Acute Effects of Coffee Consumption on Health among Ambulatory Adults.

BACKGROUND: Coffee is one of the most commonly consumed beverages in the world, but the acute health effects of coffee consumption remain uncertain. METHODS: We conducted a prospective, randomized, case-crossover trial to examine the effects of caffeinated coffee on cardiac ectopy and arrhythmias, daily step counts, sleep minutes, and serum glucose levels. A total of 100 adults were fitted with a continuously recording electrocardiogram device, a wrist-worn accelerometer, and a continuous glucose monitor. Participants downloaded a smartphone application to collect geolocation data. We used daily text messages, sent over a period of 14 days, to randomly instruct participants to consume caffeinated coffee or avoid caffeine. The primary outcome was the mean number of daily premature atrial contractions. Adherence to the randomization assignment was assessed with the use of real-time indicators recorded by the participants, daily surveys, reimbursements for date-stamped receipts for coffee purchases, and virtual monitoring (geofencing) of coffee-shop visits. RESULTS: The mean (±SD) age of the participants was 39±13 years; 51% were women, and 51% were non-Hispanic White. Adherence to the random assignments was assessed to be high. The consumption of caffeinated coffee was associated with 58 daily premature atrial contractions as compared with 53 daily events on days when caffeine was avoided (rate ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). The consumption of caffeinated coffee as compared with no caffeine consumption was associated with 154 and 102 daily premature ventricular contractions, respectively (rate ratio, 1.51; 95% CI, 1.18 to 1.94); 10,646 and 9665 daily steps (mean difference, 1058; 95% CI, 441 to 1675); 397 and 432 minutes of nightly sleep (mean difference, 36; 95% CI, 25 to 47); and serum glucose levels of 95 mg per deciliter and 96 mg per deciliter (mean difference, -0.41; 95% CI, -5.42 to 4.60). CONCLUSIONS: In this randomized trial, the consumption of caffeinated coffee did not result in significantly more daily premature atrial contractions than the avoidance of caffeine. (Funded by the University of California, San Francisco, and the National Institutes of Health; CRAVE ClinicalTrials.gov number, NCT03671759.).

Cardiac contraction and relaxation are regulated by distinct subcellular cAMP pools.

Cells interpret a variety of signals through G-protein-coupled receptors (GPCRs) and stimulate the generation of second messengers such as cyclic adenosine monophosphate (cAMP). A long-standing puzzle is deciphering how GPCRs elicit different physiological responses despite generating similar levels of cAMP. We previously showed that some GPCRs generate cAMP from both the plasma membrane and the Golgi apparatus. Here we demonstrate that cardiomyocytes distinguish between subcellular cAMP inputs to elicit different physiological outputs. We show that generating cAMP from the Golgi leads to the regulation of a specific protein kinase A (PKA) target that increases the rate of cardiomyocyte relaxation. In contrast, cAMP generation from the plasma membrane activates a different PKA target that increases contractile force. We further validated the physiological consequences of these observations in intact zebrafish and mice. Thus, we demonstrate that the same GPCR acting through the same second messenger regulates cardiac contraction and relaxation dependent on its subcellular location.

Frequent Premature Atrial Contractions Lead to Adverse Atrial Remodeling and Atrial Fibrillation in a Swine Model.

BACKGROUND: Frequent premature atrial complexes (PACs) are associated with future incident atrial fibrillation (AF), but whether PACs contribute to development of AF through adverse atrial remodeling has not been studied. This study aimed to explore the effect of frequent PACs from different sites on atrial remodeling in a swine model. METHODS: Forty swine underwent baseline electrophysiologic studies and echocardiography followed by pacemaker implantations and paced PACs (50% burden) at 250-ms coupling intervals for 16 weeks in 4 groups: (1) lateral left atrium (LA) PACs by the coronary sinus (Lat-PAC; n=10), (2) interatrial septal PACs (Sep-PAC; n=10), (3) regular LA pacing at 130 beats/min (Reg-130; n=10), and (4) controls without PACs (n=10). At the final study, repeat studies were performed, followed by tissue histology and molecular analyses focusing on fibrotic pathways. RESULTS: Lat-PACs were associated with a longer P-wave duration (93.0±9.0 versus 74.2±8.2 and 58.8±7.6 ms; P<0.001) and greater echocardiographic mechanical dyssynchrony (57.5±11.6 versus 35.7±13.0 and 24.4±11.1 ms; P<0.001) compared with Sep-PACs and controls, respectively. After 16 weeks, Lat-PACs led to slower LA conduction velocity (1.1±0.2 versus 1.3±0.2 [Sep-PAC] versus 1.3±0.1 [Reg-130] versus 1.5±0.2 [controls] m/s; P<0.001) without significant change in atrial ERP. The Lat-PAC group had a significantly increased percentage of LA fibrosis and upregulated levels of extracellular matrix proteins (lysyl oxidase and collagen 1 and 8), as well as TGF-ß1 (transforming growth factor-ß1) signaling proteins (latent and monomer TGF-ß1 and phosphorylation/total ratio of SMAD2/3; P<0.05). The Lat-PAC group had the longest inducible AF duration (terminal to baseline: 131 [interquartile range 30, 192] seconds versus 16 [6, 26] seconds [Sep-PAC] versus 22 [11, 64] seconds [Reg-130] versus -1 [-16, 7] seconds [controls]; P<0.001). CONCLUSIONS: In this swine model, frequent PACs resulted in adverse atrial structural remodeling with a heightened propensity to AF. PACs originating from the lateral LA produced greater atrial remodeling and longer induced AF duration than the septal-origin PACs. These data provide evidence that frequent PACs can cause adverse atrial remodeling as well as AF, and that the location of ectopic PACs may be clinically meaningful.

A novel speckle-tracking echocardiography parameter assessing left ventricular afterload.

BACKGROUND: Left ventricular stroke work index (LVSWI) and afterload-related cardiac performance (ACP) consider left ventricular (LV) afterload and could be better prognosticators in septic cardiomyopathy. However, their invasive nature prevents their routine clinical applications. This study aimed to investigate (1) whether a proposed speckle-tracking echocardiography parameter, Pressure-Strain Product (PSP), can non-invasively predict catheter-based LVSWI, ACP and serum lactate in an ovine model of septic cardiomyopathy; and (2) whether PSP can distinguish the sub-phenotypes of acute respiratory distress syndrome (ARDS) with or without sepsis-like conditions. METHODS: Sixteen sheep with ARDS were randomly assigned to either (1) sepsis-like (n = 8) or (2) non-sepsis-like (n = 8) group. Each ARDS and sepsis-like condition was induced by intravenous infusion of oleic acid and lipopolysaccharide, respectively. Pulmonary artery catheter-based LVSWI (the product of stroke work index, mean arterial pressure and .0136), ACP (the percentage of cardiac output measured to cardiac output predicted as normal) and serum lactate were measured simultaneously with transthoracic echocardiography. Two PSP indices were calculated by multiplying the mean arterial blood pressure and either global circumferential strain (PSPcirc) or radial strain (PSPrad). RESULTS: PSPcirc showed a significant correlation with LVSWI (r2 = .66, p < .001) and ACP (r2 = .82, p < .001) in the sepsis-like group. Although PSP could not distinguish subphenotypes, PSPcirc predicted LVSWI (AUC .86) and ACP (AUC .88), and PSPrad predicted serum lactate (AUC .75) better than LV ejection fraction, global circumferential and radial strain. CONCLUSIONS: A novel PSP has the potential to non-invasively predict catheter-based LVSWI and ACP, and was associated with serum lactate in septic cardiomyopathy.

A novel echocardiographic parameter considering left ventricular afterload during V-A ECMO support.

BACKGROUND: Left ventricular stroke work index (LVSWI) and cardiac power index (CPI) account for the haemodynamic load of the left ventricle and are promising prognostic values in cardiogenic shock. However, accurately and non-invasively measuring these parameters during veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is challenging and potentially biased by the extracorporeal circulation. This study aimed to investigate, in an ovine model of cardiogenic shock, whether Pressure-Strain Product (PSP), a novel speckle-tracking echocardiography parameter, (1) can correlate with pressure-volume catheter-based LVSWI and CPI, and (2) can be load-independent during the flow modification of V-A ECMO. METHODS: Nine Dorset-cross ewes (51 ± 4 kg) were included. After cardiogenic shock was induced, full support V-A ECMO (X L/min based on 60 mL/kg/min) commenced. At seven time points during 24-h observation, echocardiographic parameters as well as pressure-volume catheter-based LVSWI and CPI were simultaneously measured with X and following X-1 L/min of ECMO flow. PSP was calculated by multiplying global circumferential strain or global radial strain, and mean arterial pressure, for PSPcirc or PSPrad, respectively. RESULTS: PSPcirc showed a stronger correlation with LVSWI (correlation coefficient, CC = .360, p < .001) and CPI (CC = .283, p < .001) than other echocardiographic parameters. The predictability of PSPcirc for pressure-volume catheter-based LVSWI (AUC .82) and CPI (AUC .80) was also higher than other echocardiographic parameters. No statistically significant differences were identified between the two ECMO flow variations in PSPcirc (p = .558). CONCLUSIONS: A novel echocardiographic parameter, PSP, may non-invasively predict pressure-volume catheter-based LVSWI and CPI in a load-independent manner in a cardiogenic shock supported by V-A ECMO.

Echocardiographic surrogate of left ventricular stroke work in a model of brain stem death donors.

BACKGROUND: The commonest echocardiographic measurement, left ventricular ejection fraction, can not necessarily predict mortality of recipients following heart transplantation potentially due to afterload dependency. Afterload-independent left ventricular stroke work index (LVSWI) is alternatively recommended by the current guideline; however, pulmonary artery catheters are rarely inserted in organ donors in most jurisdictions. We propose a novel non-invasive echocardiographic parameter, Pressure-Strain Product (PSP), as a potential surrogate of catheter-based LVSWI. This study aimed to investigate if PSP could correlate with catheter-based LVSWI in an ovine model of brain stem death (BSD) donors. The association between PSP and myocardial mitochondrial function in the post-transplant hearts was also evaluated. METHODS: Thirty-one female sheep (weight 47 ± 5 kg) were divided into two groups; BSD (n = 15), and sham neurologic injury (n = 16). Echocardiographic parameters including global circumferential strain (GCS) and global radial strain (GRS) and pulmonary artery catheter-based LVSWI were simultaneously measured at 8-timepoints during 24-h observation. PSP was calculated as a product of GCS or GRS, and mean arterial pressure for PSPcirc or PSPrad, respectively. Myocardial mitochondrial function was evaluated following 6-h observation after heart transplantation. RESULTS: In BSD donor hearts, PSPcirc (n = 96, rho = .547, p < .001) showed the best correlation with LVSWI among other echocardiographic parameters. PSPcirc returned AUC of .825 to distinguish higher values of cardiomyocyte mitochondrial function (cut-off point; mean value of complex 1,2 O2 Flux) in post-transplant hearts, which was greater than other echocardiographic parameters. CONCLUSIONS: PSPcirc could be used as a surrogate of catheter-based LVSWI reflecting mitochondrial function.

Lipid metabolism in dopaminergic neurons influences light entrainment.

Dietary lipids, particularly omega-3 polyunsaturated fatty acids, are speculated to impact behaviors linked to the dopaminergic system, such as movement and control of circadian rhythms. However, the ability to draw a direct link between dopaminergic omega-3 fatty acid metabolism and behavioral outcomes has been limited to the use of diet-based approaches, which are confounded by systemic effects. Here, neuronal lipid metabolism was targeted in a diet-independent manner by manipulation of long-chain acyl-CoA synthetase 6 (ACSL6) expression. ACSL6 performs the initial reaction for cellular fatty acid metabolism and prefers the omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA). The loss of Acsl6 in mice (Acsl6-/- ) depletes neuronal membranes of DHA content and results in phenotypes linked to dopaminergic control, such as hyperlocomotion, impaired short-term spatial memory, and imbalances in dopamine neurochemistry. To investigate the role of dopaminergic ACSL6 on these outcomes, a dopaminergic neuron-specific ACSL6 knockout mouse was generated (Acsl6DA-/- ). Acsl6DA-/- mice demonstrated hyperlocomotion and imbalances in striatal dopamine neurochemistry. Circadian rhythms of both the Acsl6-/- and the Acsl6DA-/- mice were similar to control mice under basal conditions. However, upon light entrainment, a mimetic of jet lag, both the complete knockout of ACSL6 and the dopaminergic-neuron-specific loss of ACSL6 resulted in a longer recovery to entrainment compared to control mice. In conclusion, these data demonstrate that ACSL6 in dopaminergic neurons alters dopamine metabolism and regulation of light entrainment suggesting that DHA metabolism mediated by ACSL6 plays a role in dopamine neuron biology.

Modulation of pulmonary immune function by inhaled cannabis products and consequences for lung disease.

The lungs, in addition to participating in gas exchange, represent the first line of defense against inhaled pathogens and respiratory toxicants. Cells lining the airways and alveoli include epithelial cells and alveolar macrophages, the latter being resident innate immune cells important in surfactant recycling, protection against bacterial invasion and modulation of lung immune homeostasis. Environmental exposure to toxicants found in cigarette smoke, air pollution and cannabis can alter the number and function of immune cells in the lungs. Cannabis (marijuana) is a plant-derived product that is typically inhaled in the form of smoke from a joint. However, alternative delivery methods such as vaping, which heats the plant without combustion, are becoming more common. Cannabis use has increased in recent years, coinciding with more countries legalizing cannabis for both recreational and medicinal purposes. Cannabis may have numerous health benefits owing to the presence of cannabinoids that dampen immune function and therefore tame inflammation that is associated with chronic diseases such as arthritis. The health effects that could come with cannabis use remain poorly understood, particularly inhaled cannabis products that may directly impact the pulmonary immune system. Herein, we first describe the bioactive phytochemicals present in cannabis, with an emphasis on cannabinoids and their ability to interact with the endocannabinoid system. We also review the current state-of-knowledge as to how inhaled cannabis/cannabinoids can shape immune response in the lungs and discuss the potential consequences of altered pulmonary immunity. Overall, more research is needed to understand how cannabis inhalation shapes the pulmonary immune response to balance physiological and beneficial responses with potential deleterious consequences on the lungs.

The O-GlcNAc dichotomy: when does adaptation become pathological?

O-Linked attachment of ß-N-acetylglucosamine (O-GlcNAc) on serine and threonine residues of nuclear, cytoplasmic, and mitochondrial proteins is a highly dynamic and ubiquitous post-translational modification that impacts the function, activity, subcellular localization, and stability of target proteins. Physiologically, acute O-GlcNAcylation serves primarily to modulate cellular signaling and transcription regulatory pathways in response to nutrients and stress. To date, thousands of proteins have been revealed to be O-GlcNAcylated and this number continues to grow as the technology for the detection of O-GlcNAc improves. The attachment of a single O-GlcNAc is catalyzed by the enzyme O-GlcNAc transferase (OGT), and their removal is catalyzed by O-GlcNAcase (OGA). O-GlcNAcylation is regulated by the metabolism of glucose via the hexosamine biosynthesis pathway, and the metabolic abnormalities associated with pathophysiological conditions are all associated with increased flux through this pathway and elevate O-GlcNAc levels. While chronic O-GlcNAcylation is well associated with cardiovascular dysfunction, only until recently, and with genetically modified animals, has O-GlcNAcylation as a contributing mechanism of cardiovascular disease emerged. This review will address and critically evaluate the current literature on the role of O-GlcNAcylation in vascular physiology, with a view that this pathway can offer novel targets for the treatment and prevention of cardiovascular diseases.

Volatile Organic Compounds in Disposable Diapers and Baby Wipes in the US: A Survey of Products and Health Risks.

Many thousands of diapers are worn by young children and the elderly, who have thin and sensitive skin that is highly vulnerable to chemicals, including volatile organic compounds (VOCs) that may be ingredients of these products or present as inadvertent or residual components. The levels and potential health risks of VOCs in diapers have not been reported previously. In this study, we collected 31 disposable hygiene products in the US market based on market share and analyzed 98 target VOCs using purge and trap sampling and thermal desorption/gas chromatography/mass spectrometer analysis. Exposures and risks were modeled using reasonable upper level exposure scenarios. Adult diapers contained the highest total target VOC concentration (median level of 23.5 µg/g), and the predominant VOCs were alkanes. In some diapers, the estimated noncancer risk from these VOCs was sometimes very large (hazard quotient of 1609) due to n-heptane. Baby diapers contained several known or suspected carcinogens, including benzene and 1,4-dioxane, and the lifetime cancer risk from some diapers approached 1 per million under a worst-case scenario. Store-brand products had higher levels of VOCs than generic brands, and products labeled "organic" or "for sensitive skin" did not necessarily have lower levels. Our results show that toxic VOCs were found in all tested disposable diapers and wipes at trace levels, and risks from using some diapers in high use exposure scenarios are high enough to warrant additional attention and possibly corrective measures. We recommend eliminating and monitoring toxic ingredients and disclosing all chemicals that may be in these products.

Conformational diversity facilitates antibody mutation trajectories and discrimination between foreign and self-antigens.

Conformational diversity and self-cross-reactivity of antigens have been correlated with evasion from neutralizing antibody responses. We utilized single cell B cell sequencing, biolayer interferometry and X-ray crystallography to trace mutation selection pathways where the antibody response must resolve cross-reactivity between foreign and self-proteins bearing near-identical contact surfaces, but differing in conformational flexibility. Recurring antibody mutation trajectories mediate long-range rearrangements of framework (FW) and complementarity determining regions (CDRs) that increase binding site conformational diversity. These antibody mutations decrease affinity for self-antigen 19-fold and increase foreign affinity 67-fold, to yield a more than 1,250-fold increase in binding discrimination. These results demonstrate how conformational diversity in antigen and antibody does not act as a barrier, as previously suggested, but rather facilitates high affinity and high discrimination between foreign and self.

Red Cabbage Juice-Mediated Gut Microbiota Modulation Improves Intestinal Epithelial Homeostasis and Ameliorates Colitis.

Gut microbiota plays a crucial role in inflammatory bowel diseases (IBD) and can potentially prevent IBD through microbial-derived metabolites, making it a promising therapeutic avenue. Recent evidence suggests that despite an unclear underlying mechanism, red cabbage juice (RCJ) alleviates Dextran Sodium Sulfate (DSS)-induced colitis in mice. Thus, the study aims to unravel the molecular mechanism by which RCJ modulates the gut microbiota to alleviate DSS-induced colitis in mice. Using C57BL/6J mice, we evaluated RCJ's protective role in DSS-induced colitis through two cycles of 3% DSS. Mice were daily gavaged with PBS or RCJ until the endpoint, and gut microbiota composition was analyzed via shotgun metagenomics. RCJ treatment significantly improved body weight (p ≤ 0.001), survival in mice (p < 0.001) and reduced disease activity index (DAI) scores. Further, RCJ improved colonic barrier integrity by enhancing the expression of protective colonic mucins (p < 0.001) and tight junction proteins (p ≤ 0.01) in RCJ + DSS-treated mice compared to the DSS group. Shotgun metagenomic analysis revealed an enrichment of short-chain fatty acids (SCFAs)-producing bacteria (p < 0.05), leading to increased Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) activation (p ≤ 0.001). This, in turn, resulted in repression of the nuclear factor κB (NFκB) signaling pathway, causing decreased production of inflammatory cytokines and chemokines. Our study demonstrates colitis remission in a DSS-induced mouse model, showcasing RCJ as a potential modulator for gut microbiota and metabolites, with promising implications for IBD prevention and treatment.

Initial Derivation of a Predictive Model for Left Ventricular Longitudinal Strain (LS) in Early Sepsis.

Septic shock is a common deadly disease often associated with cardiovascular dysfunction. Left ventricular longitudinal strain (LV LS) has been proposed as a sensitive marker to measure cardiovascular function; however, it is not available universally in standard clinical echocardiograms. We sought to derive a predictive model for LV LS, using machine learning techniques with the hope that we may uncover surrogates for LV LS. We found that left ventricular ejection fraction, tricuspid annular plane systolic excursion, sepsis source, height, mitral valve Tei index, LV systolic dimension, aortic valve ejection time, and peak acceleration rate were all predictive of LV LS in this initial exploratory model. Future modeling work may uncover combinations of these variables which may be powerful surrogates for LV LS and cardiovascular function.

Sensitivity of Vowel-Evoked Envelope Following Responses to Spectra and Level of Preceding Phoneme Context.

OBJECTIVE: Vowel-evoked envelope following responses (EFRs) could be a useful noninvasive tool for evaluating neural activity phase-locked to the fundamental frequency of voice (f0). Vowel-evoked EFRs are often elicited by vowels in consonant-vowel syllables or words. Considering neural activity is susceptible to temporal masking, EFR characteristics elicited by the same vowel may vary with the features of the preceding phoneme. To this end, the objective of the present study was to evaluate the influence of the spectral and level characteristics of the preceding phoneme context on vowel-evoked EFRs. DESIGN: EFRs were elicited by a male-spoken /i/ (stimulus; duration = 350 msec), modified to elicit two EFRs, one from the region of the first formant (F1) and one from the second and higher formants (F2+). The stimulus, presented at 65 dB SPL, was preceded by one of the four contexts: /∫/, /m/, /i/ or a silent gap of duration equal to that of the stimulus. The level of the context phonemes was either 50 or 80 dB SPL, 15 dB lower and higher than the level of the stimulus /i/. In a control condition, EFRs to the stimulus /i/ were elicited in isolation without any preceding phoneme contexts. The stimulus and the contexts were presented monaurally to a randomly chosen test ear in 21 young adults with normal hearing. EFRs were recorded using single-channel electroencephalogram between the vertex and the nape. RESULTS: A repeated measures analysis of variance indicated a significant three-way interaction between context type (/∫/, /i/, /m/, silent gap), level (50, 80 dB SPL), and EFR-eliciting formant (F1, F2+). Post hoc analyses indicated no influence of the preceding phoneme context on F1-elicited EFRs. Relative to a silent gap as the preceding context, F2+-elicited EFRs were attenuated by /∫/ and /m/ presented at 50 and 80 dB SPL, as well as by /i/ presented at 80 dB SPL. The average attenuation ranged from 14.9 to 27.9 nV. When the context phonemes were presented at matched levels of 50 or 80 dB SPL, F2+-elicited EFRs were most often attenuated when preceded by /∫/. At 80 dB SPL, relative to the silent preceding gap, the average attenuation was 15.7 nV, and at 50 dB SPL, relative to the preceding context phoneme /i/, the average attenuation was 17.2 nV. CONCLUSION: EFRs elicited by the second and higher formants of /i/ are sensitive to the spectral and level characteristics of the preceding phoneme context. Such sensitivity, measured as an attenuation in the present study, may influence the comparison of EFRs elicited by the same vowel in different consonant-vowel syllables or words. However, the degree of attenuation with realistic context levels exceeded the minimum measurable change only 12% of the time. Although the impact of the preceding context is statistically significant, it is likely to be clinically insignificant a majority of the time.

Exploring neuropsychological underpinnings of poor communication after traumatic brain injury: The role of apathy, disinhibition and social cognition.

BACKGROUND: Dysarthria, aphasia and executive processes have been examined for their role in producing impaired communicative competence post traumatic brain injury (TBI). Less understood is the role of emotional dysregulation, that is, apathy and disinhibition, and social cognition, that is, reading and interpreting social cues. METHODS & PROCEDURES: In this study, we examined 49 adults with moderate to severe TBI and 18 neurologically healthy adults. We hypothesised that apathy and disinhibition would predict communication outcomes as would social cognition. We also predicted that apathy and disinhibition would influence social cognition. Communication outcomes were measured by the La Trobe Communication Questionnaire (LCQ) and the Social Skills Questionnaire-TBI (SSQ-TBI). Apathy and disinhibition were measured by the Frontal Systems Behavior Scale (FrSBe). We measured four aspects of social cognition: emotion perception and theory of mind using The Awareness of Social Inference Test (TASIT) and the Complex Audio-Visual Evaluation of Affect Test (CAVEAT), empathy using the Questionnaire of Cognitive and Affective Empathy (QCAE) and the Balanced Emotional Empathy Scale (BEES), and alexithymia using the Toronto Alexithymia Scale (TAS-20) and the Bermond-Vorst Alexithymia Questionnaire. OUTCOMES & RESULTS: Consistent with predictions, the LCQ and SSQ-TBI were associated with disinhibition and the LCQ was also associated with apathy. The LCQ was associated with the full range of social cognition constructs although the SSQ-TBI was not. Finally, apathy and disinhibition predicted a number of social cognition measures. CONCLUSIONS AND IMPLICATIONS: These results are discussed in relation to understanding the nature of communication disorders following TBI and how they are measured, as well as the interrelation between emotion dysregulation and social cognition. WHAT THIS STUDY ADDS: What is already known on this subject The role of emotional dysregulation and social cognition in producing impaired communicative competence post traumatic brain injury (TBI) is not well understood. Although most adults with severe TBI have minimal or possibly no language impairment, they often struggle with functional communication in everyday situations. Many have been reported to be overtalkative, insensitive, childish and self-centred, displaying an inappropriate level of self-disclosure and making tangential and irrelevant comments. Conversely, some speakers with TBI have been noted to have impoverished communication, producing little language either spontaneously or in response to the speaker's questions and prompts. What this paper adds to existing knowledge We found that both apathy and disinhibition were strongly associated with the Latrobe Communication Questionnaire both empirically and conceptually, despite the LCQ being developed from a different, pragmatic orientation. Disinhibition was also associated with the Social Skills Questionnaire for TBI. We also found that poor social cognition scores predicted communication difficulties. Finally, we found that behavioural dysregulation itself, i.e., both apathy and disinhibition, predicted poor social cognition. What are the potential or actual clinical implications of this work? Our findings highlight the central role that apathy and disinhibition play in both communication and social cognition. These insights point to the importance of remediation to target behavioural and autonomic dysregulation as a means to improve everyday social function.

Assessment of von Willebrand disease and pregnancy outcomes at regional Australian hospitals.

BACKGROUND: von Willebrand disease (vWD) is a heterogeneous hereditary bleeding disorder and is associated with risk of primary postpartum haemorrhage (PPH). DESIGN AND METHODS: An observational study at a tertiary referral centre in Australia of 16 women with 23 deliveries with a median age of 27.5 years (range, 21-39; IQR = 9). Median gestational age at delivery was 39 weeks (range, 35-41; IQR = 1.1). RESULTS: All cases had type 1 vWD, apart from one case with type 2. Patients were managed in combined obstetrics and haematology clinics. PPH occurred in ten deliveries (44%). Intravenous desmopressin was administered in 6 cases, and IV human vWF was administered in 4 cases. Two cases with mild vWD had received oral tranexamic acid. The median Apgar score at 1 and 5 min was 9 (IQR = 1.0), while the median Apgar score at 10 min was 10.0 (IQR = 0.0). One case required transfusion of blood products postdelivery. There were no other significant complications observed. CONCLUSIONS: vWD was associated with a high incidence of primary PPH. Individualised treatment to restore haemostasis, according to the severity of the disease, could achieve as possible, normal haemostasis with favourable outcomes for both mothers and their infants. Further studies to confirm our findings are warranted.

Postseptic Cognitive Impairment and Expression of APOE in Peripheral Blood: The Cognition After SepsiS (CASS) Observational Pilot Study.

BACKGROUND: Cognitive impairment after sepsis is an important clinical problem. Determinants of postseptic cognitive impairment are not well understood. We thus undertook a systems biology approach to exploring a possible role for apolipoprotein E (APOE) in postseptic cognitive impairment. DESIGN: Prospective, observational cohort. SETTING: Intermountain Medical Center, a tertiary referral center in Utah. PATIENTS/PARTICIPANTS: Patients with sepsis admitted to study intensive care units. INTERVENTIONS: None. METHODS: We obtained peripheral blood for deep sequencing of RNA and followed up survivors at 6 months with a battery of cognitive instruments. We defined cognitive impairment based on the 6-month Hayling test of executive function. In our primary analysis, we employed weighted network analysis. Secondarily, we compared variation in gene expression between patients with normal versus impaired cognition. MEASUREMENTS AND MAIN RESULTS: We enrolled 40 patients, of whom 34 were follow-up eligible and 31 (91%) completed follow-up; 1 patient's RNA sample was degraded-the final analytic cohort was 30 patients. Mean Hayling test score was 5.8 (standard deviation 1.1), which represented 20% with impaired executive function. The network module containing APOE was dominated by low-expression genes, with no association on primary analysis (P = .8). Secondary analyses suggested several potential lines of future investigation, including oxidative stress. CONCLUSIONS: In this prospective pilot cohort, executive dysfunction affected 1 in 5 survivors of sepsis. The APOE gene was sparsely transcribed in peripheral leukocytes and not associated with cognitive impairment. Future lines of research are suggested.

Occupational exposure and health risks of volatile organic compounds of hotel housekeepers: Field measurements of exposure and health risks.

Hotel housekeepers represent a large, low-income, predominantly minority, and high-risk workforce. Little is known about their exposure to chemicals, including volatile organic compounds (VOCs). This study evaluates VOC exposures of housekeepers, sources and factors affecting VOC levels, and provides preliminary estimates of VOC-related health risks. We utilized indoor and personal sampling at two hotels, assessed ventilation, and characterized the VOC composition of cleaning agents. Personal sampling of hotel staff showed a total target VOC concentration of 57 ± 36 µg/m3 (mean ± SD), about twice that of indoor samples. VOCs of greatest health significance included chloroform and formaldehyde. Several workers had exposure to alkanes that could cause non-cancer effects. VOC levels were negatively correlated with estimated air change rates. The composition and concentrations of the tested products and air samples helped identify possible emission sources, which included building sources (for formaldehyde), disinfection by-products in the laundry room, and cleaning products. VOC levels and the derived health risks in this study were at the lower range found in the US buildings. The excess lifetime cancer risk (average of 4.1 × 10-5 ) still indicates a need to lower exposure by reducing or removing toxic constituents, especially formaldehyde, or by increasing ventilation rates.

The role of gender power relations on women's health outcomes: evidence from a maternal health coverage survey in Simiyu region, Tanzania.

BACKGROUND: Gender is a crucial consideration of human rights that impacts many priority maternal health outcomes. However, gender is often only reported in relation to sex-disaggregated data in health coverage surveys. Few coverage surveys to date have integrated a more expansive set of gender-related questions and indicators, especially in low- to middle-income countries that have high levels of reported gender inequality. Using various gender-sensitive indicators, we investigated the role of gender power relations within households on women's health outcomes in Simiyu region, Tanzania. METHODS: We assessed 34 questions around gender dynamics reported by men and women against 18 women's health outcomes. We created directed acyclic graphs (DAGs) to theorize the relationship between indicators, outcomes, and sociodemographic covariates. We grouped gender variables into four categories using an established gender framework: (1) women's decision-making, (2) household labor-sharing, (3) women's resource access, and (4) norms/beliefs. Gender indicators that were most proximate to the health outcomes in the DAG were tested using multivariate logistic regression, adjusting for sociodemographic factors. RESULTS: The overall percent agreement of gender-related indicators within couples was 68.6%. The lowest couple concordance was a woman's autonomy to decide to see family/friends without permission from her husband/partner (40.1%). A number of relationships between gender-related indicators and health outcomes emerged: questions from the decision-making domain were found to play a large role in women's health outcomes, and condoms and contraceptive outcomes had the most robust relationship with gender indicators. Women who reported being able to make their own health decisions were 1.57 times (95% CI: 1.12, 2.20) more likely to use condoms. Women who reported that they decide how many children they had also reported high contraception use (OR: 1.79, 95% CI: 1.34, 2.39). Seeking care at the health facility was also associated with women's autonomy for making major household purchases (OR: 1.35, 95% CI: 1.13, 1.62). CONCLUSIONS: The association between decision-making and other gender domains with women's health outcomes highlights the need for heightened attention to gender dimensions of intervention coverage in maternal health. Future studies should integrate and analyze gender-sensitive questions within coverage surveys.

tDCS effects on task-related activation and working memory performance in traumatic brain injury: A within group randomized controlled trial.

Non-invasive transcranial direct current stimulation (tDCS) has been reported to facilitate working memory in normal adults. There is some evidence in people with Traumatic Brain Injury (TBI) but overall evidence is mixed. This study aimed to address shortcomings of prior study designs in TBI to examine whether a single dose of tDCS would lead to benefits in working memory. Thirty people with severe, chronic TBI were administered a single session of either anodal tDCS (2 mA for 20 min) or sham tDCS (2 mA for 30 s), in a counterbalanced order, over the left parietal cortex while performing 1-back and 2-back working memory tasks. Skin conductance levels were examined as a measure of task activated arousal, a possible functional analogue of cortical excitability. We found that tDCS led to no improvements in accuracy on the working memory tasks. A slight increase in variability and reaction time with tDCS was related to decreased task activated arousal. Overall, this study yielded no evidence that a single session of tDCS can facilitate working memory for people with TBI.