Alcohol-derived DNA crosslinks are repaired by two distinct mechanisms.

Acetaldehyde is a highly reactive, DNA-damaging metabolite that is produced upon alcohol consumption1. Impaired detoxification of acetaldehyde is common in the Asian population, and is associated with alcohol-related cancers1,2. Cells are protected against acetaldehyde-induced damage by DNA crosslink repair, which when impaired causes Fanconi anaemia (FA), a disease resulting in failure to produce blood cells and a predisposition to cancer3,4. The combined inactivation of acetaldehyde detoxification and the FA pathway induces mutation, accelerates malignancies and causes the rapid attrition of blood stem cells5-7. However, the nature of the DNA damage induced by acetaldehyde and how this is repaired remains a key question. Here we generate acetaldehyde-induced DNA interstrand crosslinks and determine their repair mechanism in Xenopus egg extracts. We find that two replication-coupled pathways repair these lesions. The first is the FA pathway, which operates using excision-analogous to the mechanism used to repair the interstrand crosslinks caused by the chemotherapeutic agent cisplatin. However, the repair of acetaldehyde-induced crosslinks results in increased mutation frequency and an altered mutational spectrum compared with the repair of cisplatin-induced crosslinks. The second repair mechanism requires replication fork convergence, but does not involve DNA incisions-instead the acetaldehyde crosslink itself is broken. The Y-family DNA polymerase REV1 completes repair of the crosslink, culminating in a distinct mutational spectrum. These results define the repair pathways of DNA interstrand crosslinks caused by an endogenous and alcohol-derived metabolite, and identify an excision-independent mechanism.

Isolated central hypothyroidism: Underlying pathophysiology and relation to antidepressant and antipsychotic medications-A multi-centre South Wales study.

OBJECTIVE: Isolated biochemical central hypothyroidism is a presentation we are experiencing more frequently as endocrinologists, with variation in levels of investigation between physicians. We therefore conducted research to investigate the final diagnosis and clinical outcome of patients across multiple hospitals in South Wales with biochemical isolated central hypothyroidism; namely to establish whether this isolated biochemical picture was clinically significant. We also analysed whether there is an association between this biochemical picture and treatment with antidepressant and antipsychotic medications, and how common this is. DESIGN: We performed a retrospective observational study of patients across nine different hospitals in South Wales. We analysed patients referred to endocrinology at each site over a 6-year period with unexplained isolated biochemical central hypothyroidism. MATERIALS AND METHODOLOGY: 1022 individual patients' thyroid function test results were identified from our biochemical database using our inclusion criteria. After exclusion criteria were applied, 71 patients' results were analysed as to the final pathophysiology of their central hypothyroidism. RESULT: Of the 71 patients included in the study, none were found to have any clinically significant pathology on pituitary imaging. On reviewing their medications, 46/71 (65%) were found to be taking psychotropic medications. CONCLUSIONS: Our study strongly suggests isolated central hypothyroidism, in the absence of other pituitary hormone dysfunction or visual field defect, does not require further investigation, saving resources as well as sparing patients unnecessary anxiety. It also strongly supports a relationship between patients taking psychotropic medications and biochemical isolated central hypothyroidism, an association only described in a very limited amount of literature before this, and further supporting our previous single-centre study findings. The mechanism behind this is likely to be the suppression of thyrotropin secretion via antagonism of the dopamine-serotoninergic pathway. In our opinion, patients found to have isolated biochemical central hypothyroidism who are taking psychotropic medications can therefore be regarded to have a recognised cause for this biochemical finding and do not require further radiological investigation.

Six-Month Outcomes of a Theory- and Technology-Enhanced Physical Activity Intervention for Latina Women (Pasos Hacia La Salud II): Randomized Controlled Trial.

BACKGROUND: More than half (55%) of Latina women do not meet aerobic physical activity (PA) guidelines, and frequently cite time, childcare, and transportation as barriers to PA. In addition to linguistic adaptations for this population, successful PA interventions for Latina women addressed these barriers through remote intervention delivery approaches (eg, mail, phone, or web delivery). OBJECTIVE: We aimed to evaluate 6-month outcomes of a randomized trial comparing a Spanish-language, individually tailored, web-delivered PA intervention (original) to an enhanced version with text messages and additional features (enhanced). Further, we evaluated if increases in PA at 6 months were moderated by baseline activity status. METHODS: In total, 195 Latina women aged 18-65 years participated in a trial comparing the efficacy of the enhanced versus original interventions at initiating PA behavior change. We examined minutes per week of accelerometer-measured PA in the enhanced versus original arms, and the proportion of each arm meeting aerobic PA guidelines (150 min/wk at 6 mo). For moderator analyses, participants were classified as inactive (0 min/wk) or low active (1-90 min/wk) at baseline, measured via the 7 Day Physical Activity Recall interview. RESULTS: PA increased from 19.7 (SD 47.9) minutes per week at baseline to 46.9 (SD 66.2) minutes per week at 6 months in the enhanced arm versus 20.6 (SD 42.7) minutes per week to 42.9 (SD 78.2) minutes per week in the original arm (P=.78). Overall, 30% (31/103) of the enhanced group met aerobic PA guidelines at 6 months, compared to 21% (19/92) of the original group (odds ratio [OR] 1.75, 95% CI 0.87-3.55). Baseline PA (inactive vs low active) moderated treatment effects on PA. For inactive participants, there were no group differences at 6 months (b=7.1; SE 22.8; P=.75), while low-active participants increased more in enhanced than original (b=72.5; SE 27.9; P=.01). For low-active participants, 45% (46/103) of the enhanced group met PA guidelines at 6 months, versus 20% (18/92) of the original arm (OR 3.29, 95% CI 1.05-11.31). For inactive participants, there were no group differences (25/103, 24% vs n=19/92, 21% for enhanced vs original, respectively; OR 1.28, 95% CI 0.54-3.06). CONCLUSIONS: Intervention effects were conditional on baseline PA. For low-active Latina women, the enhanced intervention was more effective at increasing PA. Additional tailored intervention enhancements may be necessary to increase PA for inactive Latina women. TRIAL REGISTRATION: ClinicalTrials.gov NCT03491592; https://www.clinicaltrials.gov/study/NCT03491592. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-022-06575-4.

Stroke Prevention and Treatment in People With Type 2 Diabetes: Is There a Role for GLP-1 (Glucagon-Like Peptide-1) Analogues?

Stroke is a leading cause of disability and death, and people with type 2 diabetes (T2D) have a greater risk of stroke and death or disability from stroke. The underlying pathophysiology associating stroke and T2D is complicated by the association of risk factors for stroke frequently seen in people with T2D. Treatments to reduce the excess risk of new-onset stroke or to improve outcomes in people with T2D following stroke would be of major clinical interest. In practice, the focus of care in people with T2D remains treating risk factors for stroke, such as lifestyle and pharmacological interventions for hypertension, dyslipidemia, obesity, and glycemic control. More recently, cardiovascular outcome trials primarily designed to assess the cardiovascular safety of GLP-1RAs (glucagon-like peptide-1 receptor analogues) have consistently observed a reduced stroke risk in people with T2D. This is supported by several meta-analyses of cardiovascular outcome trials observing clinically important risk reductions in stroke. Moreover, phase II trials have described reductions in poststroke hyperglycemia in people with acute ischemic stroke suggestive of improved outcomes following admission to hospital with acute stroke. In this review, we discuss the increased risk of stroke in people with T2D and outline the key associated mechanisms responsible. We discuss the evidence from cardiovascular outcome trials exploring GLP-1RA use and highlight areas of potential interest for future work in this rapidly developing area of clinical research.

Efficient Synthesis of DNA Duplexes Containing Reduced Acetaldehyde Interstrand Cross-Links.

DNA interstrand cross-links (ICLs) prevent DNA replication and transcription and can lead to potentially lethal events, such as cancer or bone marrow failure. ICLs are typically repaired by proteins within the Fanconi Anemia (FA) pathway, although the details of the pathway are not fully established. Methods to generate DNA containing ICLs are key to furthering the understanding of DNA cross-link repair. A major route to ICL formation in vivo involves reaction of DNA with acetaldehyde, derived from ethanol metabolism. This reaction forms a three-carbon bridged ICL involving the amino groups of adjacent guanines in opposite strands of a duplex resulting in amino and imino functionalities. A stable reduced form of the ICL has applications in understanding the recognition and repair of these types of adducts. Previous routes to creating DNA duplexes containing these adducts have involved lengthy post-DNA synthesis chemistry followed by reduction of the imine. Here, an efficient and high-yielding approach to the reduced ICL using a novel N2-((R)-4-trifluoroacetamidobutan-2-yl)-2'-deoxyguanosine phosphoramidite is described. Following standard automated DNA synthesis and deprotection, the ICL is formed overnight in over 90% yield upon incubation at room temperature with a complementary oligodeoxyribonucleotide containing 2-fluoro-2'-deoxyinosine. The cross-linked duplex displayed a melting transition 25 °C higher than control sequences. Importantly, we show using the Xenopus egg extract system that an ICL synthesized by this method is repaired by the FA pathway. The simplicity and efficiency of this methodology for preparing reduced acetaldehyde ICLs will facilitate access to these DNA architectures for future studies on cross-link repair.

Mass Spectrometric Analysis of the Active Site Tryptic Peptide of Recombinant O6-Methylguanine-DNA Methyltransferase Following Incubation with Human Colorectal DNA Reveals the Presence of an O6-Alkylguanine Adductome.

Human exposure to DNA alkylating agents is poorly characterized, partly because only a limited range of specific alkyl DNA adducts have been quantified. The human DNA repair protein, O6-methylguanine O6-methyltransferase (MGMT), irreversibly transfers the alkyl group from DNA O6-alkylguanines (O6-alkGs) to an acceptor cysteine, allowing the simultaneous detection of multiple O6-alkG modifications in DNA by mass spectrometric analysis of the MGMT active site peptide (ASP). Recombinant MGMT was incubated with oligodeoxyribonucleotides (ODNs) containing different O6-alkGs, Temozolomide-methylated calf thymus DNA (Me-CT-DNA), or human colorectal DNA of known O6-MethylG (O6-MeG) levels. It was digested with trypsin, and ASPs were detected and quantified by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. ASPs containing S-methyl, S-ethyl, S-propyl, S-hydroxyethyl, S-carboxymethyl, S-benzyl, and S-pyridyloxobutyl cysteine groups were detected by incubating MGMT with ODNs containing the corresponding O6-alkGs. The LOQ of ASPs containing S-methylcysteine detected after MGMT incubation with Me-CT-DNA was <0.05 pmol O6-MeG per mg CT-DNA. Incubation of MGMT with human colorectal DNA produced ASPs containing S-methylcysteine at levels that correlated with those of O6-MeG determined previously by HPLC-radioimmunoassay (r2 = 0.74; p = 0.014). O6-CMG, a putative O6-hydroxyethylG adduct, and other potential unidentified MGMT substrates were also detected in human DNA samples. This novel approach to the identification and quantitation of O6-alkGs in human DNA has revealed the existence of a human DNA alkyl adductome that remains to be fully characterized. The methodology establishes a platform for characterizing the human DNA O6-alkG adductome and, given the mutagenic potential of O6-alkGs, can provide mechanistic information about cancer pathogenesis.

Development and Validation of a Two-component Perceived Control Measure.

BACKGROUND: Research indicates that perceived behavioral control (PBC) is an important determinant of behavior and that it is composed of perceived capability and opportunity. However, typical measurement of these constructs may be confounded with motivation and outcome expectations. Vignettes presented before questionnaire items may clarify construct meaning leading to precise measurement. PURPOSE: The purpose of this study was to develop and validate measures of perceived capability and opportunity that parse these constructs from the influence of motivation and outcome expectations using vignettes. METHODS: Study 1 collected feedback from experts (N = 9) about the initial measure. Study 2a explored internal consistency reliability and construct and discriminant validity of the revised measure using two independent samples (N = 683 and N = 727). Finally, using a prospective design, Study 2b (N = 1,410) investigated test-retest reliability, construct and discriminant validity at Time 2, and nomological validity. RESULTS: After Study 1, the revised measure was tested in Studies 2a and 2b. Overall, the evidence suggests that the measure is optimal with four items for perceived capability and three for the perceived opportunity. The measure demonstrated strong internal consistency ( > 0.90) and test-retest reliability (intraclass correlation coefficients [ICCs] > .78). The measure also showed construct and discriminant validity by differentiating itself from behavioral intentions (i.e., motivation) and affective attitude (based on expected outcomes) (SRMR = 0.03; RMSEA = 0.06). It also demonstrated evidence of nomological validity as behavior 2 weeks later was predicted. CONCLUSIONS: We recommend researchers use this tool in future correlational and intervention studies to parse motivation and outcome expectations from perceived capability and opportunity measurement.

Geometric phase in coupled cluster theory.

It has been well-established that the topography around conical intersections between excited electronic states is incorrectly described by coupled cluster and many other single reference theories (the intersections are "defective"). Despite this, we show both analytically and numerically that the geometric phase effect (GPE) is correctly reproduced upon traversing a path around a defective excited-state conical intersection (CI) in coupled cluster theory. The theoretical analysis is carried out by using a non-Hermitian generalization of the linear vibronic coupling approach. Interestingly, the approach qualitatively explains the characteristic (incorrect) shape of the defective CIs and CI seams. Moreover, the validity of the approach and the presence of the GPE indicate that defective CIs are local (and not global) artifacts. This implies that a sufficiently accurate coupled cluster method could predict nuclear dynamics, including geometric phase effects, as long as the nuclear wavepacket never gets too close to the conical intersections.

A Systematic Review and Meta-analysis of the Outcome Expectancy Construct in Physical Activity Research.

BACKGROUND: Cognition-based theories dominate physical activity (PA) research, and many include a construct broadly defined as "beliefs about the consequences of behavior" (e.g., outcome expectancies, perceived benefits) hereafter referred to as perceived consequences. PURPOSE: With the quantity of available research on this topic, it is important to examine whether the literature supports perceived consequences as a predictor of PA. METHODS: A meta-analysis examining longitudinal associations between perceived consequences and PA in adults was conducted. Studies were eligible if (a) perceived consequences were measured at a time point prior to PA, and (b) the target behavior was a form of PA. An omnibus meta-analysis estimating the mean effect of all included studies, and separate meta-analyses for perceived consequences content categories were conducted. RESULTS: This search yielded 6,979 articles, of these, 110 studies met inclusion criteria. Studies were published between 1989 and 2020, with sample sizes ranging from 16 to 2,824. All studies were evaluated as moderate to high quality. A small positive bivariate association was identified (r = 0.11; 95% CI [0.09, 0.13]) between perceived consequences and PA. Significant associations were identified for time, health, self-evaluative, psychological, and affective consequences. There was no association between perceived weight-related consequences and PA. CONCLUSIONS: The findings emphasize the variability with which existing studies have examined perceived consequences in the PA literature. Future research might examine whether these are important distinctions for understanding PA. Overall, the results suggest utility in examining perceived consequences as a predictor of PA, but constructs with more robust associations may require priority.

Daily Instrumental and Affective Attitudes About Exercise: An Ecological Momentary Assessment Study.

BACKGROUND: Daily decisions to exercise may be influenced by day-to-day changes in affective attitudes (AA) and instrumental attitudes (IA) toward exercise. However, the within-day association between AA, IA, and exercise behavior has received little attention. PURPOSE: To examine the effects of more temporally proximal (daily) AA and IA on daily exercise behavior beyond traditionally assessed distal (at the beginning of an exercise program) AA and IA. METHODS: In the context of a 3-month exercise promotion program (N = 50), distal AA and IA were assessed at baseline. Ecological momentary assessment was used to assess proximal AA, IA, and exercise each day. RESULTS: Between-subject differences in distal AA (OR = 1.28, p = .03) and distal IA (OR = 1.34, p = .01) were predictive of average likelihood of exercise each day over the 3-month period. Within-subject differences in proximal AA (OR = 1.19, p = .007), but not proximal IA (OR = 1.11, p = .18), predicted exercise each day beyond the between-subjects effects of distal AA and IA. Exploratory analysis revealed an interaction, such that the within-subjects impact of proximal AA on daily exercise was most evident among individuals who held more negative distal AA at baseline (OR = 0.80, p < .0001). CONCLUSIONS: Attitude type (affective versus instrumental) and temporality (distal versus proximal) are important to consider in attempts to predict and understand exercise behavior. In addition to targeting change in distal attitudes, exercise interventions should target changes in daily AA to impact exercise later in the same day.

Optimal Medical Therapy Following Deep Venous Interventions: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

The optimal medical management of patients following endovascular deep venous interventions remains ill-defined. As such, the Society of Interventional Radiology Foundation (SIRF) convened a multidisciplinary group of experts in a virtual Research Consensus Panel (RCP) to develop a prioritized research agenda regarding antithrombotic therapy following deep venous interventions. The panelists presented the gaps in knowledge followed by discussion and ranking of research priorities based on clinical relevance, overall impact, and technical feasibility. The following research topics were identified as high priority: 1) characterization of biological processes leading to in-stent stenosis/rethrombosis; 2) identification and validation of methods to assess venous flow dynamics and their effect on stent failure; 3) elucidation of the role of inflammation and anti-inflammatory therapies; and 4) clinical studies to compare antithrombotic strategies and improve venous outcome assessment. Collaborative, multicenter research is necessary to answer these questions and thereby enhance the care of patients with venous disease.

Simulation of the photodetachment spectra of the nitrate anion (NO3-) in the B̃ 2E' energy range and non-adiabatic electronic population dynamics of NO3.

The photodetachment spectrum of the nitrate anion (NO3-) in the energy range of the NO3 second excited state is simulated from first principles using quantum wave packet dynamics. The prediction at 10 K and 435 K relies on the use of an accurate full-dimensional fully coupled five state diabatic potential model utilizing an artificial neural network. The ability of this model to reproduce experimental spectra was demonstrated recently for the lower energy range [A. Viel, D. M. G. Williams and W. Eisfeld, J. Chem. Phys. 2021, 154, 084302]. Analysis of the spectra indicates a weaker Jahn-Teller coupling compared to the first excited state. The detailed non-adiabatic dynamics is studied by computing the population dynamics. An ultra-fast non-statistical radiationless decay is found only among the Jahn-Teller components, which is followed by a slow statistical non-radiative decay among the different state manifolds. The latter is reproduced perfectly by a simple first order kinetics model. The dynamics in the second excited state is not affected by the presence of a conical intersection with the first excited state manifold.

Implicit and Explicit Gender-Related Cognition, Gender Dysphoria, Autistic-Like Traits, and Mentalizing: Differences Between Autistic and Non-Autistic Cisgender and Transgender Adults.

Evidence indicates a link between autism spectrum disorder (ASD) and gender diversity, yet this intersection remains insufficiently understood. Here, we investigated whether (1) ASD affects gender-related cognition (i.e., mental processes of perceiving and interpreting one's own gender self-concept), (2) autistic people have increased gender dysphoria and recall limited gender-typed behavior from childhood, and (3) transgender individuals have increased ASD-like traits and difficulties in mentalizing. A total of 106 non-autistic cisgender (51 birth-assigned female), 107 autistic cisgender (57 birth-assigned female), 78 non-autistic transgender (41 birth-assigned female), and 56 autistic transgender adults (27 birth-assigned female) participated in the study. The mean age of participants was 31.01 years (range = 18 to 70). Using an explicit as well as an implicit measure, for the first time, we found that ASD affected gender-related cognition only in autistic cisgender people. Sex differences were also observed in this group. Whereas autistic cisgender birth-assigned males showed a stronger implicit gender-group identification than non-autistic cisgender birth-assigned males, autistic cisgender birth-assigned females showed a weaker gender-group identification than non-autistic cisgender birth-assigned females. Furthermore, autistic cisgender people reported significantly more gender dysphoric feelings and recalled significantly less gender-typed behavior from childhood than non-autistic cisgender individuals. No difference was observed between non-autistic and autistic transgender people. We also found that relative to non-autistic cisgender individuals, both non-autistic transgender and autistic transgender people reported significantly more ASD-like traits. However, mentalizing difficulties were observed only in the latter group. This research enhances our understanding of the link between ASD and gender diversity.

Activity-induced pain as a predictor of physical activity behavior among individuals with chronic pain: the role of physical activity enjoyment.

Nearly 70% of adults with chronic pain experience increased pain during activity, and this may reduce enjoyment of physical activity (PA), and subsequent PA intention/behavior. The goal of this study was to examine increased pain during activity as a predictor of PA, via its effects on PA enjoyment. Participants included 178 overweight/obese midlife adults with chronic pain who completed an online prospective survey. Results indicated that greater increases in pain during activity were associated with less PA enjoyment, and, in turn, lower intention to exercise over the next week (p < 0.05). Activity-induced pain also predicted lower total volume of PA at 1-week follow-up, and this relationship was mediated by PA enjoyment (p < 0.05). These findings have the potential to inform the refinement of PA promotion interventions for individuals with chronic pain.

Diabetes mellitus: what the neurologists need to know.

Diabetes mellitus is a common condition associated with numerous complications and comorbidities. The diabetes spectrum includes type 1, type 2 and other forms of diabetes, which may be associated with medical therapies and genetic factors. Type 2 diabetes is managed with lifestyle, oral therapies, non-insulin-based injectables and subsequently insulin. Type 1 diabetes requires insulin from the time of diagnosis. In recent years, there have been considerable developments in the therapies available to treat type 2 diabetes and some of these also afford cardiorenal protection. This review summarises the nature, complications and therapeutic advances in the field of diabetes and provides a concise review for neurologists. Managing diabetes optimally prevents complications and all medical specialties need a basic understanding of the principles involved in diabetes care.

The Moderating Effects of Genetic Variations on Changes in Physical Activity Level and Cardiorespiratory Fitness in Response to a Life-Style Intervention: A Randomized Controlled Trial.

OBJECTIVE: Prior studies identified single nucleotide polymorphisms (SNPs) associated with physical activity (PA) level in a natural environment and intervention study: rs978656-DNAPTP6, rs10887741-PAPSS2, rs7279064-C18orf2, and rs6265-BDNF. Using the four SNPs' polygenic score (PGS), we examined whether PGS moderates a life-style intervention's effect on changes in PA level and cardiorespiratory fitness (CRF). METHODS: This is a secondary analysis of Look AHEAD, a multicenter randomized controlled trial designed to test the health benefits of a life-style intervention among 2675 participants with overweight/obesity and type 2 diabetes (ages, 45-76 years). Using linear mixed-effects models, level of PA (Paffenbarger PA questionnaire) and treadmill-assessed CRF were each regressed on four SNPs' PGS, study time (baseline, year 1, and year 4), intervention arm, and interactions between the three. Models adjusted for age, sex, body mass index, ancestry principal components (population stratification), and study sites, with Bonferroni corrections for multiple testing (α < .005). Effect modification by age was examined. RESULTS: PGS was not predictive of change in CRF or PA level in response to intervention. In analyses without PGS by intervention by time, the relationships between PGS and PA phenotypes were modified by age (p interaction = .048 for CRF and .058 for PA), such that a 1-unit increase in PGS was associated with 24 kcal · wk-1 more in moderate-intensity PA and 0.004 MET higher CRF only among older groups (age >55 years for CRF, >60 years for PA level). CONCLUSIONS: The effects of the intervention on PA and CRF were not moderated by the four SNPs. Future studies with extended SNP list should confirm the findings on effect modification by age.

Personalized feedback improves cardiovascular risk perception and physical activity levels in persons with HIV: results of a pilot randomized clinical trial.

People with HIV (PWH) have an elevated risk for cardiovascular disease (CVD) compared with the general population. This study examined the feasibility, acceptability and preliminary efficacy of a tailored intervention aimed at increasing CVD risk perception and the adoption of heart-healthy behaviors in PWH. Forty adults were randomized to receive personalized feedback on CVD risk and discussion of risk reduction or health education. Participants were issued pedometers and seen for two treatment sessions. Participants were 60% male and had a mean age of 51.5 years. Ninety percent of participants completed all study sessions indicating good feasibility and acceptability. A medium effect size for the difference between treatment and control groups was found on both the Perceived Risk for Heart Disease (d = .38) and the Rapid Eating and Activity for Patients scales (d = .56) at 12 weeks. Atherosclerotic cardiovascular disease (ASCVD) risk score moderated the effect of treatment, such that at high (but not low) ASCVD risk, active intervention, compared to control, was associated with a greater increase in steps between baseline and both 8 (d = .38) and 12 weeks (d = .55). Findings provide preliminary evidence that tailored interventions delivered by nurses may be effective for primary prevention of CVD in PWH.

Extent and prevalence of post-exercise and nocturnal hypoglycemia following peri-exercise bolus insulin adjustments in individuals with type 1 diabetes.

AIM: To detail the extent and prevalence of post-exercise and nocturnal hypoglycemia following peri-exercise bolus insulin dose adjustments in individuals with type 1 diabetes (T1D) using multiple daily injections of insulins aspart (IAsp) and degludec (IDeg). METHODS AND RESULTS: Sixteen individuals with T1D, completed a single-centred, randomised, four-period crossover trial consisting of 23-h inpatient phases. Participants administered either a regular (100%) or reduced (50%) dose (100%; 5.1 ± 2.4, 50%; 2.6 ± 1.2 IU, p < 0.001) of individualised IAsp 1 h before and after 45-min of evening exercise at 60 ± 6% V̇O2max. An unaltered dose of IDeg was administered in the morning. Metabolic, physiological and hormonal responses during exercise, recovery and nocturnal periods were characterised. The primary outcome was the number of trial day occurrences of hypoglycemia (venous blood glucose ≤ 3.9 mmol L -1). Inclusion of a 50% IAsp dose reduction strategy prior to evening exercise reduced the occurrence of in-exercise hypoglycemia (p = 0.023). Mimicking this reductive strategy in the post-exercise period decreased risk of nocturnal hypoglycemia (p = 0.045). Combining this strategy to reflect reductions either side of exercise resulted in higher glucose concentrations in the acute post-exercise (p = 0.034), nocturnal (p = 0.001), and overall (p < 0.001) periods. Depth of hypoglycemia (p = 0.302), as well as ketonic and counter-regulatory hormonal profiles were similar. CONCLUSIONS: These findings demonstrate the glycemic safety of peri-exercise bolus dose reduction strategies in minimising the prevalence of acute and nocturnal hypoglycemia following evening exercise in people with T1D on MDI. Use of newer background insulins with current bolus insulins demonstrates efficacy and advances current recommendations for safe performance of exercise. CLINICAL TRIALS REGISTER: DRKS00013509.

Accurate quantum dynamics simulation of the photodetachment spectrum of the nitrate anion (NO3 -) based on an artificial neural network diabatic potential model.

The photodetachment spectrum of the nitrate anion (NO3 -) is simulated from first principles using wavepacket quantum dynamics propagation and a newly developed accurate full-dimensional fully coupled five state diabatic potential model. This model utilizes the recently proposed complete nuclear permutation inversion invariant artificial neural network diabatization technique [D. M. G. Williams and W. Eisfeld, J. Phys. Chem. A 124, 7608 (2020)]. The quantum dynamics simulations are designed such that temperature effects and the impact of near threshold detachment are taken into account. Thus, the two available experiments at high temperature and at cryogenic temperature using the slow electron velocity-map imaging technique can be reproduced in very good agreement. These results clearly show the relevance of hot bands and vibronic coupling between the X̃ 2A2 ' ground state and the B̃ 2E' excited state of the neutral radical. This together with the recent experiment at low temperature gives further support for the proper assignment of the ν3 fundamental, which has been debated for many years. An assignment of a not yet discussed hot band line is also proposed.

Exercise as a smoking cessation treatment for women: a randomized controlled trial.

Cigarette smoking remains the leading behavioral risk factor for chronic disease and premature mortality. This RCT tested the efficacy of moderate intensity aerobic exercise as an adjunctive smoking cessation treatment among women. Participants (N = 105; age = 42.5, SD = 11.2) received brief smoking cessation counseling and 10 weeks of nicotine replacement therapy and were randomized to 12 weeks of moderate intensity exercise (Exercise; n = 53) or 12 weeks of health education (Control; n = 52). Longitudinal models, with Generalized Estimating Equations, showed no differences between Exercise and Control in cotinine-verified 7-day point prevalence abstinence (Wald = 1.96, p = 0.10) or continuous abstinence (Wald = 1.45, p = 0.23) at 12-weeks (post-treatment) or 6-, 9-, or 12-month follow-up, controlling for differences in baseline nicotine dependence. There was no effect of exercise on smoking cessation. The present study adds to the literature suggesting null effects of exercise as a smoking cessation adjunctive treatment despite promising findings in short-term laboratory based studies.