Now showing items 1-20 of 14632

    • Impact of Andrographolide and Melatonin Combinatorial Drug Therapy on Metastatic Colon Cancer Cells and Organoids

      Sharda, Neha; Ikuse, Tamaki; Hill, Elizabeth; Garcia, Sonia; Czinn, Steven J.; Bafford, Andrea; Blanchard, Thomas G.; Banerjee, Aditi (SAGE Publications Inc., 2021-06-04)
      Background: The death rate (the number of deaths per 100 000 people per year) of colorectal cancer (CRC) has been dropping since 1980 due to increased screening, lifestyle-related risk factors, and improved treatment options; however, CRC is the third leading cause of cancer-related deaths in men and women in the United States. Therefore, successful therapy for CRC is an unmet clinical need. This study aimed to investigate the impacts of andrographolide (AGP) and melatonin (MLT) on CRC and the underlying mechanism. Methods: To investigate AGP and MLT anticancer effects, a series of metastatic colon cancer cell lines (T84, Colo 205, HT-29, and DLD-1) were selected. In addition, a metastatic patient-derived organoid model (PDOD) was used to monitor the anticancer effects of AGP and MLT. A series of bioassays including 3D organoid cell culture, MTT, colony formation, western blotting, immunofluorescence, and quantitative polymerase chain reaction (qPCR) were performed. Results: The dual therapy significantly promotes CRC cell death, as compared with the normal cells. It also limits CRC colony formation and disrupts the PDOD membrane integrity along with decreased Ki-67 expression. A significantly higher cleaved caspase-3 and the endoplasmic reticulum (ER) stress proteins, IRE-1 and ATF-6 expression, by 48 hours were found. This combinatorial treatment increased reactive oxygen species (ROS) levels. Apoptosis signaling molecules BAX, XBP-1, and CHOP were significantly increased as determined by qPCR. Conclusions: These findings indicated that AGP and MLT associated ER stress-mediated apoptotic metastatic colorectal cancer (mCRC) cell death through the IRE-1/XBP-1/CHOP signaling pathway. This novel combination could be a potential therapeutic strategy for mCRC cells. © The Author(s) 2021.
    • Platform Incubator with Movable XY Stage: A New Platform for Implementing In-Cell Fast Photochemical Oxidation of Proteins

      Johnson, Danté; Punshon-Smith, Benjamin; Espino, Jessica A; Gershenson, Anne; Jones, Lisa M (MYJoVE Corporation, 2021-05-17)
      Fast Photochemical Oxidation of proteins (FPOP) coupled with mass spectrometry (MS) has become an invaluable tool in structural proteomics to interrogate protein interactions, structure, and protein conformational dynamics as a function of solvent accessibility. In recent years, the scope of FPOP, a hydroxyl radical protein foot printing (HRPF) technique, has been expanded to protein labeling in live cell cultures, providing the means to study protein interactions in the convoluted cellular environment. In-cell protein modifications can provide insight into ligand induced structural changes or conformational changes accompanying protein complex formation, all within the cellular context. Protein footprinting has been accomplished employing a customary flow-based system and a 248 nm KrF excimer laser to yield hydroxyl radicals via photolysis of hydrogen peroxide, requiring 20 minutes of analysis for one cell sample.To facilitate time-resolved FPOP experiments, the use of a new 6-well plate-based IC-FPOP platform was pioneered. In the current system, a single laser pulse irradiates one entire well, which truncates the FPOP experimental time frame resulting in 20 seconds of analysis time, a 60-fold decrease. This greatly reduced analysis time makes it possible to research cellular mechanisms such as biochemical signaling cascades, protein folding, and differential experiments (i.e., drug-free vs. drug bound) in a time-dependent manner. This new instrumentation, entitled Platform Incubator with Movable XY Stage (PIXY), allows the user to perform cell culture and IC-FPOP directly on the optical bench using a platform incubator with temperature, CO2 and humidity control. The platform also includes a positioning stage, peristaltic pumps, and mirror optics for laser beam guidance. IC-FPOP conditions such as optics configuration, flow rates, transient transfections, and H2O2 concentration in PIXY have been optimized and peer-reviewed. Automation of all components of the system will reduce human manipulation and increase throughput.
    • Current mental health clients’ attitudes regarding religion and spirituality in treatment: A national survey

      Oxhandler, Holly K.; Pargament, Kenneth I.; Pearce, Michelle J.; Vieten, Cassandra; Moffatt, Kelsey M. (MDPI AG, 2021-05-21)
      Over the last several years, there has been a growing interest in clients’ views toward integrating their religion and spirituality (RS) into mental health treatment. However, most of these studies have been limited to small samples and specific populations, regions, and/or clinical issues. This article describes the first national survey of current mental health clients across the US regarding their attitudes towards integrating their RS in treatment using a revised version of the Religious/Spiritually Integrated Practice Assessment Scale-Client Attitudes, version 2 (RSIPAS-CAv2) with a sample of 989 clients. Our findings indicate mental health clients have overwhelmingly positive attitudes regarding integrating their RS into mental health treatment. Additionally, we explored what background characteristics predict clients’ attitudes toward this area of practice and found the top predictor was their intrinsic religiosity, followed by whether they had previously discussed RS with their current provider, age, gender, organized and non-organized religious activities, belief in God/Higher Power, and frequency of seeing their mental health provider. The reliability and validity of the RSIPAS-CAv2 was also explored and this scale is recommended for future use. Implications and recommendations for practice, research, and future training efforts are discussed.
    • Prevalence and seroprevalence of Plasmodium infection in Myanmar reveals highly heterogeneous transmission and a large hidden reservoir of infection

      Edwards, Hannah M; Dixon, Ruth; Zegers de Beyl, Celine; Celhay, Olivier; Rahman, Mousumi; Myint Oo, Moe; Lwin, Thandar; Lin, Zaw; San, Thiri; Thwe Han, Kay; et al. (Public Library of Science, 2021-06-09)
      Malaria incidence in Myanmar has significantly reduced over recent years, however, completeness and timeliness of incidence data remain a challenge. The first ever nationwide malaria infection and seroprevalence survey was conducted in Myanmar in 2015 to better understand malaria epidemiology and highlight gaps in Annual Parasite Index (API) data. The survey was a cross-sectional two-stage stratified cluster-randomised household survey conducted from July-October 2015. Blood samples were collected from household members for ultra-sensitive PCR and serology testing for P. falciparum and P. vivax. Data was gathered on demography and a priori risk factors of participants. Data was analysed nationally and within each of four domains defined by API data. Prevalence and seroprevalence of malaria were 0.74% and 16.01% nationwide, respectively. Prevalent infection was primarily asymptomatic P. vivax, while P. falciparum was predominant in serology. There was large heterogeneity between villages and by domain. At the township level, API showed moderate correlation with P. falciparum seroprevalence. Risk factors for infection included socioeconomic status, domain, and household ownership of nets. Three K13 P. falciparum mutants were found in highly prevalent villages. There results highlight high heterogeneity of both P. falciparum and P. vivax transmission between villages, accentuated by a large hidden reservoir of asymptomatic P. vivax infection not captured by incidence data, and representing challenges for malaria elimination. Village-level surveillance and stratification to guide interventions to suit local context and targeting of transmission foci with evidence of drug resistance would aid elimination efforts.
    • A Versatile Human Intestinal Organoid-Derived Epithelial Monolayer Model for the Study of Enteric Pathogens

      Nickerson, Kourtney P; Llanos-Chea, Alejandro; Ingano, Laura; Serena, Gloria; Miranda-Ribera, Alba; Perlman, Meryl; Lima, Rosiane; Sztein, Marcelo B; Fasano, Alessio; Senger, Stefania; et al. (ASM Press, 2021-06-09)
      Gastrointestinal infections cause significant morbidity and mortality worldwide. The complexity of human biology and limited insights into host-specific infection mechanisms are key barriers to current therapeutic development. Here, we demonstrate that two-dimensional epithelial monolayers derived from human intestinal organoids, combined with in vivo-like bacterial culturing conditions, provide significant advancements for the study of enteropathogens. Monolayers from the terminal ileum, cecum, and ascending colon recapitulated the composition of the gastrointestinal epithelium, in which several techniques were used to detect the presence of enterocytes, mucus-producing goblet cells, and other cell types following differentiation. Importantly, the addition of receptor activator of nuclear factor kappa-B ligand (RANKL) increased the presence of M cells, critical antigen-sampling cells often exploited by enteric pathogens. For infections, bacteria were grown under in vivo-like conditions known to induce virulence. Overall, interesting patterns of tissue tropism and clinical manifestations were observed. Shigella flexneri adhered efficiently to the cecum and colon; however, invasion in the colon was best following RANKL treatment. Both Salmonella enterica serovars Typhi and Typhimurium displayed different infection patterns, with S. Typhimurium causing more destruction of the terminal ileum and S. Typhi infecting the cecum more efficiently than the ileum, particularly with regard to adherence. Finally, various pathovars of Escherichia coli validated the model by confirming only adherence was observed with these strains. This work demonstrates that the combination of human-derived tissue with targeted bacterial growth conditions enables powerful analyses of human-specific infections that could lead to important insights into pathogenesis and accelerate future vaccine development. IMPORTANCE While traditional laboratory techniques and animal models have provided valuable knowledge in discerning virulence mechanisms of enteric pathogens, the complexity of the human gastrointestinal tract has hindered our understanding of physiologically relevant, human-specific interactions; and thus, has significantly delayed successful vaccine development. The human intestinal organoid-derived epithelial monolayer (HIODEM) model closely recapitulates the diverse cell populations of the intestine, allowing for the study of human-specific infections. Differentiation conditions permit the expansion of various cell populations, including M cells that are vital to immune recognition and the establishment of infection by some bacteria. We provide details of reproducible culture methods and infection conditions for the analyses of Shigella, Salmonella, and pathogenic Escherichia coli in which tissue tropism and pathogen-specific infection patterns were detected. This system will be vital for future studies that explore infection conditions, health status, or epigenetic differences and will serve as a novel screening platform for therapeutic development.
    • Management of Patients with Asymptomatic Carotid Stenosis May Need to Be Individualized: A Multidisciplinary Call for Action

      Paraskevas, Kosmas I; Mikhailidis, Dimitri P; Baradaran, Hediyeh; Davies, Alun H; Eckstein, Hans-Henning; Faggioli, Gianluca; Fernandes, Jose Fernandes E; Gupta, Ajay; Jezovnik, Mateja K; Kakkos, Stavros K; et al. (Korean Stroke Society, 2021-05-31)
      The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g., silent embolic infarcts on brain computed tomography/magnetic resonance imaging, progression in the severity of ACS, a history of contralateral transient ischemic attack/stroke, microemboli detection on transcranial Doppler, etc.), provided documented perioperative stroke/death rates are <3% and the patient's life expectancy is >5 years. Besides these clinical/imaging characteristics, there are additional individual, ethnic/racial or social factors that should probably be evaluated in the decision process regarding the optimal management of these patients, such as individual patient needs/patient choice, patient compliance with best medical treatment, patient sex, culture, race/ethnicity, age and comorbidities, as well as improvements in imaging/operative techniques/outcomes. The present multispecialty position paper will present the rationale why the management of patients with ACS may need to be individualized.
    • Selection of pfcrt k76 and pfmdr1 n86 coding alleles after uncomplicated malaria treatment by artemether-lumefantrine in Mali

      Maiga, Hamma; Grivoyannis, Anastasia; Sagara, Issaka; Traore, Karim; Traore, Oumar B.; Tolo, Youssouf; Traore, Aliou; Bamadio, Amadou; Traore, Zoumana I.; Sanogo, Kassim; et al. (MDPI AG, 2021-06-03)
      Background: Artemether-lumefantrine is a highly effective artemisinin-based combination therapy that was adopted in Mali as first-line treatment for uncomplicated Plasmodium falciparum malaria. This study was designed to measure the efficacy of artemether-lumefantrine and to assess the selection of the P. falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multi-drug resistance 1 (pfmdr1) genotypes that have been associated with drug resistance. Methods: A 28-day follow-up efficacy trial of artemether-lumefantrine was conducted in patients aged 6 months and older suffering from uncomplicated falciparum malaria in four different Malian areas during the 2009 malaria transmission season. The polymorphic genetic markers MSP2, MSP1, and Ca1 were used to distinguish between recrudescence and reinfection. Reinfection and recrudescence were then grouped as recurrent infections and analyzed together by PCR-restriction fragment length polymorphism (RFLP) to identify candidate markers for artemether-lumefantrine tolerance in the P. falciparum chloroquine resistance transporter (pfcrt) gene and the P. falciparum multi-drug resistance 1 (pfmdr1) gene. Results: Clinical outcomes in 326 patients (96.7%) were analyzed and the 28-day uncorrected adequate clinical and parasitological response (ACPR) rate was 73.9%. The total PCR-corrected 28-day ACPR was 97.2%. The pfcrt 76T and pfmdr1 86Y population prevalence decreased from 49.3% and 11.0% at baseline (n = 337) to 38.8% and 0% in patients with recurrent infection (n = 85); p = 0.001), respectively. Conclusion: Parasite populations exposed to artemether-lumefantrine in this study were selected toward chloroquine-sensitivity and showed a promising trend that may warrant future targeted reintroduction of chloroquine or/and amodiaquine. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
    • Risk factors associated with atraumatic posterolateral rotatory instability

      Gilotra, Mohit N.; Fridman, Jake; Enobun, Blessing; Kuntz, Andrew F.; Glaser, David L.; Huffman, G. Russell (Elsevier B.V., 2021-04-09)
      Background: Traumatic posterolateral rotatory instability after elbow dislocation or fracture dislocation has been well described. However, few reports cover atraumatic posterolateral rotatory instability as a cause of lateral-sided elbow pain. We assessed the risk factors and epidemiology of atraumatic posterolateral rotatory instability in a case-control study. Methods: A retrospective review of all patients treated operatively for atraumatic posterolateral rotatory instability during a 6-year period was compared with a group of patients with extensor carpi radialis brevis tendinopathy without instability treated during the same time period. Bivariate and multiple logistic regression statistical analyses were used to investigate the following risk factors: gender, age, hand dominance, diabetes, smoking, body mass index, corticosteroid injection history, and duration of symptoms. Disabilities of the Arm, Shoulder, and Hand and pain scores were obtained preoperatively and postoperatively. Results: Thirteen patients with atraumatic posterolateral rotatory instability were compared with 12 patients with extensor carpi radialis brevis tendinopathy. Multivariate analysis revealed patients with atraumatic posterolateral rotatory instability were more likely to have multiple corticosteroid injections (P =.05) and present with a longer duration of symptoms (P =.03). Postoperative pain scores improved in both groups. Conclusions: Atraumatic posterolateral rotatory instability should be considered in the differential diagnosis of lateral elbow when patients present with a protracted clinical course. Statistically, posterolateral rotatory instability patients more often present with a history of multiple corticosteroid injections. © 2021 The Authors
    • Academic Achievement, Professionalism, and Burnout in Family Medicine Residents

      Davis, Caitlin; Krishnasamy, Meenu; Morgan, Zachary J; Bazemore, Andrew W; Peterson, Lars E (Society of Teachers of Family Medicine, 2021-06)
      Background and objectives: Physician burnout has been shown to have roots in training environments. Whether burnout in residency is associated with the attainment of critical educational milestones has not been studied, and is the subject of this investigation. Methods: We used data from a cohort of graduating family medicine residents registering for the 2019 American Board of Family Medicine initial certification examination with complete data from registration questionnaire, milestone data, in-training examination (ITE) scores, and residency characteristics. We used bivariate and multilevel multivariate analyses to measure the associations between four professionalism milestones ratings and ITE performance with burnout. Results: Our sample included 2,509 residents; 36.8% met the criteria for burnout. Multilevel regression modeling showed a correlation between burnout and failure to meet only one of four professionalism milestones, specifically professional conduct and accountability (OR 1.41, 95% CI 1.07-1.87), while no statistically significant relationship was demonstrated between burnout and being in the lowest quartile of ITE scores. Other factors negatively associated with burnout included international medical education (OR 0.60, 95% CI 0.48-0.76) and higher salary compared to cost of housing (OR 0.62, 95% CI 0.46-0.82). Conclusions: We found significant association between self-reported burnout and failing to meet expectations for professional conduct and accountability, but no relationship between burnout and medical knowledge as measured by lower ITE performance. Further investigation of how this impacts downstream conduct and accountability behaviors is needed, but educators can use this information to examine program-level interventions that can specifically address burnout and development of physician professionalism.
    • Safety and immunogenicity of Vi-typhoid conjugate vaccine co-administration with routine 9-month vaccination in Burkina Faso: A randomised controlled phase 2 trial

      Sirima, Sodiomon B; Ouedraogo, Alphonse; Barry, Nouhoun; Siribie, Mohamadou; Tiono, Alfred; Nébié, Issa; Konaté, Amadou; Berges, Gloria Damoaliga; Diarra, Amidou; Ouedraogo, Moussa; et al. (Elsevier Ltd., 2021-06-01)
      Objectives: In 2017, the World Health Organisation (WHO) pre-qualified a single-dose typhoid conjugate vaccine (TCV) and identified TCV co-administration studies as a research priority. We tested co-administration of Typbar TCV® (Bharat Biotech International) with measles-rubella (MR) and yellow fever (YF) vaccines. Methods: We conducted a randomised, double-blind, and controlled, phase 2 trial in Ouagadougou, Burkina Faso. Healthy children aged 9-11 months were randomised 1:1 to receive TCV (Group 1) or control vaccine (inactivated polio vaccine (IPV), Group 2). Vaccines were administered intramuscularly with routine MR and YF vaccines. Safety was assessed by 1) local and systemic reactions on days 0, 3, and 7; 2) unsolicited adverse events within 28 days; and 3) serious adverse events (SAEs) within 6 months after immunisation. Results: We enrolled, randomised, and vaccinated 100 eligible children (49 Group 1 and 51 Group 2). Safety outcomes occurred with similar frequency in both groups: local/solicited reactions (Group 1: 1/49, Group 2: 3/50), systemic/solicited reactions (Group 1: 4/49, Group 2: 9/50), unsolicited adverse events (Group 1: 26/49, Group 2: 33/51), and SAEs (Group 1: 2/49, Group 2: 3/51). TCV conferred robust immunogenicity without interference with MR or YF vaccines. Conclusion: TCV can be safely co-administered with MR and YF vaccines to children at the 9-month vaccination visit.
    • Evidence on yoga for health: a bibliometric analysis of systematic reviews

      Wieland, L S; Cramer, H; Lauche, R; Verstappen, A; Parker, E A; Pilkington, K (Elsevier Inc., 2021-06-04)
      Objective: To support the research agenda in yoga for health by comprehensively identifying systematic reviews of yoga for health outcomes and conducting a bibliometric analysis to describe their publication characteristics and topic coverage. Methods: We searched 7 databases (MEDLINE/PubMed, Embase, PsycINFO, CINAHL, AMED, the Cochrane Database of Systematic Reviews, and PROSPERO) from their inception to November 2019 and 1 database (INDMED) from inception to January 2017. Two authors independently screened each record for inclusion and one author extracted publication characteristics and topics of included reviews. Results: We retrieved 2710 records and included 322 systematic reviews. 157 reviews were exclusively on yoga, and 165 were on yoga as one of a larger class of interventions (e.g., exercise). Most reviews were published in 2012 or later (260/322; 81%). First/corresponding authors were from 32 different countries; three-quarters were from the USA, Germany, China, Australia, the UK or Canada (240/322; 75%). Reviews were most frequently published in speciality journals (161/322; 50%) complementary medicine journals (66/322; 20%) or systematic review journals (59/322; 18%). Almost all were present in MEDLINE (296/322; 92%). Reviews were most often funded by government or non-profits (134/322; 42%), unfunded (74/322; 23%), or not explicit about funding (111/322; 34%). Common health topics were psychiatric/cognitive (n = 56), cancer (n = 39) and musculoskeletal conditions (n = 36). Multiple reviews covered similar topics, particularly depression/anxiety (n = 18), breast cancer (n = 21), and low back pain (n = 16). Conclusions: Further research should explore the overall quality of reporting and conduct of systematic reviews of yoga, the direction and certainty of specific conclusions, and duplication or gaps in review coverage of topics.
    • Effect of mupirocin for Staphylococcus aureus decolonization on the microbiome of the nose and throat in community and nursing home dwelling adults

      Roghmann, Mary-Claire; Lydecker, Alison D; Shardell, Michelle; DeBoy, Robert T; Johnson, J Kristie; Zhao, LiCheng; Hittle, Lauren L; Mongodin, Emmanuel F (Public Library of Science, 2021-06-08)
      Objective: To characterize the microbial communities of the anterior nares (nose) and posterior pharynx (throat) of adults dwelling in the community and in nursing homes before and after treatment with intranasal mupirocin. Methods: Staphylococcus aureus-colonized adults were recruited from the community (n = 25) and from nursing homes (n = 7). S. aureus colonization was confirmed using cultures. Participants had specimens taken from nose and throat for S. aureus quantitation using quantitative PCR for the nuc gene and bacterial profiling using 16S rRNA gene sequencing over 12 weeks. After two baseline study visits 4 weeks apart, participants received intranasal mupirocin for 5 days with 3 further visits over a 8 week follow-up period. Results: We found a decrease in the absolute abundance of S. aureus in the nose for 8 weeks after mupirocin (1693 vs 141 fg/ul, p = 0.047). Mupirocin caused a statistically significant disruption in bacterial communities of the nose and throat after 1 week, which was no longer detected after 8 weeks. Bacterial community profiling demonstrated that there was a decrease in the relative abundance of S. aureus (8% vs 0.3%, p<0.01) 8 weeks after mupirocin and a transient decrease in the relative abundance of Staphylococcus epidermidis in the nose (21% vs 5%, p<0.01) 1 week after mupirocin. Conclusions: Decolonization with mupirocin leads to a sustained effect on absolute and relative abundance of S. aureus but not for other bacteria in the nose. This demonstrates that a short course of mupirocin selectively decreases S. aureus in the nose for up to 8 weeks.
    • Beyond the jab: A need for global coordination of pharmacovigilance for COVID-19 vaccine deployment

      Naniche, Denise; Hotez, Peter; Bottazzi, Maria Elena; Ergonul, Onder; Figueroa, J Peter; Gilbert, Sarah; Gursel, Mayda; Hassanain, Mazen; Kang, Gagandeep; Kaslow, David; et al. (Elsevier Ltd., 2021-06-03)
    • Implementation of peer specialist services in VA primary care: a cluster randomized trial on the impact of external facilitation

      Chinman, Matthew; Goldberg, Richard; Daniels, Karin; Muralidharan, Anjana; Smith, Jeffrey; McCarthy, Sharon; Medoff, Deborah; Peeples, Amanda; Kuykendall, Lorrianne; Vineyard, Natalie; et al. (Springer Nature, 2021-06-07)
      Background: Over 1100 veterans work in the Veterans Health Administration (VHA) as peer specialists (PSs)-those with formal training who support other veterans with similar diagnoses. A White House Executive Action mandated the pilot reassignment of VHA PSs from their usual placement in mental health to 25 primary care Patient Aligned Care Teams (PACTs) in order to broaden the provision of wellness services that can address many chronic illnesses. An evaluation of this initiative was undertaken to assess the impact of outside assistance on the deployment of PSs in PACTs, as implementation support is often needed to prevent challenges commonly experienced when first deploying PSs in new settings. Methods: This study was a cluster-randomized hybrid II effectiveness-implementation trial to test the impact of minimal implementation support vs. facilitated implementation on the deployment of VHA PSs in PACT over 2 years. Twenty-five Veterans Affairs Medical Centers (VAMCs) were recruited to reassign mental health PSs to provide wellness-oriented care in PACT. Sites in three successive cohorts (n = 7, 10, 8) over 6-month blocks were matched and randomized to each study condition. In facilitated implementation, an outside expert worked with site stakeholders through a site visit and regular calls, and provided performance data to guide the planning and address challenges. Minimal implementation sites received a webinar and access to the VHA Office of Mental Health Services work group. The two conditions were compared on PS workload data and veteran measures of activation, satisfaction, and functioning. Qualitative interviews collected information on perceived usefulness of the PS services. Results: In the first year, sites that received facilitation had higher numbers of unique veterans served and a higher number of PS visits, although the groups did not differ after the second year. Also, sites receiving external facilitation started delivering PS services more quickly than minimal support sites. All sites in the external facilitation condition continued in the pilot into the second year, whereas two of the sites in the minimal assistance condition dropped out after the first year. There were no differences between groups on veterans' outcomes-activation, satisfaction, and functioning. Most veterans were very positive about the help they received as evidenced in the qualitative interviews. Discussion: These findings demonstrate that external facilitation can be effective in supporting the implementation of PSs in primary care settings. The lack of significant differences across conditions after the second year highlights the positive outcomes associated with active facilitation, while also raising the important question of whether longer-term success may require some level of ongoing facilitation and implementation support. Trial registration: This project is registered at with number NCT02732600 (URL: ).
    • An accurate method of measuring shoulder sling compliance: a validation study

      Sood, Anshum; Klein, Ashley; Kaveeshwar, Samir; Jones, Derek L; Duvall, Grant; Hovis, James Paul; Weir, Tristan B; Enobun, Blessing; Hasan, S Ashfaq; Henn, R Frank; et al. (Springer Nature, 2021-06-07)
      Background The effect of postoperative shoulder sling compliance on surgical outcomes is unknown. The goal was to determine an accurate method to measure sling compliance. We compared volunteer recorded sling wear time with temperature-based sensors to monitor sling compliance. Methods Data loggers sutured at three locations measured heat generated in 15-minute intervals. Slings wearers logged sling wear to accurately cross-reference with temperature sensors. Secondary experiments analyzed whether surrounding ambient temperature can be discerned from actual sling wear. We created an algorithm to describe actual sling wear time as a function of heat recorded and calculated percent wear accuracy. Results The modified sling was worn for 172 h. The algorithm modeled sling on/off times by analyzing cutoff temperatures. Diagnostic accuracy was >99 % for the three locations, with no statistically significant differences among them. Compared with sling wear, ambient temperature took longer to reach critical temperature values determined by the algorithm, helping distinguish compliance from false positives. Conclusions The described algorithm can effectively quantify shoulder sling wear time based on heat-generated sensor readings. False positives from ambient temperature are minimal. This measurement method could be used to study the relationship between postoperative sling use and functional outcomes after shoulder surgery.
    • SARS-CoV-2 infection and paediatric endocrine disorders: Risks and management considerations

      Miller, Ryan; Ashraf, Ambika P.; Gourgari, Evgenia; Gupta, Anshu; Kamboj, Manmohan K.; Kohn, Brenda; Lahoti, Amit; Mak, Daniel; Mehta, Shilpa; Mitchell, Deborah; et al. (Blackwell Publishing, 2021-06-03)
      Background: Coronavirus-19 (COVID-19) is a disease caused by the SARS-CoV-2 virus, the seventh coronavirus identified as causing disease in humans. The SARS-CoV-2 virus has multiple potential pathophysiologic interconnections with endocrine systems, potentially causing disturbances in glucose metabolism, hypothalamic and pituitary function, adrenal function and mineral metabolism. A growing body of data is revealing both the effects of underlying endocrine disorders on COVID-19 disease outcome and the effects of the SARS-CoV-2 virus on endocrine systems. However, comprehensive assessment of the relationship to endocrine disorders in children has been lacking. Content: In this review, we present the effects of SARS-CoV-2 infection on endocrine systems and review the current literature on complications of COVID-19 disease in underlying paediatric endocrine disorders. We provide recommendations on management of endocrinopathies related to SARS-CoV-2 infection in this population. Summary and outlook: With the surge in COVID-19 cases worldwide, it is important for paediatric endocrinologists to be aware of the interaction of SARS-CoV-2 with the endocrine system and management considerations for patients with underlying disorders who develop COVID-19 disease. While children and adults share some risk factors that influence risk of complications in SARS-CoV-2 infection, it is becoming clear that responses in the paediatric population are distinct and outcomes from adult studies cannot be extrapolated. Evidence emerging from paediatric studies provides some guidance but highlights the need for more research in this area. © 2021 The Authors.
    • The healthcare sector employer’s duty of care: Implications for worker well-being

      McDiarmid, Melissa; Condon, Marian; Gaitens, Joanna (MDPI AG, 2021-06-03)
      Pandemic diseases of this century have differentially targeted healthcare workers globally. These infections include Severe Acute Respiratory Syndrome SARS, the Middle East respiratory syndrome coronavirus Middle East respiratory syndrome coronavirus (MERS-CoV) and Ebola. The COVID-19 pandemic has continued this pattern, putting healthcare workers at extreme risk. Just as healthcare workers have historically been committed to the service of their patients, providing needed care, termed their “duty of care”, so too do healthcare employers have a similar ethical duty to provide care toward their employees arising from historical common law requirements. This paper reports on results of a narrative review performed to assess COVID-19 exposure and disease development in healthcare workers as a function of employer duty of care program elements adopted in the workplace. Significant duty of care deficiencies reported early in the pandemic most commonly involved lack of personal protective equipment (PPE) availability. Beyond worker safety, we also provide evidence that an additional benefit of employer duty of care actions is a greater sense of employee well-being, thus aiding in the prevention of healthcare worker burnout. © 2021 by the authors.
    • Effectiveness of Buffered Lidocaine for Local Anesthesia During Liver Biopsy

      Hockett, Deborah; Kress, Laura; Mac Donald, Ryan; Krenzischek, Dina A; Maheshwari, Anurag
      The aim of this research study was to evaluate the effectiveness of lidocaine versus lidocaine with sodium bicarbonate in reducing anxiety and pain, using visual analog scales, in subjects receiving local anesthetic during liver biopsies. The project included 199 subjects presenting for percutaneous liver biopsy using local anesthesia. Subjects were randomized into 2 groups: the control group, which received lidocaine alone, and the experimental group, which received lidocaine buffered with sodium bicarbonate. Immediately after they received the lidocaine injection, both groups were asked to rate their preprocedure anxiety and pain using a 0-10 visual analog scale. Mean postprocedure pain was statistically significantly different between the two arms with the intervention group reporting less pain (1.65 vs. 2.27, p = .037). Change in pain scores between the two groups were also statistically significantly different with the intervention group reporting a mean change in pain score of 0.93 compared to 1.63 in the control group (p = .021). However, no differences were found for reported anxiety. This study has shown that using sodium bicarbonate with lidocaine significantly decreased pain sensation at the injection site when used for deep visceral anesthesia during percutaneous liver biopsy. Copyright © 2021 The Authors.
    • Considering Sex as a Biological Variable in Basic and Clinical Studies: An Endocrine Society Scientific Statement

      Bhargava, Aditi; Arnold, Arthur P; Bangasser, Debra A; Denton, Kate M; Gupta, Arpana; Hilliard Krause, Lucinda M; Mayer, Emeran A; McCarthy, Margaret; Miller, Walter L; Raznahan, Armin; et al. (Oxford University Press, 2021-03-11)
      In May 2014, the National Institutes of Health (NIH) stated its intent to "require applicants to consider sex as a biological variable (SABV) in the design and analysis of NIH-funded research involving animals and cells." Since then, proposed research plans that include animals routinely state that both sexes/genders will be used; however, in many instances, researchers and reviewers are at a loss about the issue of sex differences. Moreover, the terms sex and gender are used interchangeably by many researchers, further complicating the issue. In addition, the sex or gender of the researcher might influence study outcomes, especially those concerning behavioral studies, in both animals and humans. The act of observation may change the outcome (the "observer effect") and any experimental manipulation, no matter how well-controlled, is subject to it. This is nowhere more applicable than in physiology and behavior. The sex of established cultured cell lines is another issue, in addition to aneuploidy; chromosomal numbers can change as cells are passaged. Additionally, culture medium contains steroids, growth hormone, and insulin that might influence expression of various genes. These issues often are not taken into account, determined, or even considered. Issues pertaining to the "sex" of cultured cells are beyond the scope of this Statement. However, we will discuss the factors that influence sex and gender in both basic research (that using animal models) and clinical research (that involving human subjects), as well as in some areas of science where sex differences are routinely studied. Sex differences in baseline physiology and associated mechanisms form the foundation for understanding sex differences in diseases pathology, treatments, and outcomes. The purpose of this Statement is to highlight lessons learned, caveats, and what to consider when evaluating data pertaining to sex differences, using 3 areas of research as examples; it is not intended to serve as a guideline for research design. © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.