Cardiovascular magnetic resonance (CMR) has improved diagnostic and management strategies in hypertrophic cardiomyopathy (HCM) by expanding our appreciation for the diverse phenotypic expression. We ...sought to characterize the prevalence and clinical significance of a recently identified accessory left ventricular (LV) muscle bundle extending from the apex to the basal septum or anterior wall (i.e. apical-basal).
CMR was performed in 230 genotyped HCM patients (48 ± 15 years, 69% male), 30 genotype-positive/phenotype-negative (G+/P-) family members (32 ± 15 years, 30% male), and 126 controls. Left ventricular apical-basal muscle bundle was identified in 145 of 230 (63%) HCM patients, 18 of 30 (60%) G+/P- family members, and 12 of 126 (10%) controls (G+/P- vs. controls; P < 0.01). In HCM patients, the prevalence of an apical-basal muscle bundle was similar among those with disease-causing sarcomere mutations compared with patients without mutation (64 vs. 62%; P = 0.88). The presence of an LV apical-basal muscle bundle was not associated with LV outflow tract obstruction (P = 0.61). In follow-up, 33 patients underwent surgical myectomy of whom 22 (67%) were identified to have an accessory LV apical-basal muscle bundle, which was resected in all patients.
Apical-basal muscle bundles are a unique myocardial structure commonly present in HCM patients as well as in G+/P- family members and may represent an additional morphologic marker for HCM diagnosis in genotype-positive status.
To understand the relationship between key non-canonical NF-κB kinase IKK-alpha(α), tumour mutational profile and survival in primary colorectal cancer.
Immunohistochemical expression of IKKα was ...assessed in a cohort of 1030 patients who had undergone surgery for colorectal cancer using immunohistochemistry. Mutational tumour profile was examined using a customised gene panel. Immunofluorescence was used to identify the cellular location of punctate IKKα expression.
Two patterns of IKKα expression were observed; firstly, in the tumour cell cytoplasm and secondly as discrete 'punctate' areas in a juxtanuclear position. Although cytoplasmic expression of IKKα was not associated with survival, high 'punctate' IKKα expression was associated with significantly reduced cancer-specific survival on multivariate analysis. High punctate expression of IKKα was associated with mutations in KRAS and PDGFRA. Dual immunofluorescence suggested punctate IKKα expression was co-located with the Golgi apparatus.
These results suggest the spatial expression of IKKα is a potential biomarker in colorectal cancer. This is associated with a differential mutational profile highlighting possible distinct signalling roles for IKKα in the context of colorectal cancer as well as potential implications for future treatment strategies using IKKα inhibitors.
Whether gastric metaplasia (GM) of the oesophagus should be considered as Barrett's oesophagus (BO) is controversial. Given concern intestinal metaplasia (IM) may be missed due to sampling, the UK ...guidelines include GM as a type of BO. Here, we investigated whether the risk of misdiagnosis and the malignant potential of GM warrant its place in the UK surveillance.
We performed a thorough pathology and endoscopy review to follow clinical outcomes in a novel UK cohort of 244 patients, covering 1854 person years of follow-up. We complemented this with a comparative genomic analysis of 160 GM and IM specimens, focused on early molecular hallmarks of BO and oesophageal adenocarcinoma (OAC).
We found that 58 of 77 short-segment (
3 cm) GM (SS-GM) cases (75%) continued to be observed as GM-only across a median of 4.4 years of follow-up. We observed that disease progression in GM-only cases and GM+IM cases (cases with reported GM on some occasions, IM on others) was significantly lower than in the IM-only cases (Kaplan-Meier, p=0.03). Genomic analysis revealed that the mutation burden in GM is significantly lower than in IM (p<0.01). Moreover, GM does not bear the mutational hallmarks of OAC, with an absence of associated signatures and driver gene mutations. Finally, we established that GM found adjacent to OAC is evolutionarily distant from cancer.
SS-GM is a distinct entity from SS-IM and the malignant potential of GM is lower than IM. It is questionable whether SS-GM warrants inclusion in BO surveillance.
Spontaneous septostomy is a rare complication of multiple gestations. Related complications include cord entanglement and preterm delivery. Limited data exist to guide the management of these ...high-risk patients. The majority of spontaneous septostomy cases have been reported in monochorionic diamniotic twins. We present 2 cases of spontaneous septostomy occurring in a monochorionic/dichorionic hybrid twin gestation (chorionicity transitions from dichorionicity to monochorionicity within the placenta) and in a dichorionic triamniotic triplet gestation.
Case 1 was a monochorionic/dichorionic hybrid twin gestation with a septostomy complicated by fetal parts of one twin protruding into the co-twin's sac as well as symptomatic polyhydramnios. Fetal magnetic resonance imaging confirmed the septostomy. Case 2 was a dichorionic triamniotic triplet gestation with septostomy and cord entanglement. Both patients were managed akin to a pseudo-monoamniotic gestation with serial ultrasound surveillance and eventual inpatient admission for heightened fetal monitoring. Case 1 underwent elective scheduled cesarean delivery at 33 weeks, and case 2 underwent emergent cesarean delivery for fetal heart rate decelerations at 28 weeks.
With a high degree of clinical suspicion, spontaneous septostomy can be diagnosed in uncommon settings such as hybrid twin gestations and higher order multiples. Management of such patients is individualized and may include a combination of heightened outpatient and inpatient surveillance.
We compare real-world trends in population-level cigarette discontinuation rates among adults (ages ≥21) who smoked cigarettes, by electronic nicotine delivery systems (ENDS) use.
U.S nationally ...representative data from adults in the Population Assessment of Tobacco and Health (PATH) Study (2013/14-2021, Waves 1-6) who smoked cigarettes in the past 30 days (P30D) were analyzed (n = 13 640). The exposure was P30D ENDS use. The outcome was P30D cigarette discontinuation at biennial follow-up. Weighted trend analyses were conducted to test for differences in cigarette discontinuation trends by ENDS use.
Between 2013/14 and 2015/16, cigarette discontinuation rates were both 16% for those who used ENDS and for those who did not; between 2018/19 and 2021, rates were ~30% for those who used ENDS and ~20% for those who did not; the time by ENDS use interaction was significant.
The relationship between adults' ENDS use and cigarette discontinuation in the context of an expanded ENDS marketplace, new tobacco regulatory actions, and COVID-19 differs from the relationship in earlier years.
It is important for public health decisions to be informed by research based on the contemporary ENDS marketplace and circumstances.
•Thermal properties of U-Mo alloy irradiated under high fission power density•Specific heat capacity sensitive to fuel thickness, temperature and fission density.•Density sensitive to fission power ...density (and rate).•Thermal diffusivity sensitive to microstructure and/or irradiation variations.•Thermal conductivity results agree with empirical model to ±30%.
A variety of physical and thermal property measurements made on irradiated U-Mo alloy monolithic fuel samples with a Zr diffusion barrier and clad in Al alloy 6061 are reported. These properties form the basis for additional investigations in thermal behavior of U-Mo fuel under high performance research reactor irradiation conditions. Measurements were performed on samples harvested from fuel plates irradiated under high fission power density and surface heat flux and complement previous measurements on samples subjected to moderate fission power density and surface heat flux. Sample measurements reported in this work represented fission density ranging from 2.42 – 4.81 × 1027 fissions•m−3 (20.8 – 36.5 235U depletion) and average plate surface temperatures from 355 – 414 K. Specific heat capacity of irradiated monolithic U-Mo increases with increasing temperature and fission density, but carries large uncertainties associated with thickness measurements used to determine the mass fraction of the layer constituents for extraction of the U-Mo specific heat capacity, specifically the very thin and nonuniform Zr diffusion barrier. Density of irradiated monolithic U-Mo decreases with increasing fission density resulting from fission gas swelling and porosity formation. Thermal diffusivity of irradiated monolithic U-Mo increased with increasing temperature and decreased with increasing fission density. Thermal conductivity of irradiated monolithic U-Mo increased with increasing temperature, and in general, appeared to decrease and become less sensitive to temperature with increasing fission density. Thermal conductivity measurements compared to a semi-empirical model agreed within ±30%. It is suspected that the main driver in deviation between model calculations and measurements is the fission gas swelling determination, which does not account for fission power density or irradiation temperature.
Colubridae represents the most phenotypically diverse and speciose family of snakes, yet no well-assembled and annotated genome exists for this lineage. Here, we report and analyze the genome of the ...garter snake, Thamnophis sirtalis, a colubrid snake that is an important model species for research in evolutionary biology, physiology, genomics, behavior, and the evolution of toxin resistance. Using the garter snake genome, we show how snakes have evolved numerous adaptations for sensing and securing prey, and identify features of snake genome structure that provide insight into the evolution of amniote genomes. Analyses of the garter snake and other squamate reptile genomes highlight shifts in repeat element abundance and expansion within snakes, uncover evidence of genes under positive selection, and provide revised neutral substitution rate estimates for squamates. Our identification of Z and W sex chromosome-specific scaffolds provides evidence for multiple origins of sex chromosome systems in snakes and demonstrates the value of this genome for studying sex chromosome evolution. Analysis of gene duplication and loss in visual and olfactory gene families supports a dim-light ancestral condition in snakes and indicates that olfactory receptor repertoires underwent an expansion early in snake evolution. Additionally, we provide some of the first links between secreted venom proteins, the genes that encode them, and their evolutionary origins in a rear-fanged colubrid snake, together with new genomic insight into the coevolutionary arms race between garter snakes and highly toxic newt prey that led to toxin resistance in garter snakes.
Abstract
Introduction
We examined the relationship between current tobacco use and functionally important respiratory symptoms.
Methods
Longitudinal cohort study of 16 295 US adults without COPD in ...Waves 2–3 (W2–3, 2014–2016) of the Population Assessment of Tobacco and Health Study. Exposure—Ten mutually exclusive categories of tobacco use including single product, multiple product, former, and never use (reference). Outcome—Seven questions assessing wheezing/cough were summed to create a respiratory symptom index; cutoffs of ≥2 and ≥3 were associated with functional limitations and poorer health. Multivariable regressions examined both cutoffs cross-sectionally and change over approximately 12 months, adjusting for confounders.
Results
All tobacco use categories featuring cigarettes (>2/3’s of users) were associated with higher risk (vs. never users) for functionally important respiratory symptoms at W2, for example, at symptom severity ≥ 3, risk ratio for exclusive cigarette use was 2.34 95% CI, 1.92, 2.85 and for worsening symptoms at W3 was 2.80 2.08, 3.76. There was largely no increased symptom risk for exclusive use of cigars, smokeless tobacco, hookah, or e-cigarettes (adjustment for pack-years and marijuana attenuated the cross-sectional e-cigarette association from 1.53(95% CI 0.98, 2.40) to 1.05 (0.67, 1.63); RRs for these products were also significantly lower compared to exclusive use of cigarettes. The longitudinal e-cigarette–respiratory symptom association was sensitive to the respiratory index cutoff level; exclusive e-cigarette use was associated with worsening symptoms at an index cutoff ≥ 2 (RR = 1.63 1.02, 2.59) and with symptom improvement at an index cutoff of ≥ 3 (RR = 1.64 1.04, 2.58).
Conclusions
Past and current cigarette smoking drove functionally important respiratory symptoms, while exclusive use of other tobacco products was largely not associated. However, the relationship between e-cigarette use and symptoms was sensitive to adjustment for pack-years and symptom severity.
Implications
How noncigarette tobacco products affect respiratory symptoms is not clear; some studies implicate e-cigarettes. We examined functionally important respiratory symptoms (wheezing/nighttime cough) among US adults without COPD. The majority of adult tobacco users smoke cigarettes and have higher risk of respiratory symptoms and worsening of symptoms, regardless of other products used with them. Exclusive use of other tobacco products (e-cigarettes, cigars, smokeless, hookah) was largely not associated with functionally important respiratory symptoms and risks associated with their use was significantly lower than for cigarettes. The association for e-cigarettes was greatly attenuated by adjustment for cigarette pack-years and sensitive to how symptoms were defined.
Life expectancy for people diagnosed with HIV has improved dramatically however the number of new infections in the UK remains high. Understanding patterns of sexual behaviour among people living ...with diagnosed HIV, and the factors associated with having condom-less sex, is important for informing HIV prevention strategies and clinical care. In addition, in view of the current interest in a policy of early antiretroviral treatment (ART) for all people diagnosed with HIV in the UK, it is of particular importance to assess whether ART use is associated with increased levels of condom-less sex. In this context the ASTRA study was designed to investigate current sexual activity, and attitudes to HIV transmission risk, in a large unselected sample of HIV-infected patients under care in the UK. The study also gathered background information on demographic, socio-economic, lifestyle and disease-related characteristics, and physical and psychological symptoms, in order to identify other key factors impacting on HIV patients and the behaviours which underpin transmission. In this paper we describe the study rationale, design, methods, response rate and the demographic characteristics of the participants. People diagnosed with HIV infection attending 8 UK HIV out-patient clinics in 2011-2012 were invited to participate in the study. Those who agreed to participate completed a confidential, self-administered pen-and-paper questionnaire, and their latest CD4 count and viral load test results were recorded. During the study period, 5112 eligible patients were invited to take part in the study and 3258 completed questionnaires were obtained, representing a response rate of 64% of eligible patients. The study includes 2248 men who have sex with men (MSM), 373 heterosexual men and 637 women. Future results from ASTRA will be a key resource for understanding HIV transmission within the UK, targeting prevention efforts, and informing clinical care of individuals living with HIV.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
