In the past 25 years, major advances were achieved in the nosography of cardiomyopathies, influencing the definition and taxonomy of this important chapter of cardiovascular disease. Nearly, 50% of ...patients dying suddenly in childhood or adolescence or undergoing cardiac transplantation are affected by cardiomyopathies. Novel cardiomyopathies have been discovered (arrhythmogenic, restrictive, and noncompacted) and added to update the World Health Organization classification. Myocarditis has also been named inflammatory cardiomyopathy. Extraordinary progress accomplished in molecular genetics of inherited cardiomyopathies allowed establishment of dilated cardiomyopathy as mostly cytoskeleton, force transmission disease; hypertrophic-restrictive cardiomyopathies as sarcomeric, force generation disease; and arrhythmogenic cardiomyopathy as desmosome, cell junction disease. Channelopathies (short and long QT, Brugada, and catecholaminergic polymorphic ventricular tachycardia syndromes) should also be considered cardiomyopathies because of electric myocyte dysfunction. Cardiomyopathies are easily diagnosed but treated only with palliative pharmacological or invasive therapy. Curative therapy, thanks to insights into the molecular pathogenesis, has to target the fundamental mechanisms involved in the onset and progression of these conditions.
While multiple studies have examined the brain functional correlates of reward, meta-analyses have either focused on studies using the monetary incentive delay (MID) task, or have adopted a broad ...strategy, combining data from studies using both monetary and non-monetary reward, as probed using a wide range of tasks. To meta-analyze fMRI studies that used monetary reward and in which there was a definable cue-reward contingency. Studies were limited to those using monetary reward in order to avoid potential heterogeneity from use of other rewards, especially social rewards. Studies using gambling or delay discounting tasks were excluded on the grounds that reward anticipation is not easily quantifiable. Ovid, Medline and PsycInfo, from 2000 to 2020, plus checking of review articles and meta-analyses. Pooled data from 45 studies of reward anticipation revealed activations in the ventral striatum, the middle cingulate cortex/supplementary motor area and the insula. Pooled data from 28 studies of reward delivery again revealed ventral striatal activation, plus cortical activations in the anterior and posterior cingulate cortex. There was relatively little evidence of publication bias. Among moderating variables, only whether the task was pre-learnt exerted an influence. According to this meta-analysis monetary reward anticipation and delivery both activate the ventral but not the dorsal striatum, and are associated with different patterns of cortical activation.
Schizophrenia has often been conceived as a disorder of connectivity between components of large-scale brain networks. We tested this hypothesis by measuring aspects of both functional connectivity ...and functional network topology derived from resting-state fMRI time series acquired at 72 cerebral regions over 17 min from 15 healthy volunteers (14 male, 1 female) and 12 people diagnosed with schizophrenia (10 male, 2 female). We investigated between-group differences in strength and diversity of functional connectivity in the 0.06-0.125 Hz frequency interval, and some topological properties of undirected graphs constructed from thresholded interregional correlation matrices. In people with schizophrenia, strength of functional connectivity was significantly decreased, whereas diversity of functional connections was increased. Topologically, functional brain networks had reduced clustering and small-worldness, reduced probability of high-degree hubs, and increased robustness in the schizophrenic group. Reduced degree and clustering were locally significant in medial parietal, premotor and cingulate, and right orbitofrontal cortical nodes of functional networks in schizophrenia. Functional connectivity and topological metrics were correlated with each other and with behavioral performance on a verbal fluency task. We conclude that people with schizophrenia tend to have a less strongly integrated, more diverse profile of brain functional connectivity, associated with a less hub-dominated configuration of complex brain functional networks. Alongside these behaviorally disadvantageous differences, however, brain networks in the schizophrenic group also showed a greater robustness to random attack, pointing to a possible benefit of the schizophrenia connectome, if less extremely expressed.
To evaluate the technical feasibility and safety of video-assisted thoracic surgery (VATS) lobectomy for small lung cancers.
The Cancer and Leukemia Group B 39802 trial was a prospective, ...multi-institutional study designed to elucidate the technical feasibility of VATS in early non-small-cell lung cancer (NSCLC) using a standard definition for VATS lobectomy (one 4- to 8-cm access and two 0.5-cm port incisions) that mandated videoscopic guidance and a traditional hilar dissection without rib spreading. Between 1998 and 2001, 128 patients with peripheral lung nodules < or = 3 cm in size with suspected NSCLC were prospectively registered for VATS lobectomy.
One hundred twenty-seven patients (66 males and 61 females; median age, 66 years; range, 37 to 86 years), with a performance status of 0 (74%) or 1 (26%), underwent surgery. Patients with lymph nodes more than 1 cm by computed tomography scan underwent mediastinal lymph node sampling to rule out N2 disease. One hundred eleven patients (87%) had stage I lung cancer, and 96 (86.5%) of these 111 patients underwent successful VATS lobectomies. The median procedure length was 130 minutes (range, 47 to 428 minutes), and median chest tube duration was 3 days (range, 1 to 14 days). Fifty-eight (60%) of 97 patients underwent diagnostic biopsy at lobectomy. Within 30 days, three (2.7%) of 111 patient deaths occurred, none of which were directly related to VATS technique; seven (7.4%) of 95 patients had grade 3 or greater complications, with only one case of bleeding.
A standardized approach to VATS lobectomy as specifically defined with avoidance of rib spreading is feasible.
Organelle identity depends on protein composition. How mistargeted proteins are selectively recognized and removed from organelles is incompletely understood. Here, we found that the orphan ...P5A-adenosine triphosphatase (ATPase) transporter ATP13A1 (Spf1 in yeast) directly interacted with the transmembrane segment (TM) of mitochondrial tail-anchored proteins. P5A-ATPase activity mediated the extraction of mistargeted proteins from the endoplasmic reticulum (ER). Cryo-electron microscopy structures of
Spf1 revealed a large, membrane-accessible substrate-binding pocket that alternately faced the ER lumen and cytosol and an endogenous substrate resembling an α-helical TM. Our results indicate that the P5A-ATPase could dislocate misinserted hydrophobic helices flanked by short basic segments from the ER. TM dislocation by the P5A-ATPase establishes an additional class of P-type ATPase substrates and may correct mistakes in protein targeting or topogenesis.
Although many video-assisted thoracic surgery (VATS) lobectomies have been performed over the 12 years since the first VATS lobectomy, controversies about the procedure remain regarding the safety ...and associated morbidity and mortality of that procedure. This series is reviewed to assess these issues.
Between 1992 and 2004, we performed 1,100 VATS lobectomies in 595 women (54.1%) and 505 men (45.9%), with a mean age of 71.2 years. Diagnoses were as follows: benign disease (53), pulmonary metastases (27), lymphoma (5), and lung cancer (1,015). Of the primary lung cancers, 641 (63.1%) were adenocarcinoma. With visualization on a monitor, anatomic hilar dissection and lymph node sampling or dissection were performed, primarily through a 5-cm incision without spreading the ribs.
There were 9 deaths (0.8%), and none was intraoperative or due to bleeding; 932 patients had no postoperative complications (84.7%). Blood transfusion was required in 45 of 1,100 patients (4.1%). Length of stay was median 3 days (mean, 4.78). One hundred eighty patients (20%) were discharged on postoperative day 1 or 2. Conversion to a thoracotomy occurred in 28 patients (2.5%). Recurrence developed in the incisions in 5 patients (0.57%). In 2003, 89% of 224 lobectomies were performed with VATS.
VATS lobectomy with anatomic dissection can be performed with low morbidity and mortality rates. The risk of intraoperative bleeding or recurrence in an incision seems minimal.
Cognitive-behavioural therapy (CBT) is considered to be effective for the symptoms of schizophrenia. However, this view is based mainly on meta-analysis, whose findings can be influenced by failure ...to consider sources of bias.
To conduct a systematic review and meta-analysis of the effectiveness of CBT for schizophrenic symptoms that includes an examination of potential sources of bias.
Data were pooled from randomised trials providing end-of-study data on overall, positive and negative symptoms. The moderating effects of randomisation, masking of outcome assessments, incompleteness of outcome data and use of a control intervention were examined. Publication bias was also investigated.
Pooled effect sizes were -0.33 (95% CI -0.47 to -0.19) in 34 studies of overall symptoms, -0.25 (95% CI -0.37 to -0.13) in 33 studies of positive symptoms and -0.13 (95% CI -0.25 to -0.01) in 34 studies of negative symptoms. Masking significantly moderated effect size in the meta-analyses of overall symptoms (effect sizes -0.62 (95% CI -0.88 to -0.35) v. -0.15 (95% CI -0.27 to -0.03), P = 0.001) and positive symptoms (effect sizes -0.57 (95% CI -0.76 to -0.39) v. -0.08 (95% CI -0.18 to 0.03), P<0.001). Use of a control intervention did not moderate effect size in any of the analyses. There was no consistent evidence of publication bias across different analyses.
Cognitive-behavioural therapy has a therapeutic effect on schizophrenic symptoms in the 'small' range. This reduces further when sources of bias, particularly masking, are controlled for.
The effects of sodium tripolyphosphate replacement with citrus fiber on color, texture, lipid oxidation, and sensory characteristics of an alternatively-cured all-pork Bologna sausage during 98 d of ...storage at storage 0–1 °C were studied. Replacement of sodium phosphates in processed meat with citrus fiber could enable manufacturers to make their products more consistent with the current “clean label” trend. The Bologna sausage was assigned one of five treatments: sodium tripolyphosphate control (0.38%), no-sodium-tripolyphosphate control, or one of several citrus fiber levels (0.50%, 0.75%, 1.00%). Citrus fiber treatments resulted in Bologna sausage with acceptable technological parameters, as indicated by similar cook/chill yields and emulsion stability compared to the sodium tripolyphosphate control. The results showed the replacement of sodium tripolyphosphate with citrus fiber did not significantly alter most physical, chemical or sensory characteristics of the Bologna sausage during refrigerated storage.
PDF
