A multi-center analysis of individuals with a 47,XXY/46,XX karyotype.

INTRODUCTION: Klinefelter syndrome (KS), a sex chromosome aneuploidy, is associated with a 47,XXY chromosomal complement and is diagnosed in ∼1:600 live male births. Individuals with a 46,XX cell line in addition to 47,XXY are less common with a limited number of published case reports. METHODOLOGY: To better understand the implications of a 47,XXY/46,XX karyotype, we conducted a retrospective, multi-center analysis of the cytogenetic findings and associated clinical records of 34 patients diagnosed with this SCA across 14 institutions. RESULTS: Presence of the XX cell line ranged from 5-98% in patient specimens. Phenotypes also exhibited significant heterogeneity with some reporting a single reason for referral and others presenting with a constellation of symptoms, including ambiguous genitalia and ovotestes. Ovotestes were present in 12% of individuals in this cohort, who had a significantly higher percentage of XX cells. Notably, two patients were assigned female sex at birth DISCUSSION: These findings highlight the variability of the clinical phenotypes associated with this SCA as well as the challenges of clinical management for this population. Karyotype or FISH analysis, which offer single-cell resolution, rather than chromosomal microarray or molecular testing, is the ideal test strategy in these instances as mosaicism can occur at low levels.

" I'm not a risk taker " : Risk Perceptions of Nursing Home Residents With Dementia.

BACKGROUND: Persons living with Alzheimer disease and related dementia (ADRD) in nursing homes (NH) are often excluded from conversations about their health/safety. These omissions impinge on personhood and the rights to have care preferences heard and honored. While persons with ADRD maintain the ability to communicate their preferences long after their decision-making abilities are affected, little is known about how persons with ADRD understand the risks associated with their preferences. METHODS: As part of a larger focused ethnography, in-depth interviews and an adapted risk propensity questionnaire explored the risk perceptions of NH residents with ADRD (N=7) associated with their preferences for care and activities of daily living. RESULTS: Residents generally self-identified as risk avoiders ( M =3.2±1.84) on the risk propensity scale and were able to rate risk associated with preferences described within 5 thematic categories: 1) participation in decision-making, 2) risk awareness, 3) paying attention to safety, 4) reliance on nursing home staff and family, and 5) impacts on quality of life and quality of care. DISCUSSION: Results suggest NH residents with ADRD can express risk surrounding their preferences and should be encouraged to participate in discussions about their health and safety.

Inequity is woven into the fabric: a discourse analysis of assessment in pediatric residency training.

Intrinsic inequity in assessment refers to sources of harmful discrimination inherent in the design of assessment tools and systems. This study seeks to understand intrinsic inequity in assessment systems by studying assessment policies and associated procedures in residency training, using general pediatrics as a discourse case study. Foucauldian discourse analysis (FDA) was conducted on assessment policy and procedure documents. Two authors independently prepared structured analytic notes using guiding questions. Documents and respective analytic notes were subsequently reviewed independently by all authors. Each author prepared further unstructured analytic notes on the documents' discourse. The authors then compared notes and constructed truth statements (i.e., interpretations of what the discourse establishes as true about the construct under study) and sub-strands (i.e., themes) that were repeated and legitimized across the documents via iterative discussion. Based on analysis, the authors constructed two truth statements. These truth statements, "good assessment is equitable assessment," and "everyone is responsible for inequity," conceptualized inequity in assessment as an isolated or individual-level aberration in an otherwise effective or neutral system. Closer examination of the truth statements and sub-strands in the discourse presented an alternative view, suggesting that inequity may in fact not be an aberration but rather an inherent feature of assessment systems.

Temporal variability in nutrient use among Streptomyces suggests dynamic niche partitioning.

Soil bacteria spend significant periods in dormant or semi-dormant states that are interrupted by resource pulses which can lead to periods of rapid growth and intense nutrient competition. Microbial populations have evolved diverse strategies to circumvent competitive interactions and facilitate coexistence. Here, we show that nutrient use of soilborne Streptomyces is temporally partitioned during experimental resource pulses, leading to reduced niche overlap, and potential coexistence. Streptomyces grew rapidly on the majority of distinct 95 carbon sources but varied in which individual resources were utilized in the first 24 h. Only a handful of carbon sources (19 out of 95) were consistently utilized (>95% of isolates) most rapidly in the first 24 h. These consistently utilized carbon sources also generated the majority of biomass accumulated by isolates. Our results shed new light on a novel mechanism microbes may employ to alleviate competitive interactions by temporally partitioning the consumption of carbon resources. As competitive interactions have been proposed to drive the suppression of disease-causing microbes in agronomic soils, our findings may hold widespread implications for soil management for plant health.

Size-dependent colouration balances conspicuous aposematism and camouflage.

Colour is an important component of many different defensive strategies, but signal efficacy and detectability will also depend on the size of the coloured structures, and how pattern size interacts with the background. Consequently, size-dependent changes in colouration are common among many different species as juveniles and adults frequently use colour for different purposes in different environmental contexts. A widespread strategy in many species is switching from crypsis to conspicuous aposematic signalling as increasing body size can reduce the efficacy of camouflage, while other antipredator defences may strengthen. Curiously, despite being chemically defended, the gold-striped frog (Lithodytes lineatus, Leptodactylidae) appears to do the opposite, with bright yellow stripes found in smaller individuals, whereas larger frogs exhibit dull brown stripes. Here, we investigated whether size-dependent differences in colour support distinct defensive strategies. We first used visual modelling of potential predators to assess how colour contrast varied among frogs of different sizes. We found that contrast peaked in mid-sized individuals while the largest individuals had the least contrasting patterns. We then used two detection experiments with human participants to evaluate how colour and body size affected overall detectability. These experiments revealed that larger body sizes were easier to detect, but that the colours of smaller frogs were more detectable than those of larger frogs. Taken together our data support the hypothesis that the primary defensive strategy changes from conspicuous aposematism to camouflage with increasing size, implying size-dependent differences in the efficacy of defensive colouration. We discuss our data in relation to theories of size-dependent aposematism and evaluate the evidence for and against a possible size-dependent mimicry complex with sympatric poison frogs (Dendrobatidae).

Paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome: Part I. clinical overview and pathophysiology.

Paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome (PNP/PAMS) is a highly fatal autoimmune blistering disease. The condition occurs in patients with underlying benign or malignant neoplasms, most commonly lymphoproliferative disorders. Both humoral and cell-mediated immunities contribute to the pathogenesis, and autoantibodies against plakin family proteins are characteristic. Patients typically present with severe stomatitis and polymorphous skin lesions, which are often resistant to treatment. Bronchiolitis obliterans (BO) is a frequent complication which contributes to the high mortality rate of PNP/PAMS. Given the rarity of this disorder and heterogeneity of clinical presentation, clinicians should maintain a high index of suspicion for PNP/PAMS to avoid delayed diagnosis. In this first part of a two-part continuing medical education (CME) series, risk factors, pathogenesis, and clinical features of PNP/PAMS are discussed.

Paraneoplastic Pemphigus/Paraneoplastic Autoimmune Multiorgan Syndrome: Part II. Diagnosis and Management.

In the second part of this Continuing Medical Education article on paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome (PNP/PAMS), its diagnostic criteria, investigative work-up, and management are reviewed. PNP/PAMS is a rare autoimmune blistering disorder associated with high morbidity and mortality. Recognizing PNP/PAMS's key features and its diagnostic criteria is critical in initiating appropriate work-up. Evaluating PNP/PAMS requires knowledge of its findings on histopathology, direct immunofluorescence, indirect immunofluorescence, and enzyme-linked immunosorbent assay. Lastly, treatments for PNP/PAMS are reviewed with suggestions based on case reports and expert opinions in the literature. LEARNING OBJECTIVES: After completing this learning objective, the reader will be able to identify the criteria necessary for diagnosing paraneoplastic pemphigus (PNP/PAMS), learn how to work-up a diagnosis of PNP/PAMS, and understand important principles in the management of PNP/PAMS.

Global stability and parameter analysis reinforce therapeutic targets of PD-L1-PD-1 and MDSCs for glioblastoma.

Glioblastoma (GBM) is an aggressive primary brain cancer that currently has minimally effective treatments. Like other cancers, immunosuppression by the PD-L1-PD-1 immune checkpoint complex is a prominent axis by which glioma cells evade the immune system. Myeloid-derived suppressor cells (MDSCs), which are recruited to the glioma microenviroment, also contribute to the immunosuppressed GBM microenvironment by suppressing T cell functions. In this paper, we propose a GBM-specific tumor-immune ordinary differential equations model of glioma cells, T cells, and MDSCs to provide theoretical insights into the interactions between these cells. Equilibrium and stability analysis indicates that there are unique tumorous and tumor-free equilibria which are locally stable under certain conditions. Further, the tumor-free equilibrium is globally stable when T cell activation and the tumor kill rate by T cells overcome tumor growth, T cell inhibition by PD-L1-PD-1 and MDSCs, and the T cell death rate. Bifurcation analysis suggests that a treatment plan that includes surgical resection and therapeutics targeting immune suppression caused by the PD-L1-PD1 complex and MDSCs results in the system tending to the tumor-free equilibrium. Using a set of preclinical experimental data, we implement the approximate Bayesian computation (ABC) rejection method to construct probability density distributions that estimate model parameters. These distributions inform an appropriate search curve for global sensitivity analysis using the extended fourier amplitude sensitivity test. Sensitivity results combined with the ABC method suggest that parameter interaction is occurring between the drivers of tumor burden, which are the tumor growth rate and carrying capacity as well as the tumor kill rate by T cells, and the two modeled forms of immunosuppression, PD-L1-PD-1 immune checkpoint and MDSC suppression of T cells. Thus, treatment with an immune checkpoint inhibitor in combination with a therapeutic targeting the inhibitory mechanisms of MDSCs should be explored.

Differences in food parenting at home versus restaurants among parents of 3-to-8-year-old children.

Indulgent parent feeding styles have been linked to less healthful eating behaviors and higher BMI among children. Restaurants are becoming a frequent eating environment for children. Frequent intake of food from restaurants has been associated with increased weight status, making restaurants a target for childhood obesity prevention efforts. Currently, little research has considered parent feeding styles in restaurants and how they might differ from the home setting. Given the increased frequency of children's restaurant consumption, examining parent feeding styles in restaurants may contribute to future research in this area. Therefore, the objective of this study was to examine parent feeding styles at home and in restaurants. Parents whose 3-to-8-year-old children dined out regularly completed a one-time, online survey in February/March 2022. The Caregiver's Feeding Style Questionnaire assessed parent feeding styles at home and in restaurants. Differences in feeding styles were examined across settings. Indulgent feeding styles were most common overall. Parents (n = 117; 92% mothers; 85% white; 61% reported household income > $75,000/year) reported higher demandingness at home (M = 2.6 ± 0.5) compared to restaurants (M = 2.4 ± 0.5; t(116) = 6.7, P < 0.001). Parents were more likely to use indulgent feeding styles (X2 = 11.6, P < 0.001) and less likely to use authoritarian feeding styles (X2 = 4.6, P < 0.05) in restaurants compared to the home, suggesting parent feeding styles are less structured in restaurants. Results may have implications for future healthy eating interventions in away-from-home contexts.

Imperfect transparency and camouflage in glass frogs.

Camouflage patterns prevent detection and/or recognition by matching the background, disrupting edges, or mimicking particular background features. In variable habitats, however, a single pattern cannot match all available sites all of the time, and efficacy may therefore be reduced. Active color change provides an alternative where coloration can be altered to match local conditions, but again efficacy may be limited by the speed of change and range of patterns available. Transparency, on the other hand, creates high-fidelity camouflage that changes instantaneously to match any substrate but is potentially compromised in terrestrial environments where image distortion may be more obvious than in water. Glass frogs are one example of terrestrial transparency and are well known for their transparent ventral skin through which their bones, intestines, and beating hearts can be seen. However, sparse dorsal pigmentation means that these frogs are better described as translucent. To investigate whether this imperfect transparency acts as camouflage, we used in situ behavioral trials, visual modeling, and laboratory psychophysics. We found that the perceived luminance of the frogs changed depending on the immediate background, lowering detectability and increasing survival when compared to opaque frogs. Moreover, this change was greatest for the legs, which surround the body at rest and create a diffuse transition from background to frog luminance rather than a sharp, highly salient edge. This passive change in luminance, without significant modification of hue, suggests a camouflage strategy, "edge diffusion," distinct from both transparency and active color change.

What is the Perceived Role of the Dietitian Amongst People with Cystic Fibrosis? Results of an International survey.

Cystic fibrosis (CF) is a chronic condition requiring continued input from the CF dietitian as an integral part of the CF multidisciplinary team. In recent years, the longer life expectancy experienced by people with CF (PwCF) means that nutrition advice and therapy are evolving from a focus on nutrition support to prevention and management of comorbidities. Little has been reported regarding the perceived role of the CF dietitian amongst PwCF. We report the responses to 11 questions that were part of a larger international survey distributed to members of national CF charities in 2018-2019. These questions evaluated PwCFs' perspectives on (i) the importance of the CF diet, (ii) how often PwCF obtain dietary/nutritional advice from their dietitian, (iii) the perceived reliability of information given by the dietitian, (iv) other sources of CF information and their perceived reliability, and (v) how CF nutrition/diet, as well as CF-related diabetes, ranked as research priorities. There were 295 respondents from 13 countries. Almost half of the respondents (46.8%) contacted their CF dietitian on a frequent/more regular basis, compared to medical/scientific journals/medical/scientific search engines. The CF dietitian was considered a reliable source of information, as 84% of the respondents indicated that the information provided was very/generally reliable. At a time when CF care and expectations are changing rapidly, PwCF are in need of trusted and reliable information to make positive changes in lifestyle and habits. Dietitians working with PwCF should appreciate the pivotal and valued role they perform as purveyors of robust evidence-based information to this chronic disease population.

MR susceptibility imaging for detection of tumor-associated macrophages in glioblastoma.

PURPOSE: Tumor-associated macrophages (TAMs) are a key component of glioblastoma (GBM) microenvironment. Considering the differential role of different TAM phenotypes in iron metabolism with the M1 phenotype storing intracellular iron, and M2 phenotype releasing iron in the tumor microenvironment, we investigated MRI to quantify iron as an imaging biomarker for TAMs in GBM patients. METHODS: 21 adult patients with GBM underwent a 3D single echo gradient echo MRI sequence and quantitative susceptibility maps were generated. In 3 subjects, ex vivo imaging of surgical specimens was performed on a 9.4 Tesla MRI using 3D multi-echo GRE scans, and R2* (1/T2*) maps were generated. Each specimen was stained with hematoxylin and eosin, as well as CD68, CD86, CD206, and L-Ferritin. RESULTS: Significant positive correlation was observed between mean susceptibility for the tumor enhancing zone and the L-ferritin positivity percent (r = 0.56, p = 0.018) and the combination of tumor's enhancing zone and necrotic core and the L-Ferritin positivity percent (r = 0.72; p = 0.001). The mean susceptibility significantly correlated with positivity percent for CD68 (ρ = 0.52, p = 0.034) and CD86 (r = 0.7 p = 0.001), but not for CD206 (ρ = 0.09; p = 0.7). There was a positive correlation between mean R2* values and CD68 positive cell counts (r = 0.6, p = 0.016). Similarly, mean R2* values significantly correlated with CD86 (r = 0.54, p = 0.03) but not with CD206 (r = 0.15, p = 0.5). CONCLUSIONS: This study demonstrated the potential of MR quantitative susceptibility mapping as a non-invasive method for in vivo TAM quantification and phenotyping. Validation of these findings with large multicenter studies is needed.

Replace, amplify, transform: a qualitative study of how postgraduate trainees and supervisors experience and use telehealth for instruction in ambulatory patient care.

BACKGROUND: Little is known about using telehealth patient visits as an educational mode. Therefore, rapid implementation of telehealth during the COVID-19 pandemic had to be done without understanding how to optimize telehealth for education. With the likely sustained/post-pandemic use of telehealth in ambulatory patient care, filling gaps in our understanding of how telehealth can be used for instruction in this context is critical. This study sought to understand perceptions of pediatric postgraduate trainees and supervisors on the use of telehealth for instruction in ambulatory settings with the goal of identifying effective ways to enhance learning during telehealth visits. METHODS: In May-June of 2020, the authors purposefully sampled first- and third-year postgraduate trainees and supervising attendings from pediatric fellowship programs at one institution that implemented telehealth for instructional activities. They conducted semi-structured interviews; interviews lasted a median of 51 min (trainees) and 41 min (supervisors). They conducted interviews and data analysis iteratively until reaching saturation. Using thematic analysis, they created codes and constructed themes from coded data. They organized themes using the Replace-Amplify-Transform (RAT) model, which proposes that technology can replace in-person learning and/or amplify and transform learning. RESULTS: First-year trainees (n = 6), third-year trainees (n = 5) and supervisors (n = 6) initially used telehealth to replace in-person learning. However, skills that could be practiced in telehealth visits differed from in-person visits and instructional activities felt rushed or awkward. Trainees and supervisors adapted and used telehealth to amplify learning by enhancing observation and autonomy. They also transformed learning, using telehealth to develop novel skills. CONCLUSIONS: To harness telehealth for instructional activities, our findings indicated that trainees and supervisors should shift from using it as a direct replacement for in-person education to taking advantage of novel opportunities to amplify and transform education in PGME. The authors provide data-driven recommendations to help PGME trainees, supervisors and educators capitalize on the educational advantages of telehealth.

Assessing clinical education tools for expanded carrier screening.

Expanded carrier screening (ECS) is increasingly offered to a broader population and raises challenges of how to best educate and counsel the volume of screened individuals. For this study, we compared three educational tools (brochure, video and comic) about ECS on knowledge and decision making. A convenience online sample of 151 pregnant women was randomized to one of three groups (Video, n = 42; Comic n = 54; Brochure n = 55). Knowledge scores were significantly higher for the comic group compared to the video or the brochure groups (p < .001). No significant differences in preparation for decision making, decisional conflict, or perceptions of shared decision making were identified between the study groups. This study suggests that a comic about ECS may improve patient attention and retention of information. The use of graphic narratives may enable individuals to better understand medical information in general.

A Review of Fixed Drug Eruption with a Special Focus on Generalized Bullous Fixed Drug Eruption.

Fixed drug eruption (FDE) is a cutaneous adverse drug reaction characterized by the onset of rash at a fixed location on the body each time a specific medication is ingested. With each recurrence, the eruption can involve additional sites. Lesions can have overlying vesicles and/or bullae, and when they cover a significant percentage of body surface area, the eruption is referred to as generalized bullous fixed drug eruption (GBFDE). Due to the widespread skin denudation that can be seen in this condition, GBFDE may be confused clinically with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). While treatments described for GBFDE include supportive care, topical and/or systemic steroids, and, recently, cyclosporine, the mainstay of management involves identifying and discontinuing the causative drug. This review article will provide an overview of FDE with an emphasis on its generalized bullous variant.

Behavioral and physiological evidence that increasing group size ameliorates the impacts of social disturbance.

Intra-group social stability is important for the long-term productivity and health of social organisms. We evaluated the effect of group size on group stability in the face of repeated social perturbations using a cooperatively breeding fish, Neolamprologus pulcher In a laboratory study, we compared both the social and physiological responses of individuals from small versus large groups to the repeated removal and replacement of the most dominant group member (the breeder male), either with a new male (treatment condition) or with the same male (control condition). Individuals living in large groups were overall more resistant to instability but were seemingly slower to recover from perturbation. Members of small groups were more vulnerable to instability but recovered faster. Breeder females in smaller groups also showed greater physiological preparedness for instability following social perturbations. In sum, we discover both behavioral and physiological evidence that living in larger groups helps to dampen the impacts of social instability in this system.

A Late Attempt to Involve End Users in the Design of Medication-Related Alerts: Survey Study.

BACKGROUND: When users of electronic medical records (EMRs) are presented with large numbers of irrelevant computerized alerts, they experience alert fatigue, begin to ignore alert information, and override alerts without processing or heeding alert recommendations. Anecdotally, doctors at our study site were dissatisfied with the medication-related alerts being generated, both in terms of volume being experienced and clinical relevance. OBJECTIVE: This study aimed to involve end users in the redesign of medication-related alerts in a hospital EMR, 4 years post implementation. METHODS: This work was undertaken at a private not-for-profit teaching hospital in Sydney, Australia. Since EMR implementation in 2015, the organization elected to implement all medication-related alert types available in the system for prescribers: allergy and intolerance alerts, therapeutic duplication alerts, pregnancy alerts, and drug-drug interaction alerts. The EMR included no medication administration alerts for nurses. To obtain feedback on current alerts and suggestions for redesign, a Web-based survey was distributed to all doctors and nurses at the site via hospital mailing lists. RESULTS: Despite a general dissatisfaction with alerts, very few end users completed the survey. In total, only 3.37% (36/1066) of doctors and 14.5% (60/411) of nurses took part. Approximately 90% (30/33) of doctors who responded held the view that too many alerts were triggered in the EMR. Doctors suggested that most alerts be removed and that alerts be more specific and less sensitive. In contrast, 97% (58/60) of the nurse respondents indicated that they would like to receive medication administration alerts in the EMR. Most nurses indicated that they would like to receive all the alert types available at all severity levels. CONCLUSIONS: Attempting to engage with end users several years post implementation was challenging. Involving users so late in the implementation process may lead to clinicians viewing the provision of feedback to be futile. Seeking user feedback on usefulness, volume, and design of alerts is extremely valuable; however, we suggest this is undertaken early, preferably before system implementation.

Wilderness Falls: An Analysis and Comparison of Rock Climbers and Nonclimbers.

BACKGROUND: Wilderness travel and rock climbing are increasingly popular. Urban falls from height have been reported from trauma centers; however, there have been no trauma center reports of rock climbing or wilderness falls (WFs) in the United States. We sought to describe the injury pattern of WF and to determine whether rock climbers represent a distinct pattern of injury. MATERIALS AND METHODS: The trauma database from our level 1 trauma center was queried from 1/1/06 to 12/31/16 for the diagnosis of "fall from cliff" (ICD9: e884.1, ICD10: w15.xx). Demographics, injury characteristics, and trauma center care were analyzed. Data were analyzed using two sample unequal variance T-tests, two sample Z-tests for proportions, and Fisher's exact tests. RESULTS: One hundred fifty-one falls were analyzed (40 climbers, 111 nonclimbers). WF victims were predominantly male (79%), moderately injured (mean injury severity score = 13.2), frequently intoxicated (34%), and fell from an average of 43 feet (7-200 ft). The most frequent injures were soft tissue (55%), spine (50%), head (43%), lower extremity (38%), and chest (39%). Climbers were younger, more often sustained upper extremity and soft tissue injuries, more often flown from the scene, injured during daytime, and were better insured. Helmet use was rare (one climber and one nonclimber). There were 3 (2%) deaths, including one climber. CONCLUSIONS: WFs have a distinct injury pattern and demographic and occur from a height greater than twice those reported in urban falls. Rock climbing falls involve another distinct demographic and pattern of injury. Injury prevention strategies may include helmet use and avoiding nighttime wilderness travel and drug/alcohol use.

The doctor's office is the best setting for most cutaneous procedures.

Although most dermatologic procedures are done in an office setting, some providers are performing them instead in ambulatory surgery centers (ASCs). This relocation of care comes with significantly higher expenses for patients and insurers. Compounding the issue of increased costs is the paucity of evidence demonstrating better outcomes associated with the use of ASCs. The most common cutaneous procedures have low complication rates when performed in an office setting and regular use of ASCs for these procedures is not justified.