Impact of Monkeypox Virus Infection on Immune Parameters in a Woman With Human Immunodeficiency Virus Receiving Clinically Effective Antiretroviral Therapy.

We describe the immunologic and virologic impact of monkeypox (mpox) infection in a woman with human immunodeficiency virus (HIV) whose plasma HIV viremia was suppressed by clinically effective antiretroviral therapy. Extensive phenotypic analyses of B and T cells in peripheral blood and biomarkers in plasma showed significant immunologic perturbations despite the presence of mild mpox disease. Dramatic shifts were noted in the frequencies of total B cells, plasmablasts, and plasmablast immunoglobulin isotypes. Flow cytometric analyses showed a dramatic increase in the frequency of CD38+HLA-DR+ CD8+ T cells after mpox infection. Our data offer guidance for future studies involving mpox infection in affected populations.

Resolution of metabolic dysfunction-associated steatohepatitis with estradiol in a transgender female: A case report.

A 16-year-old trans female patient presented to our Gender Health Program for gender-affirming care. Her intake evaluation revealed signs of hepatocellular injury and fibrosis concerning for metabolic dysfunction-associated steatohepatitis (MASH) and she was referred to a Pediatric Hepatologist. Subsequent delays in initiating hormone therapy caused a decline in her mental health, and she began experiencing suicidal ideations. Gender-affirming hormone therapy has been shown to significantly reduce depressive symptoms and suicidal ideations in transgender and gender diverse youth, and studies in animal models suggest improvement in hepatic steatosis in response to estrogen. A multidisciplinary meeting with Gender Health, Psychiatry, and Hepatology appropriately weighed the benefits of life-saving hormone therapy and the possibility of an improvement in her comorbid liver condition with the risk of further liver damage from estrogen therapy. The teams and the patient agreed to start estradiol with subsequent resolution of laboratory and radiographic evidence of MASH.

Brief Report: Updated Data From IMscin001 Part 2, a Randomized Phase III Study of Subcutaneous Versus Intravenous Atezolizumab in Patients With Locally Advanced or Metastatic NSCLC.

INTRODUCTION: Subcutaneous atezolizumab is approved for the treatment of various solid tumors. Previous results from the IMscin001 study (NCT03735121) revealed that the pharmacokinetics, efficacy, immunogenicity, and safety of subcutaneous and intravenous atezolizumab were consistent (data cutoff: April 26, 2022). We present updated data from this trial (data cutoff: January 16, 2023). METHODS: Eligible patients aged above or equal to 18 years with locally advanced or metastatic NSCLC were randomized (2:1) to receive atezolizumab subcutaneously (1875 mg, n = 247) or intravenously (1200 mg, n = 124) every 3 weeks. Here, we present updated efficacy (overall survival [OS]; progression-free survival; objective response rate; duration of response), safety, and immunogenicity end points, alongside patient-reported outcomes and health care practitioner (HCP) perspectives. RESULTS: In this updated analysis, the median survival follow-up was 9.5 months. Median subcutaneous injection time was 7.1 minutes, with an average subcutaneous injection time of 4 to 8 minutes in most patients (75.7%). OS data were mature: median OS was similar between treatment arms, at 10.7 and 10.1 months in the subcutaneous and intravenous arms, respectively (hazard ratio: 0.88; 95% confidence interval: 0.67-1.16). Other efficacy end points, as well as immunogenicity, patient-reported outcomes, and safety, were similar between arms. Most HCPs found subcutaneous administration convenient (79.5%), easy to administer (89.7%), and were satisfied with the treatment (84.6%); 75.0% of HCPs agreed that administering atezolizumab subcutaneously compared with intravenously could save time. CONCLUSIONS: In this analysis, mature OS data were similar between treatments. The updated efficacy and safety profile of subcutaneous atezolizumab is consistent with previous findings and equivalent to intravenous atezolizumab.

Cardiac K(ATP) channel alterations associated with acclimation to hypoxia in goldfish (Carassius auratus L.).

Goldfish (Carassius auratus L.) are highly tolerant of environmental hypoxia, and with appropriate acclimation may survive and remain active for several days in the complete absence of oxygen. Previous work suggests that the hypoxia-induced activation of cardiac ATP-sensitive potassium (KATP) channels serves to increase tolerance of low oxygen in many species. For goldfish, we have previously characterized a nitric oxide (NO)- and cGMP-dependent pathway by which this channel activation occurs in acute hypoxia. The purpose of the present study was to resolve alterations in KATP channel activity and relevant gene expression in response to acclimation under moderately hypoxic conditions (2.6mg O2/L for seven days at 22°C). Intracellular action potential duration in excised ventricles from hypoxia-acclimated animals was significantly (p<0.05) reduced at both 50% and 90% of full repolarization relative to those from normoxia-acclimated fish. In cell-attached ventricular membrane patches from hypoxia-acclimated goldfish, sarcolemmal KATP channel open probability (NPo) was significantly enhanced vs. control. Of the two genes coding for the pore-forming subunits of cardiac KATP channels (Kir6.1 and Kir6.2), mRNA transcription of kcnj8 (revealed by quantitative real-time PCR) was unchanged while kcnj11 was downregulated in response to chronic low oxygen. The mRNA levels for hif1a (hypoxia inducible factor 1α) in the hearts of hypoxia-acclimated fish were significantly enhanced, as was nitric oxide synthase (nos2) and the sulfonylurea receptor regulatory subunit (sur2, abcc9). These data suggest that prior whole-animal acclimation to chronic hypoxia enhances cardioprotective sarcolemmal KATP currents by altering transcription of regulatory proteins.

Easily accessible but easily forgettable: How ease of access to information online affects cognitive miserliness.

Ubiquitous Internet access has provided easy access to information and has influenced users' attention and knowledge management. In an online information service context, this research examines how the perception of easy access to information affects strategies to learn two types of information: "what it is" and "how to access it." This study also examines how the learning process is moderated by individual differences in working memory capacity, which can determine efficient management of attentional resources. The results show that individuals, especially those who rank high in working memory capacity, are less likely to remember the details but are more likely to remember how to access the information (e.g., a keyword for a search engine query). Those with higher working memory capacity are also more likely to ensure easy access to information by subscribing to information sources. The findings suggest that cognitive miserliness is not due to users' lack of cognitive capacity but to the accessibility of online information and efficient execution of attentional resources. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Disposition to pediatric intensive care unit post supraglottoplasty repair: a systematic review.

BACKGROUND: Patients undergoing supraglottoplasty are often routinely admitted post-operatively to the pediatric intensive care unit (PICU) due to rare but potentially fatal complications such as airway compromise. A systematic review was performed to determine the rate of post-operative PICU-level respiratory support required by pediatric patients following supraglottoplasty, to identify risk factors for patients who may benefit from post-operative PICU admission and limit unnecessary use of intensivist resources. REVIEW METHODS: Key search terms 'supraglottoplasty' OR 'supraglottoplasties' were queried on three databases: CINHAL, Medline and Embase. Inclusion criteria were pediatric patients under 18 years of age who underwent a supraglottoplasty procedure with either an admission to PICU or requirement for PICU-level respiratory support. Risk of bias was assessed by two independent reviewers using QUADAS-2. Findings were critically appraised by three independent reviewers and pooled proportions of criteria meeting PICU admission were calculated for meta-analysis. RESULTS: Nine studies met inclusion criteria, totaling 922 patients. Age at time of surgery ranged from 19 days to 15.7 years with mean age of 5.65 months. A weighted pooled estimate suggested that 19% (95% CI 14-24%) of patients who underwent supraglottoplasty required PICU-admission. The included studies revealed several patient and surgical factors have been linked to postoperative respiratory issues requiring PICU admission, including: neurological disease, perioperative oxygen saturation < 95%, prolonged surgical time and age < 2 months. CONCLUSIONS: This study found that the majority of supraglottoplasty patients do not require significant postoperative respiratory support and suggests that routine PICU admission of these patients may be avoided by careful patient selection. Given the wide heterogeneity of outcome measures, further studies are needed to determine the ideal PICU admission criteria following supraglottoplasty.

Adding a dose of empathy to healthcare: What can healthcare systems do?

RATIONALE, AIMS AND OBJECTIVES: Healthcare practitioners often note system-level barriers to empathy between patients and practitioners. These include burnout-inducing administrative workloads, unfriendly meeting times, burdensome protocols, lack of wellbeing spaces, and undervaluing empathy as a core part of an institution's mission. The need for empathy in healthcare has been magnified with the current SARS-COV-2 outbreak which has limited the expression of interpersonal empathy due to rigid isolation protocols and the use of personal protective equipment. METHOD: This study-the first of its kind that we are aware of-outlines the details of a facilitated workshop run with the leadership of a tertiary level pediatric center in Canada. The workshop used a modified nominal group technique to discuss and prioritize actions to enhance empathy into the hospital system. RESULTS: Inter-professional and inter-disciplinary group of healthcare leader participants agreed on several immediately actionable steps, including embedding patient satisfaction with care measures as standard, and streamlining booking appointments. A roadmap was created to implement the other priorities. CONCLUSION: A systematic approach to infusing empathy into the structure of our healthcare system is much needed. Furthermore, inter-professional and inter-disciplinary educational workshops was well-received as a way to facilitate discussion and drive change.

Pitch and Rhythm Perception and Verbal Short-Term Memory in Acute Traumatic Brain Injury.

Music perception deficits are common following acquired brain injury due to stroke, epilepsy surgeries, and aneurysmal clipping. Few studies have examined these deficits following traumatic brain injury (TBI), resulting in an under-diagnosis in this population. We aimed to (1) compare TBI patients to controls on pitch and rhythm perception during the acute phase; (2) determine whether pitch and rhythm perception disorders co-occur; (3) examine lateralization of injury in the context of pitch and rhythm perception; and (4) determine the relationship between verbal short-term memory (STM) and pitch and rhythm perception. Music perception was examined using the Scale and Rhythm tests of the Montreal Battery of Evaluation of Amusia, in association with CT scans to identify lesion laterality. Verbal short-term memory was examined using Digit Span Forward. TBI patients had greater impairment than controls, with 43% demonstrating deficits in pitch perception, and 40% in rhythm perception. Deficits were greater with right hemisphere damage than left. Pitch and rhythm deficits co-occurred 31% of the time, suggesting partly dissociable networks. There was a dissociation between performance on verbal STM and pitch and rhythm perception 39 to 42% of the time (respectively), with most individuals (92%) demonstrating intact verbal STM, with impaired pitch or rhythm perception. The clinical implications of music perception deficits following TBI are discussed.

Integration of Gross Anatomy Laboratory Sessions into Medical Physics Curriculum.

BACKGROUND: Gross anatomy laboratory sessions with hands-on activities using specimens are essential for teaching anatomy in the medical field. However, they are not seen in medical physics programs. The objective of this pilot study at McGill University was to explore the educational potential of integrated gross anatomy laboratory sessions tailored to the medical physics curriculum. METHODS: The study included 21 medical physics and 11 radiation oncology participants. It was conducted over four 2-h laboratory sessions on pelvic, thoracic, and head and neck anatomy. A radiotherapy applicator device and augmented reality tools were brought in to focus on radiological anatomy and radiation therapy. Students' lab experiences were evaluated through post-laboratory surveys using a mixed methodology. Qualitative data from short-answer questions were analyzed using an inductive coding approach. Quantitative data from Likert scale questions were analyzed with descriptive statistics. RESULTS: All participants reported gross anatomy laboratory sessions as a superior method of learning anatomy compared with a single didactic course (mean Likert: 4.38; median = 5; SD = 0.74). Participants also expressed greater comfort with radiological anatomy and the lab environment with gradual exposure from pelvic prosections to full-body cadavers. Lastly, all participants showed enthusiasm for multidisciplinary activities. CONCLUSION: Carefully designed gross anatomy laboratory sessions were very well received by medical physics students as they transition into a clinical role in healthcare. This pilot study serves as a foundation for future studies exploring anatomical education in medical physics. These sessions will continue to be offered at our school and could be adopted also by other medical physics departments in their courses.

ENaC, renal sodium excretion and extracellular ATP.

Sodium balance determines the extracellular fluid volume and sets arterial blood pressure (BP). Chronically raised BP (hypertension) represents a major health risk in Western societies. The relationship between BP and renal sodium excretion (the pressure/natriuresis relationship) represents the key element in defining the BP homeostatic set point. The renin-angiotensin-aldosterone system (RAAS) makes major adjustments to the rates of renal sodium secretion, but this system works slowly over a period of hours to days. More rapid adjustments can be made by the sympathetic nervous system, although the kidney can function well without sympathetic nerves. Attention has now focussed on regulatory mechanisms within the kidney, including extracellular nucleotides and the P2 receptor system. Here, we discuss how extracellular ATP can control renal sodium excretion by altering the activity of epithelial sodium channels (ENaC) present in the apical membrane of principal cells. There remains considerable controversy over the molecular targets for released ATP, although the P2Y(2) receptor has received much attention. We review the available data and reflect on our own findings in which ATP-activated P2Y and P2X receptors make adjustments to ENaC activity and therefore sodium excretion.

Narcissism and Self- Versus Recipient-Oriented Imagery in Charitable Giving.

Prior research documents extensively that high-narcissism individuals largely tend to be self-centered and often lack empathy. This research outlines the charitable appeal types that can activate empathic responses and other-centered behaviors from high-narcissism individuals. Across four studies, we show that donors who are higher in narcissism exhibit greater charitable intentions when appealed to via imagine-self charitable appeals (as opposed to imagine-recipient types of appeals). Imagine-self appeals enable high-narcissism donors to project themselves into the recipient's situation and, in doing so, elicit greater empathy and, consequently, greater charity. This effect dissipates when projecting oneself is very difficult or impossible-such as with animal recipients or the other gender suffering a gender-specific ailment. We also explicate the underlying process role of self-focused imagination and empathy in heightening charitable outcomes from high-narcissism individuals.

Does knowledge matter?: intentional medication nonadherence among middle-aged Korean Americans with high blood pressure.

AIM: To examine predictors of intentional and unintentional nonadherence to antihypertensive medication regimens and their relationships to blood pressure outcomes. BACKGROUND: Although poor adherence to medical regimens is a major concern in the care of patients with high blood pressure (HBP), our understanding of the complex behavior related to adherence is limited. Moreover, few studies have been devoted to understanding adherence issues in ethnic minority groups, such as the interplay between cultural beliefs and HBP medication-taking behaviors. DESIGN: A cross-sectional analysis was performed to assess the factors affecting nonadherence to antihypertensive medication regimens. METHODS: The data used in this analysis came from an ongoing HBP intervention trial involving middle-aged (40-64 years) Korean Americans with HBP. A total of 445 Korean Americans with HBP was enrolled in the trial at baseline. Of these, 208 participants who were on antihypertensive medication were included in the analysis. Using multivariate logistic regression, we examined theoretically selected variables to assess their relationships to intentional and unintentional nonadherence in this sample. RESULTS: Approximately 53.8% of the subjects endorsed 1 or more types of nonadherent behaviors. After controlling for demographic variables, multivariate analysis revealed that a greater number of side effects from the medication (adjusted odds ratio [OR], 1.19; 95% confidence interval [CI], 1.07 to 1.33) and a lower level of HBP knowledge (adjusted OR, 0.89; 95% CI, 0.79 to 0.99) were significantly associated with intentional nonadherence. Unintentional nonadherence was less strongly associated with the study variables examined in the analysis. CONCLUSION: Our findings indicate that intentional nonadherence to antihypertensive medication that stems from incomplete knowledge of HBP treatment is prevalent among middle-aged Korean Americans with HBP. The results highlight the strong need for an intervention that focuses on increasing patient knowledge about HBP, including the benefits and side effects of antihypertensive medication. This type of focused intervention may help reduce intentional nonadherence to antihypertensive medications and ultimately result in achieving adequate BP control in this high-risk group.

Root cause analysis and Bayesian networks of Down syndrome and necrotizing enterocolitis.

OBSERVATION: This study demonstrates the use of root cause analysis and Bayesian networks in assessing risk of Down syndrome and infant mortality due to necrotizing enterocolitis (NEC). SUBJECTS AND METHODS: The contribution of maternal age, ethnicity, smoking, and infant's comorbidities on mortality associated with NEC (83 cases) was investigated using data obtained from the North Carolina linked birth/infant death files from 1999 to 2003. The data related to Down syndrome, which included 747 infants born with Down syndrome between the years of 1999 and 2003, were provided by the North Carolina Birth defects Monitoring Program. Flowcharts were built to identify potential risk factors and their associations, while the Bayesian network methodology was utilized to encode probabilistic relationships among these variables. RESULTS AND CONCLUSIONS: On the basis of the NEC model, the 3 most common causes of NEC infant mortality were respiratory tract conditions, cardiac, and infection-related problems. For the second application, prior live births (at least 1 prior birth) and infant's gender (male) were found to be the most prevalent causes of Down syndrome. Bayesian belief networks constitute an excellent tool for explorative and causal data analysis, and can assist health care providers in gaining insight into a complex problem.

Preliminary evidence of cognitive and brain abnormalities in uncomplicated adolescent obesity.

OBJECTIVE: To ascertain whether pediatric obesity without clinically significant insulin resistance (IR) impacts brain structure and function. METHODS: Thirty obese and 30 matched lean adolescents, all without clinically significant IR or a diagnosis of metabolic syndrome (MetS), received comprehensive endocrine, neuropsychological, and MRI evaluations. RESULTS: Relative to lean adolescents, obese non-IR adolescents had significantly lower academic achievement (i.e., arithmetic and spelling) and tended to score lower on working memory, attention, psychomotor efficiency, and mental flexibility. In line with our prior work on adolescent MetS, memory was unaffected in uncomplicated obesity. Reductions in the thickness of the orbitofrontal and anterior cingulate cortices as well as reductions of microstructural integrity in major white matter tracts without gross volume changes were also uncovered. CONCLUSIONS: It was documented, for the first time, that adolescents with uncomplicated obesity already have subtle brain alterations and lower performance in selective cognitive domains. When interpreting these preliminary data in the context of our prior reports of similar, but more extensive brain findings in obese adolescents with MetS and T2DM, it was concluded that "uncomplicated" obesity may also result in subtle brain alterations, suggesting a possible dose effect with more severe metabolic dysregulation giving rise to greater abnormalities.