Activity

  • Ewing Forrest posted an update 1 week, 5 days ago

    To measure gamma and alpha brain wave activity as a measurement of concentration and stress levels during surgical simulator performance of laparoscopic tasks to determine if expert surgeons have different brain activity patterns compared with intermediate and novice surgeons.

    After obtaining Institutional Review Board approval, 1st and 2nd year medical students, urology residents (PGY2-PGY5), and attending urologists from one institution were recruited. Participants were stratified by level of experience and performed laparoscopic tasks on the EDGE laparoscopic simulator. Subjects were evaluated for concentration and stress levels using the electroencephalography (EEG) data extracted from the MUSE(™) headband. The MUSE software developer kit (SDK) allowed quantification of gamma and alpha waves during each task. An analysis of variance was used to compare concentration and stress levels between groups.

    A total of 19 participants were recruited for the study and stratified by surgical experience into nourgeons reveals a significant increase in concentration levels with a decrease in stress during simulated laparoscopic tasks compared with novices. This information may correlate with increased proficiency as well as provide objective feedback of progress along the learning curve with the MUSE SDK.Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. At diagnosis, half of the patients are over 70 years of age, and most present with advanced disease, for which chemotherapy is recommended as first-line treatment. However, the benefit from such therapy is modest and it is at times poorly tolerated. The discovery of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has significantly impacted the treatment of patients with EGFR mutation-positive advanced NSCLC. These novel agents demonstrate efficacy and a favorably mild toxicity profile. Despite limited data in elderly patients, the largest subpopulation in NSCLC, EGFR-TKIs are considered the standard of care therapy for advanced EGFR-positive disease in the elderly. In this review, we seek to compile the available data about the EGFR-TKIs use in elderly patients with advanced NSCLC, with the hope to better understand its role in this major yet, underrepresented, group of patients.Techniques for measuring the motion of single motor proteins, such as FRET and optical tweezers, are limited to a resolution of ∼300 pm. We use ion current modulation through the protein nanopore MspA to observe translocation of helicase Hel308 on DNA with up to ∼40 pm sensitivity. This approach should be applicable to any protein that translocates on DNA or RNA, including helicases, polymerases, recombinases and DNA repair enzymes.We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing laboratories and fed either a low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the cataloged genes are bacterial. We identified 541 metagenomic species and defined a core set of 26 metagenomic species found in 95% of the mice. The mouse gut microbiome is functionally similar to its human counterpart, with 95.2% of its Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologous groups in common. However, only 4.0% of the mouse gut microbial genes were shared (95% identity, 90% coverage) with those of the human gut microbiome. This catalog provides a useful reference for future studies.

    Since the identification of poly-alanine expanded poly(A) binding protein nuclear 1 (PABPN1) as the genetic cause of oculopharyngeal muscular dystrophy (OPMD), considerable progress has been made in our understanding of the pathogenesis of the disease. However, the molecular mechanisms that regulate the onset and progression of the disease remain unclear.

    In this study, we show that PABPN1 interacts with and is stabilized by heat shock protein 90 (HSP90). Treatment with the HSP90 inhibitor 17-AAG disrupted the interaction of mutant PABPN1 with HSP90 and reduced the formation of intranuclear inclusions (INIs). Furthermore, mutant PABPN1 was preferentially degraded in the presence of 17-AAG compared with wild-type PABPN1 in vitro and in vivo. The effect of 17-AAG was mediated through an increase in the interaction of PABPN1 with the carboxyl terminus of heat shock protein 70-interacting protein (CHIP). The overexpression of CHIP suppressed the aggregation of mutant PABPN1 in transfected cells.

    Our results demonstrate that the HSP90 molecular chaperone system plays a crucial role in the selective elimination of abnormal PABPN1 proteins and also suggest a potential therapeutic application of the HSP90 inhibitor 17-AAG for the treatment of OPMD.

    Our results demonstrate that the HSP90 molecular chaperone system plays a crucial role in the selective elimination of abnormal PABPN1 proteins and also suggest a potential therapeutic application of the HSP90 inhibitor 17-AAG for the treatment of OPMD.Plasmodium falciparum is an apicomplexan parasite and the etiological agent of severe human malaria. The complex P. falciparum life cycle is supported by a diverse repertoire of surface proteins including the family of 6-Cys s48/45 antigens. Of these, Pf41 is localized to the surface of the blood-stage merozoite through its interaction with the glycophosphatidylinositol-anchored Pf12. Our recent structural characterization of Pf12 revealed two juxtaposed 6-Cys domains (D1 and D2). Pf41, however, contains an additional segment of 120 residues predicted to form a large spacer separating its two 6-Cys domains. To gain insight into the assembly mechanism and overall architecture of the Pf12-Pf41 complex, we first determined the 2.45 Å resolution crystal structure of Pf41 using zinc single-wavelength anomalous dispersion. Structural analysis revealed an unexpected domain organization where the Pf41 6-Cys domains are, in fact, intimately associated and the additional residues instead map predominately to an inserted domain-like region (ID) located between two β-strands in D1. Adenosine Cyclophosphate order Notably, the ID is largely proteolyzed in the final structure suggesting inherent flexibility. To assess the contribution of the ID to complex formation, we engineered a form of Pf41 where the ID was replaced by a short glycine-serine linker and showed by isothermal titration calorimetry that binding to Pf12 was abrogated. Finally, protease protection assays showed that the proteolytic susceptibility of the ID was significantly reduced in the complex, consistent with the Pf41 ID directly engaging Pf12. Collectively, these data establish the architectural organization of Pf41 and define an essential role for the Pf41 ID in promoting assembly of the Pf12-Pf41 heterodimeric complex.

    Although there are many special exercise-based therapy approaches for the working population suffering chronic low back pain, similar programmes for older individuals are rare.

    To summarise all evaluated physical therapy approaches, and assess the effects on older people with chronic low back pain.

    Medline, CINAHL, Cochrane, Embase, PEDro, PsychINFO and Psyndex.

    Age≥65 years, subacute or chronic non-specific low back pain of ≥6weeks’ duration, and a physical therapy approach.

    Study selection, data extraction, and assessment of methodological quality and clinical relevance were performed independently by two reviewers. As there were only a few controlled trials and wide heterogeneity in observation periods and outcome measures, pooling of data was not feasible. Therefore, the results are presented descriptively.

    In total, nine studies were included; six related to mixed physiotherapy modalities, one related to strength training, and two related to endurance training. Low-quality evidence suggests that physical therapy modalities are associated with a small-to-moderate reduction in pain and a small improvement in function.

    The results must be interpreted with caution due to poor methodological quality.

    Few studies have been performed in this highly relevant and growing age group. It is not possible to recommend one particular modality or programme; as such, prescriptions should reflect patients’ preferences and local conditions. Further research of higher methodological quality is needed urgently.

    Few studies have been performed in this highly relevant and growing age group. It is not possible to recommend one particular modality or programme; as such, prescriptions should reflect patients’ preferences and local conditions. Further research of higher methodological quality is needed urgently.

    We determined the level of knowledge about epilepsy in Korean people with epilepsy (PWE) and evaluated whether this is associated with self-efficacy, perceived stigma, anxiety, and depressive mood in these patients.

    This was a cross-sectional multicenter study. A total of 530 PWE participated from 31 secondary or tertiary hospitals in Korea. Knowledge about epilepsy was assessed using 34 medical items (EKP-M) of the Epilepsy Knowledge Profile-General. Additional questionnaires included the Epilepsy Self-Efficacy Scale (ESES), Stigma Scale, and Hospital Anxiety and Depression Scale (HADS). Multiple linear regression analyses were used.

    The mean EKP-M score was 22.2 (SD 4.1). By univariate analyses, the EKP-M was related to ESES (r=0.220, p<0.001) and HADS-D (r=-0.154, p<0.001) scores but not to the Stigma Scale or HADS-A. By linear regression analyses, after adjusting for the confounding variables, the higher EKP-M scores were independently related to both higher ESES (p<0.001) and lower HADS-D scores (p<0.05).

    Korean PWE have a relatively low level of knowledge about their condition. Knowledge about epilepsy is associated with a high level of self-efficacy and less depressive symptoms in affected individuals.

    Korean PWE have a relatively low level of knowledge about their condition. Knowledge about epilepsy is associated with a high level of self-efficacy and less depressive symptoms in affected individuals.The purposes of this study were to determine whether personalities of patients with nonepileptic psychogenic status (NEPS) are different from those of patients with typical intermittent psychogenic nonepileptic seizures (iPNES) using the Personality Assessment Inventory (PAI) and to compare their PAI profiles with the population norms. We hypothesized that patients with NEPS have more psychopathology compared with patients with iPNES and that, as a group, patients with PNES (iPNES+NEPS) would have more psychopathology compared with healthy individuals. We first compared the PAI profiles of patients with iPNES and NEPS and then the profiles of patients with NEPS, iPNES, and PNES with population norms in order to assess which PAI specific scales differed between groups in order to better characterize the psychopathology of PNES. All patients admitted for diagnostic evaluation to the epilepsy monitoring unit (EMU) were prospectively approached for participation. All patient/family interviews were conducted by an epileptologist, and the diagnosis of iPNES or NEPS was confirmed in all cases through video/EEG and/or family interview.