Understanding equitable and affirming communication moments and relationship milestones during the intensive care unit journey: findings from stage 1 of a design thinking project.

PURPOSE: Communication is vital to facilitate patient and family-centred care (PFCC) and to build trusting relationships between intensive care unit (ICU) health care providers, the patient, and their loved ones in the ICU. The focus of this investigation was to identify, define, and refine key moments of communication, connection, and relationship building in the ICU through a lens of Equity, Diversity, Decolonization, and Inclusion (EDDI) to encourage meaningful communication and development of trusting relationships. METHODS: We conducted 13 journey mapping interviews with ICU health care providers, patients, and their loved ones as the first stage in a design thinking project. We used directed content analysis to identify intersections where principles of EDDI directly or indirectly impacted communication, relationships, and trust throughout the ICU journey. To serve diverse patients and their loved ones, accessibility, inclusivity, and cultural safety were foundational pillars of the design thinking project. RESULTS: Thirteen ICU health care providers, patients, and their loved ones participated in journey mapping interviews. We defined and refined 16 communication moments and relationship milestones in the journey of a patient through the ICU (e.g., admission, crises, stabilization, discharge), and intersections where EDDI directly or indirectly impacted communication and connection during the ICU journey. CONCLUSION: Our findings highlight that diverse intersectional identities impact communication moments and relationship milestones during an ICU journey. To fully embrace a paradigm of PFCC, consideration should be given to creating an affirming and safe space for patients and their loved ones in the ICU.

RéSUMé: OBJECTIF : La communication est essentielle pour faciliter les soins axés sur la patientèle et la famille et pour établir des relations de confiance entre les prestataires de soins de santé de l'unité de soins intensifs (USI), la patientèle, et ses proches à l'USI. L'objectif de cette enquête était d'identifier, de définir et de peaufiner les moments clés de communication, de connexion et de création de relation aux soins intensifs sous l'angle de l'équité, de la diversité, de l'inclusion et de la décolonisation (EDID) afin d'encourager une communication profonde et la création de relations de confiance. MéTHODE: Nous avons mené 13 entretiens de cartographie du parcours avec des prestataires de soins et des patient·es de l'USI ainsi qu'avec leurs proches dans le cadre de la première étape d'un projet de réflexion conceptuelle. Nous avons utilisé l'analyse de contenu dirigée pour identifier les intersections où les principes de l'EDID ont eu un impact direct ou indirect sur la communication, les relations et la confiance tout au long du parcours aux soins intensifs. L'accessibilité, l'inclusivité et la sécurité culturelle ont constitué des piliers fondamentaux du projet de réflexion conceptuelle pour desservir une patientèle diverse et ses proches. RéSULTATS: Treize prestataires de soins et patient·es de l'USI et leurs proches ont participé à des entrevues de cartographie du parcours. Nous avons défini et affiné 16 moments de communication et jalons de la relation dans le parcours d'un·e patient·e à l'USI (p. ex. admission, crises, stabilisation, congé) et les intersections où l'EDID a eu une incidence directe ou indirecte sur la communication et la connexion pendant le parcours aux soins intensifs. CONCLUSION: Nos résultats soulignent que les diverses identités intersectionnelles ont un impact sur les moments de communication et les jalons de la relation lors d'une trajectoire aux soins intensifs. Pour adopter pleinement un paradigme de soins axés sur la patientèle et sa famille, il faudrait envisager de créer un espace d'affirmation et de sécurité pour les patient·es et leurs proches à l'unité de soins intensifs.

Asymmetric Hsp90 N domain SUMOylation recruits Aha1 and ATP-competitive inhibitors.

The stability and activity of numerous signaling proteins in both normal and cancer cells depends on the dimeric molecular chaperone heat shock protein 90 (Hsp90). Hsp90's function is coupled to ATP binding and hydrolysis and requires a series of conformational changes that are regulated by cochaperones and numerous posttranslational modifications (PTMs). SUMOylation is one of the least-understood Hsp90 PTMs. Here, we show that asymmetric SUMOylation of a conserved lysine residue in the N domain of both yeast (K178) and human (K191) Hsp90 facilitates both recruitment of the adenosine triphosphatase (ATPase)-activating cochaperone Aha1 and, unexpectedly, the binding of Hsp90 inhibitors, suggesting that these drugs associate preferentially with Hsp90 proteins that are actively engaged in the chaperone cycle. Importantly, cellular transformation is accompanied by elevated steady-state N domain SUMOylation, and increased Hsp90 SUMOylation sensitizes yeast and mammalian cells to Hsp90 inhibitors, providing a mechanism to explain the sensitivity of cancer cells to these drugs.

Patterned Synthesis of ZnO Nanorod Arrays for Nanoplasmonic Waveguide Applications.

We report the patterned synthesis of ZnO nanorod arrays of diameters between 50 nm and 130 nm and various spacings. This was achieved by patterning hole arrays in a polymethyl methacrylate layer with electron beam lithography, followed by chemical synthesis of ZnO nanorods in the patterned holes using the hydrothermal method. The fabrication of ZnO nanorod waveguide arrays is also demonstrated by embedding the nanorods in a silver film using the electroplating process. Optical transmission measurement through the nanorod waveguide arrays is performed and strong resonant transmission of visible light is observed. We have found the resonance shifts to a longer wavelength with increasing nanorod diameter. Furthermore, the resonance wavelength is independent of the nanowaveguide array period, indicating the observed resonant transmission is the effect of a single ZnO nanorod waveguide. These nanorod waveguides may be used in single-molecule imaging and sensing as a result of the nanoscopic profile of the light transmitted through the nanorods and the controlled locations of these nanoscale light sources.

Gender Discrimination among Medical Students in Pakistan: A Cross Sectional Survey.

OBJECTIVE: To examine the prevalence and magnitude of gender discrimination experienced by undergraduate medical students, and its repercussions on their academic performance and emotional health. METHODOLOGY: A cross sectional study of 500 medical and dental students studying at a private medical college in Lahore, Pakistan. RESULTS: Majority (78%) of students reported being victims of gender discrimination. Females were the main perpetrators (70.8%).Most common forms were denied opportunities (63%), followed by neglecting students' needs (44.3%), and unethical talk (43.6%). Most common places of gender discrimination were teachers' offices (43.7%) and lecture halls (37.2%). Most of the perpetrators were clerical staff (48%) and professors (43%).Gender discrimination did not affect the academic performance of most victims (62.6%). The most common emotional responses were anger (57.6%), frustration (46.7%) and helplessness (40.3%). 52.4% of students said that gender discrimination still continues and the majority (83.3%) did not report the problem to college authorities. CONCLUSIONS: RESULTS demonstrate that gender discrimination is widely prevalent in undergraduate medical education. Females are both the main victims as well as the main perpetrators. In most cases gender discrimination does not affect academic performance but does cause emotional distress.

Modeling Dynamics of the Cardiovascular System Using Fluid-Structure Interaction Methods.

Using fluid-structure interaction algorithms to simulate the human circulatory system is an innovative approach that can provide valuable insights into cardiovascular dynamics. Fluid-structure interaction algorithms enable us to couple simulations of blood flow and mechanical responses of the blood vessels while taking into account interactions between fluid dynamics and structural behaviors of vessel walls, heart walls, or valves. In the context of the human circulatory system, these algorithms offer a more comprehensive representation by considering the complex interplay between blood flow and the elasticity of blood vessels. Algorithms that simulate fluid flow dynamics and the resulting forces exerted on vessel walls can capture phenomena such as wall deformation, arterial compliance, and the propagation of pressure waves throughout the cardiovascular system. These models enhance the understanding of vasculature properties in human anatomy. The utilization of fluid-structure interaction methods in combination with medical imaging can generate patient-specific models for individual patients to facilitate the process of devising treatment plans. This review evaluates current applications and implications of fluid-structure interaction algorithms with respect to the vasculature, while considering their potential role as a guidance tool for intervention procedures.

Post Salvage Therapy Autologous Transplant for Relapsed Myeloma, Ongoing Relevance within Modern Treatment Paradigms?

BACKGROUND: Salvage transplant has been historically considered effective therapy for myeloma patients relapsing after first transplant, if they achieved adequate remission duration. However, the efficacy of novel agent combinations has called this paradigm into question. MATERIALS AND METHODS: We performed a retrospective analysis in a homogeneously treated cohort of 106 patients undergoing ASCT2 at our institution, all of whom received novel agent-based chemotherapy (immunomodulatory agent [IMiD] and/or proteasome inhibitor [PI]) for both induction and relapse. As an exploratory objective we assessed whether predictive thresholds of progression free survival post first transplant (ASCT1) for benefit post ASCT2 vary with use of IMiD maintenance post ASCT1. RESULTS: The overall response rate (ORR) was 98% post-ASCT2 and treatment-related mortality (TRM) was low at 1.8%. With a median follow-up of 26 months (range 0.5-85) from ASCT2, median overall survival (OS) is estimated at 80 months (95% CI: ≥ 49-months) and median progression-free survival after ASCT2 (PFS2) at 24 months (95% CI 19-39). PFS post first transplant (PFS1) at >/= 50 months was associated with improved OS. Predictors of PFS2 included PFS1 ≤42 months and progression on IMiD-based maintenance post- ASCT1. CONCLUSION: ASCT2 continues to offer acceptable outcomes for most patients treated within modern day treatment paradigms, with longer PFS after ASCT1 and IMiD non-refractory disease being associated with improved outcomes.

A phase-1 trial of linsitinib (OSI-906) in combination with bortezomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma.

We report results of a phase-1 study evaluating the safety and anti-cancer activity of the small molecule insulin-like growth factor-1 receptor (IGF-1R) inhibitor, linsitinib combined with bortezomib, and dexamethasone in relapsed/refractory multiple myeloma. Nineteen patients were enrolled across four dose-escalation cohorts (75-150 mg bid). The maximum tolerated dose of linsitinib was 125 mg. The most frequent Grade 3/4 AEs occurring in ≥10% of patients were thrombocytopenia (53%), bone pain (26%), neutropenia (21%), diarrhea (14%), anemia (14%), rash (10%), and lung infection (10%). Study discontinuation due to treatment-related AEs was low (16%). Across all cohorts the ORR was 61% (95% CI: 28.9-75.6%). Three partial response or greater and one stable disease were observed in proteasome inhibitor (PI) refractory patients (n = 5). Median PFS was 7.1 months (95% CI: 3.6-NA). Linsitinib plus bortezomib and dexamethasone demonstrate a manageable safety profile while the clinical benefit particularly in PI refractory patients warrants further exploration.

The Association Between Cannabis Use and Schizophrenia: Causative or Curative? A Systematic Review.

Marijuana is one of the most abused substances in the world. Marijuana is getting legalized around the world. So, it is crucial to understand its effect on our mental health. Its impact on the schizophrenia spectrum needs our special attention. Even though marijuana has been around for a long time, its exact effects are still unknown. Schizophrenia is a chronic illness affecting approximately 20 million people worldwide. Schizophrenia and cannabis seem to have a close relationship, and we want to explore this. We want to know if marijuana is causing, exacerbating, or treating schizophrenia. This systematic review explores this question. We searched online resources like PubMed, PubMed Central, Cochrane Library, and Google Scholar for systematic reviews, traditional reviews, randomized controlled trials, and meta-analysis on cannabis and schizophrenia/ psychosis. We included human studies published in peer-reviewed journals in the English language in the last five years. After reviewing 96 initial results of our search, we excluded 25 duplicates, 29 abstracts, and 18 irrelevant articles. We did a quality assessment for the remaining 24 studies using various quality assessment tools. After the quality assessment, we found 12 articles were of low quality and excluded those. We included the remaining 12 final studies in our systematic review. Out of these 12 studies, five were traditional reviews, two systematic reviews, two meta-analysis, and three observational studies. Six of the articles were on cannabis's effect on just schizophrenia or psychotic disorder. The other six included schizophrenia plus other psychiatric or neurological illnesses. Ten of the studies had data supporting the causative link between cannabis and schizophrenia. Eight records had data supporting the exacerbating effect of marijuana. Six studies had data supporting the therapeutic effect of the cannabidiol (CBD) component of cannabis. From the current data, we can conclude that the tetrahydrocannabinol (THC) component of cannabis can be the main culprit causing psychosis and schizophrenia in the at-risk population. THC can also be the one exacerbating symptoms and causing an adverse prognosis in already diagnosed patients. Even though CBD shows therapeutic effects and THC opposing effects, the data is minimal and low safety and efficacy warrants more research. The relation between cannabis and schizophrenia needs further investigation. We need more case-control studies and clinical trials with a larger population to get conclusive data.

Another Chicken and Egg Story: Systematic Review on Lichen Planus as a Precursor for Celiac Disease in Adult Population.

Celiac disease is receiving much attention due to the gluten-free diet trend. Many health-conscious individuals practice a gluten-free diet, even if they do not have celiac disease. As it is an autoimmune disorder, it is associated with many other autoimmune diseases. We were interested in one skin condition, another autoimmune disorder lichen planus as a correlative factor for celiac disease. The following systematic review may give some clues. We searched online resources including PubMed, PubMed Central, Cochrane library, and Google scholar for systematic reviews, traditional reviews, randomized controlled trials, and meta-analysis on celiac disease and lichen planus. We included human studies published in peer-reviewed journals in the English language. After reviewing 2389 initial results of our search, we excluded 1250 duplicates, 1108 abstracts, 42 irrelevant articles. We assessed the remaining 26 articles for their quality using various quality assessment tools. After the quality assessment, we included nine final articles in our systematic review. Out of these nine studies, there were four systematic reviews, one traditional review, two case reports, and two observational studies. Only two articles had exclusively studied the specific association between celiac and lichen planus. The remaining studies included data that gave an overall association between other skin manifestations of celiac disease. From our study, we could not establish the relationship between celiac disease and lichen planus. We need more case-control studies and clinical trials with a larger population to get conclusive data. From current data, we can conclude that both immunological processes correlate but there is no causation. There is also a need for clinical trials to explore the exacerbation of lichen planus due to celiac disease.

Premature mortality from all causes and drug poisonings in the USA according to socioeconomic status and rurality: an analysis of death certificate data by county from 2000-15.

BACKGROUND: Increasing premature mortality among some groups of Americans has been largely driven by increases in drug poisoning deaths. However, to our knowledge, a formal descriptive study by race and ethnicity, socioeconomic status, rurality, and geography has not been done. In this study, we examined US trends in premature all-cause and drug poisoning mortality between 2000 and 2015 at the county level among white, black, and Latino people. METHODS: We used US mortality data for the period Jan 1, 2000, to Dec 31, 2015, including underlying cause of death and demographic data, collected from death certificates by the Centers for Disease Control and Prevention National Center for Health Statistics, and ascertained county attributes from the 2011-15 Census American Community Survey. We categorised counties into quintiles on the basis of the percentage of people unemployed, the percentage of people with a bachelor's degree, median income, and rurality. We estimated premature (ie, deaths in those aged 25-64 years) age-standardised mortality for all causes (by race and ethnicity) and drug poisoning, by county, for the periods of 2000-03 and 2012-15. We estimated annual percentage changes in mortality (2000-15) by county-level characteristics. FINDINGS: Premature mortality declined from 2000-03 to 2012-15 among black and Latino people, but increased among white people in many US counties. Drug poisoning mortality increased in counties throughout the country. Significant increases between 2000 and 2015 occurred across low and high socioeconomic status and urban and rural counties among white people aged 25-64 years (annual percentage change range 4·56% per year [95% CI 3·56-5·57] to 11·51% per year [9·41-13·65]), black people aged 50-64 years (2·27% per year [0·42-4·16] to 9·46% per year [7·02-11·96]), Latino women aged 25-49 years (2·43% per year [1·18-3·71] to 5·01% per year [3·80-6·23]), and Latino men aged 50-64 years (2·42% per year [0·53-4·34] to 5·96% per year [3·86-8·11]). Although drug poisoning mortality increased rapidly in counties with the lowest socioeconomic status and in rural counties, most deaths during 2012-15 occurred in the largest metropolitan counties (121 395 [76%] in metropolitan counties with ≥250 000 people vs 2175 [1%] in the most rural counties), reflecting population size. INTERPRETATION: Premature mortality has declined among black and Latino people in the USA, and increased among white people, particularly in less affluent and rural counties. Increasing drug poisoning mortality was not limited to poor white people in rural areas. Rapid increases have occurred in communities throughout the USA regardless of race and ethnicity, socioeconomic status, or rurality. Widespread public health interventions are needed to addess this public health emergency. FUNDING: National Institutes of Health.

Infant and Youth Mortality Trends by Race/Ethnicity and Cause of Death in the United States.

Importance: The United States has higher infant and youth mortality rates than other high-income countries, with striking disparities by racial/ethnic group. Understanding changing trends by age and race/ethnicity for leading causes of death is imperative for focused intervention. Objective: To estimate trends in US infant and youth mortality rates from 1999 to 2015 by age group and race/ethnicity, identify leading causes of death, and compare mortality rates with Canada and England/Wales. Design, Setting, and Participants: This descriptive study analyzed death certificate data from the US National Center for Health Statistics, Statistics Canada, and the UK Office of National Statistics for all deaths among individuals younger than 25 years. The study took place from January 1, 1999, to December 31, 2015, and analyses started in September 2017. Exposures: Race/ethnicity. Main Outcomes and Measures: Average annual percent changes in mortality rates from 1999 to 2015 and absolute rate change between 1999 to 2002 and 2012 to 2015 for each age group, race/ethnicity, and cause of death. Results: Among individuals from birth to age 24 years, 1 169 537 deaths occurred in the United States, 80 540 in Canada, and 121 183 in England/Wales from 1999 to 2015. In the United States, 64% of deaths occurred in male individuals and 52.6% occurred in white individuals (25.1% deaths occurred in black individuals and 17.9% in Latino individuals). All-cause mortality declined for all age groups (infants younger than 1 year [38.5% of deaths], children aged 1-9 years [10.6%], early adolescents aged 10-14 years [5%], late adolescents aged 15-19 years [17.7%], and young adults aged 20-24 years [28.1%]) in the United States, Canada, and England/Wales from 1999 to 2015. However, rates were highest in the United States. Within the United States, annual declines in all-cause mortality rates occurred among all age groups of black, Latino, and white individuals, except for white individuals aged 20 to 24 years, whose rates remained stable. Mortality rates declined across most major causes of death from 1999 to 2002 and 2012 to 2015, with notable declines observed for sudden infant death syndrome, unintentional injury death, and homicides. Among infants, unintentional suffocation and strangulation in bed increased (difference between 2012-2015 and 1999-2002 range, 6.11-29.03 per 100 000). Further, suicide rates among Latino and white individuals aged 10 to 24 years (range, 0.21-2.63 per 100 000) and black individuals aged 10 to 19 years (range, 0.10-0.45 per 100 000) increased, as did unintentional injury deaths in white young adults (0.79 per 100 000). The rise in unintentional injury deaths is attributed to increases in drug poisonings and was also observed in black and Latino young adults. Conclusions and Relevance: Mortality rates in the United States have generally declined for infants and youths from 1999 to 2015 owing to reductions in sudden infant death syndrome, unintentional injury death, and homicides. However, US mortality rates remain higher than Canada and England/Wales, with particularly elevated rates among black and American Indian/Alaskan Native youth. Further, there is a concerning increase in suicide and drug poisoning death rates among US adolescents and young adults.

Neuronal excitability and network formation on optically transparent electrode materials.

With the advent of genetically-encoded optical tools to trigger or report neuronal activity, new designs for multielectrode arrays (MEAs) used in neural interfacing incorporate both optical and electrical modes of stimulating or recording neural activity. Likewise, the need to improve upon the biocompatibility of implanted MEAs has moved the field towards the use of softer, more compliant materials in device fabrication. However, there is limited available information on the impact of the materials used in MEAs on the function of interfaced individual neurons and neuronal networks. We assessed the responses of rat cortical neurons on optically transparent materials commonly used in the construction of "next-generation" devices: indium tin oxide (ITO), parylene-C, and polydimethylsiloxane (PDMS). We found that neuronal network formation and spiking responses to electrical stimulation were enhanced in neurons cultured on ITO. We observed reduced excitability and synaptic connectivity between neurons cultured on PDMS. We hypothesize that the superior conductivity of ITO and suboptimal neuronal attachment to PDMS contributed to our results.

Influence of Eysenckian Personality Traits in Choice of Specialization by Young Omani Doctors.

OBJECTIVES: The role of personality in occupational specialty choices has been explored in many parts of the world. To our knowledge, there is a dearth of such studies in the Arab/Islamic population and Oman is no exception. This study aimed to explore the relationship between personality traits and specialty choice among residents of Oman Medical Specialty Board (OMSB). METHODS: A cross-sectional study was carried out among Omani resident physicians working under OMSB. The Eysenck Personality Questionnaire-Revised was employed to quantify personality subtypes (e.g., psychoticism, extraversion, and neuroticism). Specialties were categorized as surgical, medical, and diagnostics as per standard of North American medical specialties. A total of 255 residents in 17 medical specialties participated in the study (m = 40.4%; f = 59.6%) of 300 eligible subjects giving a response rate of 85.0%. RESULTS: Respondents who had chosen surgical specialties scored significantly higher on the psychoticism subscale than those who had opted for medical and diagnostic specialties. As for individual specialties, orthopedic respondents had statistically significant higher mean scores on psychoticism and neuroticism compared to radiologists and psychiatrists who scored the lowest in the two personality traits, respectively. CONCLUSIONS: This study found statistically significant associations between personality traits and choices of specialty by young Omani doctors. We recommend more detailed studies that examine further psychological and cultural variables that are likely to affect the choices of specializations by young Omani professionals in both medical and non-medical fields.

Contributions of co-chaperones and post-translational modifications towards Hsp90 drug sensitivity.

Hsp90 is a molecular chaperone and important driver of stabilization and activation of several oncogenic proteins that are involved in the malignant transformation of tumor cells. Therefore, it is not surprising that Hsp90 has been reported to be a promising target for the treatment of several neoplasias, such as non-small-cell lung cancer and HER2-positive breast cancer. Hsp90 chaperone function depends on its ability to bind and hydrolyze ATP and Hsp90 inhibitors have been shown to compete with nucleotides for binding to Hsp90. Multiple factors, such as co-chaperones and post-translational modification, are involved in regulating Hsp90 ATPase activity. Here, the impact of post-translational modifications and co-chaperones on the efficacy of Hsp90 inhibitors are reviewed.

The Association between Marital Transitions, Body Mass Index, and Weight: A Review of the Literature.

Objective. To examine the association between different marital transitions and changes in body mass index (BMI) and body weight. Methods. A systematic literature search was conducted for peer-reviewed articles published between January 1990 and December 2011. Longitudinal studies were included if they compared dependent variables, such as BMI or weight, before and after a change in marital status. Results. Twenty articles were included: 4 articles described only transitions into marriage and/or cohabitation, 2 articles described only transitions out of marriage and/or cohabitation, and 14 articles described both. Overall, transitions into marriage were associated with weight gain, whereas transitions out of marriage were associated with weight loss. No major differences were observed between genders or across specific marital transition states. Conclusions. Additional research is warranted to better understand this phenomenon and the impact of marital transitions on obesity and obesity-related behaviors. This paper highlights potential opportunities to incorporate programs, practices, and policies that aim to promote and support healthy weights and lifestyles upon entering or leaving a marriage or cohabiting relationship.