Long-term evaluation of anterior thalamic deep brain stimulation for epilepsy in the European MORE registry.

OBJECTIVE: Short-term outcomes of deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) were reported for people with drug-resistant focal epilepsy (PwE). Because long-term data are still scarce, the Medtronic Registry for Epilepsy (MORE) evaluated clinical routine application of ANT-DBS. METHODS: In this multicenter registry, PwE with ANT-DBS were followed up for safety, efficacy, and battery longevity. Follow-up ended after 5 years or upon study closure. Clinical characteristics and stimulation settings were compared between PwE with no benefit, improvers, and responders, that is, PwE with average monthly seizure frequency reduction rates of ≥50%. RESULTS: Of 170 eligible PwE, 104, 62, and 49 completed the 3-, 4-, and 5-year follow-up, respectively. Most discontinuations (68%) were due to planned study closure as follow-up beyond 2 years was optional. The 5-year follow-up cohort had a median seizure frequency reduction from 16 per month at baseline to 7.9 per month at 5-year follow-up (p < .001), with most-pronounced effects on focal-to-bilateral tonic-clonic seizures (n = 15, 77% reduction, p = .008). At last follow-up (median 3.5 years), 41% (69/170) of PwE were responders. Unifocal epilepsy (p = .035) and a negative history of epilepsy surgery (p = .002) were associated with larger average monthly seizure frequency reductions. Stimulation settings did not differ between response groups. In 179 implanted PwE, DBS-related adverse events (AEs, n = 225) and serious AEs (n = 75) included deterioration in epilepsy or seizure frequency/severity/type (33; 14 serious), memory/cognitive impairment (29; 3 serious), and depression (13; 4 serious). Five deaths occurred (none were ANT-DBS related). Most AEs (76.3%) manifested within the first 2 years after implantation. Activa PC depletion (n = 37) occurred on average after 45 months. SIGNIFICANCE: MORE provides further evidence for the long-term application of ANT-DBS in clinical routine practice. Although clinical benefits increased over time, side effects occurred mainly during the first 2 years. Identified outcome modifiers can help inform PwE selection and management.

Probing the neurocardiac circuit in trauma and posttraumatic stress.

The neurocardiac circuit is integral to physiological regulation of threat and trauma-related responses. However, few direct investigations of brain-behavior associations with replicable physiological markers of PTSD have been conducted. The current study probed the neurocardiac circuit by examining associations among its core regions in the brain (e.g., insula, hypothalamus) and the periphery (heart rate [HR], high frequency heart rate variability [HF-HRV], and blood pressure [BP]). We sought to characterize these associations and to determine whether there were differences by PTSD status. Participants were N = 315 (64.1 % female) trauma-exposed adults enrolled from emergency departments as part of the prospective AURORA study. Participants completed a deep phenotyping session (e.g., fear conditioning, magnetic resonance imaging) two weeks after emergency department admission. Voxelwise analyses revealed several significant interactions between PTSD severity 8-weeks posttrauma and psychophysiological recordings on hypothalamic connectivity to the prefrontal cortex (PFC), insula, superior temporal sulcus, and temporoparietaloccipital junction. Among those with PTSD, diastolic BP was directly correlated with right insula-hypothalamic connectivity, whereas the reverse was found for those without PTSD. PTSD status moderated the association between systolic BP, HR, and HF-HRV and hypothalamic connectivity in the same direction. While preliminary, our findings may suggest that individuals with higher PTSD severity exhibit compensatory neural mechanisms to down-regulate autonomic imbalance. Additional study is warranted to determine how underlying mechanisms (e.g., inflammation) may disrupt the neurocardiac circuit and increase cardiometabolic disease risk in PTSD.

Benchmarking breath analysis using peppermint approach with gas chromatography ion mobility spectrometer coupled to micro thermal desorber.

Background The Peppermint Initiative, established within the International Association of Breath Research, introduced the peppermint protocol, a breath analysis benchmarking effort designed to address the lack of inter-comparability of outcomes across different breath sampling techniques and analytical platforms. Benchmarking with gas chromatography - ion mobility spectrometry (GC-IMS) using peppermint has been previously reported however, coupling micro-thermal desorption (µTD) to GC-IMS has not yet, been benchmarked for breath analysis. Objective To benchmark µTD-GC-IMS for breath analysis using the peppermint protocol. Methods Ten healthy participants (4 males and 6 females, aged 20 - 73 years), were enrolled to give six breath samples into Nalophan bags via a modified peppermint protocol. Breath sampling after peppermint ingestion occurred over 6 h at t = 60, 120, 200, 280, and 360 minutes. The breath samples (120 cm3) were pre-concentrated in the µTD before being transferred into the GC-IMS for detection. Data was processed using VOCal, including background subtractions, peak volume measurements, and room air assessment. Results During peppermint washout, eucalyptol showed the highest change in concentration levels, followed by α-pinene and ß-pinene. The reproducibility of the technique for breath analysis was demonstrated by constructing logarithmic washout curves, with the average linearity coefficient of R2 = 0.99. The time to baseline (benchmark) value for the eucalyptol washout was 1111 minutes (95% CI: 529-1693 minutes), obtained by extrapolating the average logarithmic washout curve. Conclusion Using the peppermint protocol, we demonstrated that µTD-GC-IMS is reproducible and suitable for breath analysis. We obtained a benchmark value (eucalyptol washout) for the µTD-GC-IMS of 1111 minutes (95% CI: 529-1693 minutes) for eucalyptol, which is comparable to the gold standard GC-MS. .

Size-classifiable quantification of nanoplastic by rate zonal centrifugation coupled with pyrolysis-gas chromatography-mass spectrometry.

Particle size is an important indicator to evaluate the environmental risk and biotoxicity of nanoplastic (NP, particle diameter <1000 nm). The methods available to determine size classes of NP in environmental samples are few and are rare to achieve efficient separation and recycling of NP with close particle sizes. Here, we show that rate-zonal centrifugation (RZC) can quickly and efficiently collect NP of different sizes based on their sedimentation coefficients. When combined with cloud-point extraction (CPE) and pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS), our method can quantify three NP particle-size classes separately (including 100 nm, 300 nm, and 600 nm) in aqueous samples with high recovery (81.4 %-89.4 %), limits of detections (LODs, 33.5-53.4 µg/L), and limits of quantifications (LOQs, 110.6-167.2 µg/L). Compared with the conventional sample pretreatment process, our method can effectively extract and determine the NP with different sizes. Our approach is highly scalable and can be effectively applied to NP in a wide range of aquatic environments. Meanwhile, our approach is highly scalable to incorporate diverse assays to study the environmental behaviours and ecological risks of NP.

Outcome and safety of mechanical thrombectomy in patients with acute ischemic stroke due to internal carotid artery dissection.

BACKGROUND: Mechanical thrombectomy (MT) in patients with symptoms of acute ischemic stroke (AIS) due to internal carotid artery dissection (ICAD) remains controversial. In this study, we present clinical outcome and safety of MT in acute ICAD compared to other acute carotid artery pathology. METHODS: Patients with symptoms of AIS due to internal carotid artery pathology, treated with MT from 2017-2021, were categorized as ICAD or non-ICAD. Baseline and procedural characteristics, complications, and functional outcome at 90 days were compared between the two groups. Factors associated with a favorable outcome (modified Rankin Scale 0-2) were analyzed using multivariate logistic regression. Safety analyses included in-stent thrombosis, perforation, intracranial hemorrhage, and mortality. RESULTS: Sixty-seven ICAD patients (14.8%) and 387 non-ICAD patients (85.2%) were enrolled. ICAD patients were younger, median age 53 years (interquartile range (IQR) 47-61) vs. non-ICAD 72 years (IQR 64-79), p < 0.001. Favorable outcome was more common in ICAD patients, 49 ICAD patients (76.6%) vs. 158 non-ICAD patients (42.4%), p < 0.001. Post-procedural symptomatic intracranial hemorrhage occurred in 41 patients, 5 (7.5%) ICAD patients vs. 36 (9.3%) non-ICAD patients, p = 0.6. Mortality differed significantly, 6 (9%) ICAD patients vs. 94 (24.3%) non-ICAD patients, p = 0.01. ICAD was not associated with functional outcome in multivariate analysis, OR = 1.25 [95%confidence interval:0.55-2.86]. CONCLUSION: ICAD patients achieved a better 90-day functional outcome compared with non-ICAD patients. ICAD patients did not perform worse in safety measures than non-ICAD patients. Our data provide indirect evidence that MT is of clinical benefit in ICAD patients with symptoms of AIS.

What makes a good scientific presentation on artificial intelligence in medical imaging?

PURPOSE: Adequate communication of scientific findings is crucial to enhance knowledge transfer. This study aimed to determine the key features of a good scientific oral presentation on artificial intelligence (AI) in medical imaging. METHODS: A total of 26 oral presentations dealing with original research on AI studies in medical imaging at the 2023 RSNA annual meeting were included and systematically assessed by three observers. The presentation quality of the research question, inclusion criteria, reference standard, method, results, clinical impact, presentation clarity, presenter engagement, and the presentation's quality of knowledge transfer were assessed using five-point Likert scales. The number of slides, the average number of words per slide, the number of interactive slides, the number of figures, and the number of tables were also determined for each presentation. Mixed-effects ordinal regression was used to assess the association between the above-mentioned variables and the quality of knowledge transfer of the presentation. RESULTS: A significant positive association was found between the quality of the presentation of the research question and the presentation's quality of knowledge transfer (odds ratio [OR]: 2.5, P = 0.005). The average number of words per slide was significantly negatively associated with the presentation's quality of knowledge transfer (OR: 0.9, P < 0.001). No other significant associations were found. CONCLUSION: Researchers who orally present their scientific findings in the field of AI and medical imaging should pay attention to clearly communicating their research question and minimizing the number of words per slide to maximize the value of their presentation.

An ape partial postcranial skeleton (KNM-NP 64631) from the Middle Miocene of Napudet, northern Kenya.

An ape partial postcranial skeleton (KNM-NP 64631) was recovered during the 2015-2021 field seasons at Napudet, a Middle Miocene (∼13 Ma) locality in northern Kenya. Bony elements representing the shoulder, elbow, hip, and ankle joints, thoracic and lumbar vertebral column, and hands and feet, offer valuable new information about the body plan and positional behaviors of Middle Miocene apes. Body mass estimates from femoral head dimensions suggest that the KNM-NP 64631 individual was smaller-bodied (c. 13-17 kg) than some Miocene taxa from eastern Africa, including Ekembo nyanzae, and probably Equatorius africanus or Kenyapithecus wickeri, and was more comparable to smaller-bodied male Nacholapithecus kerioi individuals. Similar to many Miocene apes, the KNM-NP 64631 individual had hip and hallucal tarsometatarsal joints reflecting habitual hindlimb loading in a variety of postures, a distal tibia with a large medial malleolus, an inflated humeral capitulum, probably a long lumbar spine, and a long pollical proximal phalanx relative to femoral head dimensions. The KNM-NP 64631 individual departs from most Early Miocene apes in its possession of a more steeply beveled radial head and deeper humeral zona conoidea, reflecting enhanced supinating-pronating abilities at the humeroradial joint. The KNM-NP 64631 individual also differs from Early Miocene Ekembo heseloni in having a larger elbow joint (inferred from radial head size) relative to the mediolateral width of the lumbar vertebral bodies and a more asymmetrical talar trochlea, and in these ways recalls inferred joint proportions for, and talocrural morphology of, N. kerioi. Compared to most Early Miocene apes, the KNM-NP 64631 individual likely relied on more forelimb-dominated arboreal behaviors, perhaps including vertical climbing (e.g., extended elbow, hoisting). Moreover, the Napudet ape partial postcranial skeleton suggests that an arboreally adapted body plan characterized by relatively large (here, based on joint size) forelimbs, but lacking orthograde suspensory adaptations, may not have been 'unusual' among Middle Miocene apes.

Pictorial review of multiparametric MRI in bladder urothelial carcinoma with variant histology: pearls and pitfalls.

Bladder cancer (BC), predominantly comprising urothelial carcinomas (UCs), ranks as the tenth most common cancer worldwide. UCs with variant histology (variant UC), including squamous differentiation, glandular differentiation, plasmacytoid variant, micropapillary variant, sarcomatoid variant, and nested variant, accounting for 5-10% of cases, exhibit more aggressive and advanced tumor characteristics compared to pure UC. The Vesical Imaging-Reporting and Data System (VI-RADS), established in 2018, provides guidelines for the preoperative evaluation of muscle-invasive bladder cancer (MIBC) using multiparametric magnetic resonance imaging (mpMRI). This technique integrates T2-weighted imaging (T2WI), dynamic contrast-enhanced (DCE)-MRI, and diffusion-weighted imaging (DWI) to distinguish MIBC from non-muscle-invasive bladder cancer (NMIBC). VI-RADS has demonstrated high diagnostic performance in differentiating these two categories for pure UC. However, its accuracy in detecting muscle invasion in variant UCs is currently under investigation. These variant UCs are associated with a higher likelihood of disease recurrence and require precise preoperative assessment and immediate surgical intervention. This review highlights the potential value of mpMRI for different variant UCs and explores the clinical implications and prospects of VI-RADS in managing these patients, emphasizing the need for careful interpretation of mpMRI examinations including DCE-MRI, particularly given the heterogeneity and aggressive nature of variant UCs. Additionally, the review addresses the fundamental MRI reading procedures, discusses potential causes of diagnostic errors, and considers future directions in the use of artificial intelligence and radiomics to further optimize the bladder MRI protocol.

Insights on kraft lignin degradation in an anaerobic environment.

Lignin is an aromatic macromolecule and one of the main constituents of lignocellulosic materials. Kraft lignin is generated as a residual by-product of the lignocellulosic biomass industrial process, and it might be used as a feedstock to generate low molecular weight aromatic compounds. In this study, we seek to understand and explore the potential of ruminal bacteria in the degradation of kraft lignin. We established two consortia, KLY and KL, which demonstrated significant lignin-degrading capabilities. Both consortia reached maximum growth after two days, with KLY showing a higher growth and decolorization rate. Additionally, SEM analysis revealed morphological changes in the residual lignin from both consortia, indicating significant degradation. This was further supported by FTIR spectra, which showed new bands corresponding to the C-H vibrations of guaiacyl and syringyl units, suggesting structural transformations of the lignin. Taxonomic analysis showed enrichment of the microbial community with members of the Dickeya genus. Seven metabolic pathways related to lignin metabolism were predicted for the established consortia. Both consortia were capable of consuming aromatic compounds such as 4-hydroxybenzoic acid, syringaldehyde, acetovanillone, and syringic acid, highlighting their capacity to convert aromatic compounds into commercially valuable molecules presenting antifungal activity and used as food preservatives as 4-hydroxyphenylacetic, 3-phenylacetic, and phenylacetic acids. Therefore, the microbial consortia shown in the present work are models for understanding the process of lignin degradation and consumption in bacterial anaerobic communities and developing biological processes to add value to industrial processes based on lignocellulosic biomass as feedstock.

Initiation of retinopathy of prematurity screening examinations in extremely premature infants.

PURPOSE: To determine whether extremely premature infants require screening for retinopathy of prematurity (ROP) if <31 weeks' postmenstrual age (PMA). METHODS: The medical records of infants born in community hospital settings at <31 weeks' gestational age (GA) were reviewed retrospectively. Prevalence and progression of ROP in infants born at <24 weeks' GA were compared with infants born at 24-30 weeks' GA. RESULTS: A total of 2,061 records were reviewed: 1,969 infants were born at 24-30 weeks' GA; 92, at <24 weeks. Infants born <24 weeks' GA were more likely to develop pre-plus and plus disease or require treatment than infants born 24-30 weeks' GA (P < 0.0001) and did so earlier (P = 0.0001). Eight infants developed pre-plus or greater ROP <31 weeks' PMA; 6 were born <24 weeks' GA. Three infants developed plus disease or required treatment <31 weeks' PMA, the earliest at 27 and 3/7 weeks. CONCLUSIONS: Clinicians should consider initiating ROP screening examinations before 31 weeks' PMA, particularly for infants born <24 weeks' GA and those with lower birth weights.

Autonomous navigation of catheters and guidewires in mechanical thrombectomy using inverse reinforcement learning.

PURPOSE: Autonomous navigation of catheters and guidewires can enhance endovascular surgery safety and efficacy, reducing procedure times and operator radiation exposure. Integrating tele-operated robotics could widen access to time-sensitive emergency procedures like mechanical thrombectomy (MT). Reinforcement learning (RL) shows potential in endovascular navigation, yet its application encounters challenges without a reward signal. This study explores the viability of autonomous guidewire navigation in MT vasculature using inverse reinforcement learning (IRL) to leverage expert demonstrations. METHODS: Employing the Simulation Open Framework Architecture (SOFA), this study established a simulation-based training and evaluation environment for MT navigation. We used IRL to infer reward functions from expert behaviour when navigating a guidewire and catheter. We utilized the soft actor-critic algorithm to train models with various reward functions and compared their performance in silico. RESULTS: We demonstrated feasibility of navigation using IRL. When evaluating single- versus dual-device (i.e. guidewire versus catheter and guidewire) tracking, both methods achieved high success rates of 95% and 96%, respectively. Dual tracking, however, utilized both devices mimicking an expert. A success rate of 100% and procedure time of 22.6 s were obtained when training with a reward function obtained through 'reward shaping'. This outperformed a dense reward function (96%, 24.9 s) and an IRL-derived reward function (48%, 59.2 s). CONCLUSIONS: We have contributed to the advancement of autonomous endovascular intervention navigation, particularly MT, by effectively employing IRL based on demonstrator expertise. The results underscore the potential of using reward shaping to efficiently train models, offering a promising avenue for enhancing the accessibility and precision of MT procedures. We envisage that future research can extend our methodology to diverse anatomical structures to enhance generalizability.

Tracking protein-protein interactions by NMR: conformational selection in human steroidogenic cytochrome P450 CYP17A1 induced by cytochrome b5.

The human steroidogenic cytochrome P450 CYP17A1 catalyzes two types of reactions in the biosynthetic pathway leading from pregnenolone to testosterone and several other steroid hormones. The first is the hydroxylation of pregnenolone or progesterone to the corresponding 17α-hydroxy steroid, followed by a lyase reaction that converts these 17α-hydroxy intermediates to the androgens dehydroepiandrosterone and androstenedione, respectively. cytochrome b5 (cytb5) is known to act as both an effector and electron donor for the lyase oxidations, markedly stimulating the rate of the lyase reaction in its presence relative to the rate in its absence. Extensive sequential backbone 1H,15N and 13C nuclear magnetic resonance assignments have now been made for oxidized CYP17A1 bound to the prostate cancer drug and inhibitor abiraterone. This is the first eukaryotic P450 for which such assignments are now available. These assignments allow more complete interpretation of the structural perturbations observed upon cytb5 addition. Possible mechanism(s) for the effector activity of cytb5 are discussed in light of this new information.

Epidemiology and Management of Pediatric Group A Streptococcal Pneumonia With Parapneumonic Effusion: An Observational Study.

BACKGROUND: During autumn/winter 2022, UK pediatricians reported an unseasonal increase in invasive group A streptococcal infections; a striking proportion presenting with pneumonia with parapneumonic effusion. METHODS: Clinicians across the United Kingdom were requested to submit pseudonymized clinical data using a standardized report form for children (<16 years) admitted between September 30, 2022 and February 17, 2023, with microbiologically confirmed group A streptococcal pneumonia with parapneumonic effusion. RESULTS: From 185 cases submitted, the median patient age was 4.4 years, and 163 (88.1%) were previously healthy. Respiratory viral coinfection was detected on admission for 101/153 (66.0%) children using extended respiratory pathogen polymerase chain reaction panel. Molecular testing was the primary method of detecting group A streptococcus on pleural fluid (86/171; 50.3% samples). Primary surgical management was undertaken in 171 (92.4%) children; 153/171 (89.4%) had pleural drain inserted (96 with fibrinolytic agent), 14/171 (8.2%) had video-assisted thoracoscopic surgery. Fever duration after admission was prolonged (median, 12 days; interquartile range, 9-16). Intravenous antibiotic courses varied in length (median, 14 days; interquartile range, 12-21), with many children receiving multiple broad-spectrum antibiotics, although evidence for additional bacterial infection was limited. CONCLUSIONS: Most cases occurred with viral coinfection, a previously well-recognized risk with influenza and varicella zoster, highlighting the need to ensure routine vaccination coverage and progress on vaccines for other common viruses (eg, respiratory syncytial virus, human metapneumovirus) and for group A streptococcus. Molecular testing is valuable to detect viral coinfection and confirm invasive group A streptococcal diagnosis, expediting the incorporation of cases into national reporting systems. Range and duration of intravenous antibiotics administered demonstrated the need for research on the optimal duration of antimicrobials and improved stewardship.

Short lifespan is one's fate, long lifespan is one's achievement: lessons from Daphnia.

Studies of longevity rely on baseline life expectancy of reference genotypes measured in standardized conditions. Variation among labs, protocols, and genotypes makes longevity intervention studies difficult to compare. Furthermore, extending lifespan under suboptimal conditions or that of a short-lived genotype may be of a lesser theoretical and translational value than extending the maximal possible lifespan. Daphnia is becoming a model organism of choice for longevity research complementing data obtained on traditional models. In this study, we report longevity of several genotypes of a long-lived species D. magna under a variety of protocols, aiming to document the highest lifespan, factors reducing it, and parameters that change with age and correlate with longevity. Combining longevity data from 25 experiments across two labs, we report a strong intraspecific variation, moderate effects of group size and medium composition, and strong genotype-by-environment interactions with respect to food level. Specifically, short-lived genotypes show no caloric restriction (CR) effect, while long-lived ones expand their lifespan even further under CR. We find that the CR non-responsive clones show little correlation between longevity and two measures of lipid peroxidation. In contrast, the long-lived, CR-responsive clones show a positive correlation between longevity and lipid hydroperoxide abundance, and a negative correlation with MDA concentration. This indicates differences among genotypes in age-related accumulation and detoxification of LPO products and their effects on longevity. Our observations support the hypothesis that a long lifespan can be affected by CR and levels of oxidative damage, while genetically determined short lifespan remains short regardless.

Kinetic and Spectroscopic Investigation of the Y157F and C93G/Y157F Variants of Cysteine Dioxygenase: Dissecting the Roles of the Second-Sphere Residues C93 and Y157.

In mammals, l-cysteine (Cys) homeostasis is maintained by the mononuclear nonheme iron enzyme cysteine dioxygenase (CDO), which oxidizes Cys to cysteine sulfinic acid. CDO contains a rare post-translational modification, involving the formation of a thioether cross-link between a Cys residue at position 93 (Mus musculus CDO numbering) and a nearby tyrosine at position 157 (Cys-Tyr cross-link). As-isolated CDO contains both the cross-linked and non-cross-linked isoforms, and formation of the Cys-Tyr cross-link during repeated enzyme turnover increases CDO's catalytic efficiency by ∼10-fold. Interestingly, while the C93G CDO variant lacks the Cys-Tyr cross-link, it is similarly active as cross-linked wild-type (WT) CDO. Alternatively, the Y157F CDO variant, which also lacks the cross-link but maintains the free thiolate at position 93, exhibits a drastically reduced catalytic efficiency. These observations suggest that the untethered thiolate moiety of C93 is detrimental to CDO activity and/or that Y157 is essential for catalysis. To further assess the roles of residues C93 and Y157, we performed a spectroscopic and kinetic characterization of Y157F CDO and the newly designed C93G/Y157F CDO variant. Our results provide evidence that the non-cross-linked C93 thiolate stabilizes a water at the sixth coordination site of Cys-bound Y157F Fe(II)CDO. A water is also present, though more weakly coordinated, in Cys-bound C93G/Y157F Fe(II)CDO. The presence of a water molecule, which must be displaced by cosubstrate O2, likely makes a significant contribution to the ∼15-fold and ∼7-fold reduced catalytic efficiencies of the Y157F and C93G/Y157F CDO variants, respectively, relative to cross-linked WT CDO.

Daylight Saving Time Transitions and Risk of Heart Attack­a Systematic Review and Meta-Analysis.

BACKGROUND: The health risks of daylight saving time transitions are intensely debated. Disturbed circadian rhythms and lack of sleep after transitions might increase the risk of acute myocardial infarction (AMI). The only meta-analysis on the risk of AMI has now been considerably expanded. METHODS: In this systematic review and meta-analysis (including meta-regressions and sensitivity analyses), we examine the frequency of AMI in the first few weeks after daylight saving time transitions (OSF registration www.doi.org/10.17605/OSF.IO/7CFKS). Eight databases were searched for pertinent literature up to September 2023. Authors were contacted for additional information. Study quality was rated using the Newcastle-Ottawa Scale. RESULTS: Twelve studies from ten countries were included in the meta-analysis. Nine were of adequate quality, and three were of good quality. The pooled relative risk (RR) of AMI after daylight saving time onset (spring) was 1.04 (95% confidence interval [1.02; 1.07], I2: 57.3%), and 1.02 ([0.99; 1.05], I2: 51.6%) after daylight saving time offset (autumn). Recalculation after the exclusion of one study with inconsistencies yielded pooled RR values of 1.04 [1.01; 1.06] and 1.00 [0.99; 1.02], with the spring results being heterogeneous (I2: 56.9%) and the autumn results homogeneous (I2: 17.1%). CONCLUSION: Current evidence suggests that there may be an increased risk of AMI after the spring transition, although there is moderate to marked heterogeneity among the studies that support this conclusion. More easily interpretable studies, such as those already conducted in the field of economics, should clarify associations with the aid of discontinuity regression and placebo tests. To this end, comparative risk analyses using years or places wherein daylight saving time was not practiced would be suitable.

Associations of role, area deprivation index, and race with health behaviors and body mass index among localized prostate cancer patients and their partners.

PURPOSE: To examine the associations of role (localized prostate cancer (PCa) patient vs. their intimate partner), area deprivation index (ADI-higher scores indicating higher neighborhood deprivation levels), and race (Black/African American (AA) vs. White) with health behaviors and body mass index (BMI) among PCa patients and partners. The behaviors include smoking, alcohol consumption, diet quality, sedentary behaviors, and physical activity (PA). METHODS: This study used the baseline data collected in a clinical trial. Given the nested structure of the dyadic data, multi-level models were used. RESULTS: Significant role-race interaction effects on smoking, ADI-race effects on alcohol consumption, and role-ADI effects on BMI were found. Meanwhile, patients smoked more cigarettes, decreased alcohol consumption, had less healthful diets, spent longer time watching TV, did fewer sedentary hobbies, had more confidence in PA, and had higher BMIs than their partners. High ADI was independently associated with lower odds of drinking alcohol, using computer/Internet, and doing non-walking PA, and higher BMI compared to low ADI controlling for role and race. Black/AA dyads had less smoking amount and alcohol consumption and higher sedentary time and BMI than White dyads when adjusted for role and ADI. CONCLUSIONS: This study identified significant interaction and main effects of role, ADI, or race on health behaviors and BMI. IMPLICATIONS FOR CANCER SURVIVORS: Future behavioral interventions should address divergent individual needs between patients and partners, social and neighborhood barriers, and cultural indicators of racial groups to promote healthful behaviors and improve the quality of survivorship for PCa patients and partners.

KRAS promotes GLI2-dependent transcription during pancreatic carcinogenesis.

Aberrant activation of GLI transcription factors has been implicated in the pathogenesis of different tumor types including pancreatic ductal adenocarcinoma (PDAC). However, the mechanistic link with established drivers of this disease remains in part elusive. Here, using a new genetically-engineered mouse model overexpressing constitutively active mouse form of GLI2 and a combination of genome wide assays, we provide evidence of a novel mechanism underlying the interplay between KRAS, a major driver of PDAC development, and GLI2 to control oncogenic gene expression. These mice, also expressing KrasG12D, show significantly reduced median survival rate and accelerated tumorigenesis compared to the KrasG12D only expressing mice. Analysis of the mechanism using RNA-seq demonstrate higher levels of GLI2 targets, particularly tumor growth promoting genes including Ccnd1, N-Myc and Bcl2, in KrasG12D mutant cells. Further, ChIP-seq studies showed that in these cells KrasG12D increases the levels of H3K4me3 at the promoter of GLI2 targets without affecting significantly the levels of other major active chromatin marks. Importantly, Gli2 knockdown reduces H3K4me3 enrichment and gene expression induced by mutant Kras. In summary, we demonstrate that Gli2 plays a significant role in pancreatic carcinogenesis by acting as a downstream effector of KrasG12D to control gene expression.