Changes in alcohol consumption and binge drinking during the COVID-19 pandemic among American Indians residing in California and Oklahoma.

Background: This study explored the increased quantity and frequency of alcohol use in the American Indian (AI) population during the COVID-19 pandemic.Objectives: The aims of this study were to explore possible associations between covariables and both binge drinking and alcohol consumption during COVID-19.Methods: This cross-sectional survey study analyzed data from a sample of AI individuals (63% female) residing in California (n = 411) and Oklahoma (n = 657) between October 2020-January 2021. Analysis included summary statistics and multivariable logistic regression, including a variety of socio-economic, COVID-19 concern, and tobacco and marijuana use variables.Results: One or more alcohol binge episodes were reported between October 2020-January 2021 in 19.3% of participants and elevated overall alcohol consumption was reported by 21.6% of participants. Higher odds of elevated alcohol consumption occurred in women and those following more social distancing measures. The odds of binge drinking or elevated alcohol consumption in those using both marijuana and tobacco (aOR/ adjusted odds ratio:18.9, 95% CI = 8.5, 42.2, and aOR:3.9, 95% CI = 1.7, 8.6, respectively) were higher compared to those using neither. Similarly, the odds of binge drinking or elevated alcohol consumption in those using tobacco only (aOR:4.7, 95% CI = 2.9, 7.7 and aOR: 2.0, 95% CI = 1.1, 3.5, respectively) were higher compared to those using neither.Conclusions: This study found high rates of alcohol use and bingeing during the COVID-19 pandemic. Offering collaborative, culturally sensitive, and affordable support services are important components of intervention and preparation for future stressful events on local, as well as global levels.

Corrigendum: High-definition transcranial direct current stimulation for upper extremity rehabilitation in moderate-to-severe ischemic stroke: a pilot study.

[This corrects the article DOI: 10.3389/fnhum.2023.1286238.].

Susceptibility to e-cigarette use and associated factors in high school youth, Oklahoma Youth Tobacco Survey, 2021-2022.

Introduction: Susceptibility predicts subsequent uptake of e-cigarettes (EC) by youth. This study identified factors associated with EC susceptibility among high school students who have never used a tobacco/nicotine product. Methods: The Oklahoma Youth Tobacco Survey was administered to a random sample of 36 Oklahoma High Schools during the 2021-2022 school year (n = 1,220 participating students). Associations between EC susceptibility and covariates were identified using stepwise logistic regression for weighted survey data. Results: More than one third of Oklahoma high school students who had never used tobacco or nicotine products (36.4%) were susceptible, and males had higher susceptibility than females (38.8 and 33.9%, respectively). In males, EC susceptibility was associated with race (Black, American Indian, and other were less susceptible), psychological distress (aOR = 2.4, 95% CI = 1.1, 4.8), disagreement that all tobacco products are dangerous (aOR = 3.1, 95% CI = 1.2, 7.9), and perception of little/no harm from secondhand vapor (aOR = 3.4, 95% CI = 2.1, 5.3). In females, identifying as gay, lesbian, or bisexual (aOR = 2.1, 95% CI = 1.1, 3.9), poor academic performance (aOR = 4.5, 95% CI = 1.6, 12.6), psychological distress (aOR = 2.6, 95% CI = 1.2, 5.5) and interacting with EC content on social media (aOR = 5.9, 95% CI = 1.9, 18.1) were associated with EC susceptibility. Conclusion: Males and females had different patterns of susceptibility to EC use. Understanding groups of adolescents most susceptible to using nicotine products can help target prevention efforts at home, in schools, and within communities.

Sex differences in interacting genetic and functional connectivity biomarkers in Alzheimer's disease.

As of 2023, it is estimated that 6.7 million individuals in the United States live with Alzheimer's disease (AD). Prior research indicates that AD disproportionality affects females; females have a greater incidence rate, perform worse on a variety of neuropsychological tasks, and have greater total brain atrophy. Recent research shows that hippocampal functional connectivity differs by sex and may be related to the observed sex differences in AD, and apolipoprotein E (ApoE) ε4 carriers have reduced hippocampal functional connectivity. The purpose of this study was to determine if the ApoE genotype plays a role in the observed sex differences in hippocampal functional connectivity in Alzheimer's disease. The resting state fMRI and T2 MRI of individuals with AD (n = 30, female = 15) and cognitively normal individuals (n = 30, female = 15) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed using the functional connectivity toolbox (CONN). Our results demonstrated intrahippocampal functional connectivity differed between those without an ε4 allele and those with at least one ε4 allele in each group. Additionally, intrahippocampal functional connectivity differed only by sex when Alzheimer's participants had at least one ε4 allele. These results improve our current understanding of the role of the interacting relationship between sex, ApoE genotype, and hippocampal function in AD. Understanding these biomarkers may aid in the development of sex-specific interventions for improved AD treatment.

Alteration in Resting-State Brain Activity in Stroke Survivors After Repetitive Finger Stimulation.

OBJECTIVE: This quasi-experimental study examined the effect of repetitive finger stimulation on brain activation in eight stroke and seven control subjects, measured by quantitative electroencephalogram. METHODS: We applied 5 mins of 2-Hz repetitive bilateral index finger transcutaneous electrical nerve stimulation and compared differences pre- and post-transcutaneous electrical nerve stimulation using quantitative electroencephalogram metrics delta/alpha ratio and delta-theta/alpha-beta ratio. RESULTS: Between-group differences before and after stimulation were significantly different in the delta/alpha ratio ( z = -2.88, P = 0.0040) and the delta-theta/alpha-beta ratio variables ( z = -3.90 with P < 0.0001). Significant decrease in the delta/alpha ratio and delta-theta/alpha-beta ratio variables after the transcutaneous electrical nerve stimulation was detected only in the stroke group (delta/alpha ratio diff = 3.87, P = 0.0211) (delta-theta/alpha-beta ratio diff = 1.19, P = 0.0074). CONCLUSIONS: The decrease in quantitative electroencephalogram metrics in the stroke group may indicate improved brain activity after transcutaneous electrical nerve stimulation. This finding may pave the way for a future novel therapy based on transcutaneous electrical nerve stimulation and quantitative electroencephalogram measures to improve brain recovery after stroke.

Determining the effects of targeted high-definition transcranial direct current stimulation on reducing post-stroke upper limb motor impairments-a randomized cross-over study.

BACKGROUND: Stroke is one of the leading causes of death in the USA and is a major cause of serious disability for adults. This randomized crossover study examines the effect of targeted high-definition transcranial direct current transcranial brain stimulation (tDCS) on upper extremity motor recovery in patients in the post-acute phase of stroke recovery. METHODS: This randomized double-blinded cross-over study includes four intervention arms: anodal, cathodal, and bilateral brain stimulation, as well as a placebo stimulation. Participants receive each intervention in a randomized order, with a 2-week washout period between each intervention. The primary outcome measure is change in Motor Evoked Potential. Secondary outcome measures include the Fugl-Meyer Upper Extremity (FM-UE) score, a subset of FM-UE (A), related to the muscle synergies, and the Modified Ashworth Scale. DISCUSSION: We hypothesize that anodal stimulation to the ipsilesional primary motor cortex will increase the excitability of the damaged cortico-spinal tract, reducing the UE flexion synergy and enhancing UE motor function. We further hypothesize that targeted cathodal stimulation to the contralesional premotor cortex will decrease activation of the cortico-reticulospinal tract (CRST) and the expression of the upper extremity (UE) flexion synergy and spasticity. Finally, we hypothesize bilateral stimulation will achieve both results simultaneously. Results from this study could improve understanding of the mechanism behind motor impairment and recovery in stroke and perfect the targeting of tDCS as a potential stroke intervention. With the use of appropriate screening, we anticipate no ethical or safety concerns. We plan to disseminate these research results to journals related to stroke recovery, engineering, and medicine. TRIAL REGISTRATION: ClinicalTrials.gov NCT05479006 . Registered on 26 July 2022.

A Novel Combinatorial Regimen Using Sorafenib and Uttroside B, A US FDA-designated 'Orphan Drug', for the Treatment of Hepatocellular Carcinoma.

INTRODUCTION: Sorafenib (Sor) is the first-line treatment option in clinics for treating advanced unresectable hepatocellular carcinoma (HCC). However, acquired chemoresistance and adverse side effects associated with Sor monotherapy limit its clinical benefits. We have previously reported the exceptional anti-HCC potential of uttroside B (Utt-B), a furostanol saponin isolated in our lab from Solanum nigrum Linn. leaves. The current study has evaluated the supremacy of a combinatorial regimen of Sor and Utt-B over Sor monotherapy. METHODS: MTT assay was used for In vitro cytotoxicity studies. A clonogenic assay was conducted to assess the anti-proliferative effect of the combination. Annexin V/PI staining, confocal microscopy, FACS cell cycle analysis, and Western blotting experiments were performed to validate the pro-apoptotic potential of the combination in HepG2 and Huh7 cell lines. Pharmacological safety evaluation was performed in Swiss albino mice. RESULTS: Our results indicate that Utt-B augments Sor-induced cytotoxicity in HepG2 and Huh7 cells. The combination inhibits the proliferation of liver cancer cells by inducing apoptosis through activation of the caspases 7 and 3, leading to PARP cleavage. Furthermore, the combination does not induce any acute toxicity in vivo, even at a dose five times that of the effective therapeutic dose. CONCLUSION: Our results highlight the potential of Utt-B as an effective chemosensitizer, which can augment the efficacy of Sor against HCC and circumvent Sor-induced toxic side effects. Moreover, this is the first and only report to date on the chemosensitizing potential of Utt-B and the only report that demonstrates the therapeutic efficacy and pharmacological safety of a novel combinatorial regimen involving Utt-B and Sor for combating HCC.

Targeting acid ceramidase enhances antitumor immune response in colorectal cancer.

INTRODUCTION: Acid ceramidase (hereafter referred as ASAH1) is an enzyme in sphingolipid metabolism that converts pro-survival ceramide into sphingosine. ASAH1 has been shown to be overexpressed in certain cancers. However, the role of ASAH1 in colorectal cancer still remain elusive. OBJECTIVE: The present study is aimed to understand how ASAH1 regulates colorectal cancer (CRC) progression and resistance to checkpoint inhibitor therapy. METHODS: Both pharmacological and genetic silencing of ASAH1 was used in the study. In vitro experiments were done on human and mouse CRC cell lines. The in vivo studies were conducted in NOD-SCID and BALB/c mice models. The combination of ASAH1 inhibitor and checkpoint inhibitor was tested using a syngeneic tumor model of CRC. Transcriptomic and metabolomic analyses were done to understand the effect of ASAH1 silencing. RESULTS: ASAH1 is overexpressed in human CRC cases, and silencing the expression resulted in the induction of immunological cell death (ICD) and mitochondrial stress. The ASAH1 inhibitor (LCL-521), either as monotherapy or in combination with an anti-PD-1 antibody, resulted in reduction of tumors and, through induction of type I and II interferon response, activation of M1 macrophages and T cells, leading to enhanced infiltration of cytotoxic T cells. Our findings supported that the combination of LCL-521 and ICIs, which enhances the antitumor responses, and ASAH1 can be a druggable target in CRC.