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Neurobiology of Stress Jul 2024High stress is a key risk factor for alcohol use disorder (AUD) and often accompanied by physiological dysregulation including autonomic nervous system (ANS)...
High stress is a key risk factor for alcohol use disorder (AUD) and often accompanied by physiological dysregulation including autonomic nervous system (ANS) disruptions. However, neural mechanisms underlying drinking behaviors associated with stress and ANS disruptions remain unclear. The current study aims to understand neural correlates of stress, ANS disruptions, and subsequent alcohol intake in social drinkers with risky drinking. Using functional magnetic resonance imaging (fMRI), we investigated brain and heart rate (HR) autonomic responses during brief exposure to stress, alcohol, and neutral cues utilizing a well-validated, individualized imagery paradigm in 48 social drinkers of which 26 reported high-risk drinking (HD) while 22 reported low-risk drinking (LD) patterns. Results indicated that HD individuals showed stress and ANS disruptions with increased basal HR, stress-induced craving, and decreased brain response to stress exposure in frontal-striatal regions including the ventromedial prefrontal cortex (VmPFC), anterior cingulate cortex, striatum, insula, and temporal gyrus. Furthermore, whole-brain correlation analysis indicated that greater basal HR was associated with hypoactive VmPFC, but hyperactive medulla oblongata (MOb) responses during stress, with an inverse association between activity in the VmPFC and Mob (whole-brain corrected (WBC), p < 0.05). Functional connectivity with the MOb as a seed to the whole brain indicated that HD versus LD had decreased functional connectivity between the VmPFC and MOb during stress (WBC, p < 0.05). In addition, those with more compromised functional connectivity between the VmPFC and MOb during stress consumed greater amount of alcohol beverage during an experimental alcohol taste test conducted on a separate day, as well as in their self-reported weekly alcohol intake. Together, these results indicate that stress-related, dysfunctional VmPFC control over brain regions of autonomic arousal contributes to greater alcohol motivation and may be a significant risk factor for hazardous alcohol use in non-dependent social drinkers. Findings also suggest that restoring VmPFC integrity in modulating autonomic arousal during stress may be critical for preventing the development of AUD.
PubMed: 38933283
DOI: 10.1016/j.ynstr.2024.100645 -
Acta Endocrinologica (Bucharest,... 2023This study aimed to determine predictive clinical and endoscopic ultrasound (EUS) features for pancreatic neuroendocrine tumor (PNET) diagnosis, utilizing EUS-guided...
BACKGROUND
This study aimed to determine predictive clinical and endoscopic ultrasound (EUS) features for pancreatic neuroendocrine tumor (PNET) diagnosis, utilizing EUS-guided tissue acquisition.
METHODS
A prospective study from 2018-2022 included patients with pancreatic masses undergoing EUS with elastography. Univariate binomial logistic regression followed by multiple logistic regression with significant predictors was employed. A forward selection algorithm identified optimal models based on predictor numbers. Variables encompassed EUS tumor characteristics (e.g., location, size, margins, echogenicity, vascularity on Doppler, main pancreatic duct dilation, elastography appearance, vascular invasion, and hypoechoic rim), alongside demographic and risk factors (smoking, alcohol, diabetes).
RESULTS
We evaluated 165 patients (24 PNETs). EUS features significantly linked with PNET diagnosis were well-defined margins (79% . 26%, p < 0.001), blue elastography appearance (46% . 9.9%, p < 0.001), vascularization (67% . 25%, p < 0.001), hypoechoic rim (46% . 10%, p < 0.001). The top-performing model, with 89.1% accuracy, included two predictors: a homogeneous lesion (OR, 95% CI) and a hypoechoic rim (OR, 95% CI).
CONCLUSIONS
EUS appearance can differentiate PNETs from non-PNETs, with the hypoechoic rim being an independent predictor of PNET diagnosis. The most effective predictive model for PNETs combined the homogeneous lesion and presence of the hypoechoic rim.
PubMed: 38933251
DOI: 10.4183/aeb.2023.407 -
Frontiers in Public Health 2024There are various detrimental effects of excessive added sugar consumption on health, but the association of added sugars with frailty remains elusive. We aimed to...
OBJECTIVE
There are various detrimental effects of excessive added sugar consumption on health, but the association of added sugars with frailty remains elusive. We aimed to examine the association between added sugar intake and frailty among American adults in the present cross-sectional study.
METHODS
This cross-sectional study is based on the National Health and Nutrition Examination Survey (NHANES) database. Data from NHANES spanning from 2007 to 2018 on frailty, added sugars, and covariates were collected. Added sugars were categorized into quartiles according to the recommended percentages by institutions. Weighted multivariable logistic regression was used to analyze the relationship between frailty and added sugars. Subgroup analysis was conducted based on sex, age, body mass index (BMI), smoking, alcohol consumption, hypertension, and diabetes status.
RESULTS
This study included 16,381 participants, with 13,352 (81.51%) in the non-frailty group and 3,029 (18.49%) in the frailty group. We found that added sugars were positively associated with frailty, and subgroup analysis showed that participants who were male, over the age of 60, had a low BMI, had previously smoked and consumed alcohol, had no hypertension, or had diabetes mellitus (DM) were more likely to be frail. Added sugar intake was positively associated with frailty. Subgroup analysis showed that the association was strongest in males, those aged >60, those with a low BMI, former smokers, former alcohol consumers, and people with no hypertension or DM. When added sugars are classified by energy percentage, populations with more than 25% of their energy coming from added sugars have similar results, with a higher prevalence of frailty.
CONCLUSION
Added sugars are positively associated with a higher risk of frailty, and the association is stable among different populations.
Topics: Humans; Male; Cross-Sectional Studies; Female; Nutrition Surveys; Middle Aged; Frailty; United States; Adult; Aged; Body Mass Index; Risk Factors
PubMed: 38932782
DOI: 10.3389/fpubh.2024.1403409 -
Environment & Health (Washington, D.C.) Jun 2024A healthy lifestyle has been associated with decreased risk of developing breast cancer. Using untargeted metabolomics profiling, which provides unbiased information...
A healthy lifestyle has been associated with decreased risk of developing breast cancer. Using untargeted metabolomics profiling, which provides unbiased information regarding lifestyle choices such as diet and exercise, we aim to identify the molecular mechanisms connecting lifestyle and breast cancer through network analysis. A total of 100 postmenopausal women, 50 with breast cancer and 50 cancer-free controls, were selected from the Long Island Breast Cancer Study Project (LIBCSP). We measured untargeted plasma metabolomics using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Using the "enet" package, we retained highly correlated metabolites representing active molecular network (AMN) clusters for analysis. LASSO was used to examine associations between cancer status and AMN metabolites and covariates such as BMI, age, and reproductive factors. LASSO was then repeated to examine associations between AMN metabolites and 10 lifestyle-related variables including smoking, physical activity, alcohol consumption, meat consumption, fruit and vegetable consumption, and supplemental vitamin use. Results were displayed as a network to uncover biological pathways linking lifestyle factors to breast cancer status. After filtering, 851 "active" metabolites out of 1797 metabolomics were retained in 197 correlation AMN clusters. Using LASSO, breast cancer status was associated with 71 "active" metabolites. Several of these metabolites were associated with lifestyle variables including meat consumption, alcohol consumption, and supplemental β-carotene, B12, and folate use. Those metabolites could potentially serve as molecular-level biological intermediaries connecting healthy lifestyle factors to breast cancer, even though direct associations between breast cancer and the investigated lifestyles at the phenotype level are not evident. In particular, DiHODE, a metabolite linked with inflammation, was associated with breast cancer status and connected to β-carotene supplement usage through an AMN. We found several plasma metabolites associated with lifestyle factors and breast cancer status. Future studies investigating the mechanistic role of inflammation in linking supplement usage to breast cancer status are warranted.
PubMed: 38932753
DOI: 10.1021/envhealth.3c00218 -
Viruses Jun 2024C-terminal binding protein (CtBP), a transcriptional co-repressor, significantly influences cellular signaling, impacting various biological processes including cell... (Review)
Review
C-terminal binding protein (CtBP), a transcriptional co-repressor, significantly influences cellular signaling, impacting various biological processes including cell proliferation, differentiation, apoptosis, and immune responses. The CtBP family comprises two highly conserved proteins, CtBP1 and CtBP2, which have been shown to play critical roles in both tumorigenesis and the regulation of viral infections. Elevated CtBP expression is noted in various tumor tissues, promoting tumorigenesis, invasiveness, and metastasis through multiple pathways. Additionally, CtBP's role in viral infections varies, exhibiting differing or even opposing effects depending on the virus. This review synthesizes the advances in CtBP's function research in viral infections and virus-associated tumorigenesis, offering new insights into potential antiviral and anticancer strategies.
Topics: Humans; Carcinogenesis; Virus Diseases; Alcohol Oxidoreductases; DNA-Binding Proteins; Animals; Neoplasms
PubMed: 38932279
DOI: 10.3390/v16060988 -
Viruses Jun 2024Illicit drug and alcohol abuse have significant negative consequences for individuals who inject drugs/use drugs (PWID/UDs), including decreased immune system function... (Review)
Review
Illicit drug and alcohol abuse have significant negative consequences for individuals who inject drugs/use drugs (PWID/UDs), including decreased immune system function and increased viral pathogenesis. PWID/UDs are at high risk of contracting or transmitting viral illnesses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). In South Africa, a dangerous drug-taking method known as "Bluetoothing" has emerged among nyaope users, whereby the users of this drug, after injecting, withdraw blood from their veins and then reinject it into another user. Hence, the transmission of blood-borne viruses (BBVs) is exacerbated by this "Bluetooth" practice among nyaope users. Moreover, several substances of abuse promote HIV, HBV, and HCV replication. With a specific focus on the nyaope drug, viral replication, and transmission, we address the important influence of abused addictive substances and polysubstance use in this review.
Topics: Humans; Substance-Related Disorders; South Africa; Hepatitis C; Hepatitis B; HIV Infections; Virus Replication; Illicit Drugs; Hepatitis B virus; Virus Diseases; Blood-Borne Infections; Hepacivirus; Substance Abuse, Intravenous
PubMed: 38932263
DOI: 10.3390/v16060971 -
Viruses Jun 2024Hepatitis C (HCV) reinfection studies have not focused on primary healthcare services in Australia, where priority populations including people who inject drugs (PWID)...
Hepatitis C (HCV) reinfection studies have not focused on primary healthcare services in Australia, where priority populations including people who inject drugs (PWID) typically engage in healthcare. We aimed to describe the incidence of HCV reinfection and associated risk factors in a cohort of people most at risk of reinfection in a real-world community setting. We conducted a secondary analysis of routinely collected HCV testing and treatment data from treatment episodes initiated with direct-acting antiviral (DAA) therapy between October 2015 and June 2021. The overall proportion of clients (N = 413) reinfected was 9% (N = 37), and the overall incidence rate of HCV reinfection was 9.5/100PY (95% CI: 6.3-14.3). Reinfection incidence rates varied by sub-group and were highest for Aboriginal and/or Torres Strait Islander people (20.4/100PY; 95% CI: 12.1-34.4). Among PWID (N= 321), only Aboriginality was significantly associated with reinfection (AOR: 2.73, 95% CI: 1.33-5.60, = 0.006). High rates of HCV reinfection in populations with multiple vulnerabilities and continued drug use, especially among Aboriginal and Torres Strait Islander people, highlight the need for ongoing regular HCV testing and retreatment in order to achieve HCV elimination. A priority is resourcing testing and treatment for Aboriginal and/or Torres Strait Islander people. Our findings support the need for novel and holistic healthcare strategies for PWID and the upscaling of Indigenous cultural approaches and interventions.
Topics: Humans; Male; Female; Risk Factors; Adult; Substance Abuse, Intravenous; Hepatitis C; Australia; Reinfection; Primary Health Care; Middle Aged; Incidence; Antiviral Agents; Hepacivirus; Native Hawaiian or Other Pacific Islander; Young Adult
PubMed: 38932249
DOI: 10.3390/v16060957 -
Viruses Jun 2024The thermostability of vaccines, particularly enveloped viral vectored vaccines, remains a challenge to their delivery wherever needed. The freeze-drying of viral...
The thermostability of vaccines, particularly enveloped viral vectored vaccines, remains a challenge to their delivery wherever needed. The freeze-drying of viral vectored vaccines is a promising approach but remains challenging due to the water removal process from the outer and inner parts of the virus. In the case of enveloped viruses, freeze-drying induces increased stress on the envelope, which often leads to the inactivation of the virus. In this study, we designed a method to freeze-dry a recombinant vesicular stomatitis virus (VSV) expressing the SARS-CoV-2 spike glycoprotein. Since the envelope of VSV is composed of 50% lipids and 50% protein, the formulation study focused on both the protein and lipid portions of the vector. Formulations were prepared primarily using sucrose, trehalose, and sorbitol as cryoprotectants; mannitol as a lyoprotectant; and histidine as a buffer. Initially, the infectivity of rVSV-SARS-CoV-2 and the cake stability were investigated at different final moisture content levels. High recovery of the infectious viral titer (~0.5 to 1 log loss) was found at 3-6% moisture content, with no deterioration in the freeze-dried cakes. To further minimize infectious viral titer loss, the composition and concentration of the excipients were studied. An increase from 5 to 10% in both the cryoprotectants and lyoprotectant, together with the addition of 0.5% gelatin, resulted in the improved recovery of the infectious virus titer and stable cake formation. Moreover, the secondary drying temperature of the freeze-drying process showed a significant impact on the infectivity of rVSV-SARS-CoV-2. The infectivity of the vector declined drastically when the temperature was raised above 20 °C. Throughout a long-term stability study, formulations containing 10% sugar (sucrose/trehalose), 10% mannitol, 0.5% gelatin, and 10 mM histidine showed satisfactory stability for six months at 2-8 °C. The development of this freeze-drying process and the optimized formulation minimize the need for a costly cold chain distribution system.
Topics: Freeze Drying; SARS-CoV-2; COVID-19 Vaccines; Spike Glycoprotein, Coronavirus; Cryoprotective Agents; Trehalose; COVID-19; Animals; Humans; Mannitol; Sucrose; Vero Cells; Chlorocebus aethiops; Sorbitol; Drug Stability; Histidine; Vesicular stomatitis Indiana virus; Vaccines, Synthetic
PubMed: 38932234
DOI: 10.3390/v16060942 -
Polymers Jun 2024In this study, seven Engineering Geopolymer Composite (EGC) groups with varying proportions were prepared. Rheological, compressive, flexural, and axial tensile tests of...
In this study, seven Engineering Geopolymer Composite (EGC) groups with varying proportions were prepared. Rheological, compressive, flexural, and axial tensile tests of the EGC were conducted to study the effects of the water/binder ratio, the cement/sand ratio, and fiber type on its properties. Additionally, a uniaxial tension constitutive model was established. The results indicate that the EGC exhibits early strength characteristics, with the 7-day compressive strength reaching 80% to 92% of the 28-day compressive strength. The EGC demonstrates high compressive strength and tensile ductility, achieving up to 70 MPa and 4%, respectively. The mechanical properties of the EGC improved with an increase in the sand/binder ratio and decreased with an increase in the water/binder ratio. The stress-strain curve of the EGC resembles that of the ECC, displaying a strain-hardening state that can be divided into two stages: before cracking, the matrix primarily bears the stress; after cracking, the slope decreases, and the fiber predominantly bears the stress.
PubMed: 38932035
DOI: 10.3390/polym16121685 -
Polymers Jun 2024Gel plugging agents have become one of the preferred methods for plugging in complex and severe loss conditions during drilling due to their good adaptability to loss...
Gel plugging agents have become one of the preferred methods for plugging in complex and severe loss conditions during drilling due to their good adaptability to loss channels. To address the common issue of poor temperature resistance in gel-based plugging agents, high-temperature-resistant gel plugging materials were synthesized through the molecular design of polymers, modifying existing agents. Based on the temperature and salt resistance of the aqueous solution of an acrylamide (AM)/N-vinylpyrrolidone (NVP) binary copolymer, temperature-resistant monomer sodium styrene sulfonate (SSS) was introduced and reacted in a polyvinyl alcohol (PVA) aqueous solution. Using ammonium persulfate (APS) as an initiator and crosslinking with N,N-methylenebisacrylamide (MBA), a gel plugging material resistant to 140 °C was synthesized. The structure, thermal stability, water absorption and expansion, and plugging performance of the gel were studied through hot rolling aging, thermogravimetric analysis, infrared spectroscopy, electron microscopy scanning, sand bed experiments, and drag reduction experiments. The results show that the gel material has good thermal stability and water absorption and expansion at 140 °C, and its temperature-resistant plugging performance is excellent, significantly slowing down the loss rate of drilling fluid. This provides a basis for the further development of gel materials.
PubMed: 38932007
DOI: 10.3390/polym16121658