Factors Associated with Delta-8 THC Retail Availability in Fort Worth, Texas, 2021-2022.

Background: Delta-8 THC is a federally unregulated psychoactive cannabis product rising in popularity. However, little is known regarding its retail availability. Method: We assessed Delta-8 THC retail by calling locations with alcohol, tobacco, and/or consumable hemp retail licenses in Fort Worth, Texas, before and after Texas announced ongoing litigation surrounding Delta-8 THC legality. We linked census block area deprivation index (ADI) scores (1-10; 10 = most disadvantaged) to locations. Logistic regression models examined associations between license type, ADI, ADI*license type interaction, and Delta-8 availability at each time. Results: Retail availability was 11% at Time 1 (n = 133/1,223) and 9% at Time 2 (n = 94/1,026). Alcohol (aORTime1 = 0.18, 95%CI = 0.12,0.28; aORTime2 = 0.14, 95%CI = 0.08,0.24), tobacco (aORTime1 = 15.13, 95%CI = 6.78,33.74; aORTime2 = 12.39, 95%CI = 4.97,30.91), and consumable hemp licenses (aORTime1 = 21.85, 95%CI = 7.91,60.39; aORTime2 = 22.93, 95%CI = 6.92,75.98) were associated with Delta-8 THC retail availability; ADI scores were borderline but not statistically significant. The multiplicative interaction at Time 2 indicated locations with both high ADI scores and alcohol retail licenses had higher odds of selling Delta-8 THC. Differential associations between ADI and Delta-8 THC availability were observed based on those with (b = 0.007) or without (b = -0.023) alcohol retail licenses. Conclusions: Both timepoints had similar proportions of Delta-8 THC retailers, indicating that despite the uncertain legal landscape in Texas, interest in Delta-8 did not appear to be declining. Geographic socioeconomic disparities were observed among locations with alcohol retail licenses. Future regulations may include minimum distances from specific locations (e.g., schools), particularly in more disadvantaged areas. Increasing the compliance of Texas Delta-8 THC retailers to have the required hemp license is important for surveillance and product safety.

Kratom Retail Availability in Fort Worth, Texas.

Kratom use is associated with cannabis use, so retail availability may also be related. Kratom and Delta-8 THC (a psychoactive cannabis product) are federally unregulated, marketed as "natural," and often used for pain relief and/or relaxation. Kratom may have greater retail availability in more socioeconomically deprived areas because harmful substances are frequently marketed to lower-income communities. This study examined kratom retail availability in Fort Worth, Texas. Locations with alcohol, tobacco, and/or CBD licenses were called in July 2022: 1,025/1,223 (84%) answered the phone. T-tests examined potential differences in socioeconomic deprivation scores surrounding outlets by whether they sold kratom. Cross-tabulations examined overlap in kratom and Delta-8 THC availability. Kratom was available in 6% of locations. Most kratom retailers had a tobacco license (92%). However, most stores with a tobacco license did not sell kratom (14%), whereas most stores with a CBD license did (55%). Kratom availability was not associated with area deprivation scores. Most kratom retailers (95%) sold Delta-8 THC and two-thirds (65%) of Delta-8 THC retailers sold kratom. This study was the first to examine retail availability of kratom. Findings indicate the presence of niche stores specializing in the retail of federally unregulated substances.

Do we need a pandemic to improve hygiene routines in the ambulance service? A cross-sectional study.

BACKGROUND: We know that ambulance staff may have sparse knowledge on how to comply with care approaches that ensure appropriate hygiene in the ambulance, but we do not know if and how the COVID-19 pandemic has affected ambulance staff's perceived compliance with hygiene routines. AIM: To investigate ambulance staff's self-reported hand hygiene (HH) perceptions and compliance; and to explore if and how the COVID-19 pandemic has affected ambulance staff's perceived compliance with hygiene routines. METHODS: A cross-sectional study design using the WHO-validated Perception Survey for Healthcare Workers regarding hygiene. Thematic analysis and descriptive statistics were used for analysis. RESULTS: 204 surveys were analysed, 92% of participants stated that their hygiene routine compliance had improved during the COVID-19 pandemic, and some participants also described that their colleagues' practice had improved. These improvements were reportedly driven by the need to acquire new knowledge to deal with the pandemic and sometimes with fear. CONCLUSIONS: Experience acquired during the pandemic needs to be sustainable if we are to increase HH and hygiene routine compliance in ambulance services. Interventions aimed at changing ambulance staff's perceived behaviour are warranted, and stakeholders should try and identify the personal motivations that lead these staff to seek self-betterment regarding HH and hygiene routine compliance. Otherwise, the risk of patients suffering from healthcare-associated infection may not decrease as wished.

Surgical intervention for intestinal typhoid perforation.

AIM: Typhoid perforation is the most fatal complication of typhoid fever in developing countries and is most often caused by the bacteria Salmonella Typhi. There are conflicting views as to which type of surgical intervention gives the best outcome. The aim of this study was to determine the mortality associated with the different types of surgical interventions employed in patients with typhoid perforation. METHOD: This was a retrospective review of the medical records of adult and paediatric surgical patients treated in the general and paediatric surgical units of the Korle Bu Teaching Hospital. Information was obtained from medical records at the Korle Bu Teaching Hospital in Accra, Ghana, between January 2009 and April 2012. The data was analysed using IBM SPSS Statistics version 20 and 22. RESULTS: 133 patients (median age of 21 years, 72.2% males) with typhoid perforation were included in the study. The typhoid perforation specific mortality rate was 12.8%. Males had a significantly lower mortality rate (7.3%) compared to females (27%). Simple bowel closure (85.7% of total) was the most common surgical intervention performed and patients operated upon with this method had a significantly lower mortality rate (9.6%) compared to patients with bowel resection (31.6%). CONCLUSIONS: In this study, patients treated with intestinal resection were more likely to die from typhoid perforation and female gender was a risk factor for death. Simple bowel closure was the predominant surgical procedure.

Association of perceived physical health and physical fitness in two Swedish national samples from 1990 and 2015.

Perceived health and physical fitness have been shown to correlate, and low levels of either variable increase the risk for future illness and mortality. However, risk factors and their interrelationship may vary between societies and over time. In this study, the associations of physical fitness and perceived health were therefore assessed in two Swedish national samples 25 years apart. Perceived physical health, dichotomized as "good" or "bad," maximal oxygen uptake (VO2 max), counter movement jump (CMJ), balance (one-legged 60 second stance), and self-reported demographics and lifestyle were recorded in two cross-sectional samples (sample size, number of eligible participants) of Swedish adults, aged 20-65 years, in 1990-1991 (2203, 1365), and 2013-2015 (3357, 422). The odds for good perceived physical health increased by 5% per mL·kg-1 ·min-1 of VO2 max, 3% per cm CMJ height, and decreased by 4% per 1 time of overbalancing, in both samples. Mutually adjusted regression models showed that perceived physical health was best predicted by VO2 max and chronic illness in 1990 and by age, BMI, and educational level in 2015. CONCLUSION: Perceived physical health was related to physical fitness in two samples of Swedish adults from 1990 and 2015. However, multivariate and mutually adjusted models indicate that the most important covariates of perceived physical health may have changed from VO2 max and chronic illness in 1990, to age, BMI, and educational level in 2015.

Non-permanent atrial fibrillation and oral anticoagulant therapy are related to survival during 10years after first-ever ischemic stroke.

BACKGROUND: Atrial fibrillation (AF) detection in ischemic stroke patients triggers initiation of oral anticoagulant therapy (OAC). However, little is known regarding whether the persistency of AF affects long-term prognosis after ischemic stroke. We aimed to assess the impact of AF types and OAC on the outcome during a 10-year follow-up (FU) after first-ever ischemic stroke. MATERIAL AND METHODS: The study sample comprised 336 first-ever ischemic stroke patients (median age 76, interquartile range 25-75% (IQR) 67-82years, 136 female) included in the Lund Stroke Register (LSR) in 2001-2002. At baseline, 109 patients had either permanent (n=44) or recurrent (n=65) AF. OAC was assessed using the Lund University Hospital anticoagulation database. All-cause mortality was assessed via linkage with the Swedish Causes of Death Register. RESULTS: During FU, 200 patients died. AF independently predicted all-cause mortality (hazard ratio (HR) 1.52 95% CI 1.14-2.04, p=0.005); the worst prognosis was observed for permanent AF (HR 1.86 95% CI 1.29-2.69, p=0.001). Patients with recurrent AF receiving OAC had similar survival rates to patients without AF (HR 0.73 95% CI 0.38-1.39, p=0.333), while prognosis was worst for patients with permanent AF without OAC (HR 2.28 95% CI 1.38-3.77, p=0.001) and intermediate for patients with permanent AF on OAC (HR 1.57 95% CI 0.92-2.67, p=0.099). CONCLUSION: All-cause mortality was independently associated with AF and was the greatest in stroke patients with permanent AF. Patients with recurrent AF receiving OAC have the most favorable outcome, similar to those without AF and significantly better than OAC-treated patients with permanent AF.

A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder.

Elevated cerebrospinal fluid (CSF) levels of the glia-derived N-methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA) have consistently been implicated in schizophrenia and bipolar disorder. Here, we conducted a genome-wide association study based on CSF KYNA in bipolar disorder and found support for an association with a common variant within 1p21.3. After replication in an independent cohort, we linked this genetic variant-associated with reduced SNX7 expression-to positive psychotic symptoms and executive function deficits in bipolar disorder. A series of post-mortem brain tissue and in vitro experiments suggested SNX7 downregulation to result in a caspase-8-driven activation of interleukin-1ß and a subsequent induction of the brain kynurenine pathway. The current study demonstrates the potential of using biomarkers in genetic studies of psychiatric disorders, and may help to identify novel drug targets in bipolar disorder.

Bayesian inference of protein ensembles from SAXS data.

The inherent flexibility of intrinsically disordered proteins (IDPs) and multi-domain proteins with intrinsically disordered regions (IDRs) presents challenges to structural analysis. These macromolecules need to be represented by an ensemble of conformations, rather than a single structure. Small-angle X-ray scattering (SAXS) experiments capture ensemble-averaged data for the set of conformations. We present a Bayesian approach to ensemble inference from SAXS data, called Bayesian ensemble SAXS (BE-SAXS). We address two issues with existing methods: the use of a finite ensemble of structures to represent the underlying distribution, and the selection of that ensemble as a subset of an initial pool of structures. This is achieved through the formulation of a Bayesian posterior of the conformational space. BE-SAXS modifies a structural prior distribution in accordance with the experimental data. It uses multi-step expectation maximization, with alternating rounds of Markov-chain Monte Carlo simulation and empirical Bayes optimization. We demonstrate the method by employing it to obtain a conformational ensemble of the antitoxin PaaA2 and comparing the results to a published ensemble.

Predictors of new onset atrial fibrillation during 10-year follow-up after first-ever ischemic stroke.

BACKGROUND: Paroxysmal atrial fibrillation (AF) may be underdiagnosed in ischemic stroke patients but may be pivotal for initiation of oral anticoagulation therapy. We assessed clinical and ECG predictors of new-onset AF during 10-year follow-up (FU) in ischemic stroke patients. METHODS: The study sample comprised of 227 first-ever ischemic stroke patients without AF (median age 73, interquartile range 25%-75% 63-80years, 92 female) and 1:1 age- and gender-matched controls without stroke and AF enrolled in the Lund Stroke Register from March 2001 to February 2002. New-onset AF during FU was assessed by screening through regional ECG database and by record linkage with Swedish National Patient Register. The standard 12-lead sinus rhythm ECGs at stroke admission were retrieved from electronic database and digitally processed. Clinical baseline characteristics were studied using medical records. RESULTS: During FU, AF was found in 39 stroke patients and 30 controls, p=0.296. In stroke patients in multivariate Cox regression analysis AF was associated with hypertension (HR 3.45 CI 95% 1.40-3.49, p=0.007) and QRS duration (HR 1.02 CI 95% 1.00-1.03, p=0.049). High cardiovascular risk was predictive for AF development: for CHADS2≥4 HR 2.46 CI 95% 1.45-4.18, p=0.001 and for CHA2DS2-VASc≥5 HR 2.29 CI 95% 1.43-3.68, p=0.001. New onset AF was not associated with baseline ischemic stroke: HR 1.46 95% CI 0.90-2.35, p=0.121. CONCLUSION: High CHADS2 and CHA2DS2-VASc scores, but not baseline ischemic stroke, predict new onset AF in FU. QRS duration might be considered a potential risk marker for prediction of AF after ischemic stroke.

Exposure-response for biomarkers of anticoagulant effects by the oral direct thrombin inhibitor AZD0837 in patients with atrial fibrillation.

AIMS: AZD0837 is a novel oral anticoagulant investigated in clinical studies for stroke prevention in patients with atrial fibrillation (AF). It is bioconverted to its active form, AR-H067637, a potent, specific and reversible thrombin inhibitor. The effects on coagulation biomarkers were correlated with the pharmacokinetic (PK) exposure of AR-H067637 to guide selection of the effective dose regimen for a confirmatory efficacy study in AF patients. METHODS: Blood samples were obtained from 601 AF patients randomized to one of four doses of AZD0837 (blinded treatment) or dose-adjusted vitamin K antagonists (VKA, open treatment) for 3-9 months. A pharmacodynamic model was developed to describe the time course of the AR-H067637 exposure dependent effects and the effect of VKA on fibrin D-dimer. The thrombin generation measured ex vivo in venous plasma was also investigated. RESULTS: The PK exposure of AR-H067637 was stable with an interindividual variability of 33% and no or minor influence of patient demographics or comedications. For AZD0837, D-dimer levels decreased with more rapid onset than for VKA. The decrease in D-dimer levels correlated with steady-state plasma concentrations (C(ss)) of AR-H067637, with a maximum decrease of baseline D-dimer levels estimated to approximately 60% for both AZD0837 and VKA therapy. The effect on thrombin generation correlated closely with the plasma concentration of AR-H067637. CONCLUSIONS: The effects on thrombin generation and fibrin D-dimer levels correlated with the plasma concentration of its active form and provided comparable effects to well-controlled VKA therapy at an exposure at least corresponding to the 300 mg once daily dose of AZD0837.

Biosynthetic infochemical communication.

There is an ever-increasing demand for data to be embedded in our environment at ever-decreasing temporal and spatial scales. Whilst current communication and storage technologies generally exploit the electromagnetic properties of media, chemistry offers us a new alternative for nanoscale signaling using molecules as messengers with high information content. Biological systems effectively overcome the challenges of chemical communication using highly specific biosynthetic pathways for signal generation together with specialized protein receptors and nervous systems. Here we consider a new approach for information transmission based upon nature's quintessential example of infochemical communication, the moth pheromone system. To approach the sensitivity, specificity and versatility of infochemical communication seen in nature, we describe an array of biologically-inspired technologies for the production, transmission, detection, and processing of molecular signals. We show how it is possible to implement each step of the moth pheromone pathway for biosynthesis, transmission, receptor protein binding/transduction, and antennal lobe processing of monomolecular and multimolecular signals. For each implemented step, we discuss the value, current limitations, and challenges for the future development and integration of infochemical communication technologies. Together, these building blocks provide a starting point for future technologies that can utilize programmable emission and detection of multimolecular information for a new and robust means of communicating chemical information.

Atrial fibrillation in patients with ischaemic stroke in the Swedish national patient registers: how much do we miss?

AIMS: Data from national discharge registers are commonly used to estimate prevalence and incidence of atrial fibrillation (AF) in epidemiology studies. However, sensitivity and specificity of register-based AF diagnosis have not been evaluated. We sought to assess the validity of AF diagnosis in the Swedish Patient Register against electrocardiography (ECG) documentation of AF. METHODS AND RESULTS: The study sample comprised of 336 patients [median age 76 (interquartile range (IQR) 67-82 years, 136 female] with first-ever ischaemic stroke, enroled in the Lund Stroke Register from March 2001 to February 2002 and 1 : 1 age- and gender-matched control subjects without stroke from the population register. Data was exported from the patient register in October 2011 (the end of follow-up). Atrial fibrillation documentation by ECG was assessed using an electronic archive containing all ECGs taken in the hospital catchment area starting in 1988. A total of 7247 ECGs were reviewed, with the median number of ECGs per person being 7.5 (IQR 3-15). Atrial fibrillation was detected by ECG in 190 patients; and in 188 patients by linkage with patient register. In most patients, AF was documented first by ECG data, with median time to register diagnosis being 16 days (IQR 3-859). Specificity of AF diagnosis in the Swedish Patient Register was 93%, sensitivity was 80%. CONCLUSION: Despite the high specificity, AF diagnosis in the Swedish Patient Register assessed in the population of ischaemic stroke patients and age- and gender-matched control subjects has modest sensitivity, which may result in underestimating prevalent and incident AF cases if only register data are used for identification of subjects with AF in epidemiology studies.

Optical signal to noise ratio improvement through unbalanced noise beating in phase-sensitive parametric amplifiers.

We investigate the beating of signal and idler waves, which have imbalanced signal to noise ratios, in a phase-sensitive parametric amplifier. Imbalanced signal to noise ratios are achieved in two ways; first by imbalanced noise loading; second by varying idler to signal input power ratio. In the case of imbalanced noise loading the phase-sensitive amplifier improved the signal to noise ratio from 3 to 6 dB, and in the case of varying idler to signal input power ratio, the signal to noise ratio improved from 3 to in excess of 20 dB.

Noise beating in hybrid phase-sensitive amplifier systems.

We investigate the effect of noise loading in a hybrid phase-sensitive amplifier system, analyzing the effect of noise beating between the signal and idler waves coupled in a parametric amplifier. Through analyzing input and output optical signal to noise ratios, we find that system performance of a phase-sensitive amplifier is 3 to 6 dB improved over a phase-insensitive amplifier, depending on the ratio of loaded noise power to that of vacuum fluctuations.

The KMO allele encoding Arg452 is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression.

The kynurenine pathway metabolite kynurenic acid (KYNA), modulating glutamatergic and cholinergic neurotransmission, is increased in cerebrospinal fluid (CSF) of patients with schizophrenia or bipolar disorder type 1 with psychotic features. KYNA production is critically dependent on kynurenine 3-monooxygenase (KMO). KMO mRNA levels and activity in prefrontal cortex (PFC) are reduced in schizophrenia. We hypothesized that KMO expression in PFC would be reduced in bipolar disorder with psychotic features and that a functional genetic variant of KMO would associate with this disease, CSF KYNA level and KMO expression. KMO mRNA levels were reduced in PFC of bipolar disorder patients with lifetime psychotic features (P=0.005, n=19) or schizophrenia (P=0.02, n=36) compared with nonpsychotic patients and controls. KMO genetic association to psychotic features in bipolar disorder type 1 was studied in 493 patients and 1044 controls from Sweden. The KMO Arg(452) allele was associated with psychotic features during manic episodes (P=0.003). KMO Arg(452) was studied for association to CSF KYNA levels in an independent sample of 55 Swedish patients, and to KMO expression in 717 lymphoblastoid cell lines and 138 hippocampal biopsies. KMO Arg(452) associated with increased levels of CSF KYNA (P=0.03) and reduced lymphoblastoid and hippocampal KMO expression (P≤0.05). Thus, findings from five independent cohorts suggest that genetic variation in KMO influences the risk for psychotic features in mania of bipolar disorder patients. This provides a possible mechanism for the previous findings of elevated CSF KYNA levels in those bipolar patients with lifetime psychotic features and positive association between KYNA levels and number of manic episodes.

Documentation of atrial fibrillation prior to first-ever ischemic stroke.

OBJECTIVES: We assessed the prevalence of atrial fibrillation (AF) prior to first-ever ischemic stroke by examining a comprehensive electronic ECG archive. METHODS: The study sample comprised 336 consecutive stroke patients (median age 76 (IQ16) y, 200 men) enrolled in Lund Stroke Register from March 2001 to February 2002 and 336 age- and gender-matched controls without stroke history. AF prior to admission was studied using the regional electronic ECG database and record linkage with the National Swedish Hospital Discharge Register (SHDR). Medical records were reviewed for AF documentation and CHA2 DS2-VASc risk score. RESULTS: Atrial fibrillation before or at stroke onset was detected in 109 (32.4%) stroke patients and 44 (13.1%) controls, P<0.001. Twenty-five of 109 stroke patients had AF detected only on previous ECG (n=14) or through the SHDR (n=11). The most prevalent type of AF in stroke group was non-permanent AF (59.6%). AF prevalence among patients admitted with sinus rhythm at hospital admission (n=266) was higher in those with CHA2 DS2 -VASc score≥6 (28.6%) than with CHA2 DS2-VASc score<6 (13.0%), P=0.043. CONCLUSION: Comprehensive approach for AF screening allows detecting AF in one-third of patients admitted with first-ever ischemic stroke. Patients with high cardiovascular risk are more likely to have non-permanent AF.

Are 25 SNPs from the CARDIoGRAM study associated with ischaemic stroke?

BACKGROUND AND PURPOSE: The Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Study (CARDIoGRAM) reported 25 single-nucleotide polymorphisms (SNPs) on 15 chromosomes to be associated with coronary artery disease (CAD) risk. Because common vascular risk factors are shared between CAD and ischaemic stroke (IS), these SNPs may also be related to IS overall or one or more of its pathogenetic subtypes. METHODS: We performed a candidate gene study comprising 3986 patients with IS and 2459 control subjects. The 25 CAD-associated SNPs reported by CARDIoGRAM were examined by allelic association analysis including logistic regression. Weighted and unweighted genetic risk scores (GRSs) were also compiled and likewise analysed against IS. We furthermore considered the IS main subtypes large-vessel disease (LVD), small-vessel disease and cardioembolic stroke [according to Trial of Org 10172 in Acute Stroke Treatment (TOAST)] separately. RESULTS: SNP rs4977574 on chromosome 9p21.3 was associated with overall IS [odds ratio (OR) = 1.12; 95% confidence interval (CI): 1.04-1.20; P = 0.002] as well as LVD (OR = 1.36; 95% CI: 1.13-1.64; P = 0.001). No other SNP was significantly associated with IS or any of its main subtypes. Analogously, the GRSs did not show any noticeable effect. CONCLUSIONS: Besides the previously reported association with SNPs on chromosome 9p21, this study did not detect any significant association between IS and CAD-susceptible genetic variants. Also, GRSs compiled from these variants did not predict IS or any pathogenetic IS subtype, despite a total sample size of 6445 participants.