Search

We conducted a single-center study at a free community testing site in Baltimore City to assess the accuracy of self-performed rapid antigen tests (RATs) for COVID-19. Self-administered BinaxNOW RATs were compared with clinician-performed RATs and against a reference lab molecular testing as the gold standard. Of the 953 participants, 14.9% were positive for SARS- CoV-2 as determined by RT-PCR. The sensitivity and specificity were similar for both self- and clinician-performed RATs (sensitivity: 83.9% vs 88.2%, P = 0.40; specificity: 99.8% vs 99.6%, P = 0.6). Subgroup comparisons based on age and race yielded similar results. Notably, 5.2% (95% CI: 1.5% to 9.5%) of positive results were potentially missed due to participant misinterpretation of the self-test card. However, the false-positive rate for RATs was reassuringly comparable in accuracy to clinician-administered tests. These findings hold significant implications for physicians prescribing treatment based on patient-reported, self-administered positive test results. Our study provides robust evidence supporting the reliability and utility of patient-performed RATs, underscoring their comparable accuracy to clinician-performed RATs, and endorsing their continued use in managing COVID-19. Further studies using other rapid antigen test brands are warranted.IMPORTANCEAccurate and accessible COVID-19 testing is crucial for effective disease control and management. A recent single-center study conducted in Baltimore City examined the reliability of self-performed rapid antigen tests (RATs) for COVID-19. The study found that self-administered RATs yielded similar sensitivity and specificity to clinician-performed tests, demonstrating their comparable accuracy. These findings hold significant implications for physicians relying on patient-reported positive test results for treatment decisions. The study provides robust evidence supporting the reliability and utility of patient-performed RATs, endorsing their continued use in managing COVID-19. Furthermore, the study highlights the need for further research using different rapid antigen test brands to enhance generalizability. Ensuring affordable and widespread access to self-tests is crucial, particularly in preparation for future respiratory virus seasons and potential waves of reinfection of SARS-CoV-2 variants such as the Omicron variant., Competing Interests: The authors declare no conflict of interest.

Background: Imposter Phenomenon (IP) is a subjective feeling of intellectual fraudulence and self-doubt experienced by individuals in goal-orientated high-achieving professions. The impact of IP within healthcare has been associated with individual physical and mental health and concerns around training, career progression and DEI at an institutional level. To effectively address IP in healthcare, this scoping review aims to explore educational interventions designed to empower high-achieving individuals with the tools needed to confront and overcome IP., Methods: The scoping review adhered to a predetermined protocol informed by the JBI methodology and PRISMA-ScR guidelines in order to identify educational interventions addressing IP in high-achieving industries. Articles were searched across multiple databases, including MEDLINE (Ovid), PsychINFO, SCOPUS, and Web of Science, alongside grey literature, without imposing any time constraints. A systematic approach including a thematic analysis allowed for a nuanced exploration and interpretation of the identified educational interventions and their impact on addressing IP., Results: Seventeen articles were incorporated into the review, with the majority originating from the USA and majority being published since 2020. Ten studies targeted healthcare professionals, undergraduate and postgraduate healthcare students. Majority of studies aimed at addressing IP, featured a larger number of female participants than males. Workshops with self-reflection and group-guided exercises to overcome IP were the most popular educational interventions. Coaching and structured supervision were also suggested. Across all papers, three themes emerged for coping strategies: individual, peer-to-peer, and institutional., Conclusions: This scoping review suggests how group and individual interventions such as workshops, small group discussions and coaching can be used to overcome IP in healthcare. Institutional changes like diversity promotion, supervisor education, and support networks are crucial in addressing IP. Further long term and speciality specific assessments are needed to measure impact. Overall, the review highlights how educational awareness and a variety of strategies can be implemented to create a supportive environment for professionals dealing with IP, promoting their well-being and success., (© 2023. The Author(s).)

Background: Monoclonal antibody (mAb) treatment for coronavirus disease 2019 (COVID-19) has been underutilized due to logistical challenges, lack of access, and variable treatment awareness among patients and health-care professionals. The use of telehealth during the pandemic provides an opportunity to increase access to COVID-19 care., Methods: This is a single-center descriptive study of telehealth-based patient self-referral for mAb therapy between March 1, 2021, and October 31, 2021, at Baltimore Convention Center Field Hospital (BCCFH)., Results: Among the 1001 self-referral patients, the mean age was 47, and most were female (57%). White (66%), and had a primary care provider (PCP) (62%). During the study period, self-referrals increased from 14/mo in March to 427 in October resulting in a 30-fold increase. Approximately 57% of self-referred patients received a telehealth visit, and of those 82% of patients received mAb infusion therapy. The median time from self-referral to onsite infusion was 2 d (1-3 IQR)., Discussion: Our study shows the integration of telehealth with a self-referral process improved access to mAb infusion. A high proportion of self-referrals were appropriate and led to timely treatment. This approach helped those without traditional avenues for care and avoided potential delay for patients seeking referral from their PCPs.

The widespread existence of expired antigen testing kits in households and potential coronavirus outbreaks necessitates evaluating the reliability of these expired kits. Our study examined BinaxNOW COVID-19 rapid antigen tests 27 months postmanufacture and 5 months past their FDA extended expiration dates, using SARS-CoV-2 variant XBB.1.5 viral stock. We conducted testing at two concentrations, the limit of detection (LOD) and 10 times the LOD. One hundred expired and unexpired kits were tested at each concentration for a total of 400 antigen tests. At the LOD (2.32 × 10 2 50% tissue culture infective dose/mL [TCID 50 /mL]), both expired and unexpired tests displayed 100% sensitivity (95% confidence interval [CI], 96.38% to 100%), with no statistical difference (95% CI, -3.92% to 3.92%). Similarly, at 10 times the LOD, unexpired tests retained 100% sensitivity (95% CI, 96.38% to 100%), while expired tests exhibited 99% sensitivity (95% CI, 94.61% to 99.99%), demonstrating a statistically insignificant 1% difference (95% CI, -2.49% to 4.49%; P  = 0.56). Expired rapid antigen tests had fainter lines than the unexpired tests at each viral concentration. The expired rapid antigen tests at the LOD were only just visible. These findings carry significant implications for waste management, cost efficiency, and supply chain resilience in pandemic readiness efforts. They also provide critical insights for formulating clinical guidelines for interpreting results from expired kits. In light of expert warnings of a potential outbreak of a severity rivaling the Omicron variant, our study underscores the importance of maximizing the utility of expired antigen testing kits in managing future health emergencies. IMPORTANCE The study examining the reliability of expired antigen testing kits in the context of COVID-19 has significant real-world implications. By demonstrating that these expired kits retain their sensitivity in detecting the virus, this work provides evidence that expired kits can still be utilized, reducing waste and optimizing resources in health care systems. These findings are especially crucial in light of potential future coronavirus outbreaks and the need to be prepared. The study's outcomes have the potential to contribute to waste management efforts, cost efficiency, and supply chain resilience, ensuring that diagnostic tests remain readily available for effective public health interventions. Furthermore, it provides critical insights for formulating clinical guidelines on interpreting results from expired kits, enhancing the accuracy of testing outcomes, and supporting informed decision-making. Ultimately, this work holds great importance in maximizing the utility of expired antigen testing kits, safeguarding public health, and enhancing pandemic readiness on a global scale., Competing Interests: The authors declare no conflict of interest.

Context: More than half of all spinal cord injuries (SCI) occur at the cervical level leading to loss of upper limb function, restricted activity and reduced independence. Several technologies have been developed to assist with upper limb functions in the SCI population., Objective: There is no clear clinical consensus on the effectiveness of the current assistive technologies for the cervical SCI population, hence this study reviews the literature in the years between 1999 and 2019., Methods: A systematic review was performed on the state-of-the-art assistive technology that supports and improves the function of impaired upper limbs in cervical SCI populations. Combinations of terms, covering assistive technology, SCI, and upper limb, were used in the search, which resulted in a total of 1770 articles. Data extractions were performed on the selected studies which involved summarizing details on the assistive technologies, characteristics of study participants, outcome measures, and improved upper limb functions when using the device., Results: A total of 24 articles were found and grouped into five categories, including neuroprostheses (invasive and non-invasive), orthotic devices, hybrid systems, robots, and arm supports. Only a few selected studies comprehensively reported characteristics of the participants. There was a wide range of outcome measures and all studies reported improvements in upper limb function with the devices., Conclusions: This study highlighted that assistive technologies can improve functions of the upper limbs in SCI patients. It was challenging to draw generalizable conclusions because of factors, such as heterogeneity of recruited participants, a wide range of outcome measures, and the different technologies employed.

During the COVID-19 pandemic, access to addiction treatment has plummeted. At the same time, patients with opioid use disorder are at higher risk of COVID-19 infection and experience worse outcomes. The Baltimore Convention Center Field Hospital (BCCFH), a state-run COVID-19 disaster hospital operated by Johns Hopkins Medicine and the University of Maryland Medical System, continues to operate 14 months into the pandemic to serve as an overflow unit for the state's hospitals. BCCFH staff observed the demand for opioid use disorder care and developed admission criteria, a pharmacy formulary, and case management procedures to meet this need. This article describes generalized lessons from the BCCFH experience treating substance use disorder during a pandemic.

SARS-CoV-2 continues to develop new, increasingly infectious variants including delta and omicron. We evaluated the efficacy of the Abbott BinaxNOW Rapid Antigen Test against Reverse Transcription PCR (RT-PCR) in 1,054 pediatric participants presenting to a high-volume Coronavirus Disease 2019 (COVID-19) testing site while the delta variant was predominant. Both tests utilized anterior nares swabs. Participants were grouped by COVID-19 exposure and symptom status. 5.2% of samples tested positive by RT-PCR for SARS-CoV-2. For all participants, sensitivity of the BinaxNOW was 92.7% (95% CI 82.4%-98.0%), and specificity was 98.0% (95% CI 97.0%-98.8%). For symptomatic participants, positive predictive value (PPV) was 72.7% (95% CI 54.5%-86.7%) and negative predictive value (NPV) was 99.2% (95% CI 98.2%-100%). Among asymptomatic participants, PPV was 71.4% (95% CI 53.7%-85.4%) and NPV was 99.7% (95% CI 99.0%-100%). Our reported sensitivity and NPV are higher than other pediatric studies, potentially because of higher viral load from the delta variant, but specificity and PPV are lower. IMPORTANCE The BinaxNOW rapid antigen COVID-19 test had a sensitivity of nearly 92% in both symptomatic and asymptomatic children when performed at a high-throughput setting during the more transmissible delta variant dominant period. The test may play an invaluable role in asymptomatic screening and keeping children safe in school.

Background: Early reports of increased thrombosis risk with SARS-CoV-2 infection led to changes in venous thromboembolism (VTE) management. Real-world data on the prevalence, efficacy and harms of these changes informs best practices., Objective: Define practice patterns and clinical outcomes related to VTE diagnosis, prevention, and management in hospitalized patients with coronavirus disease-19 (COVID-19) using a multi-hospital US sample., Methods: In this retrospective cross-sectional study of 1121 patients admitted to 33 hospitals, exposure was dose of anticoagulant prescribed for VTE prophylaxis (standard, intensified, therapeutic), and primary outcome was VTE (pulmonary embolism [PE] and deep vein thrombosis [DVT]); secondary outcomes were PE, DVT, arterial thromboembolism (ATE), and bleeding events. Multivariable logistic regression models accounting for clustering by site and adjusted for risk factors were used to estimate odds ratios (ORs). Inverse probability weighting was used to account for confounding by indication., Results: 1121 patients (mean age 60 ± 18, 47% female) admitted with COVID-19 between February 2, 2020 and December 31, 2020 to 33 US hospitals were included. Pharmacologic VTE prophylaxis was prescribed in 86%. Forty-seven patients (4.2%) had PE, 51 (4.6%) had DVT, and 23 (2.1%) had ATE. Forty-six patients (4.1%) had major bleeding and 46 (4.1%) had clinically relevant non-major bleeding. Compared to standard prophylaxis, adjusted odds of VTE were 0.67 (95% CI 0.21-2.1) with no prophylaxis, 1.0 (95% CI 0.06-17) with intensified, and 3.0 (95% CI 0.89-10) with therapeutic. Adjusted odds of bleeding with no prophylaxis were 5.6 (95% CI 3.0-11) and 5.3 (95% CI 3.0-10) with therapeutic (no events on intensified dosing)., Conclusions: Therapeutic anticoagulation was associated with a 3-fold increased odds of VTE and 5-fold increased odds of bleeding. While higher bleeding rates with high-intensity prophylaxis were likely due to full-dose anticoagulation, we conclude that high thrombosis rates were due to clinical concern for thrombosis before formal diagnosis., Competing Interests: The authors have declared that no competing interests exist.

In response to the coronavirus disease (COVID-19) pandemic, the State of Maryland established a 250-bed emergency response field hospital at the Baltimore Convention Center to support the existing health care infrastructure. To operationalize this hospital with 65 full-time equivalent clinicians in less than 4 weeks, more than 300 applications were reviewed, 186 candidates were interviewed, and 159 clinicians were credentialed and onboarded. The key steps to achieve this undertaking involved employing multidisciplinary teams with experienced personnel, mass outreach, streamlined candidate tracking, pre-interview screening, utilizing all available expertise, expedited credentialing, and focused onboarding. To ensure staff preparedness, the leadership developed innovative team models, applied principles of effective team building, and provided "just in time" training on COVID-19 and non-COVID-19-related topics to the staff. The leadership focused on staff safety and well-being, offered appropriate financial remuneration, and provided leadership opportunities that allowed retention of staff.

Rapid antigen tests are simple to perform and provide results within 15 min. We describe our implementation and assess performance of the BinaxNOW COVID-19 Antigen Test (Abbott Laboratories) in 6,099 adults at a self-referred walk-up testing site. Participants were grouped by self-reported COVID-19 exposure and symptom status. Most (89%) were asymptomatic, of whom 17% reported potential exposure. Overall test sensitivity compared with reference laboratory reverse-transcription [RT] PCR testing was 81% (95% confidence interval [CI] 75%, 86%). It was higher in symptomatic (87%; 95% CI 80%, 91%) than asymptomatic (71%; 95% CI 61%, 80%) individuals. Sensitivity was 82% (95% CI 66%, 91%) for asymptomatic individuals with potential exposure and 64% (95% CI 51%, 76%) for those with no exposure. Specificity was greater than 99% for all groups. BinaxNOW has high accuracy among symptomatic individuals and is below the FDA threshold for emergency use authorization in asymptomatic individuals. Nonetheless, rapid antigen testing quickly identifies positive among those with symptoms and/or close contact exposure and could expedite isolation and treatment. IMPORTANCE The BinaxNOW rapid antigen COVID-19 test had a sensitivity of 87% in symptomatic and 71% asymptomatic individuals when performed by health care workers in a high-throughput setting. The performance may expedite isolation decisions or referrals for time-sensitive monoclonal antibody treatment in communities where timely COVID PCR tests are unavailable.

Abstract: Rehabilitation experts play an important role in preventing hospital-acquired debility, increasing patients' abilities to safely perform activities of daily living, and facilitating discharge to the home setting for patients with COVID-19. Surges in COVID-19 hospitalization rates combined with increases in length of hospital stay and decreases in postacute care placements have necessitated the opening of COVID-19 field hospitals around the country. Most field hospitals lack the resources to offer a full suite of rehabilitation services, but there are opportunities for small teams of rehabilitation experts to increase their reach by using innovative strategies. This article describes the implementation of a small team of rehabilitation experts in a COVID-19 field hospital and strategies used by this team to maximize patient activity and mobility, facilitate timely discharge, and maximize the number of patients discharged to the home setting. Strategies include training nonclinical staff to assist with activity and mobility promotion and using a rehabilitation triage system to determine needs of individual patients and facilitate efficient resource utilization. The authors reflect on successful aspects of these strategies, as well as barriers to rehabilitation implementation, and make recommendations for other field hospitals seeking to implement rehabilitation during the COVID-19 pandemic or future health crises., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To document demographic profile, clinical features and management of patients presented with PPD/Kala Pathar poisoning at District Teaching Hospital Sahiwal, Pakistan., Methods: This cross-sectional study utilized data for cases of PPD poisoning presented at study place from 1 st July 2019 to 30 th June 2020. Relevant information was recorded on a proforma., Results: A total of 111 cases were included in study. Mean age was 23.01 ± 7.24 years. Majority of cases were observed in females (82%) and majority presented from rural areas (87.4%). Cervico-facial edema (78.4%) and respiratory distress (66.7%) were the most common findings. Evidence of some level of organ damage was recorded in following manner: kidneys (44.1%), musculoskeletal (50.5%) and cardiac (45.9%). Tracheostomy was carried out in 47.7% cases and dialysis in 11.7% cases. All cases ingested PPD in raw form. Mortality rate was 50.5%., Conclusion: PPD poisoning is associated with high rate of morbidity and mortality. Effective clinical management requires multidisciplinary approach. Measures to restrict access to this means of suicide are urgently needed. We need to set up a surveillance system for cases of attempted suicide., Competing Interests: Conflict of Interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

The state of Maryland identified its first case of coronavirus disease 2019 (COVID-19) on March 5, 2020. The Baltimore Convention Center (BCCFH) quickly became a selected location to set up a 250-bed inpatient field hospital and alternate care site. In contrast to other field hospitals throughout the United States, the BCCFH remained open throughout the pandemic and took on additional COVID-19 missions, including community severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic testing, monoclonal antibody infusions for COVID-19 outpatients, and community COVID-19 vaccinations.To prevent the spread of pathogens during operations, infection prevention and control guidelines were essential to ensure the safety of staff and patients. Through multi-agency collaboration, use of infection prevention best practices, and answering what we describe as PPE-ESP, an operational framework was established to reduce infection risks for those providing or receiving care at the BCCFH during the COVID-19 pandemic.

The aim of the study was to determine the result of conservative management of Graves ophthalmopathy in a multi-disciplinary setting by a team of ophthalmologists and endocrinologists. Twenty-seven patients of thyroid eye disease were included in the study who underwent complete ocular examination and complete thyroid biochemical profile. Each patient was advised lubrication with artificial tears, cool compresses, sleeping with elevated head at bed, taping of the eyelids while sleeping and avoidance of smoking. Follow-ups were done at one and six months. EUGOGO classification was used to classify severity of the disease in mild, moderate, severe, and very severe; whereas, clinical activity score (CAS) was implied to categorise the disease activity. Mild to moderate Graves ophthalmopathy responded very well to conservative management. Moderate cases required additional steroids. Whereas, severe and very severe cases require additional surgical intervention. Key Words: Graves ophthalmology, Conservative management, Lubrication, Multidisciplinary approach.

Objective: Hospitalized patients placed in isolation due to a carrier state or infection with resistant or highly communicable organisms report higher rates of anxiety and loneliness and have fewer physician encounters, room entries, and vital sign records. We hypothesized that isolation status might adversely impact patient experience as reported through Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys, particularly regarding communication., Design: Retrospective analysis of HCAHPS survey results over 5 years., Setting: A 1,165-bed, tertiary-care, academic medical center., Patients: Patients on any type of isolation for at least 50% of their stay were the exposure group. Those never in isolation served as controls., Methods: Multivariable logistic regression, adjusting for age, race, gender, payer, severity of illness, length of stay and clinical service were used to examine associations between isolation status and "top-box" experience scores. Dose response to increasing percentage of days in isolation was also analyzed., Results: Patients in isolation reported worse experience, primarily with staff responsiveness (help toileting 63% vs 51%; adjusted odds ratio [aOR], 0.77; P = .0009) and overall care (rate hospital 80% vs 73%; aOR, 0.78; P < .0001), but they reported similar experience in other domains. No dose-response effect was observed., Conclusion: Isolated patients do not report adverse experience for most aspects of provider communication regarded to be among the most important elements for safety and quality of care. However, patients in isolation had worse experiences with staff responsiveness for time-sensitive needs. The absence of a dose-response effect suggests that isolation status may be a marker for other factors, such as illness severity. Regardless, hospitals should emphasize timely staff response for this population.

Expression of the adenoviral protein, E1A, sensitizes mammalian cells to a wide variety of apoptosis-inducing agents through multiple cellular pathways. For example, E1A sensitizes cells to apoptosis induced by TNF-superfamily members by inhibiting NF-kappa B (NF- κ B)-dependent gene expression. In contrast, E1A sensitization to nitric oxide, an inducer of the intrinsic apoptotic pathway, is not dependent upon repression of NF- κ B-dependent transcription but rather is dependent upon caspase-2 activation. The latter observation suggested that E1A-induced enhancement of caspase-2 activation might be a critical factor in cellular sensitization to other intrinsic apoptosis pathway-inducing agents. Etoposide and gemcitabine are two DNA damaging agents that induce intrinsic apoptosis. Here we report that E1A-induced sensitization to both of these agents, like NO, is independent of NF- κ B activation but dependent on caspase-2 activation. The results show that caspase-2 is a key mitochondrial-injuring caspase during etoposide and gemcitabine-induced apoptosis of E1A-positive cells, and that caspase-2 is required for induction of caspase-3 activity by both chemotherapeutic agents. Expression of PIDD was required for caspase-2 activation, mitochondrial injury and enhanced apoptotic cell death. Furthermore, E1A-enhanced sensitivity to injury-induced apoptosis required PIDD cleavage to PIDD-CC. These results define the PIDD/caspase-2 pathway as a key apical, mitochondrial-injuring mechanism in E1A-induced sensitivity of mammalian cells to chemotherapeutic agents.

Importance: There is an increasing trend toward designing hospitals with patient-centered features like reduced noise, improved natural light, visitor friendly facilities, well-decorated rooms, and hotel-like amenities. It has also been suggested that because patients cannot reliably distinguish positive experiences with the physical environment from positive experience with care, an improved hospital environment leads to higher satisfaction with physicians, nursing, food service, housekeeping, and higher overall satisfaction., Objective: To characterize changes in patient satisfaction that occurred when clinical services (comprised of stable nursing, physician, and unit teams) were relocated to a new clinical building with patient-centered features. We hypothesized that new building features would positively impact provider, ancillary staff, and overall satisfaction, as well as improved satisfaction with the facility., Design: Natural experiment utilizing a pre-post design with concurrent controls., Setting: Academic tertiary care hospital., Participants: We included all patients discharged from 12 clinical units that relocated to the new clinical building who returned surveys in the 7.5-month period following the move. Premove baseline data were captured from the year prior to the move. Patients on unmoved clinical units who returned satisfaction surveys served as concurrent controls., Exposure: Patient-centered design features incorporated into the new clinical building. All patients during the baseline period and control patients during the study period were located in usual patient rooms with standard hospital amenities., Main Outcomes and Measures: The primary outcome was satisfaction scores on the Press Ganey and Hospital Consumer Assessment of Healthcare Providers and Systems survey, dichotomized at highest category versus lower categories. We performed logistic regression to identify predictors of "top-box" scores., Results: The move was associated with improved room- and visitor-related satisfaction without significant improvement in satisfaction with clinical providers, ancillary staff, and only 1 of 4 measures of overall satisfaction improved. The most prominent increase was with pleasantness of décor (33.6% vs 64.8%) and visitor accommodation and comfort (50.0% vs 70.3%)., Conclusion and Relevance: Patients responded positively to pleasing surroundings and comfort, but were able to discriminate their experiences with the hospital environment from those with physicians and nurses. The move to a new building had significant impact on only 1 of the 4 measures of overall patient satisfaction, as clinical care is likely to be the most important determinant of this outcome. Hospital administrators should not use outdated facilities as an excuse for suboptimal provider satisfaction scores., (© 2014 Society of Hospital Medicine.)

Background: Specialty hospitals are a subset of acute-care hospitals that provide a narrower set of services than general medical hospitals (GMHs), predominantly in areas such as cardiac disease and surgery. Although specialty hospitals also advertise high patient satisfaction, this has not been examined using national data. We examined the differences in Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) satisfaction scores in a national sample., Methods: HCAHPS results were obtained for July 2007 to June 2010. Specialty hospitals were identified using the American Hospital Association's Annual Survey, the Physician Hospital Association's directory, a name search of hospitals on the HCAHPS database, contact with experts, and online searches. Multiple linear regression was performed to examine the relationship between overall satisfaction and hospital specialty status, survey response rate, and subdomains of patient satisfaction., Results: We identified 188 specialty hospitals and 4368 GMHs. Specialty hospitals were disproportionately located in states that do not require Certification Of Need (47.9%), and had a higher overall patient satisfaction score (86.6 vs 67.8%, P < 0.0001) and survey response rates (49.6% vs 32.2%, P < 0.0001). After adjusting for response rate, the difference in overall patient satisfaction decreased by >50% (from 18.5 to 8.7) but remained significantly higher (P < 0.0001). Similar results were obtained for patient satisfaction subdomains., Conclusion: Specialty hospitals have a significantly higher overall HCAHPS patient satisfaction score than GMHs, although more than half of this difference disappears when adjusted for survey response rate. Comparisons among healthcare organizations should take into account survey response rates., (© 2014 Society of Hospital Medicine.)

The adenovirus E1A oncogene induces innate immune rejection of tumors by sensitizing tumor cells to apoptosis in response to injuries, such as those inflicted by macrophage-produced TNF alpha and NO. E1A sensitizes cells to TNF by repressing its activation of NF-kappaB-dependent, antiapoptotic defenses. This suggested the hypothesis that E1A blockade of the NF-kappaB activation response might be the central mechanism of E1A induced cellular sensitivity to other proapoptotic injuries, such as macrophage-produced NO. However, creation of E1A-positive NIH-3T3 mouse cell variants with high-level, NF-kappaB-dependent resistance to TNF did not coselect for resistance to apoptosis induced by either macrophage-NO or chemical-NO, as the hypothesis would predict. E1A expression did block cellular recovery from NO-induced mitochondrial injury and converted the reversible, NO-induced cytostasis response of cells to an apoptotic response. This viral oncogene-induced phenotypic conversion of the cellular injury response of mouse and human cells was mediated by an E1A-related increase in NO-induced activation of caspase-2, an apical initiator of intrinsic apoptosis. Blocking caspase-2 activation or expression eliminated the NO-induced apoptotic response of E1A-positive cells. These results define an NF-kappaB-independent pathway through which the E1A gene of human adenovirus sensitizes mouse and human cells to apoptosis by enhancement of caspase-2-mediated mitochondrial injury.

Autosomal-recessive inheritance is believed to be relatively common in mental retardation (MR), although only four genes for nonsyndromic autosomal-recessive mental retardation (ARMR) have been reported. In this study, we ascertained a consanguineous Pakistani family with ARMR in four living individuals from three branches of the family, plus an additional affected individual later identified as a phenocopy. Retinitis pigmentosa was present in affected individuals, but no other features suggestive of a syndromic form of MR were found. We used Affymetrix 500K microarrays to perform homozygosity mapping and identified a homozygous and haploidentical region of 11.2 Mb on chromosome 4p15.33-p15.2. Linkage analysis across this region produced a maximum two-point LOD score of 3.59. We sequenced genes within the critical region and identified a homozygous splice-site mutation segregating in the family, within a coiled-coil and C2 domain-containing gene, CC2D2A. This mutation leads to the skipping of exon 19, resulting in a frameshift and a truncated protein lacking the C2 domain. Conservation analysis for CC2D2A suggests a functional domain near the C terminus as well as the C2 domain. Preliminary functional studies of CC2D2A suggest a possible role in Ca(2+)-dependent signal transduction. Identifying the function of CC2D2A, and a possible common pathway with CC2D1A, in correct neuronal development and functioning may help identify possible therapeutic targets for MR.

We show in rat lung microvessel endothelial cells (RLMVEC) that endocytosis is a critical determinant of activation of mitogen-activated protein kinase (MAPK) and thereby regulates endothelial monolayer integrity. In RLMVEC grown in serum-free medium, we observed that albumin supplementation induced the phosphorylation of p38 MAPK within 30 min, which persisted for up to 2 h. Engagement of the endocytic machinery regulated the activation of p38 MAPK that contributed to endothelial cell proliferation and reduction of apoptosis. We also observed an interaction between the caveolar protein caveolin-1 and p38 MAPK with reciprocal coimmunoprecipitation assays and colocalization using double-label immunofluorescence staining. Knockdown of caveolin-1 expression with small interfering RNA significantly reduced endocytosis and activation of p38 MAPK and interfered with the ability of endothelial cells to form a confluent monolayer. Thus caveolae-mediated endocytosis and concomitant activation of p38 MAPK may help to maintain endothelial monolayer integrity by signaling proliferation and survival of endothelial cells.

Vascular endothelial cells undergo albumin endocytosis using a set of albumin binding proteins. This process is important for maintaining cellular homeostasis. We showed by several criteria that the previously described 73-kDa endothelial cell surface albumin binding protein is the 75-kDa transforming growth factor (TGF)-beta receptor type II (TbetaRII). Albumin coimmunoprecipitated with TbetaRII from a membrane fraction from rat lung microvascular endothelial cells. Albumin endocytosis-negative COS-7 cells became albumin endocytosis competent when transfected with wild-type TbetaRII but not when transfected with a domain-negative kinase mutant of TbetaRII. An antibody specific for TbetaRII inhibited albumin endocytosis. A mink lung epithelial cell line, which expresses both the TGF-beta receptor type I (TbetaRI) and the TbetaRII receptor, exhibited albumin binding to the cell surface and endocytosis. In contrast, mutant L-17 and DR-26 cells lacking TbetaRI or TbetaRII, respectively, each showed a dramatic reduction in binding and endocytosis. Albumin endocytosis induced Smad2 phosphorylation and Smad4 translocation as well as increased protein expression of the inhibitory Smad, Smad7. We identified regions of significant homology between amino acid sequences of albumin and TGF-beta, suggesting a structural basis for the interaction of albumin with the TGF-beta receptors and subsequent activation of TbetaRII signaling. The observed albumin-induced internalization of TbetaRII signaling may be an important mechanism in the vessel wall for controlling TGF-beta responses in endothelial cells.

G alpha 12/13-mediated pathways have been shown to be involved in various fundamental cellular functions in mammalian cells such as axonal guidance, apoptosis, and chemotaxis. Here, we identified a homologue of Rho-guanine nucleotide exchange factor (GEF) in Caenorhabditis elegans (CeRhoGEF), which functions downstream of gpa-12, the C. elegans homologue of G alpha 12/13. CeRhoGEF contains a PSD-95/Dlg/ZO-1 domain and a regulator of G protein signaling (RGS) domain upstream of the Dbl homology-pleckstrin homology region similar to mammalian RhoGEFs with RGS domains, PSD-95/Dlg/ZO-1-RhoGEF and leukemia-associated RhoGEF. It has been shown in mammalian cells that these RhoGEFs interact with activated forms of G alpha 12 or G alpha 13 through their RGS domains. We demonstrated by coimmunoprecipitation that the RGS domain of CeRhoGEF interacts with GPA-12 in an AIF4- activation-dependent manner and confirmed that the Dbl homology-pleckstrin homology domain of CeRhoGEF was capable of Rho-dependent signaling. These results proved conservation of the G alpha 12-RhoGEF pathway in C. elegans. Expression of DsRed or GFP under the control of the promoter of CeRhoGEF or gpa-12 revealed an overlap of their expression patterns in ventral cord motor neurons and several neurons in the head. RNA-mediated gene interference for CeRhoGEF and gpa-12 resulted in similar phenotypes such as embryonic lethality and sensory and locomotive defects in adults. Thus, the G alpha 12/13-RhoGEF pathway is likely to be involved in embryonic development and neuronal function in C. elegans.

Kinesins are intracellular multimeric transport motor proteins that move cellular cargo on microtubule tracks. It has been shown that the sea urchin KRP85/95 holoenzyme associates with a KAP115 non-motor protein, forming a heterotrimeric complex in vitro, called the Kinesin-II. Here we describe isolation of a cDNA clone corresponding to the klp-11 kinesin in C. elegans. Our sequence analysis of the encoded KLP-11 shows that it shares high homology with the OSM-3 kinesin. We also describe a nematode cDNA encoding KAP-1 that shares extensive homology with the sea urchin KAP115 kinesin associated protein. Sequence-based structural analysis of the OSM-3, KLP-11, and KAP-1, presented here suggests that these may form a heterotrimeric complex. We also describe the presence of a Drosophila armadillo consensus motif in CeKAP-1, first found in spKAP115, that suggests a possible role for the KAP-1 in signal transduction.

C-terminal kinesin motor proteins, such as the Drosophila NCD and yeast KAR3, are involved in chromosomal segregation. Previously we have described two orthologs of NCD in Caenorhabditis elegans, KLP-3 and KLP-17, which also participate in chromosome movement. Here we report cDNA cloning of klp-15 and klp-16, and the expression pattern of the genes encoding C-terminal motor kinesins including klp-15 and klp-16. Interestingly KLP-15 and KLP-16 form a unique class of C-terminal kinesins, distinct from the previously known C-terminal motors in other organisms. Using in situ hybridization and RNA interference assay, we show that although all of these motors mediate chromosome segregation, they do so in a combination of unique and overlapping manners, suggesting a complex hierarchy of kinesin motor function in metazoans.

mec-12 is one of a dozen genes required for touch receptor neuron function in Caenorhabditis elegans. Some mec-12 mutants (mechanosensory-defective) lack the large-diameter microtubules that are characteristic of these neurons (15 protofilaments, as opposed to 11). Mutants of mec-7, a alpha-tubulin encoding gene, have a similar phenotype. We have identified the nature of mec-12 by germline transformation rescue and characterization of a point mutation. Sequence analysis of the mec-12 encoded product (MEC-12) indicates that it corresponds to a novel C. elegans alpha-tubulin. MEC-12 is the only identified C. elegans alpha-tubulin that contains a lysine at position 40, a known site of post-translational acetylation. Some mec-12 mutations eliminate microtubule acetylation as assayed immunocyto-chemically; phenotypic rescue using a MEC-12 variant lacking the lysine-40 showed that acetylation is not required for MEC-12 activity. Although functionally needed only in the touch neurons, mec-12 is expressed in several other neuron types. These results support the notion that tubulin isotype diversity contributes to the formation of distinct classes of microtubules; 15-protofilament microtubule assembly requires MEC-12 alpha-tubulin and MEC-7 beta-tubulin, which are both highly expressed in the touch receptor neurons. MEC-12 is the first reported alpha-tubulin isotype that appears to be required in a single class of neuronal microtubules.

Common to all eukaryotes, kinesins are cytoskeletal motor proteins that mediate intracellular transport on microtubule tracks, using ATP hydrolysis. A Caenorhabditis elegans cDNA clone corresponding to the klp-3 gene, encoding a novel kinesin, was isolated, and mapped on LGII. Northern blot analysis using the klp-3 cDNA probe reveals a 1.9 kb mRNA that is transcribed at a low level during development. Temporal and spatial expression of the klp-3::lacZ fusion gene is limited to the marginal cells in the pharynx, and a group of muscle cells in the posterior gut region. The nucleotide sequence of klp-3 has been deduced from the cDNA and nematode genome sequencing consortium data. Conceptual translation of the klp-3 gene reveals a kinesin-like protein with its conserved motor domain containing the ATP binding and microtubule binding sites located in the C terminus. KLP-3 shares extensive homology with the yeast Kar3 and Drosophila ncd kinesins, which have previously been shown to mediate chromosomal movement and segregation during meiosis and mitosis. Overexpression of the klp-3 gene partially rescues the lethal phenotype of the maternal lethal him-14 ts(it44) mutants at non-permissive temperatures, and reduces the incidence of males caused by non-disjunction of the X-chromosome. Similarly, expression of a klp-3 antisense RNA, under the control of a heat shock promoter, causes embryonic arrest, dead eggs and polyploid cells in transgenic lines, suggesting a critical role for the klp-3 function in chromosome segregation. Further analysis of the klp-3 gene in C. elegans may elucidate diverse functions of the C terminus mitotic motor proteins during development.

In Caenorhabditis elegans three genetic loci osm-3, unc-104 and unc-116 have been identified, which encode anterograde motor kinesin. Here we show that osm-3 encodes a 672 amino acid long kinesin-like protein (KLP) that contains all three functional domains similar to the kinesin heavy chain, including a globular motor region, an alpha-helical coiled-coil rod, and a globular tail region. OSM-3 shows homology in both the motor and rod domains with kinesins from divergent species such as mouse KIF3, and sea urchin KRP95, and also with the rod domains of several non-kinesin proteins, such as myosin, ezrin, outer membrane proteins alpha precursor OMPA, yeast intracellular protein transport USO1, and the rat neurofilament NF-H. Temporal and spatial expression of the osm-3::lacZ fusion gene during development is limited to an exclusive set of 26 chemosensory neurons whose dendritic endings are exposed to the external environment, including six IL2 neurons of the inner labial sensilla, eight pairs of amphid neurons (ADF, ADL, ASE, ASG, ASH, ASI, ASJ, ASK) in the head, and two pairs of phasmid neurons (PHA and PHB) in the tail. Our data are consistent with the known structural defects in the amphid and phasmid sensilla in osm-3 mutants and also show the expression of the gene in IL2 neurons. Temporally, the gene is differentially expressed in all three types of chemosensory sensilla. Further work on osm-3, unc-104 and unc-116 mutants should give insight into the in vivo functions of the kinesin family during C. elegans neurogenesis.