Effects of different seat cushions on interface pressure distribution: a pilot study.

[Purpose] The purpose of this study was to evaluate pressure redistribution on the supporting area of healthy volunteers when using different cushions. [Subjects and Methods] Twenty healthy individuals ranging in age from 19-23 years old and 20 older adults age 60 or above participated in the study. All participants lived in urban communities in South Korea. Group differences according to gender, age, and cushion types were analyzed with one-way analysis of variance and post-hoc analysis. [Results] Statistically significant differences in peak pressure and mean pressure were identified between age, gender, and cushion types. Peak pressure and mean pressure were higher on firm surfaces and on the air cushion than other cushion types. The pressure ratio was lower when an air cushion was used in the buttock area and was higher when it was used under the thighs compared to that in other conditions. [Conclusion] This study showed that interface pressure can be distributed differently depending on what cushions are used. Therefore, when using seat cushions, individuals should seek advice to help them choose the appropriate cushion for their needs.

A simulation-based continuing professional development course for the first 5 minutes of cardiac arrest in the resource-limited local clinics.

PURPOSE: Using simulation in continuing professional development (CPD) courses for local practitioners is uncommon in Korea. The aim of our study was to evaluate the responses of the local practitioners for a simulation-based short CPD course. METHODS: Following the targeted needs assessment of local practitioners, we developed and implemented a 3-hour simulation-based CPD course for the first 5 minutes of cardiac arrest in the resource-limited local clinics. We evaluated the participant's responses to the course using a questionnaire. RESULTS: During the 3-year implementation period, 115 practitioners participated in 10 courses, and 113 (98%) responded to the questionnaire. The overall course satisfaction (10-point scale) was very positive (10 in 93 [82.3%], 9 in 19 [16.8%], and 8 in 1 [0.8%]). The level (5-point scale) of recommendation to the others was also high (5 in 103 [91.2%] and 4 in 10 [8.8%]). Many participants positively commented on the authentic practical experience of the uncommon crisis in their contexts. CONCLUSION: A simulation-based short CPD course for in-hospital cardiac arrest could provide an authentic practical experience for local practitioners working in resource-limited clinics.

The association between sleep and psychological distress among New York City healthcare workers during the COVID-19 pandemic.

BACKGROUND: Healthcare workers (HCWs) treating patients with COVID-19 report psychological distress. We examined whether disturbed sleep was associated with psychological distress in New York City (NYC) HCWs during the initial peak of the COVID-19 pandemic (April-May 2020). METHODS: HCWs completed a survey screening for acute stress (4-item Primary Care PTSD screen), depressive (Patient Health Questionaire-2), and anxiety (2-item Generalized Anxiety Disorder scale) symptoms. Insomnia symptoms (modified item from the Insomnia Severity Index) and short sleep (SS, sleep duration <6 h/day) were assessed. Poisson regression analyses predicting psychological distress from SS and insomnia symptoms, adjusting for demographics, clinical role/setting, redeployment status, shifts worked, and multiple comparisons were performed. RESULTS: Among 813 HCWs (80.6% female, 59.0% white) mean sleep duration was 5.8 ± 1.2 h/night. Prevalence of SS, insomnia, acute stress, depressive, and anxiety symptoms were 38.8%, 72.8%, 57.9%, 33.8%, and 48.2%, respectively. Insomnia symptoms was associated with acute stress (adjusted prevalence ratio [PR]: 1.51, 95% CI: 1.35, 1.69), depressive (PR: 2.04, 95% CI: 1.78, 2.33), and anxiety (PR: 1.74, 95% CI: 1.55, 1.94) symptoms. SS was also associated with acute stress (PR: 1.17, 95% CI: 1.07, 1.29), depressive (PR: 1.36, 95% CI: 1.233, 1.51), and anxiety (PR: 1.38, 95% CI: 1.26, 1.50) symptoms. LIMITATIONS: Our cross-sectional analysis may preclude the identification of temporal associations and limit causal claims. CONCLUSIONS: In our study, SS and insomnia were associated with psychological distress symptoms in NYC HCWs during the COVID-19 pandemic. Sleep may be a target for interventions to decrease psychological distress among HCWs.

Factors Associated with Insomnia Symptoms in a Longitudinal Study among New York City Healthcare Workers during the COVID-19 Pandemic.

BACKGROUND: Few studies have examined the longer-term psychological impact of COVID-19 in healthcare workers (HCWs). PURPOSE: We examined the 10-week trajectory of insomnia symptoms in HCWs during the COVID-19 pandemic. METHODS: HCWs completed a web-based survey at baseline (9 April-11 May 2020) and every 2 weeks for 10 weeks. The main outcome was the severity of insomnia symptoms in the past week. Multivariable-adjusted generalized estimating equation analyses examined factors associated with insomnia symptoms. RESULTS: n = 230 completed surveys at baseline. n = 155, n = 130, n = 118, n = 95, and n = 89 completed follow-ups at weeks 2, 4, 6, 8, and 10, respectively. Prevalence of insomnia symptoms of at least moderate severity was 72.6% at baseline, and 63.2%, 44.6%, 40.7%, 34.7%, and 39.3% at weeks 2, 4, 6, 8, and 10, respectively. In multivariable analyses, factors significantly associated with increased odds of insomnia symptoms were younger age (OR: 0.98, 95% CI: 0.96-1.00), working in a COVID-facing environment (OR: 1.75, 95% CI: 1.15-2.67) and hours worked (OR: 1.16, 95% CI: 1.06-1.27). CONCLUSIONS: The initial high rates of insomnia symptoms improved as time passed from the peak of local COVID-19 cases but four out of ten HCWs still had moderate-to-severe insomnia symptoms ten weeks after baseline.

Psychological distress, coping behaviors, and preferences for support among New York healthcare workers during the COVID-19 pandemic.

OBJECTIVE: The mental health toll of COVID-19 on healthcare workers (HCW) is not yet fully described. We characterized distress, coping, and preferences for support among NYC HCWs during the COVID-19 pandemic. METHODS: This was a cross-sectional web survey of physicians, advanced practice providers, residents/fellows, and nurses, conducted during a peak of inpatient admissions for COVID-19 in NYC (April 9th-April 24th 2020) at a large medical center in NYC (n = 657). RESULTS: Positive screens for psychological symptoms were common; 57% for acute stress, 48% for depressive, and 33% for anxiety symptoms. For each, a higher percent of nurses/advanced practice providers screened positive vs. attending physicians, though housestaff's rates for acute stress and depression did not differ from either. Sixty-one percent of participants reported increased sense of meaning/purpose since the COVID-19 outbreak. Physical activity/exercise was the most common coping behavior (59%), and access to an individual therapist with online self-guided counseling (33%) garnered the most interest. CONCLUSIONS: NYC HCWs, especially nurses and advanced practice providers, are experiencing COVID-19-related psychological distress. Participants reported using empirically-supported coping behaviors, and endorsed indicators of resilience, but they also reported interest in additional wellness resources. Programs developed to mitigate stress among HCWs during the COVID-19 pandemic should integrate HCW preferences.

Extent of Exclusions for Chronic Conditions in Breast Cancer Trials.

Experts have expressed concerns that patients with chronic conditions are being excessively excluded from cancer randomized clinical trials (RCTs), limiting generalizability. Accordingly, we queried clinicaltrials.gov to determine the extent to which patients with chronic conditions were excluded from phase III cancer trials, using National Cancer Institute-sponsored breast cancer RCTs as a test case. Two physicians independently coded for the presence of 19 prevalent chronic conditions within eligibility criteria. They also coded for exclusions based on performance status and vague criteria that could have broadly excluded patients with chronic conditions. The search identified 58 RCTs, initiated from 1993 to 2012. Overall, 88% of trials had at least one exclusion for a chronic condition, performance status, or vague criterion. The three most commonly excluded conditions were chronic kidney disease, heart failure, and ischemic heart disease. Our study demonstrated that patients with prevalent chronic conditions were commonly excluded from National Cancer Institute-sponsored RCTs.

Evaluation using simulated students for reliability of multiple standardized-patients scoring in clinical performance examinations.

BACKGROUND: The consistency of rating among different standardized patients (SPs) is very important in clinical performance examinations (CPX). AIMS: We evaluated the usefulness of simulated students to assess the reliability of a group of standardized patients in a CPX. METHODS: Five SPs in each case were trained to simulate the same patient in a CPX. Ten fourth-year medical student volunteers were selected to act as simulated students. After the simulated students encountered the first SP, they reviewed a video of their performance and sequentially repeated the performance with the other 4 SPs. RESULTS: The average maximum difference (Deltamax +/- SD) of multiple SPs' percent scores on a simulated student was 18 +/- 7. In 10 pairs of SPs who gave largest Deltamax on a given student, the median Deltamax was 30 (range, 26-38) while median difference of percent score in the faculty scoring on the same simulated student was 3 (range, 0-7). Five problematic SPs whose ratings were significantly different from 3 or more other SPs' ratings in each case were identified. CONCLUSIONS: Simulated students may be a useful means to check the consistency of rating among different SPs in a CPX.

The p65 subunit of nuclear factor-kappaB is a molecular target for radiation sensitization of human squamous carcinoma cells.

The transcription factor nuclear factor-kappaB (NF-kappaB) is activated in response to various stimuli including ionizing radiation. Disruption of NF-kappaB activation by mutant forms of the NF-kappaB inhibitor IkappaB-alpha or by proteasome inhibitors enhances both sensitivity to radiation and radiation-induced apoptosis. Human squamous carcinoma SCC-35 cells stably expressing a fragment (residues 1 to 84) of human p65 have been shown to exhibit down-regulation of both endogenous p65 mRNA and its protein. The mutant protein also inhibited radiation-induced NF-kappaB activation by preventing the proteolysis of IkappaB-alpha. This resulted in enhancement of cellular radiosensitivity and radiation-induced apoptosis. The NH(2)-terminal region of p65 is thus a potential molecular target for disruption of NF-kappaB activation and sensitization of tumors to radiotherapy.

Tissue ischemia time affects gene and protein expression patterns within minutes following surgical tumor excision.

The aim of this study was to determine the impact of ischemia on gene and protein expression profiles of healthy and malignant colon tissue and, thus, on screening studies for identification of molecular targets and diagnostic molecular patterns. Healthy and malignant colon tissue were snap-frozen at various time points (3-30 min) after colon resection. Gene and protein expression were determined by microarray (HG-U133A chips) and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) technology (CM10 chips, SAX2 chips, and IMAC3Ni chips), respectively. Real-time reverse transcription PCR (RT-PCR) was used for comparative measurement of expression of particular genes. Initial changes of gene and protein expression profiles were already observed 5-8 min after colon resection. Fifteen minutes after surgery, 10%-15% of molecules, and after 30 min, 20% of all detectable genes and proteins, respectively, differed significantly from the baseline values. Significant changes of expression were found in most functional groups. As confirmed by real-time RT-PCR, this included not only known hypoxia-related molecules (HIF-1 alpha, c-fos, HO-1) but also cytoskeletal genes (e.g., CK20) and tumor-associated antigens (e.g., CEA). In conclusion, preanalytical factors, such as tissue ischemia time, dramatically affect molecular data. Control of these variables is mandatory to obtain reliable data in screening programs for molecular targets and diagnostic molecular patterns.

Histone deacetylase cytoplasmic trapping by a novel fluorescent HDAC inhibitor.

Inhibitors of histone deacetylases (HDAC) are an important emerging class of drugs for the treatment of cancers. HDAC inhibitors are currently under evaluation in clinical trials as single agents and as sensitizers in combinations with chemotherapies and radiation therapy. Although these drugs have important effects on cancer cell growth and functions, the mechanisms underlying HDAC inhibitor activities remain to be fully defined. By using rational drug design, compound 2, a fluorescent class II HDAC targeting inhibitor, was synthesized and observed to accumulate in the cytoplasmic compartments of treated cells, but not in the nuclei. Furthermore, immunostaining of inhibitor exposed cells for HDAC4 showed accumulation of this enzyme in the cytoplasmic compartment with concomitant increased acetylation of tubulin and nuclear histones. These observations support a mechanism by which nuclear histone acetylation is increased as a result of HDAC4 trapping and sequestration in the cytoplasm after binding to compound 2. The HDAC inhibitor offers potential as a novel theranostic agent, combining diagnostic and therapeutic properties in the same molecule.

Breast examination instruction by a standardized patient instructor.

PURPOSE: The purpose of this research was to identify the effectiveness of a standardized patient (SP) instructor. The study was performed to compare the effects of two types of instruction on breast examination skills by an SP instructor and a professor. METHODS: Fifty-four medical students in the third year and 4 SPs participated in the study. In a pretest, each student was judged by the SP individually in performing a breast examination and completed a questionnaire about perception. Next, students were randomly assigned to 2 experimental groups (small-group instruction by an SP instructor or professor). A posttest of performance and perception was administered using the same procedures as in the pretest. To identify the effectiveness of the SP instructor, differences in student scores between the groups were analyzed by t-test. RESULTS: In the posttest of student performance on the breast examination, there was no significant difference between the groups (p=0.270). With regard to student perception, scores on self-confidence in the breast examination were significantly different (p=0.026) between the groups, of which students who received instruction from the professor showed a higher level. Additionally, there was a significant effect on students' perceived reliability of instruction by the SP instructor (p=0.011), and students who were instructed by the SP demonstrated higher reliability compared with professor-taught students. CONCLUSION: Instruction by an SP instructor has the same effectiveness as instruction by a professor. SP instructors have very powerful effects on student performance and perception.

The nucleoside analog sangivamycin induces apoptotic cell death in breast carcinoma MCF7/adriamycin-resistant cells via protein kinase Cdelta and JNK activation.

Sangivamycin has shown a potent antiproliferative activity against a variety of human cancers. However, little is known about the mechanism of action underlying its antitumor activity. Here we demonstrate that sangivamycin has differential antitumor effects in drug-sensitive MCF7/wild type (WT) cells, causing growth arrest, and in multidrug-resistant MCF7/adriamycin-resistant (ADR) human breast carcinoma cells, causing massive apoptotic cell death. Comparisons between the effects of sangivamycin on these two cell lines allowed us to identify the mechanism underlying the apoptotic antitumor effect. Fluorescence-activated cell sorter analysis indicated that sangivamycin induced cell cycle arrest in the G(2)/M phase in MCF7/ADR cells. A marked induction of c-Jun expression as well as phosphorylation of c-Jun and JNK was observed after sangivamycin treatment of MCF7/ADR cells but not MCF7/WT cells. Sangivamycin also induced cleavage of lamin A and poly(ADP-ribose) polymerase (PARP) in MCF7/ADR cells, probably via activation of caspase-6, -7, and -9. Pretreatment with a caspase-9-specific inhibitor or pan-caspase inhibitor abolished sangivamycin-induced cleavage of lamin A and PARP but not sangivamycin induction of c-Jun expression and phosphorylation. Pretreatment of MCF7/ADR cells with SP600125, a specific inhibitor of JNK, or with rottlerin, a specific inhibitor of protein kinase Cdelta (PKCdelta), significantly reduced the sangivamycin-induced apoptosis and almost completely abolished sangivamycin-induced phosphorylation of c-Jun and cleavage of lamin A and PARP. Transfection of MCF7/ADR cells with PKCdelta small interfering RNAs or PKCdelta antibody or rottlerin pretreatment significantly suppressed the phosphorylation of JNK. Taken together, our data suggest that sangivamycin induces mitochondria-mediated apoptotic cell death of MCF7/ADR cells via activation of JNK in a protein kinase Cdelta-dependent manner.

Functional expression and refolding of new alkaline esterase, EM2L8 from deep-sea sediment metagenome.

A metagenomics approach is an efficient method of isolating novel and useful genes from uncultured microorganisms in diverse environments. In this research, a gene encoding a new esterase (EM2L8) was cloned and characterized from the metagenomic DNA library of a deep-sea sediment. The gene consisted of 804bp encoding a polypeptide of 267 amino acids with a molecular mass of 28,952. The deduced amino acid sequence showed similarities with the BioH of Kurthia, the 3-oxoadipate enol-lactonase of Haloarcula and the acyltransferase of Thermoanaerobacter, which feature identities of 38%, 32%, and 33%, respectively. Residues essential for esterase activity, such as pentapeptide (GXSXG) and catalytic triad sequences, were uncovered. While the protein was overproduced mainly as inclusion body at 37 degrees C, it was mainly produced as a soluble active enzyme at 18 degrees C. A zymogram analysis revealed that purified EM2L8 taken from the soluble fraction could hydrolyze tributyrin substrate. Furthermore, the protein from the inclusion body fraction also showed strong activity on gel, thus indicating that the protein was refolded during SDS-gel electrophoresis and the ensuing incubation period. When the inclusion body was mixed with some anionic detergent solutions and diluted with a non-detergent buffer, the insoluble EM2L8 refolded rapidly and recovered its full esterase activity. Although EM2L8 had an optimum temperature of 50-55 degrees C, its activation energy in the range of 10-40 degrees C was 8.34kcal/mol, indicating that it is a cold-adapted enzyme. Moreover, it was found to have an optimum pH of 10-11, thus revealing that it is an alkaline enzyme. In this paper, the new esterase EM2L8 buried in a deep-sea sediment became known on the surface and was characterized biochemically.