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Biomedicines Jun 2024Chronic pancreatitis is often secondary to alcohol abuse, but pancreatitis with no other aetiology is frequently associated with variants in genes encoding proteins...
Chronic pancreatitis is often secondary to alcohol abuse, but pancreatitis with no other aetiology is frequently associated with variants in genes encoding proteins related to zymogen granule activation. Our goal was to identify genomic variants in a patient by analyzing an extended panel of genes associated with the intra-pancreatic activation of the trypsin pathway. A 23-year-old woman was addressed at our institution because of chronic pancreatitis of unknown aetiology presenting recurrent episodes since she was the age of four. Next Generation Sequencing was performed to analyze a panel of nine genes associated with pancreatitis (, , , , , , , and ). Three missense variants were found: p.Leu997Phe, maternally inherited, in the gene; p.Ile73Phe, paternally inherited, in the gene; and p.Phe790Ser, a de novo variant, in the gene. They were classified, respectively as probably benign, a Variant of Uncertain Significance, and the last one, which has never been described in the literature, as likely being pathogenic following American College of Medical Genetics and Genomics standard guidelines. Extensive intra-pancreatic activation of trypsin pathway gene sequencing detected rare variants that were not found with other gene screening and showed that variants in different genes may interact in contributing to the onset of the pancreatitis phenotype.
PubMed: 38927485
DOI: 10.3390/biomedicines12061278 -
Research Involvement and Engagement Jun 2024Clustering and co-occurring of family adversities, including mental health problems, substance use, domestic violence and abuse, as well as poverty can increase health...
Co-design workshops with families experiencing multiple and interacting adversities including parental mental health, substance use, domestic violence, and poverty: intervention principles and insights from mothers, fathers, and young people.
BACKGROUND
Clustering and co-occurring of family adversities, including mental health problems, substance use, domestic violence and abuse, as well as poverty can increase health and behavioural risks for children, which persist throughout the life course. Yet, interventions that acknowledge and account for the complex interactive nature of such risks are limited. This study aimed to develop intervention principles based on reflections from mothers, fathers, and young people who experience multiple and interacting adversities. These principles will show how family members perceive an intervention may bring about positive change and highlight key insights into design and delivery.
METHODS
A series of six co-design workshops with mothers, fathers, and young people who experienced multiple and interacting adversities (n = 41) were iteratively conducted across two regions in England (London and North-East) by four researchers. Workshop content and co-design activities were informed by advisory groups. Data from facilitator notes and activities were analysed thematically, resulting in a set of intervention principles.
RESULTS
The intervention principles highlighted that: (1) to reduce isolation and loneliness parents and young people wanted to be connected to services, resources, and peer support networks within their local community, particularly by a knowledgeable and friendly community worker; (2) to address feelings of being misunderstood, parents and young people wanted the development of specialised trauma informed training for practitioners and to have the space to build trusting, gradual, and non-stigmatising relationships with practitioners; and (3) to address the needs and strengths of individual family members, mothers, fathers, and young people wanted separate, tailored, and confidential support.
CONCLUSIONS
The current study has important implications for practice in supporting families that experience multiple and interacting adversities. The intervention principles from this study share common characteristics with other intervention models currently on offer in the United Kingdom, including social prescribing, but go beyond these to holistically consider the whole families' needs, environments, and circumstances. There should be particular focus on the child's as well as the mothers' and fathers' needs, independently of the family unit. Further refinement and piloting of the developing intervention are needed.
PubMed: 38926798
DOI: 10.1186/s40900-024-00584-0 -
Addiction (Abingdon, England) Jun 2024Previously identified national drinking patterns in Europe lack comparability and might be no longer be valid due to changes in economic conditions and policy...
BACKGROUND AND AIMS
Previously identified national drinking patterns in Europe lack comparability and might be no longer be valid due to changes in economic conditions and policy frameworks. We aimed to identify the most recent alcohol drinking patterns in Europe based on comparable alcohol exposure indicators using a data-driven approach, as well as identifying temporal changes and establishing empirical links between these patterns and indicators of alcohol-related harm.
DESIGN
Data from the World Health Organization's monitoring system on alcohol exposure indicators were used. Repeated cross-sectional hierarchical cluster analyses were applied. Differences in alcohol-attributable harm between clusters of countries were analyzed via linear regression.
SETTING
European Union countries, plus Iceland, Norway and Ukraine, for 2000, 2010, 2015 and 2019.
PARTICIPANTS/CASES
Observations consisted of annual country data, at four different time points for alcohol exposure. Harm indicators were only included for 2019.
MEASUREMENTS
Alcohol exposure indicators included alcohol per capita consumption (APC), beverage-specific consumption and prevalence of drinking status indicators (lifetime abstainers, current drinkers, former drinkers and heavy episodic drinking). Alcohol-attributable harm was measured using age-standardized alcohol-attributable Disability-Adjusted Life Years (DALYs) lost and deaths per 100 000 people.
FINDINGS
The same six clusters were identified in 2019, 2015 and 2010, mainly characterized by type of alcoholic beverage and prevalence drinking status indicators, with geographical interpretation. Two-thirds of the countries remained in the same cluster over time, with one additional cluster identified in 2000, characterized by low APC. The most recent drinking patterns were shown to be significantly associated with alcohol-attributable deaths and DALY rates. Compared with wine-drinking countries, the mortality rate per 100 000 people was significantly higher in Eastern Europe with high spirits and 'other' beverage consumption [ = 90, 95% confidence interval (CI) = 55-126], and in Eastern Europe with high lifetime abstainers and high spirits consumption ( = 42, 95% CI = 4-78).
CONCLUSIONS
European drinking patterns appear to be clustered by level of beverage-specific consumption, with heavy episodic drinkers, current drinkers and lifetime abstainers being distinguishing factors between clusters. Despite the overall stability of the clusters over time, some countries shifted between drinking patterns from 2000 to 2019. Overall, patterns of drinking in the European Union seem to be stable and partly determined by geographical proximity.
PubMed: 38924624
DOI: 10.1111/add.16567 -
Journal of Child Psychology and... Jun 2024Whether emotional problems during childhood and adolescence are longitudinally associated with adult alcohol use behaviors is unclear. This study examined associations...
BACKGROUND
Whether emotional problems during childhood and adolescence are longitudinally associated with adult alcohol use behaviors is unclear. This study examined associations between developmental trajectories of emotional problems and early adult alcohol use behaviors, while considering co-occurring conduct problems, developmental change/timing, sex differences, and potential confounds.
METHODS
Participants were from the Twins Early Development Study (analytic N = 19,908 individuals). Emotional and conduct problems were measured by parent reports at child ages 4, 7, and 9 years and via self-reports at ages 9, 11, and 16 years on the Strengths and Difficulties Questionnaire. Alcohol use behaviors (alcohol consumption and alcohol-related problems) were self-reported by the twins on the Alcohol Use Disorders Identification Test at age 22 years. Piecewise latent growth curve models described nonlinear developmental trajectories of emotional and conduct problems from ages 4 to 16. At age 22, alcohol use was regressed on emotional and conduct problems' intercepts and slopes from piecewise latent growth curve model and sex differences in regression coefficients were tested. Using twin modeling, Cholesky decompositions and direct path models were compared to test whether significant phenotypic associations were best explained by direct phenotypic influences or correlated genetic and environmental influences.
RESULTS
Emotional problems had different associations with alcohol-related problems versus alcohol consumption. After accounting for direct influences from conduct problems, emotional problems were not associated with alcohol-related problems, while emotional problems at age 9 were negatively associated with alcohol consumption in males.
CONCLUSIONS
Overall, findings did not support emotional problems as prospective risk factors for severe alcohol use above and beyond risks associated with conduct problems. Sex- and age-specific links between emotional problems and alcohol consumption in early adulthood may be worthy of further exploration, particularly as twin analyses improved our confidence that such links may be underpinned by causal mechanisms.
PubMed: 38924525
DOI: 10.1111/jcpp.14034 -
PloS One 2024Ukraine has the second-largest HIV epidemic in Europe, with most new cases officially attributed to heterosexual transmission. Indirect evidence suggested substantial...
BACKGROUND
Ukraine has the second-largest HIV epidemic in Europe, with most new cases officially attributed to heterosexual transmission. Indirect evidence suggested substantial HIV transmission from people who inject drugs (PWID) to their sexual partners. This study examined the extent of heterosexual HIV transmission between PWID and non-drug-using adolescent girls and young women (AGYW).
METHODS
A cross-sectional survey recruited AGYW diagnosed with heterosexually-acquired HIV between 2016 and 2019 in nine regions of Ukraine. AGYW were asked to identify and refer their sexual partners ('Partners'), who subsequently underwent HIV testing, and, if positive, HCV testing. Both AGYW and Partners completed an interview assessing HIV risk behaviors prior to AGYW's HIV diagnosis.
RESULTS
In August-December 2020, we enrolled 321 AGYW and 64 Partners. Among the Partners, 42% either self-reported IDU or were HCV-positive, indicating an IDU-related mode of HIV transmission. PWID Partners were more likely to report sexually transmitted infections (STI) and had lower educational levels. Of the 62 women who recruited at least one Partner, 40% had a PWID Partner. Within this subgroup, there was a higher prevalence of STIs (52% vs. 24%) and intimate partner violence (36% vs. 3%). Condom use was less common (52% vs. 38% reporting never use), and frequent alcohol or substance use before sex was higher (48% vs 30%) among AGYW with PWID Partner, although this difference did not reach statistical significance. Notably, 52% of women were aware of their Partners' IDU.
CONCLUSION
At least 40% of heterosexual transmission among AGYW in Ukraine can be linked to PWID partners. Intensified, targeted HIV prevention efforts are essential for key and bridge populations (PWID and their sexual partners), addressing the biological and structural determinants of transmission between key and bridge populations, such as IDU- and HIV status disclosure, STIs, IPV, and stigma.
Topics: Humans; Female; Ukraine; Sexual Partners; HIV Infections; Adolescent; Young Adult; Cross-Sectional Studies; Adult; Substance Abuse, Intravenous; Male; Sexual Behavior; Risk-Taking; Heterosexuality; Hepatitis C
PubMed: 38923979
DOI: 10.1371/journal.pone.0305072 -
Comparative Prevalence of Cerebrovascular Disease in Vietnamese Communities in South-Western Sydney.Journal of Cardiovascular Development... May 2024Culturally and linguistically diverse (CALD) communities are growing globally. Understanding patterns of cerebrovascular disease in these communities may improve health...
Culturally and linguistically diverse (CALD) communities are growing globally. Understanding patterns of cerebrovascular disease in these communities may improve health outcomes. We aimed to compare the rates of transient ischaemic attack (TIA), ischaemic stroke (IS), intracerebral haemorrhage (ICH), intracranial atherosclerosis (ICAD), and stroke risk factors in Vietnamese-born residents of South-Western Sydney (SWS) with those of an Australian-born cohort. A 10-year retrospective analysis (2011-2020) was performed using data extracted from the Health Information Exchange database characterising stroke presentations and risk factor profiles. The rates of hypertension (83.7% vs. 70.3%, < 0.001) and dyslipidaemia (81.0% vs. 68.2%, < 0.001) were significantly higher in Vietnamese patients, while the rates of ischaemic heart disease (10.4% vs. 20.3%, < 0.001), smoking (24.4% vs. 40.8%, < 0.001), and alcohol abuse (>1 drink/day) (9.6% vs. 15.9%, < 0.001) were lower. The rates of ICAD and ICH were higher in Vietnamese patients (30.9% vs. 6.9%, < 0.001 and 24.7% vs. 14.4%, = 0.002). Regression analysis revealed that diabetes (OR: 1.86; 95% CI: 1.14-3.04, = 0.014) and glycosylated haemoglobin (OR: 1.51; 95% CI: 1.15-1.98, = 0.003) were predictors of ICAD in Vietnamese patients. Vietnamese patients had higher rates of symptomatic ICAD and ICH, with unique risk factor profiles. Culturally specific interventions arising from these findings may more effectively reduce the community burden of disease.
PubMed: 38921664
DOI: 10.3390/jcdd11060164 -
Cureus May 2024We report a rare case of splenic tuberculosis (TB) in a male patient with a competent immune system who had no previous record of pulmonary TB. A 56-year-old male...
We report a rare case of splenic tuberculosis (TB) in a male patient with a competent immune system who had no previous record of pulmonary TB. A 56-year-old male patient came to our outpatient department complaining of upper abdominal pain with a few episodes of vomiting for three days. He had alcoholism, smoked for 15 years, and had no past history of diabetes mellitus, hypertension, TB, or HIV. An abdominal ultrasound and CT scan at admission showed pancreatitis with a splenic abscess. After five days of admission, the patient's vitals deteriorated, and he had severe abdominal pain. CT scan suggested a splenic abscess rupture with hemoperitoneum. An emergency exploratory laparotomy was performed, and a splenectomy was done due to the splenic abscess rupture. A cartridge-based nucleic acid amplification test from splenic intracapsular fluid detected a trace complex. The patient was discharged after starting first-line antitubercular treatment for six months. After three months of follow-up, the patient was doing well with no complaints.
PubMed: 38919240
DOI: 10.7759/cureus.61088 -
Addiction Science & Clinical Practice Jun 2024Clinic-based interventions are needed to promote successful direct acting antiviral (DAA) treatment for chronic hepatitis C virus (HCV) infection in patients with...
BACKGROUND
Clinic-based interventions are needed to promote successful direct acting antiviral (DAA) treatment for chronic hepatitis C virus (HCV) infection in patients with substance use disorders (SUDs) among rural Veterans.
METHODS
We implemented a clinic-based intervention which used motivational interviewing (MI) techniques to promote medication adherence and treatment completion with 12 weeks of DAA treatment among rural Veterans with chronic HCV and SUDs. Patients received an MI session with a licensed psychologist at baseline and at each two-week follow-up visit during DAA treatment. Patients received $25 per study visit completed. Patients were to attend a laboratory visit 12 weeks after treatment completion to assess for sustained virologic response (SVR).
RESULTS
Of the 20 participants who enrolled, 75% (n = 15) completed the planned 12-week course of treatment. Average adherence by pill count was 92% (SD = 3%). Overall SVR was 95% (19/20).
CONCLUSIONS
We demonstrated that a clinic-based intervention which incorporated frequent follow up visits and MI techniques was feasible and acceptable to a sample of predominantly rural Veterans with chronic HCV and SUDs.
CLINICAL TRIAL REGISTRATION
Registered at ClinicalTrials.gov (NCT02823457) on July 1, 2016. https://clinicaltrials.gov .
Topics: Humans; Veterans; Male; Antiviral Agents; Substance-Related Disorders; Hepatitis C, Chronic; Middle Aged; Rural Population; Female; Medication Adherence; Motivational Interviewing; Adult; Sustained Virologic Response; Aged
PubMed: 38918869
DOI: 10.1186/s13722-024-00480-8 -
Communications Biology Jun 2024The calcium calmodulin protein kinase II (CaMKII) is a multi-subunit ring assembly with a central hub formed by the association domains. There is evidence for hub...
The calcium calmodulin protein kinase II (CaMKII) is a multi-subunit ring assembly with a central hub formed by the association domains. There is evidence for hub polymorphism between and within CaMKII isoforms, but the link between polymorphism and subunit exchange has not been resolved. Here, we present near-atomic resolution cryogenic electron microscopy (cryo-EM) structures revealing that hubs from the α and β isoforms, either standalone or within an β holoenzyme, coexist as 12 and 14 subunit assemblies. Single-molecule fluorescence microscopy of Venus-tagged holoenzymes detects intermediate assemblies and progressive dimer loss due to intrinsic holoenzyme lability, and holoenzyme disassembly into dimers upon mutagenesis of a conserved inter-domain contact. Molecular dynamics (MD) simulations show the flexibility of 4-subunit precursors, extracted in-silico from the β hub polymorphs, encompassing the curvature of both polymorphs. The MD explains how an open hub structure also obtained from the β holoenzyme sample could be created by dimer loss and analysis of its cryo-EM dataset reveals how the gap could open further. An assembly model, considering dimer concentration dependence and strain differences between polymorphs, proposes a mechanism for intrinsic hub lability to fine-tune the stoichiometry of αβ heterooligomers for their dynamic localization within synapses in neurons.
Topics: Cryoelectron Microscopy; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Molecular Dynamics Simulation; Humans; Holoenzymes; Protein Multimerization; Animals
PubMed: 38918547
DOI: 10.1038/s42003-024-06423-y -
International Journal of Pharmaceutics Jun 2024Chronic liver inflammation, a pervasive global health issue, results in millions of annual deaths due to its progression from fibrosis to the more severe forms of... (Review)
Review
Chronic liver inflammation, a pervasive global health issue, results in millions of annual deaths due to its progression from fibrosis to the more severe forms of cirrhosis and hepatocellular carcinoma (HCC). This insidious condition stems from diverse factors such as obesity, genetic conditions, alcohol abuse, viral infections, autoimmune diseases, and toxic accumulation, manifesting as chronic liver diseases (CLDs) such as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), alcoholic liver disease (ALD), viral hepatitis, drug-induced liver injury, and autoimmune hepatitis. Late detection of CLDs necessitates effective treatments to inhibit and potentially reverse disease progression. However, current therapies exhibit limitations in consistency and safety. A potential breakthrough lies in nanoparticle-based drug delivery strategies, offering targeted delivery to specific liver cell types, such as hepatocytes, Kupffer cells, and hepatic stellate cells. This review explores molecular targets for CLD treatment, ongoing clinical trials, recent advances in nanoparticle-based drug delivery, and the future outlook of this research field. Early intervention is crucial for chronic liver disease. Having a comprehensive understanding of current treatments, molecular biomarkers and novel nanoparticle-based drug delivery strategies can have enormous impact in guiding future strategies for the prevention and treatment of CLDs.
PubMed: 38917958
DOI: 10.1016/j.ijpharm.2024.124381