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Globally, mental and substance use disorders are a leading cause of disease burden. In low- and middle-income countries, where there is an extreme shortage of trained mental health specialists, validated, brief screening tools for mental and substance use disorders are required for non-specialists to efficiently identify patients in need of mental health care. Mozambique, one of the poorest countries in the world, has fewer than two mental health specialists for every 100,000 people. In the present study, we evaluated a comprehensive set of seven measures for depression, anxiety, somatization, alcohol use disorder, substance use disorder, psychosis and mania, and suicide risk among N=911 Mozambican adults in general healthcare settings. All instruments demonstrated acceptable internal consistency (α > 0.75). Compared to diagnoses made by the Mini International Neuropsychiatric Interview, all measures showed good criterion validity (AUC > 0.75), except the Psychosis Screening Questionnaire, which showed low sensitivity (0.58) for psychotic disorder. No substantial differences were observed in internal consistency when stratifying by gender, age, education level, primary language, facility-type, and patient status; criterion validity showed some variability when stratified by sub-population, particularly for education, primary language, and whether the participant was seeking care that day. Exploratory factor analyses indicated that the measures best differentiate categories of diagnoses (common mental disorder, severe mental disorders, substance use disorders, and suicide risk) rather than individual diagnoses, suggesting the utility of a transdiagnostic approach. Our findings support the use of these measures in Mozambique to identify common mental disorders, substance use disorders, and suicide risk, but indicate further research is needed to develop an adequate screen for severe mental disorders. Given the limited mental health specialists in this and other LMIC settings, these brief measures can support non-specialist provision of mental health services and promote closure of the treatment gap.

Background: Brugada syndrome is generally considered a cardiac channelopathy disorder characterized by syncope or sudden cardiac death. The sodium voltage-gated channel alpha subunit 5 (SCN5A) gene is the most commonly mutated gene associated with Brugada syndrome. Recent discoveries of new variants of this gene, along with current guidance of family screening, have identified several asymptomatic carriers with potentially causative mutations.

Case presentation: We present the case of a 25-year-old female patient without any family history of Brugada syndrome nor related congenital cardiovascular disorders, with an extensive atrioventricular canal defect, who tested positive for a novel heterozygous variant NM_198056.3: c.3169G>C (p. Asp1057 His) in the SCN5A gene. She had no history of syncope or aborted sudden cardiac death except for recurrent chest infections since her early childhood. Intriguingly, she did not show a type I Brugada electrocardiogram pattern.

Conclusions: This report provides a novel heterozygous variant NM_198056.3: c.3169G>C (p. Asp1057 His) in the SCN5A gene, which may have a potential detrimental effect.

Chikungunya virus is an emerging pathogen with widespread distribution in regions of Africa, India, and Asia that threatens to spread into temperate climates following the introduction of its major vector, Aedes albopictus. Recent cases have been documented in Europe, the Caribbean, and the Americas. Chikungunya virus causes a disease frequently misdiagnosed as Dengue fever, with potentially life-threatening symptoms that can result in long term debilitating arthritis. There have been ongoing investigations of possible therapeutic interventions for both acute and chronic symptoms, but to date none have proven effective in reducing the severity or lasting effects of this disease. Recently, a promising vaccine candidate has received accelerated approval, indicating the importance of remedies to this emerging worldwide health threat. Nonetheless, therapeutic interventions for Chikungunya and other mosquito borne virus diseases are urgently needed yet remain elusive. The increasing risk of spread from endemic regions via human travel and commerce, coupled with the absence of a vaccine or approved therapeutic, puts a significant proportion of the world population at risk for this disease. In this report we explore the possibility of using Specific On/oFf Adapter Hepatitis Delta Virus Ribozymes as antivirals in cells infected with Chikungunya virus. The results we obtained suggest there could be some role in using these ribozyme molecules as antiviral therapies for not only Chikungunya virus, but potentially other viruses as well.

Objectives: The contribution of medical mistrust to healthcare utilization delays has been gaining increasing attention. However, few studies have examined these associations among subgroups of Black men (African Americans, Caribbean, and African immigrants) in relation to prostate cancer (PCa). This study addresses this gap by assessing how medical mistrust affects PCa screening behavior and to further understand perceptions of medical mistrust among subgroups of Black men.

Methods: This research employs a mixed-methods approach comprising two distinct phases. In Phase 1, a cross-sectional examination was conducted to evaluate the influence of medical mistrust toward healthcare organizations on prostate cancer screening among 498 Black men. In Phase 2, a qualitative investigation was undertaken to delve into the nuances of medical mistrust through six focus groups (n=51) and ten key informant interviews (n=10). Logistic regression and grounded theory methods were employed for data analysis.

Results: Quantitative findings unveiled disparities in mistrust among subgroups, with Caribbean immigrants exhibiting higher levels of medical mistrust. Nevertheless, individuals with a family history of PCa showed elevated likelihoods of undergoing screening, despite mistrust. Qualitative results revealed 1) differences in reasons for medical mistrust among Black subgroups, 2) cultural perceptions which influence medical mistrust and medical care seeking, 3) lack of education in relation to PCa that contributes to medical mistrust, 4) negative past experiences and poor provider communication contribute, and 5) when PCa directly affected one's life, either personally or within the family, there was a recognized importance placed on monitoring one's risk despite mistrust.

Conclusion: While medical mistrust may not significantly deter healthcare utilization among individuals with a family history or diagnosis of PCa, it underscores the variability of medical mistrust and its underlying reasons among different Black subgroups.

Objective: To determine the maternal risk factors for small-for-gestational-age newborns as defined by a birthweight z-score (BWZS) < -1.0.

Design: A prospective cohort study with recruitment from August 2007 to January 2015.

Setting: Recruitment at a community health centre with assessments at Tygerberg Academic Hospital, Cape Town, South Africa.

Population: A largely homogeneous population in a low socioeconomic residential area in Cape Town.

Methods: This study is a further analysis of the data of the Safe Passage Study which investigated whether exposure to alcohol and tobacco was associated with increased risk of stillbirth and sudden infant death syndrome (SIDS).

Main outcome measures: Birthweight z-score < -1.0.

Results: Individual odds ratios (ORs), in descending order, were associated with smoking, drinking, and preeclampsia (2.45), previous stillbirth (1.85), smoking (including smokers only and drinkers who also smoked) (1.55), preeclampsia (1.52), smoking and drinking (does not include smokers only or drinkers only)(1.43), hypertension (1.28), drug use (1.24), drinking during pregnancy (including drinkers only and drinkers who also smoked) (1.18), thoughts of self-harm (1.13), and crowding (1.10). After multiple logistic regression, highly significant ORs were found for previous stillbirth (1.89), cigarette smoking (1.84), hypertension (1.40), education (0.94) and body mass index (BMI) (0.95). Thoughts of self-harm then had an OR of 1.08 (95% confidence interval (CI) 1.00-1.18).

Conclusion: Previous stillbirth, cigarette smoking, hypertension, lesser education, and a lower BMI were associated with the highest risks for low BWZS.

Although it is known that APOE genotype is the strongest genetic risk factor for late-onset Alzheimer's disease, development is a multifactorial process. Alcohol use is a contributor to the epidemic of Alzheimer's disease and related dementias in the US and globally, yet mechanisms are not fully understood. Carriers of the APOE ε4 allele show elevated risk of dementia in relation to several lifestyle factors, including alcohol use. In this review, we describe how alcohol interacts with APOE genotype and aging with potential implications for Alzheimer's disease promotion. Age-related immune senescence and "inflammaging" (i.e., low-grade inflammation associated with aging) are increasingly recognized as contributors to age-related disease. We focus on three immune pathways that are likely contributors to Alzheimer's disease development, centering on alcohol and APOE genotype interactions, specifically: 1) microbial translocation and immune activation, 2) the senescence associated secretory phenotype, and 3) neuroinflammation. First, microbial translocation, the unphysiological movement of gut products into systemic circulation, elicits a proinflammatory response and increases with aging, with proposed links to Alzheimer's disease. Second, the senescence associated secretory phenotype is a set of intercellular signaling factors, e.g., proinflammatory cytokines and chemokines, growth regulators, and proteases, that drives cellular aging when senescent cells remain metabolically active. The senescence associated secretory phenotype can drive development of aging-diseases such as Alzheimer's disease. Third, neuroinflammation occurs via numerous mechanisms such as microglial activation and is gaining recognition as an etiological factor in the development of Alzheimer's disease. This review focuses on interactions of alcohol with APOE genotype and aging along these three pathways that may promote Alzheimer's disease. Further research on these processes may inform development of strategies to prevent onset and progression of Alzheimer's disease and to delay associated cognitive decline.

Adolescence is characterized by ongoing neurodevelopment and psychosocial development, resulting in a unique window to the adverse effects of traumatic events and substance use. In addition, trauma- and stressor-related disorders and substance use disorders (SUDs) commonly co-occur in adolescents. Youth with interpersonal violence and who have experienced multiple past traumas, or poly-victimization, are at the highest risk of developing these co-occurring disorders. There is a strong bidirectional relationship between traumatic events and substance use that predisposes youth to developing post-traumatic stress symptoms (PTSS) and SUDs. PTSD and states of substance intoxication and withdrawal also exhibit overlap in symptomatology. High rates of comorbidity may be explained in part by the self-medication hypothesis, that posits that individuals use substances to temporarily alleviate trauma-related symptoms. However, this results in negative reinforcement, often with increasing patterns of substance use and worsening symptoms of hyperarousal, dysphoria, and anxiety. In addition, PTSS and substance use problems share common risk factors and neurobiologic etiology, conceptualized as the susceptibility hypothesis. Youth who experience traumatic events and/or have substance use problems access the healthcare system at multiple levels, including through acute care and crisis services. Notably, substance use in adolescence increases the likelihood of experiencing a traumatic event, and youth presenting to the emergency department for substance-related problems are at higher risk of having a PTSD. Youth presenting for mental health, behavioral, or substance-related problems should be screened for PTSS and substance use problems. Given the strong clinical overlap and bidirectional relationship, evidence-based treatment integrates management of both disorders. An interdisciplinary approach with psychotherapy, psychopharmacologic therapy, and case management is often vital to engaging and maintaining youth in treatment.

Objectives: Humans, with their unique genetic profile, exhibit a greater propensity to develop and maintain addiction compared to other animals. This paper offers a detailed examination of addiction, co-occurring traits, and psychologic disorders, focusing on neurobiological and molecular aspects. Furthermore, the authors investigate the potential of the Awareness Integration Theoretical model as an effective therapeutic addiction treatment.

Methods: Using PsychINFO, PubMed, and Google Scholar, a comprehensive literature review was conducted on the evolutionary and adaptation pathways to addiction, epigenetic factors, and the potentiality of Awareness Integration Theory in treating addiction.

Results: Epigenetics allows environmental factors to create lasting and heritable phenotypic changes, enabling rapid adaptation to these stimuli. Addiction "high-jacks" this system and the neurochemical mechanisms that control flexibility and innovation and is, thus, the price we pay for adaptability. Drug addiction is thought of as an adjunctive behavior or a subordinate behavior catalyzed by more profound, more significant psychological and biological stimuli.

Conclusions: The neurochemical mechanisms underlying addiction, a complex interplay of genetic and environmental factors, are intertwined with the hallmark features of the human species, such as behavioral flexibility and pre-addictive propensity. The dopaminergic system, a key player in addiction, serves as a crucial link between addiction and the shared genetic profile evident in co-occurring traits and psychiatric and psychological disorders. Furthermore, a hypofunctioning dopaminergic system is a common characteristic of addiction and co-occurring psychiatric and psychological disorders. Early childhood preventative measures are vital in re-directing the existing predictive and poor adaptability functioning, which refers to the individual's inability to adapt to changing circumstances and reliance on maladaptive coping strategies. Awareness Integration Theory's approach encompasses a therapeutical model addressing individuals' physical, cognitive, and psychosocial domains, allowing the individual to address intergenerational and ancestral ineffective and harmful adaptability. This, in turn, AIT will allow the human genome to be on a healthier path to recovery from obstacles such as addiction. When a tendency or a characteristic improves your ability to function and survive, and especially your ability to produce and raise children, that will most likely break the cycle of addiction and addictive behavior.

Background: The clinical setting where patients with colorectal cancer (CRC), especially young adults, accessed the healthcare system during the COVID-19 pandemic to obtain their diagnosis is understudied. We hypothesized that patients with early-onset CRC (EO-CRC) present at disproportionate rates to emergency departments compared to patients with average-age onset CRC (AO-CRC).

Patient and methods: Clinical chart review was conducted for patients discussed at tumor board from the University of Texas Southwestern and Parkland Health Hospitals from August 2020 to August 2022 to compare the site of presentation that led to diagnosis: emergency department or primary care setting.

Results: Two-hundred and ninety-three patients with CRC were included (69% AO-CRC, 31% EO-CRC), presenting at similar rates to primary care providers and emergency department (55% vs 45%, respectively). Most patients who presented to the emergency department received their cancer care at the safety net hospital (70%, p <0.001). Race/ethnicity, and comorbidities like obesity and metabolic dysregulation were also associated with emergency department presentation. Patients from the safety net hospital and those with obesity-related comorbidities were more likely present to the emergency department (OR 5.98, 95% CI 2.88 - 12.41, p<0.001; OR 4.18, 95% CI 1.18 - 14.81, p=0.03). Patients with rectal cancer are less likely to present to the emergency department (OR 0.42, 95% CI 0.21 - 0.85, p=0.02). No differences were observed between EO-CRC and AO-CRC with respect to the presentation site.

Conclusion: Here we identified factors linked to CRC diagnostic access to the healthcare system during the COVID-19 pandemic in a racially and ethnically diverse population. Future research in this area can inform specialized CRC screening and diagnostic pathways for vulnerable young adults, guiding resource allocation to improve access to care and prompt diagnosis. Additionally, these insights can guide diagnostic access plans during global health crises for at-risk populations.

Five-year survival rate for pancreatic cancer patients has increased to 12.8% afterthe initial diagnosis, still making it one of the deadliest cancertypes. This disease is known as the "silent killer" because early detection is challenging due to the location of the pancreas in the body and the nonspecific clinical symptoms. The Bossmann group has developed ultrasensitive nanobiosensors for protease/arginase detection comprised of Fe/Fe₃O₄ nanoparticles, cyanine 5.5, and designer peptide sequences linked to TCPP. Initial data obtained from both gene expression analysis and protease/arginase activity detection in serum indicated the feasibility of early pancreatic cancer detection. Several matrix metalloproteinases (MMPs, -1, -3, and -9), cathepsins (CTS) B and E, neutrophil elastase, and urokinase plaminogen activator (uPA) have been identified as candidates for proximal biomarkers. In this study, we have confirmed our initial results from 2018 performing serum sample analysis assays using a larger group sample size (n = 159), which included localized (n=33) and metastatic pancreatic cancer (n=50), pancreatitis (n=26), and an age-matched healthy control group (n=50). The data obtained from the eight nanobiosensors capable of ultrasensitive protease and arginase activity measurements were analyzed by means of an optimized information fusion-based hierarchical decision structure. This permits the modeling of early-stage detection of pancreatic cancer as a multi-class classification problem. The most striking result is that this methodology permits the detection of localized pancreatic cancers from serum analyses with around 96% accuracy.