A case report of vaping-associated sudden cardiac arrest in a young healthy patient.

Introduction and importance: While vaping has increased significantly among young individuals, the effects of vape aerosol constituents on cardiac electrophysiological dynamics remain unknown. Case presentation: A 22-year-old female with a history of energy vaping presented with cardiac arrest. Found to have no pulse, CPR was started and an initial rhythm of ventricular tachycardia was obtained. Shock was administered with a follow-up rhythm of ventricular fibrillation. She was emergently defibrillated and entered atrial fibrillation with rapid ventricular response. Toxicology and troponins were all negative. Left heart catheterization and cardiac MRI were unremarkable. She was discharged with an external defibrillation vest and a tentative plan for outpatient electrophysiology study in the setting of negative work-up for cardiopulmonary arrest. Clinical discussion: Vaping-induced sudden cardiac arrest may be attributed to a reduction in cardiac repolarization reserve. Exposure to vegetable glycerin and propylene glycol, substances present in nearly all vape products, have been found to incite arrhythmias and disrupt cardiac conduction in animals. Acrolein, an aldehyde byproduct of glycerin, has also been found to induce arrhythmias due to autonomic dysfunction. Increased intracellular calcium concentration and free radical damage, which occur as a result of inhaling particulate matter generated from e-cigarettes, further propagates the risk of arrhythmia. Conclusion: The effects of inhaling vape aerosols remain not fully understood. While there is a perceived notion that nicotine-free aerosols may be harmless, that remains unclear. Further studies are needed to evaluate proarrhythmogenic effects and autonomic dysfunction from the various chemical substances present in vape aerosols.

T cell migration requires ion and water influx to regulate actin polymerization.

Migration of T cells is essential for their ability to mount immune responses. Chemokine-induced T cell migration requires WNK1, a kinase that regulates ion influx into the cell. However, it is not known why ion entry is necessary for T cell movement. Here we show that signaling from the chemokine receptor CCR7 leads to activation of WNK1 and its downstream pathway at the leading edge of migrating CD4+ T cells, resulting in ion influx and water entry by osmosis. We propose that WNK1-induced water entry is required to swell the membrane at the leading edge, generating space into which actin filaments can polymerize, thereby facilitating forward movement of the cell. Given the broad expression of WNK1 pathway proteins, our study suggests that ion and water influx are likely to be essential for migration in many cell types, including leukocytes and metastatic tumor cells.

B cell-intrinsic requirement for WNK1 kinase in antibody responses in mice.

Migration and adhesion play critical roles in B cells, regulating recirculation between lymphoid organs, migration within lymphoid tissue, and interaction with CD4+ T cells. However, there is limited knowledge of how B cells integrate chemokine receptor and integrin signaling with B cell activation to generate efficient humoral responses. Here, we show that the WNK1 kinase, a regulator of migration and adhesion, is essential in B cells for T-dependent and -independent antibody responses. We demonstrate that WNK1 transduces signals from the BCR, CXCR5, and CD40, and using intravital imaging, we show that WNK1 regulates migration of naive and activated B cells, and their interactions with T cells. Unexpectedly, we show that WNK1 is required for BCR- and CD40-induced proliferation, acting through the OXSR1 and STK39 kinases, and for efficient B cell-T cell collaboration in vivo. Thus, WNK1 is critical for humoral immune responses, by regulating B cell migration, adhesion, and T cell-dependent activation.

Which moral exemplars inspire prosociality?

Some stories of moral exemplars motivate us to emulate their admirable attitudes and behaviors, but why do some exemplars motivate us more than others? We systematically studied how motivation to emulate is influenced by the similarity between a reader and an exemplar in social or cultural background (Relatability) and how personally costly or demanding the exemplar's actions are (Attainability). Study 1 found that university students reported more inspiration and related feelings after reading true stories about the good deeds of a recent fellow alum, compared to a famous moral exemplar from decades past. Study 2A developed a battery of short moral exemplar stories that more systematically varied Relatability and Attainability, along with a set of non-moral exemplar stories for comparison. Studies 2B and 2C examined the path from the story type to relatively low stakes altruism (donating to charity and intentions to volunteer) through perceived attainability and relatability, as well as elevation and pleasantness. Together, our studies suggest that it is primarily the relatability of the moral exemplars, not the attainability of their actions, that inspires more prosocial motivation, at least regarding acts that help others at a relatively low cost to oneself.

Targeted Secondary Screening for Congenital Hypothyroidism in High-Risk Neonates: A 9 Year Review in a Large California Health Care System.

Secondary screening for missed congenital hypothyroidism (CH) has been introduced sporadically, but its necessity and optimal strategy have not been recognized. We hypothesized that a simple clinical protocol (performed by a medical group without a governmental mandate) targeting infants at high risk for missed CH can identify cases. We performed a 9-year retrospective review of 338,478 neonates within a California health plan following the introduction of thyrotropin (TSH) secondary screening for neonates at high risk for missed CH due to very-low-birthweight (VLBW), hospitalized congenital heart disease (CHD), and same-sex multiples (SSM). Screening performance by day 60 of life was 95% successful for VLBW and >50% for CHD and SSM, leading to an additional 35% CH treated cases despite re-testing only 1.7% of the cohort. Infants with VLBW or CHD were 33 times more likely (190 times more likely for CHD with Down Syndrome) to receive treatment for CH than random infants diagnosed by primary screening (p < 0.001), and 92% of these infants were not found by primary newborn screening. Currently, permanent disease has been documented in 84% of CH by primary screening compared to 27% by secondary screening (p < 0.001). This targeted secondary screening program identifies and treats additional CH cases after TSH-only newborn screening.

National Resident Matching Program Performance Among US MD and DO Seniors in the Early Single Accreditation Graduate Medical Education Era.

INTRODUCTION: As of the 2020 National Resident Matching Program (NRMP), nearly all applicants are evaluated together for graduate medical education (GME) candidacy. We set out to characterize US MD and DO Senior residency match performance in the single-accreditation GME era. METHODS: A retrospective study was conducted in 2021 utilizing data collected from the 2018 and 2020 NRMP Charting Outcomes in the Match publications aggregated and subdivided into three groups based on competitiveness: low (LC), moderate (MC), and high (HC). Nonparametric analysis was performed using Chi square or Fisher exact tests if counts were less than five. Significance was determined at p < 0.05. RESULTS: A total of 46,853 candidates were included, with 36,194 (77.3%) US MD and 10,659 (22.7%) DO Seniors. Match rates for US DO Seniors were lower than US MD Seniors across all competitiveness strata (p < 0.0001). Research item production, national licensing examination scores, and mean number of contiguous programs ranked were lower for matched US DO Seniors compared to matched US MD Seniors, with significant differences depending on competitiveness group. CONCLUSIONS: With recent changes to GME and its application process, understanding how various groups compare will be increasingly important. US DO Seniors have lower first-rank match rates for all specialty competitiveness levels. This may be due to lower research output or nuanced specialty selection. This study could aid GME stakeholders to more effectively allocate resources and better prepare residency candidates.

Defending optimistic rationalism: A reply to commentators.

In response, I elaborate on my conception of moral reasoning, as well as clarify the structure of debunking arguments and how my cautious optimism is only of the "glass half full" sort. I also explain how rationalism can capture insights purportedly only explained by sentimentalist and Humean views. The reply concludes by clarifying and admitting some limits of the book's scope.

A limited skeptical threat.

Doris argues that our choices are heavily influenced by forces that we wouldn't count as genuine reasons. This unsettling conclusion is motivated by a debunking argument so wide-ranging that it isn't foisted upon us by the sciences. Doris sometimes seems to lower his ambitions when offering instead a skeptical hypothesis argument, but that conflicts with his aims in the book.

Viral Infection Identifies Micropeptides Differentially Regulated in smORF-Containing lncRNAs.

Viral infection leads to a robust cellular response whereby the infected cell produces hundreds of molecular regulators to combat infection. Currently, non-canonical components, e.g., long noncoding RNAs (lncRNAs) have been added to the repertoire of immune regulators involved in the antiviral program. Interestingly, studies utilizing next-generation sequencing technologies show that a subset of the >10,000 lncRNAs in the mammalian genome contain small open reading frames (smORFs) associated with active translation, i.e., many lncRNAs are not noncoding. Here, we use genome-wide high-throughput methods to identify potential micropeptides in smORF-containing lncRNAs involved in the immune response. Using influenza as a viral infection model, we performed RNA-seq and ribosome profiling to track expression and translation of putative lncRNAs that may encode for peptides and identify tens of potential candidates. Interestingly, many of these peptides are highly conserved at the protein level, strongly suggesting biological relevance and activity. By perusing publicly available data sets, four potential peptides of interest seem common to stress induction and/or are highly conserved; potential peptides from the MMP24-AS1, ZFAS1, RP11-622K12.1, and MIR22HG genes. Interestingly, using an antibody against the potential peptide encoded by MIR22HG RNA, we show that the peptide is stably expressed in the absence of infection, and upregulated in response to infection, corroborating the prediction of the ribosome profiling results. These data show the utility of perturbation approaches in identifying potentially relevant novel molecules encoded in the genome.

The means/side-effect distinction in moral cognition: A meta-analysis.

Experimental research suggests that people draw a moral distinction between bad outcomes brought about as a means versus a side effect (or byproduct). Such findings have informed multiple psychological and philosophical debates about moral cognition, including its computational structure, its sensitivity to the famous Doctrine of Double Effect, its reliability, and its status as a universal and innate mental module akin to universal grammar. But some studies have failed to replicate the means/byproduct effect especially in the absence of other factors, such as personal contact. So we aimed to determine how robust the means/byproduct effect is by conducting a meta-analysis of both published and unpublished studies (k=101; 24,058 participants). We found that while there is an overall small difference between moral judgments of means and byproducts (standardized mean difference=0.87, 95% CI 0.67-1.06; standardized mean change=0.57, 95% CI 0.44-0.69; log odds ratio=1.59, 95% CI 1.15-2.02), the mean effect size is primarily moderated by whether the outcome is brought about by personal contact, which typically involves the use of personal force.

Emotional reactions to human reproductive cloning.

BACKGROUND: Extant surveys of people's attitudes towards human reproductive cloning focus on moral judgements alone, not emotional reactions or sentiments. This is especially important given that some (especially Leon Kass) have argued against such cloning on the ground that it engenders widespread negative emotions, like disgust, that provide a moral guide. OBJECTIVE: To provide some data on emotional reactions to human cloning, with a focus on repugnance, given its prominence in the literature. METHODS: This brief mixed-method study measures the self-reported attitudes and emotions (positive or negative) towards cloning from a sample of participants in the USA. RESULTS: Most participants condemned cloning as immoral and said it should be illegal. The most commonly reported positive sentiment was by far interest/curiosity. Negative emotions were much more varied, but anxiety was the most common. Only about a third of participants selected disgust or repugnance as something they felt, and an even smaller portion had this emotion come to mind prior to seeing a list of options. CONCLUSIONS: Participants felt primarily interested and anxious about human reproductive cloning. They did not primarily feel disgust or repugnance. This provides initial empirical evidence that such a reaction is not appropriately widespread.

The neuropsychological contributors to psychopathic personality traits in adolescence.

Research has consistently revealed that measures of psychopathy and psychopathic personality traits represent some of the most consistent predictors of violent criminal involvement. As a result, there has been a considerable amount of interest in trying to identify the various etiological factors related to psychopathy. The current study builds on this existing body of literature by examining the association between neuropsychological deficits and psychopathic personality traits. Data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care were analyzed. Adolescent psychopathic personality traits were measured with a 15-item scale drawn from the Youth Psychopathic Traits Inventory (YPI), whereas neuropsychological functioning was assessed with a number of standardized tests of cognitive skills. Analyses revealed that neuropsychological deficits were significantly related to psychopathy measures across all four measurement phases. Neuropsychological deficits also predicted scoring in the top 5% of psychopathic personality traits.

Transcranial direct current stimulation (tDCS) reduces postsurgical opioid consumption in total knee arthroplasty (TKA).

BACKGROUND: Although pain is often a symptom that precedes total knee arthroplasty (TKA), the procedure itself is associated with considerable postoperative pain lasting days to weeks. Postoperative pain control is an important factor in determining recovery time, hospital length of stay, and rehabilitation success. Several brain stimulation technologies including transcranial direct current stimulation (tDCS) have demonstrated promise as treatments for a variety of pain conditions. The present study examined the effects of 4 sessions of tDCS on post-TKA pain and opioid consumption. MATERIALS AND METHODS: Forty patients undergoing unilateral TKA were randomly assigned to receive a total of 80 minutes of real (n=20) or sham tDCS (n=20) with the anode over the knee representation of the motor strip (C1h or C2h corresponding to the target knee) and cathode over the right dorsolateral prefrontal cortex (F3; located by the EEG 10-20 System). Patient-controlled analgesia ( hydromorphone) use was tracked during the ∼48 hours postsurgery. RESULTS: Patients in the real tDCS group used an average of 6.6 mg (SD=5.3) of patient-controlled analgesia hydromorphone, whereas those in the sham group used 12.3 mg (SD=6.6; t37=2.93, P=0.006). Despite using less opioid medication, participants in the real tDCS group reported no pain exacerbation or worse mood with respect to those in the sham tDCS group. CONCLUSIONS: Results from this pilot feasibility study suggest that tDCS may be able to reduce post-TKA opioid requirements. Although these results are preliminary, the data support further research in the area of adjunctive cortical stimulation in the management of postsurgical pain.

Giannoti-Crosti syndrome associated with type A influenza.

Gianotti-Crosti syndrome is an entity characterized by an acute papular eruption in children and has been associated with a multitude of viruses. This is the first case reported in association with type A influenza, a virus that usually has no dermatologic findings.

Practical Interests, Relevant Alternatives, and Knowledge Attributions: an Empirical Study.

In defending his interest-relative account of knowledge, Jason Stanley relies heavily on intuitions about several bank cases. We experimentally test the empirical claims that Stanley seems to make concerning our common-sense intuitions about these cases. Additionally, we test the empirical claims that Jonathan Schaffer seems to make, regarding the salience of an alternative, in his critique of Stanley. Our data indicate that neither raising the possibility of error nor raising stakes moves most people from attributing knowledge to denying it. However, the raising of stakes (but not alternatives) does affect the level of confidence people have in their attributions of knowledge. We argue that our data impugn what both Stanley and Schaffer claim our common-sense judgments about such cases are.

Property tuning in charge-transfer chromophores by systematic modulation of the spacer between donor and acceptor.

A series of donor-acceptor chromophores was prepared in which the spacer separating 4-dimethylanilino (DMA) donor and C(CN)(2) acceptor moieties is systematically varied. All of the new push-pull systems, except 4 b, are thermally stable molecules. In series a, the DMA rings are directly attached to the central spacer, whereas in series b additional acetylene moieties are inserted. X-ray crystal structures were obtained for seven of the new, intensely colored target compounds. In series a, the DMA rings are sterically forced out of the mean plane of the residual pi system, whereas the entire conjugated pi system in series b is nearly planar. Support for strong donor-acceptor interactions was obtained through evaluation of the quinoid character of the DMA ring and by NMR and IR spectroscopy. The UV/Vis spectra feature bathochromically shifted, intense charge-transfer bands, with the lowest energy transitions and the smallest optical gap being measured for the two-dimensionally extended chromophores 6 a and 6 b. The redox behavior of the push-pull molecules was investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). In the series 1 b, 2 b, 4 b, 5 b, in which the spacer between donor and acceptor moieties is systematically enlarged, the electrochemical gap decreases steadily from 1.94 V (1 b) to 1.53 V (5 b). This decrease is shown to be a consequence of a reduction in the D-A conjugation with increasing spacer length. Degenerate four-wave mixing experiments reveal high third-order optical nonlinearities, pointing to potentially interesting applications of some of the new chromophores in optoelectronic devices.