathogenesis of other IgG4-related diseases as well as development of disease specific treatment methods (e.g. specific IgG4 inhibitors) for MuSK-related MG.     

Autonomic Nervous System Neuroanatomical Alterations Could Provoke and Maintain Gastrointestinal Dysbiosis in Autism Spectrum Disorder (ASD): A Novel Microbiome–Host Interaction Mechanistic Hypothesis

Dysbiosis secondary to environmental factors, including dietary patterns, antibiotics use, pollution exposure, and other lifestyle factors, has been associated to many non-infective chronic inflammatory diseases. Autism spectrum disorder (ASD) is related to maternal inflammation, although there is no conclusive evidence that affected individuals suffer from systemic low-grade inflammation as in many psychological and psychiatric diseases. However, neuro-inflammation and neuro–immune abnormalities are observed within ASD-affected individuals. Rebalancing human gut microbiota to treat disease has been widely investigated with inconclusive and contradictory findings. These observations strongly suggest that the forms of dysbiosis encountered in ASD-affected individuals could also originate from autonomic nervous system (ANS) functioning abnormalities, a common neuro–anatomical alteration underlying ASD. According to this hypothesis, overactivation of the sympathetic branch of the ANS, due to the fact of an ASD-specific parasympathetic activity deficit, induces deregulation of the gut–brain axis, attenuating intestinal immune and osmotic homeostasis. This sets-up a dysbiotic state, that gives rise to immune and osmotic dysregulation, maintaining dysbiosis in a vicious cycle. Here, we explore the mechanisms whereby ANS imbalances could lead to alterations in intestinal microbiome–host interactions that may contribute to the severity of ASD by maintaining the brain–gut axis pathways in a dysregulated state.     

Prophylaxis of cancer-associated venous thromboembolism with low-molecular-weight heparin-tinzaparin: Real world evidence

Thromboprophylaxis, as a preventive measure for cancer-associated thrombosis (CAT), may be beneficial for patients with active cancer and high-risk for thrombosis. The present post hoc analysis include a total of 407 patients enrolled in the Greek Management of Thrombosis study, who received thromboprophylaxis with tinzaparin. The objectives of the present analysis were: i) To obtain sufficient evidence for the administration of prophylaxis in patients with active cancer, irrespective of Khorana risk assessment model score; ii) to identify the selection criteria for both dose and duration of tinzaparin; and iii) to evaluate the efficacy and safety of tinzaparin administered for CAT prophylaxis. The main tumor types for the patients included in the present study were as follows: Lung (25.1%), pancreatic (14.3%), breast (9.1%), stomach (8.4%), colorectal (7.9%) and ovarian (7.6%). Furthermore, metastatic disease was observed in 69.5% of the patients. High thrombotic burden agents (HTBAs) were administered to 66.3% of the patients, and 17.4% received erythropoietin. A total of 43.7% of the patients exhibited a Khorana score <2. The results of the present study demonstrated that both the presence of metastatic disease and the use of HTBAs seemed to influence oncologists'' decisions for the use of thromboprophylaxis in patients with active cancer, regardless of Khorana score. Tinzaparin, in dose expressed in the standard notation for heparins, i.e., anti-Xa factor international units (Anti-Xa IU), was administered at an intermediate dose (InterD; 8,000-12,000 Anti-Xa IU; once daily) to 52.4% of patients, while the remaining patients received a prophylactic dose (ProD; ≤4,500 Anti-Xa IU; once daily). The average duration of thromoprophylaxis was 5 months. Furthermore, a total of 14 (3.4%) thrombotic events and 6 (1.5%) minor bleeding events were recorded. A total of four thrombotic events were observed following an InterD treatment of tinzaparin, while 10 thrombotic events were observed following ProD treatment. The present study also demonstrated that an InterD of tinzaparin was administered more frequently to patients with a body mass index >30 kg/m², a history of smoking and a history of metastatic disease, along with administration of erythropoietin. InterD tinzaparin treatment was found to be potentially more efficacious and without safety concerns. The present study is a registered clinical trial (ClinicalTrials.gov code, {"type":"clinical-trial","attrs":{"text":"NCT03292107","term_id":"NCT03292107"}}NCT03292107; registration date, September 25, 2017).     

Transition as a topic in psychiatry training throughout Europe: trainees’ perspectives

European Child & Adolescent Psychiatry - The majority of adolescents with mental health problems do not experience continuity of care when they reach the transition boundary of their child and...     

Management of cutaneous side effects of EGFR inhibitors: recommendations from a German expert panel for the primary treating physician

Inhibitors of the epidermal growth factor receptor (EGFR) are increasingly used in the treatment of various entities of malignant tumors. Patients treated with EGFR inhibitors very likely develop cutaneous side effects. The development of a papulopustular, follicular exanthema during the first weeks of therapy correlates with therapeutic benefit. However, this exanthema and other cutaneous side effects can impair the quality of life of the patient and might limit the therapy with the EGFR inhibitor. For an optimal therapeutic benefit and quality of life an adequate management of cutaneous side effects is necessary. A panel of German dermatologists developed on the basis of personal experience and current literature consensus recommendations for the management of cutaneous side effects of EGFR inhibitors.     

Pandemic and precocious puberty - a Google trends study

BACKGROUND Recent publications from several countries have reported that more young people(mainly girls) are experiencing precocious puberty(PP)/menarche during the coronavirus disease 2019 pandemic compared to the past. This variation is attributed to the stress of confinement, lack of exercise, obesity and disturbed sleep patterns. A common feature of the relevant papers, however, is the small number of reported cases of PP. Studies have shown that searches for diseases on the internet also re...     

History of Biliary Surgery

Since ancient times biliary surgery has been one of the major interests of doctors and other scientists around the world. From the ancient Greeks and Egyptians to the greatest scientists of modern times biliary surgery has advanced remarkably. Especially during the last century huge progress has been made in this field. Minimally invasive surgical techniques have been developed and combined with general anesthesia and antisepsis that have made biliary surgery particularly safe for every patient and have made cholecystectomy one of the most common operations in the world today.     

Infected femoral artery pseudoaneurysm in drug addicts: the beneficial use of the internal iliac artery for arterial reconstruction

BACKGROUND: Infected femoral artery pseudoaneurysm (IFAP) is a severe complication in parenteral drug abusers, with difficult and controversial management. Ligation alone without revascularization is frequently associated with later intermittent claudication and limb amputation. Furthermore, arterial reconstruction with a synthetic or venous conduit is limited because of a contaminated field and, often, unavailability of autologous venous grafts. In this study, we present our experience with the internal iliac artery (IIA) as a graft for arterial reconstruction after IFAP excision in these patients. METHODS: Data of 14 consecutive patients who presented with IFAP secondary to parenteral drug abuse from 2001 to 2005 were analyzed. Twelve patients (85.7%) were male. The median age was 27 years (range, 19-42 years). In 13 cases, the IFAP involved the common femoral artery, and in 1 case it involved the profunda femoris artery (PFA). In nine patients, we used the IIA for arterial reconstruction (five as a patch and four as an interposition graft), whereas in two patients the arterial deficit was repaired with a great saphenous vein patch. In two cases, an extra-anatomic bypass with a synthetic polytetrafluoroethylene graft was performed. In one patient, the pseudoaneurysm involved the PFA and was treated with excision and ligation of the PFA. RESULTS: All nine patients who underwent revascularization with the use of IIA were free of claudication symptoms. None of them experienced any perioperative complications, had signs of reinfection, or required limb amputation during the follow-up period (median, 19 months; range, 4-52 months). Regarding the remaining five patients, one died 25 days after surgery because of multiorgan failure, and one underwent reoperation because of proximal anastomotic rupture of a synthetic graft. The latter patient finally underwent a transmetatarsal amputation. CONCLUSIONS: The use of IIA for arterial reconstruction after IFAP excision in drug abusers is safe and effective. These preliminary results indicate that the implementation of this technique offers many advantages compared with traditional treatment options.