Modification of rat brain Kv1.4 channel gating by association with accessory Kvβ1.1 and β2.1 subunits

 We have examined the effects of co-expression of Kvβ1.1 and Kvβ2.1 subunits on the gating of rat brain Kv1.4 channels, expressed in Xenopus oocytes. Expression of Kv1.4 subunits alone produced a rapidly inactivating ”A” type current, which activated at potentials beyond –60 mV in a solution containing high levels of rubidium. Current activation curves obtained from tail current measurements were fitted with a Boltzmann function, with V _1/2 = –47 mV and k = 10 mV. Neither the Kvβ1.1 nor Kvβ2.1 subunits altered the voltage dependence of activation. Both subunits accelerated the activation time constant of Kv1.4, without affecting its voltage dependence. Surprisingly, the Kvβ2.1 subunit, which lacks an N-terminal inactivation domain, was almost as effective as the Kvβ1.1 subunit in speeding up Kv1.4. Steady-state inactivation of Kv1.4 was unchanged upon co-expression with either Kvβ1.1 or Kvβ2.1 subunits. Kv1.4 recovered from inactivation with two time constants; apart from an ≈ 50% lengthening of the slow time constant with a high Kvβ2.1 injection ratio, neither time constant was altered by either the Kvβ1.1 or Kvβ2.1 subunits, suggesting little interaction with recovery from C-type inactivation. Clearly, β subunits have the potential to modify the gating of Kv1.4 channels in the brain more subtly than has been suggested previously. Received: 17 March 1997 / Accepted: 30 June 1997     

VE1 immunohistochemistry is an adjunct tool for detection of BRAF V600E mutation: Validation in thyroid cancer patients

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy among other endocrine tumors, and BRAF ^V600E is a frequent genetic mutation occurring in the disease. Although different molecular techniques, most importantly sequencing has been widely recognized as a gold standard but molecular diagnosis remains an expensive, laborious, and time‐intensive process. Recently, immunohistochemistry (IHC) with anti‐BRAF V600E (VE1) antibody has increased practical utility and implemented clinically for the detection of BRAF ^V600E mutation. Therefore, the study aimed to evaluate diagnostic accuracy of VE1 IHC for detecting the BRAF ^V600E mutation frequency and clinical implementation in diagnostic laboratories. In this study, 72 formalin fixed paraffin‐embedded tissues (FFPE) were used to determine the BRAF ^V600E mutation status using IHC and Sanger sequencing. The mutation was found in 29% and 28% cases using IHC and Sanger sequencing, respectively. Furthermore, the results showed 100% sensitivity, 98.07% specificity, 95.2% positive predictive value, and 100% negative predictive value. Notably, significant associations were found between BRAF ^V600E status and tumor stage, tumor focality, and extrathyroidal extensions, respectively. VE1 IHC was found to be a highly sensitive, specific, and diagnostically accurate method in this cohort. Therefore, BRAF ^V600E detection through IHC has been considered as the best tailored technique for routine pathology laboratories.     

Mesenchymal Stem Cell (MSCs) Therapy for Ischemic Heart Disease: A Promising Frontier

Although tremendous progress has been made in conventional treatment for ischemic heart disease, it still remains a major cause of death and disability. Cell-based therapeutics holds an exciting frontier of research for complete cardiac recuperation. The capacity of diverse stem and progenitor cells to stimulate cardiac renewal has been analysed, with promising results in both pre-clinical and clinical trials. Mesenchymal stem cells have been ascertained to have regenerative ability via a variety of mechanisms, including differentiation from the mesoderm lineage, immunomodulatory properties, and paracrine effects. Also, their availability, maintenance, and ability to replenish endogenous stem cell niches have rendered them suitable for front-line research. This review schemes to outline the use of mesenchymal stem cell therapeutics for ischemic heart disease, their characteristics, the potent mechanisms of mesenchymal stem cell-based heart regeneration, and highlight preclinical data. Additionally, we discuss the results of the clinical trials to date as well as ongoing clinical trials on ischemic heart disease.     

Application of optical character recognition with natural language processing for large-scale quality metric data extraction in colonoscopy reports

Background and AimsColonoscopy is commonly performed for colorectal cancer screening in the United States. Reports are often generated in a non-standardized format and are not always integrated into electronic health records. Thus, this information is not readily available for streamlining quality management, participating in endoscopy registries, or reporting of patient- and center-specific risk factors predictive of outcomes. We aim to demonstrate the use of a new hybrid approach using natural language processing of charts that have been elucidated with optical character recognition processing (OCR/NLP hybrid) to obtain relevant clinical information from scanned colonoscopy and pathology reports, a technology co-developed by Cleveland Clinic and eHealth Technologies (West Henrietta, NY, USA).MethodsThis was a retrospective study conducted at Cleveland Clinic, Cleveland, Ohio, and the University of Minnesota, Minneapolis, Minnesota. A randomly sampled list of outpatient screening colonoscopy procedures and pathology reports was selected. Desired variables were then collected. Two researchers first manually reviewed the reports for the desired variables. Then, the OCR/NLP algorithm was used to obtain the same variables from 3 electronic health records in use at our institution: Epic (Verona, Wisc, USA), ProVation (Minneapolis, Minn, USA) used for endoscopy reporting, and Sunquest PowerPath (Tucson, Ariz, USA) used for pathology reporting.ResultsCompared with manual data extraction, the accuracy of the hybrid OCR/NLP approach to detect polyps was 95.8%, adenomas 98.5%, sessile serrated polyps 99.3%, advanced adenomas 98%, inadequate bowel preparation 98.4%, and failed cecal intubation 99%. Comparison of the dataset collected via NLP alone with that collected using the hybrid OCR/NLP approach showed that the accuracy for almost all variables was >99%.ConclusionsOur study is the first to validate the use of a unique hybrid OCR/NLP technology to extract desired variables from scanned procedure and pathology reports contained in image format with an accuracy >95%.     

Identifying Trends of Percutaneous Injuries at an Australian Dental School

ObjectivesThe aim of this study was to retrospectively examine trends in percutaneous exposure incidences (PEIs) at the School of Dentistry (SoD) from 2009 to 2019 and to report on the underreporting rate of PEIs, current attitudes, and awareness of PEI safety protocols from clinical staff and students at the SoD in 2019.MethodsRetrospective data were collected from deidentified archival incident reports from 2009 to 2019 from the SoD's incident reporting system (UQSafe and Legacy Database). Additionally, cross-sectional data were collected via the validated Percutaneous Exposure Incident Questionnaires (PEIQ) completed by clinical staff and students of the SoD in 2019.ResultsFrom the archival data, the majority (79.9%) of the 618 reported PEIs involved students. Local anaesthetic-related procedures were the most common cause in the archival (31.5%) and survey data (23.7%), whereas the needle-prick was the most common causative instrument in both data sets. Additionally, the finger was the most common site of injury found in the archival (53.0%) and survey data (52.8%). From 345 responses to the survey, 42.1% of PEIs sustained were not reported.ConclusionsStudents were at a higher risk of sustaining a PEI than staff members between 2009 and 2019. The reported knowledge on PEI classification and preventative measures is inadequate, suggesting that further PEI education is necessary. The study provides evidence of the trends in PEIs as well as data on the attitudes and awareness of student and staff at a dental teaching faculty to support the development of PEI safety management protocols.     

Immediate-type hypersensitivity and other clinical reactions in volunteers immunized with a synthetic multi-antigen peptide vaccine (PfCS-MAP1NYU) against Plasmodium falciparum sporozoites

We tested the clinical reactions to a synthetic, Plasmodium falciparum, circumsporozoite multiple antigen peptide (MAP) vaccine in 39 volunteers immunized two to three times over 2-8 months using a dose escalation design. Immediate pain at the injection site was associated with the adjuvant QS-21 (P<0.001), and delayed local inflammatory reactions were associated with high-titered circulating IgG anti-MAP antibody (P=0.03). Because two volunteers developed acute, systemic urticaria after the third immunization associated with development of serum IgE MAP antibody, we employed immediate-type hypersensitivity skin tests (ITH-STs) using intradermal injections of diluted MAP vaccine to identify persons sensitized to the vaccine. ITH-STs were negative in seven volunteers tested 27 days after the first vaccination, but six of these individuals developed positive wheal and flare reactions when tested 14 or 83 days after the second vaccination; IgE MAP antibody was detected in only one of them. Another cohort of 16 volunteers, including the 2 allergic individuals, were ITH-ST negative when first tested late after their second or third vaccination at 6-7 months. Five of five non-immunized persons were also ITH-ST negative. ITH-STs may help identify individuals sensitized to malaria peptides and at potential risk of developing systemic allergic reactions after re-vaccination.