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Diagnostics (Basel, Switzerland) May 2024While depression can be associated with multiple comorbidities, the association between depression and liver injury significantly increases the mortality risk. The aim...
BACKGROUND
While depression can be associated with multiple comorbidities, the association between depression and liver injury significantly increases the mortality risk. The aim of this study was to evaluate if moderate alcohol intake affects the rate of clinical relapses in patients treated with antidepressants as monotherapy.
METHODS
We assessed, over a period of 30 months, the clinical records of 254 patients with depressive disorder, of either gender, without additional pathologies, receiving monotherapy treatment with antidepressants. Thirty-three patients with alcohol abuse, alcoholism or significant cognitive impairment were excluded. The medical and psychiatric history, medication and liver enzyme values were collected and analyzed.
RESULTS
Out of the 221 patients who met the inclusion criteria, 78 experienced relapses of depression. The rate of relapse did not correlate with the levels of liver enzymes. Alcohol consumption, as objectified based on GGT levels and the AST/ALT ratio, suggested that men had higher alcohol intake compared to women. Patients treated with serotonin-norepinephrine reuptake inhibitors (SNRIs) with elevated AST levels were approximately 9 times more likely to relapse, while the ones with elevated GGT had a 5.34 times higher risk. While GGT levels remained a marker for relapse in men with elevated GGT, ALT and not AST proved to be a better risk indicator for relapses in male patients.
CONCLUSION
The use of SNRIs in depressed male patients with moderate alcohol intake should be carefully considered, as they might be susceptible to higher risks of relapse compared to alternative antidepressant therapies.
PubMed: 38893667
DOI: 10.3390/diagnostics14111140 -
Cells Jun 2024Binge drinking in obese patients positively correlates with accelerated liver damage and liver-related death. However, the underlying mechanism and the effect of alcohol...
Binge drinking in obese patients positively correlates with accelerated liver damage and liver-related death. However, the underlying mechanism and the effect of alcohol use on the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD) remain unexplored. Here, we show that short-term feeding of a metabolic-dysfunction-associated steatohepatitis (MASH) diet plus daily acute alcohol binges for three days induce liver injury and activation of the NLRP3 inflammasome. We identify that a MASH diet plus acute alcohol binges promote liver inflammation via increased infiltration of monocyte-derived macrophages, neutrophil recruitment, and NET release in the liver. Our results suggest that both monocyte-derived macrophages and neutrophils are activated via NLRP3, while the administration of MCC950, an NLRP3 inhibitor, dampens these effects.In this study, we reveal important intercellular communication between hepatocytes and neutrophils. We discover that the MASH diet plus alcohol induces IL-1β via NLRP3 activation and that IL-1β acts on hepatocytes and promotes the production of CXCL1 and LCN2. In turn, the increase in these neutrophils recruits chemokines and causes further infiltration and activation of neutrophils in the liver. In vivo administration of the NLRP3 inhibitor, MCC950, improves the early phase of MetALD by preventing liver damage, steatosis, inflammation, and immune cells recruitment.
Topics: NLR Family, Pyrin Domain-Containing 3 Protein; Animals; Liver; Interleukin-1beta; Neutrophil Infiltration; Male; Neutrophils; Mice, Inbred C57BL; Mice; Inflammasomes; Binge Drinking; Hepatocytes; Cell Communication; Sulfones; Sulfonamides; Macrophages; Furans; Humans; Indenes; Diet; Signal Transduction; Extracellular Traps; Fatty Liver; Sulfoxides
PubMed: 38891092
DOI: 10.3390/cells13110960 -
Cells May 2024Mitochondrial aldehyde dehydrogenase-2 (ALDH2) metabolizes acetaldehyde to acetate. People with ALDH2 deficiency and -knockout (KO) mice are more susceptible to...
Mitochondrial aldehyde dehydrogenase-2 (ALDH2) metabolizes acetaldehyde to acetate. People with ALDH2 deficiency and -knockout (KO) mice are more susceptible to alcohol-induced tissue damage. However, the underlying mechanisms behind ALDH2-related gut-associated brain damage remain unclear. Age-matched young female -KO and C57BL/6J wild-type (WT) mice were gavaged with binge alcohol (4 g/kg/dose, three doses) or dextrose (control) at 12 h intervals. Tissues and sera were collected 1 h after the last ethanol dose and evaluated by histological and biochemical analyses of the gut and hippocampus and their extracts. For the mechanistic study, mouse neuroblast Neuro2A cells were exposed to ethanol with or without an Aldh2 inhibitor (Daidzin). Binge alcohol decreased intestinal tight/adherens junction proteins but increased oxidative stress-mediated post-translational modifications (PTMs) and enterocyte apoptosis, leading to elevated gut leakiness and endotoxemia in -KO mice compared to corresponding WT mice. Alcohol-exposed -KO mice also showed higher levels of hippocampal brain injury, oxidative stress-related PTMs, and neuronal apoptosis than the WT mice. Additionally, alcohol exposure reduced Neuro2A cell viability with elevated oxidative stress-related PTMs and apoptosis, all of which were exacerbated by Aldh2 inhibition. Our results show for the first time that ALDH2 plays a protective role in binge alcohol-induced brain injury partly through the gut-brain axis, suggesting that ALDH2 is a potential target for attenuating alcohol-induced tissue injury.
Topics: Animals; Aldehyde Dehydrogenase, Mitochondrial; Mice, Knockout; Mice; Mice, Inbred C57BL; Binge Drinking; Brain Injuries; Ethanol; Female; Apoptosis; Oxidative Stress; Hippocampus; Mitochondria
PubMed: 38891060
DOI: 10.3390/cells13110927 -
Nature Communications Jun 2024
PubMed: 38890337
DOI: 10.1038/s41467-024-49655-6 -
Biochimica Et Biophysica Acta. Reviews... Jun 2024Head and neck cancer (HNSCC) is the 8th most common cancer in the UK, with incidence increasing due to lifestyle factors such as tobacco and alcohol abuse. HNSCC is an... (Review)
Review
Head and neck cancer (HNSCC) is the 8th most common cancer in the UK, with incidence increasing due to lifestyle factors such as tobacco and alcohol abuse. HNSCC is an immune-suppressive disease characterised by impaired cytokine secretion and dysregulation of immune infiltrate. As such, immunotherapy is a potential treatment option, with therapeutic cancer vaccination demonstrating the greatest potential. The success of cancer vaccination is dependent on informed antigen selection: an ideal antigen must be either tumour-specific or tumour-associated, as well as highly immunogenic. Stratification of the patient population for antigen expression and validated biomarkers are also vital. This review focuses on the latest developments in immunotherapy, specifically the development of therapeutic vaccines, and highlights successes, potential drawbacks and areas for future development. Immunotherapy approaches considered for HNSCC include monoclonal antibodies (mAb), Oncolytic viral (OV) therapies, Immune Checkpoint Inhibitors (ICIs) and cancer vaccines.
PubMed: 38889878
DOI: 10.1016/j.bbcan.2024.189138 -
PloS One 2024Infant regulatory problems are a common source of concern for parents, and they increase the risk of impaired infant-caregiver bonding. Despite their impact, they are...
INTRODUCTION
Infant regulatory problems are a common source of concern for parents, and they increase the risk of impaired infant-caregiver bonding. Despite their impact, they are often overlooked in Ethiopia. Hence, this study aimed to determine the prevalence and associated factors of infant regulatory problems in Arba Minch Health and Demographic Surveillance System sites in southern Ethiopia.
METHODS
A community-based cross-sectional study was conducted among 451 mother-infant pairs from February 15 to March 15, 2022. Regulatory problems were assessed using diagnostic interviews for regulatory problems. The data was collected using an open data kit Android application and analyzed with Stata version 17.0. Bivariable and multivariable logistic regression analyses were computed to identify factors associated with each infant regulatory problem. Statistical significance was declared at a p-value < 0.05.
RESULTS
In this study, four hundred forty-nine mother-infant pairs were involved, with a response rate of 99.5%. The prevalence of excessive crying, feeding problems, and sleeping difficulties was 14.03% [95% CI: 10.95, 17.59], 20.04% [95% CI: 16.44, 24.05], and 13.59% [95% CI: 10.55, 17.11], respectively. Attending primary education (AOR: 2.54, 95% CI: 1.22, 5.32), high perceived social support (AOR: 0.32, 95% CI: 0.12, 0.89), feeding problems (AOR: 5.0, 95% CI: 2.65, 9.45), and depression, anxiety, and stress (DAS) symptoms (AOR: 2.67, 95% CI: 1.19, 5.98) were associated with excessive crying. In addition, a family size of above five (AOR: 1.82, 95% CI: 1.03, 3.22), excessive crying (AOR: 3.76, 95% CI: 1.85, 7.65), sleeping problems (AOR: 2.29, 95% CI: 1.13, 4.65), comorbid DAS symptoms (AOR: 3.42, 95% CI: 1.64, 7.11), alcohol abuse (AOR: 1.89, 95% CI: 1.04, 3.42), and late initiation of complementary feeding (AOR: 2.67, 95% CI: 1.22, 5.88) were associated with feeding problems. Furthermore, attending primary education (AOR: 2.35, 95% CI: 1.16, 4.77), feeding problems (AOR: 3.47, 95% CI: 1.86, 6.48), and comorbid DAS symptoms (AOR: 3.23, 95% CI: 1.53, 6.84) were associated with sleeping problems.
CONCLUSIONS
Approximately one-third of infants encountered at least one regulatory problem. Level of education, perceived social support, feeding problems, and DAS symptoms were associated with excessive crying. Large family sizes, excessive crying, sleeping problems, comorbid DAS symptoms, alcohol abuse and, late initiation of complementary feeding increase the likelihood of feeding problems. Moreover, attending primary education, feeding problems, and comorbid DAS symptoms increase the odds of sleeping problems. Continuous guidance and support on infant soothing techniques, cognitive and behavioral therapy, and counselling on appropriate coping strategies for postpartum women are imperative to reduce the burden of infant regulatory problems.
Topics: Humans; Ethiopia; Female; Infant; Male; Cross-Sectional Studies; Adult; Prevalence; Mothers; Young Adult; Mother-Child Relations; Infant, Newborn; Adolescent
PubMed: 38889163
DOI: 10.1371/journal.pone.0305722 -
JAMA Psychiatry Jun 2024Observational studies suggest that major psychiatric disorders and substance use behaviors reduce longevity, making it difficult to disentangle their relationships with...
IMPORTANCE
Observational studies suggest that major psychiatric disorders and substance use behaviors reduce longevity, making it difficult to disentangle their relationships with aging-related outcomes.
OBJECTIVE
To evaluate the associations between the genetic liabilities for major psychiatric disorders, substance use behaviors (smoking and alcohol consumption), and longevity.
DESIGN, SETTINGS, AND PARTICIPANTS
This 2-sample mendelian randomization (MR) study assessed associations between psychiatric disorders, substance use behaviors, and longevity using single-variable and multivariable models. Multiomics analyses were performed elucidating transcriptomic underpinnings of the MR associations and identifying potential proteomic therapeutic targets. This study sourced summary-level genome-wide association study (GWAS) data, gene expression, and proteomic data from cohorts of European ancestry. Analyses were performed from May 2022 to November 2023.
EXPOSURES
Genetic susceptibility for major depression (n = 500 199), bipolar disorder (n = 413 466), schizophrenia (n = 127 906), problematic alcohol use (n = 435 563), weekly alcohol consumption (n = 666 978), and lifetime smoking index (n = 462 690).
MAIN OUTCOMES AND MEASURES
The main outcome encompassed aspects of health span, lifespan, and exceptional longevity. Additional outcomes were epigenetic age acceleration (EAA) clocks.
RESULTS
Findings from multivariable MR models simultaneously assessing psychiatric disorders and substance use behaviorsm suggest a negative association between smoking and longevity in cohorts of European ancestry (n = 709 709; 431 503 [60.8%] female; β, -0.33; 95% CI, -0.38 to -0.28; P = 4.59 × 10-34) and with increased EAA (n = 34 449; 18 017 [52.3%] female; eg, PhenoAge: β, 1.76; 95% CI, 0.72 to 2.79; P = 8.83 × 10-4). Transcriptomic imputation and colocalization identified 249 genes associated with smoking, including 36 novel genes not captured by the original smoking GWAS. Enriched pathways included chromatin remodeling and telomere assembly and maintenance. The transcriptome-wide signature of smoking was inversely associated with longevity, and estimates of individual smoking-associated genes, eg, XRCC3 and PRMT6, aligned with the smoking-longevity MR analyses, suggesting underlying transcriptomic mediators. Cis-instrument MR prioritized brain proteins associated with smoking behavior, including LY6H (β, 0.02; 95% CI, 0.01 to 0.03; P = 2.37 × 10-6) and RIT2 (β, 0.02; 95% CI, 0.01 to 0.03; P = 1.05 × 10-5), which had favorable adverse-effect profiles across 367 traits evaluated in phenome-wide MR.
CONCLUSIONS
The findings suggest that the genetic liability of smoking, but not of psychiatric disorders, is associated with longevity. Transcriptomic associations offer insights into smoking-related pathways, and identified proteomic targets may inform therapeutic development for smoking cessation strategies.
PubMed: 38888899
DOI: 10.1001/jamapsychiatry.2024.1429 -
JMIR Mental Health Jun 2024For people experiencing substance use or gambling disorders, web-based peer-supported forums are a space where they can share their experiences, gather around a... (Review)
Review
BACKGROUND
For people experiencing substance use or gambling disorders, web-based peer-supported forums are a space where they can share their experiences, gather around a collective goal, and find mutual support. Web-based peer support can help to overcome barriers to attending face-to-face meetings by enabling people experiencing addiction to seek support beyond their physical location and with the benefit of anonymity if desired. Understanding who participates in web-based peer-supported forums (and how), and the principles underpinning forums, can also assist those interested in designing or implementing similar platforms.
OBJECTIVE
This study aims to review the literature on how people experiencing substance use or gambling disorders, and their family, friends, and supporters, use and participate in web-based peer-supported forums. Specifically, we asked the following research questions: (1) What are the characteristics of people who use web-based peer-supported substance use or gambling-focused forums? (2) How do people participate in web-based peer-supported forums? (3) What are the key principles reportedly underpinning the web-based peer-supported forums? (4) What are the reported outcomes of web-based peer-supported forums?
METHODS
Inclusion criteria for our scoping review were peer-reviewed primary studies reporting on web-based addiction forums for adults and available in English. A primary search of 10 databases occurred in June 2021, with 2 subsequent citation searches of included studies in September 2022 and February 2024.
RESULTS
Of the 14 included studies, the majority of web-based peer-supported forums reported were aimed specifically for, or largely used by, people experiencing alcohol problems. Results from the 9 studies that did report demographic data suggest forum users were typically women, aged between 40 years and early 50 years. Participation in web-based peer-supported forums was reported quantitatively and qualitatively. The forums reportedly were underpinned by a range of key principles, mostly mutual help approaches and recovery identity formation. Only 3 included studies reported on outcomes for forum users.
CONCLUSIONS
Web-based peer-supported forums are used by people experiencing addiction in a number of ways, to share information and experiences, and give and receive support. Seeking web-based support offers an alternative approach to traditional face-to-face support options, and may reduce some barriers to engaging in peer support.
Topics: Humans; Substance-Related Disorders; Gambling; Peer Group; Internet; Social Support
PubMed: 38885012
DOI: 10.2196/49010 -
Frontiers in Psychiatry 2023Altered immune and inflammatory responses resulting from alcohol abuse have been implicated in increasing the risk of autoimmune connective tissue disease (ACTD)....
OBJECTIVES
Altered immune and inflammatory responses resulting from alcohol abuse have been implicated in increasing the risk of autoimmune connective tissue disease (ACTD). However, limited research has been conducted on this topic in the Asian population. Therefore, this study was undertaken to investigate and address this knowledge gap.
METHODS
Using data from Taiwan's National Health Insurance Research Database, we identified all patients with alcohol abuse between 2000 and 2017. We selected a comparison cohort without alcohol abuse, matching them in terms of age, sex, and index date at a 3:1 ratio. We collected information on common underlying comorbidities for analysis. Both cohorts were followed up until the diagnosis of ACTD or the end of 2018.
RESULTS
A total of 57,154 patients with alcohol abuse and 171,462 patients without alcohol abuse were included in the study. The age and sex distributions were similar in both cohorts, with men accounting for 89.8% of the total. After adjusting for underlying comorbidities, patients with alcohol abuse had a higher risk of developing ACTD [adjusted hazard ratio (AHR): 1.12, 95% confidence interval (CI): 1.01-1.25]. The stratified analysis revealed that this increased risk was specific to the male population. Additionally, besides alcohol abuse, liver disease, renal disease, coronary artery disease, and chronic obstructive pulmonary disease were identified as independent predictors for ACTD.
CONCLUSION
This study demonstrates that alcohol abuse increases the risk of developing ACTD in the Asian population, particularly among men. Therefore, it is important to implement alcohol cessation, especially in individuals with liver disease, renal disease, coronary artery disease, and chronic obstructive pulmonary disease.
PubMed: 38883846
DOI: 10.3389/fpsyt.2023.1308245 -
American Journal of Translational... 2024To determine the efficacy and safety of traditional Chinese medicine (TCM) external scalding therapy on spleen-stomach deficiency cold stomachache.
OBJECTIVE
To determine the efficacy and safety of traditional Chinese medicine (TCM) external scalding therapy on spleen-stomach deficiency cold stomachache.
METHODS
The medical records of 98 patients with spleen-stomach deficiency cold stomachache treated in the Affiliated Hospital of Jiangnan University from January 2019 to January 2020 were collected and analyzed retrospectively. Among them, 52 patients treated with western medicine were assigned to the control group, while the other 46 patients treated additionally with TCM external scalding therapy were assigned to the observation group. The two groups were compared in terms of serum gastrin (GAS), inflammatory factors and visual analogue scale (VAS) score, adverse reaction rate and symptom remission time.
RESULTS
After treatment, the observation group showed a significantly lower GAS level than the control group (P<0.05), along with significantly lower serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) than the control group (all P<0.05). The observation group demonstrated significantly lower VAS score than the control group (P<0.05). The observation group experienced notably shorter remission time of dull epigastric pain, epigastric distension, fatigue and belching and acid reflux than the control group (all P<0.05), and a significantly lower incidence of adverse reactions was found in the observation group than that in the control group (P<0.05). Multivariate analysis revealed that history of alcoholism and treatment method were independent risk factors affecting patient outcomes (all P<0.05).
CONCLUSION
TCM external scalding therapy has shown effectiveness in treating spleen-stomach deficiency cold stomachache. It alleviates stomachache symptoms and also reduces the occurrence of adverse reactions and inflammation, holding great potential for widespread adoption in clinical practice.
PubMed: 38883362
DOI: 10.62347/MDQV6936