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Emotional dysregulation (ED) is a common characteristic of both attention deficit hyperactivity disorder (ADHD) and major depressive disorder (MDD), especially in adolescents. However, whether ADHD and MDD may share the specific ED-related neural networks remains unknown.
In total, 43 adolescents with clinical ED (22 adolescents with ADHD and 21 with MDD) were recruited; in addition, 29 sex- and age-matched healthy controls (HCs) were included. Resting-state functional connectivity (RSFC) analysis, voxel-based morphometry, and diffusion tensor imaging analysis were performed for each patient. In addition, we determined the significant regions of interest in patients with ED due to ADHD and MDD as compared with HCs and tested their correlations with clinical rating scale scores.
Compared with HCs, patients with ED had greater RSFC in the cerebellum and supramarginal gyrus (SMG), especially between vermis VI and the SMG in the attention networks, and lower RSFC between the right supplementary motor area and right lateral parietal area. Lower gray matter (GM) volume in the SMG was also found. RSFC was significantly correlated with clinical rating scale scores for all patients with ED due to ADHD or MDD. GM change was correlated with ED and MDD rating scale scores.
The cerebellum and attention networks might play major roles in ED pathophysiology in adolescents with ADHD and MDD. Increased connectivity of the vermis to the SMG serves as a possible underlying neural network.
Sarawak is the largest state in the megadiverse country of Malaysia. Its rich biodiversity is threatened by land-use change and hunting, with mammalian carnivores particularly affected. Data on the ecology, occurrence and distribution of small carnivores are crucial to inform their effective conservation, but no large-scale assessments have previously been conducted in Sarawak. Here we examine the status of the five species of felids in Sarawak based on data from camera-trap studies over 17 years (May 2003–February 2021) across 31 study areas, including protected areas of various sizes, production forests and forest matrix within oil palm plantations. Felids were detected at 39% of 845 camera stations. The marbled cat Pardofelis marmorata and Sunda clouded leopard Neofelis diardi had higher probabilities of occurrence in protected than unprotected areas, and vice versa for the leopard cat Prionailurus bengalensis and bay cat Catopuma badia. The marbled and bay cats were mostly diurnal, and the leopard cat was predominantly nocturnal; activity patterns did not substantively differ between protected and unprotected sites. The probabilities of occurrence of marbled and bay cats increased with greater distance from roads. The leopard cat and flat-headed cat Prionailurus planiceps were more likely, and the clouded leopard less likely, to occur near rivers. Flat-headed cats preferred peat swamp forest, bay cats lowland forest, and marbled cats and clouded leopards occurred in both lowland and montane forest. Felids may tolerate higher elevations to avoid anthropogenic disturbance; therefore, it is critical to preserve lowland and mid-elevation habitats that provide refugia from climate change and the destruction of lowland habitat.
To determine associations of alcohol use with cognitive aging among middle-aged men.
1,608 male twins (mean 57 years at baseline) participated in up to three visits over 12 years, from 2003–2007 to 2016–2019. Participants were classified into six groups based on current and past self-reported alcohol use: lifetime abstainers, former drinkers, very light (1–4 drinks in past 14 days), light (5–14 drinks), moderate (15–28 drinks), and at-risk drinkers (>28 drinks in past 14 days). Linear mixed-effects regressions modeled cognitive trajectories by alcohol group, with time-based models evaluating rate of decline as a function of baseline alcohol use, and age-based models evaluating age-related differences in performance by current alcohol use. Analyses used standardized cognitive domain factor scores and adjusted for sociodemographic and health-related factors.
Performance decreased over time in all domains. Relative to very light drinkers, former drinkers showed worse verbal fluency performance, by –0.21 SD (95% CI –0.35, –0.07), and at-risk drinkers showed faster working memory decline, by 0.14 SD (95% CI 0.02, –0.20) per decade. There was no evidence of protective associations of light/moderate drinking on rate of decline. In age-based models, light drinkers displayed better memory performance at advanced ages than very light drinkers (+0.14 SD; 95% CI 0.02, 0.20 per 10-years older age); likely attributable to residual confounding or reverse association.
Alcohol consumption showed minimal associations with cognitive aging among middle-aged men. Stronger associations of alcohol with cognitive aging may become apparent at older ages, when cognitive abilities decline more rapidly.
Host density is a key regulatory factor in parasite transmission. The goldfish (Carassius auratus)-Gyrodactylus kobayashii model was used to investigate effects of host density on population growth of gyrodactylids. A donor fish infected by five gravid gyrodactylids was mixed with 11 parasite-free goldfish at five host densities. There was a significant positive correlation between host density and mean abundance of G. kobayashii throughout the 58-day experiment. During early infection (days 15–24), mean abundance in medium high (0.5 fish L−1) and high host density groups (1 and 2 fish L−1) was significantly higher than that in the low host density groups (0.125 and 0.25 fish L−1). At high host density, prevalence increased more rapidly, and the peak prevalence was higher. Fitting of an exponential growth model showed that the population growth rate of the parasite increased with host density. A hypothesis was proposed that higher host density contributed to increased reinfection of detached gyrodactylids. A reinfection experiment was designed to test this hypothesis. Both mean abundance and prevalence at a host density of 1 fish L−1 were significantly higher than those at 0.25 fish L−1 on days 1 and 3, which suggested that more reinfections of G. kobyashii occurred at the higher host density. Density-dependent transmission during the early infection was an important contributor of population growth of G. kobayashii, as well as density-dependent reinfection of the detached gyrodactylids.
OBJECTIVES/GOALS: #NAME? METHODS/STUDY POPULATION: Cell culture & protein identification: human T cells were purified from healthy blood, then activated & cultured for 5d. CAR-T cells were collected from infusion bags of cancer patients undergoing CAR-T. Silver staining of naive & activated healthy T-cell lysates was compared; B-II spectrin was upregulated and confirmed by Western blot. Migration assays: naive & activated T-cells were imaged during migration on ICAM-1 and ICAM-1 + CXCL12 coated plates. T-cells were transfected with BII-spectrin cDNA & the chemokine dependence of migration was compared with controls. In-vivo studies: in a melanoma mouse model, BII-spectrin transfected or control T-cells were injected; tumors were followed with serial imaging. Human patient records were examined to correlate endogenous BII-spectrin levels and CAR-T response. RESULTS/ANTICIPATED RESULTS: Activated T-cells downregulate the cytoskeletal protein B-II spectrin compared to naive cells, leading to chemokine-independent migration in in vitro assays and off-target trafficking when CAR-T cells are given in vivo. Restoration of B-II spectrin levels via transfection restores chemokine-dependence of activated T-cells. In a mouse melanoma model, control mice injected with standard activated T-cells showed fewer cells in the tumor site and more cells in the off-target organs (spleen, lungs) when compared to mice injected with B-II spectrin transfected cells. Furthermore, among 3 human patients undergoing CAR-T therapy, those with higher endogenous B-II spectrin levels experienced fewer side-effects, measured by the neurotoxicity and cytokine release syndrome grades. DISCUSSION/SIGNIFICANCE: A major hurdle to widespread CAR-T therapy for cancer is significant, often fatal side-effects. Our work shows that the protein B-II spectrin is downregulated during CAR-T production, and that restoring B-II spectrin levels decreases side-effects while increasing tumor clearance--hopefully translating to better CAR-T regimens for the future.
There is sparse literature on cardiac arrhythmias and the utility of ambulatory rhythm monitoring in patients with postural tachycardia syndrome and orthostatic intolerance. This study’s primary aim was to investigate the prevalence of arrhythmias in this population. Knowing the prevalence and types of arrhythmias in dysautonomia patients could influence the decision to pursue ambulatory rhythm monitoring and ultimately guide therapy.
This retrospective descriptive study examined the frequency of cardiac arrhythmias, as detected by ambulatory rhythm monitoring, in children with postural tachycardia syndrome/orthostatic intolerance or syncope who were seen at the Children’s National Hospital Electrophysiology Clinic between January 2001 and December 2020.
In postural tachycardia syndrome/orthostatic intolerance patients, arrhythmia was detected on 15% of 332 ambulatory rhythm monitors. In syncope patients, arrhythmia was detected on 16% of 157 ambulatory rhythm monitors, not significantly different from the postural tachycardia syndrome/orthostatic intolerance group. The difference in rate of arrhythmia detection between 24-hour Holter and 2-week Zio® monitoring was not statistically significant.
This study suggests that a substantial proportion of postural tachycardia syndrome/orthostatic intolerance patients may have concomitant underlying cardiac arrhythmias, at a frequency similar to what is seen in patients undergoing primary evaluation for cardiac symptoms such as chest pain, palpitations, and syncope. In the appropriate clinical context, physicians caring for postural tachycardia syndrome/orthostatic intolerance patients should consider additional evaluation for arrhythmias beyond sinus tachycardia.
After updating our health system’s Clostridioides difficile treatment protocols in 2018, we reviewed 104 unique hospital encounters involving fidaxomicin at 10 community hospitals. Half (50%) of regimens were adherent to our guidelines, with infectious diseases (ID) providers were frequently nonadherent. Antimicrobial stewardship programs are important for facilitating best practices, even among ID specialists.
Differences in physical activity (PA) might lead to long-term weight control. Studies on inverse relations between PA and changes in fatness among adolescents are limited. This paper examined the effect of PA on adolescents’ changing body fatness over 5 years in Ho Chi Minh City (HCMC). Two hundred thirty-five boys and 247 girls who have had skinfold thickness measurements in the baseline survey in 2004 were selected to follow yearly. We estimated PA as the average number of accelerometers’ counts/h. Slopes of triceps, sub-scapular skinfolds and BMI were calculated and classified as increasing or stable/decreasing. To assess the effects of the low level of activity (i.e. below the median of the average number of counts) on the fat gain (i.e. increasing slopes), relative risk and 95 % CI were estimated using Poisson regression. The average number of counts/h in boys (7·8) was significantly higher than that in girls (5·0) (P < 0·001). On average, active girls still gained 0·51 mm in triceps skinfold (TSF) over 5 years, while active boys lost 0·12 mm. After controlling for baseline energy intake, baseline triceps and baseline age, inactive adolescents were 1·39 times higher than active ones to increase the slope of triceps (95 % CI 1·19, 1·63). The risk ratio was 1·62 for those with more body fat at baseline. In general, inactive students gained substantially more subcutaneous fat, especially in their TSF, than more active ones. Thus, strategies to prevent adolescent obesity in HCMC should consider the important role of PA to control this problem in adolescents effectively.
Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis’s anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH.
263 individuals were categorized into four groups: HIV− non-cannabis users (n = 65), HIV+ non-cannabis users (n = 105), HIV+ moderate cannabis users (n = 62), and HIV+ daily cannabis users (n = 31). Differences in pro-inflammatory biomarkers (IL-6, MCP-1/CCL2, IP-10/CXCL10, sCD14, sTNFR-II, TNF-α) by study group were determined by Kruskal–Wallis tests. Multivariable linear regressions examined relationships between biomarkers and seven cognitive domains, adjusting for age, sex/gender, race, education, and current CD4 count.
HIV+ daily cannabis users showed lower MCP-1 and IP-10 levels in CSF compared to HIV+ non-cannabis users (p = .015; p = .039) and were similar to HIV− non-cannabis users. Plasma biomarkers showed no differences by cannabis use. Among PWH, lower CSF MCP-1 and lower CSF IP-10 were associated with better learning performance (all ps < .05).
Current daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning which is commonly impaired in PWH. Cannabinoid-related reductions of MCP-1 and IP-10, if confirmed, suggest a role for medicinal cannabis in the mitigation of persistent inflammation and cognitive impacts of HIV.
Previous studies have reported the basic reproduction number (R0) of coronavirus disease from publicly reported data that lack information such as onset of symptoms, presence of importations or known super-spreading events. Using data from the Republic of Korea, we illustrated how estimates of R0 can be biased and provided improved estimates with more detailed data. We used COVID-19 contact trace system in Korea, which can provide symptom onset date and also serial intervals between contacted people. The total R0 was estimated as 2.10 (95% confidence interval (CI) 1.84–2.42). Also, early transmission of COVID-19 differed by regional or social behaviours of the population. Regions affected by a specific church cluster, which showed a rapid and silent transmission under non-official religious meetings, had a higher R0 of 2.40 (95% CI 2.08–2.77).
We assessed long-term incidence and prevalence trends of dementia and parkinsonism across major ethnic and immigrant groups in Ontario.
Linking administrative databases, we established two cohorts (dementia 2001–2014 and parkinsonism 2001–2015) of all residents aged 20 to 100 years with incident diagnosis of dementia (N = 387,937) or parkinsonism (N = 59,617). We calculated age- and sex-standardized incidence and prevalence of dementia and parkinsonism by immigrant status and ethnic groups (Chinese, South Asian, and the General Population). We assessed incidence and prevalence trends using Poisson regression and Cochran–Armitage trend tests.
Across selected ethnic groups, dementia incidence and prevalence were higher in long-term residents than recent or longer-term immigrants from 2001 to 2014. During this period, age- and sex-standardized incidence of dementia in Chinese, South Asian, and the General Population increased, respectively, among longer-term immigrants (by 41%, 58%, and 42%) and long-term residents (28%, 7%, and 4%), and to a lesser degree among recent immigrants. The small number of cases precluded us from assessing parkinsonism incidence trends. For Chinese, South Asian, and the General Population, respectively, prevalence of dementia and parkinsonism modestly increased over time among recent immigrants but significantly increased among longer-term immigrants (dementia: 134%, 217%, and 117%; parkinsonism: 55%, 54%, and 43%) and long-term residents (dementia: 97%, 132%, and 71%; parkinsonism: 18%, 30%, and 29%). Adjustment for pre-existing conditions did not appear to explain incidence trends, except for stroke and coronary artery disease as potential drivers of dementia incidence.
Recent immigrants across major ethnic groups in Ontario had considerably lower rates of dementia and parkinsonism than long-term residents, but this difference diminished with longer-term immigrants.
Clarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems.
The study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse (‘baseline’) and the longitudinal Vietnam Era Twin Study of Aging (‘follow-up’). Depression symptoms were assessed at baseline [mean age 41.42 years (s.d. = 2.34)] using the Diagnostic Interview Schedule, Version III, Revised. The onset of eight cardiometabolic conditions (atrial fibrillation, diabetes, erectile dysfunction, hypercholesterolemia, hypertension, myocardial infarction, sleep apnea, and stroke) was assessed via self-reported doctor diagnosis at follow-up [mean age 67.59 years (s.d. = 2.41)].
Total depression symptoms were longitudinally associated with incident diabetes (OR 1.29, 95% CI 1.07–1.57), erectile dysfunction (OR 1.32, 95% CI 1.10–1.59), hypercholesterolemia (OR 1.26, 95% CI 1.04–1.53), and sleep apnea (OR 1.40, 95% CI 1.13–1.74) over 27 years after controlling for age, alcohol consumption, smoking, body mass index, C-reactive protein, and polygenic risk for specific health conditions. In sensitivity analyses that excluded somatic depression symptoms, only the association with sleep apnea remained significant (OR 1.32, 95% CI 1.09–1.60).
A history of depression symptoms by early midlife is associated with an elevated risk for subsequent development of several self-reported health conditions. When isolated, non-somatic depression symptoms are associated with incident self-reported sleep apnea. Depression symptom history may be a predictor or marker of cardiometabolic risk over decades.
Recently, innovations in ice drilling have yielded considerable improvements to existing drilling techniques, as well as innovative drilling technologies that can be used in new types of applications. However, some specific challenges have to be addressed for improving existing drilling methods and developing new ones: (1) combination and unification of different drilling systems; (2) facilitating ice core breaking; (3) improving existing systems and developing new rapid-access ice drilling systems; (4) reliable elimination of ice hydraulic fracturing problems; (5) developing new environment-friendly methods of drilling in the sub-glacial lake sediments; and (6) design of unconventional ice drilling systems. Possible solutions to these problems are presented herein.
Potential secondary influences on titanium distribution should be evaluated when using ash beds as volcanic source indicators and for correlation purposes. In this study, well-correlated altered ash beds in Permian–Triassic boundary (PTB) successions of various facies in South China were investigated to better understand their use in source discrimination and stratigraphic correlation. The ash beds deposited in lacustrine and paludal facies contain significantly more Ti relative to deposits in marine facies. Neoformed anatase grains nanometres to micrometres in size are associated closely with clay minerals, whereas detrital anatase was observed in the remnants of altered ash beds of terrestrial facies. Extraction of the clay fraction of altered ash beds may exclude significantly detrital accessory minerals such as anatase and rutile added during sediment reworking, and the concentrations of immobile elements in the clay fraction may therefore be used to interpret more effectively their source igneous rocks.
In order to maximize the utility of future studies of trilobite ontogeny, we propose a set of standard practices that relate to the collection, nomenclature, description, depiction, and interpretation of ontogenetic series inferred from articulated specimens belonging to individual species. In some cases, these suggestions may also apply to ontogenetic studies of other fossilized taxa.
The AD 775 peak in Δ14C (henceforth, M12) was first measured by Miyake et al. and has since been confirmed globally. Here we present earlywood and latewood Δ14C values from tree rings of pinyon pine (Pinus edulis) from Mummy Cave, Canyon de Chelly National Monument, Chinle, Arizona, USA, for the period AD 770–780. These data reconfirm the timing of M12 and show a small rise in Δ14C in AD 774 latewood. Allowing for the delay in lateral transfer of radiocarbon produced at high latitude, this suggests that 14C peak production occurred in late winter or spring of AD 774. Additionally, Δ14C decreased slightly in the earlywood of AD 775 and increased in the latewood of AD 775 to a higher level than that observed in AD 774.
Background: As carbapenem-resistant Enterobacteriaceae (CRE) prevalence increases in the United States, the risk of cocolonization with multiple CRE may also be increasing, with unknown clinical and epidemiological significance. In this study, we aimed to describe the epidemiologic and microbiologic characteristics of inpatients cocolonized with multiple CRE. Methods: We conducted a secondary analysis of a large, multicenter prospective cohort study evaluating risk factors for CRE transmission to healthcare personnel gown and gloves. Patients were identified between January 2016 and June 2019 from 4 states. Patients enrolled in the study had a clinical or surveillance culture positive for CRE within 7 days of enrollment. We collected and cultured samples from the following sites from each CRE-colonized patient: stool, perianal area, and skin. A modified carbapenem inactivation method (mCIM) was used to detect the presence or absence of carbapenemase(s). EDTA-modified CIM (eCIM) was used to differentiate between serine and metal-dependent carbapenemases. Results: Of the 313 CRE-colonized patients enrolled in the study, 28 (8.9%) were cocolonized with at least 2 different CRE. Additionally, 3 patients were cocolonized with >2 different CRE (1.0%). Of the 28 patients, 19 (67.6%) were enrolled with positive clinical cultures. Table 1 summarizes the demographic and clinical characteristics of these patients. The most frequently used antibiotic prior to positive culture was vancomycin (n = 33, 18.3%). Among the 62 isolates from 59 samples from 28 patients cocolonized patients, the most common CRE species were Klebsiella pneumoniae (n = 18, 29.0%), Escherichia coli (n = 10, 16.1%), and Enterobacter cloacae (n = 9, 14.5%). Of the 62 isolates, 38 (61.3%) were mCIM positive and 8 (12.9%) were eCIM positive. Of the 38 mCIM-positive isolates, 33 (86.8%) were KPC positive, 4 (10.5%) were NDM positive, and 1 (2.6%) was negative for both KPC and NDM. Also, 2 E. coli, 1 K. pneumoniae, and 1 E. cloacae were NDM-producing CRE. Conclusion: Cocolonization with multiple CRE occurs frequently in the acute-care setting. Characterizing patients with CRE cocolonization may be important to informing infection control practices and interventions to limit the spread of these organisms, but further study is needed.