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Background: The COVID-19 pandemic exacerbated disparities in mental healthcare and substance use disorder (SUD) treatment access, especially in under-resourced communities. This study aimed to comprehend the experiences of under-resourced women with SUD during the pandemic, their knowledge and attitudes toward it, and its impact on substance use and treatment access., Methods: A cross-sectional study included 66 under-resourced women receiving medically managed withdrawal treatment at a community residential SUD center. Data collection occurred between November 2021 and August 2022, utilizing a 75-item instrument covering COVID-19 exposure and its impact on health, substance use, treatment access, vaccination status, beliefs, and knowledge. Descriptive analyses summarized the data., Results: Participants faced various challenges during the pandemic. Many reported increased substance use, especially alcohol, opioids, benzodiazepines, and nicotine. Mental health stability was negatively affected, exacerbating existing disorders and limiting mental healthcare access. A majority (56.1%) reported that their chronic mental health disorder was less stable during the pandemic. Twenty (30.3%) participants reported that they had been diagnosed with a new mental health disorder since the pandemic, and 28.8% reported that it was harder for them to access mental healthcare during the pandemic. Job loss, housing instability, and financial strain were prevalent. Half (n=33, 50%) received a COVID-19 vaccine dose, while 27.3% (n=18) declined vaccination due to knowledge gaps and religious beliefs. The majority (n=41, 62.1%) worried about securing basic needs such as groceries and medication, with 64.6% (n=42) expressing a desire to cope using alcohol or drugs., Conclusions: This study expands upon previous research by examining the effect of the COVID-19 pandemic on mental health in the context of substance use disorder treatment. Unlike previous data, which focused solely on substance use behaviors, our study delves into the impact of the pandemic on co-occurring mental health disorders. Findings underscore the need for gender-responsive and culturally appropriate SUD treatment. Vaccine hesitancy, as reflected in the study, necessitates more effective, tailored evidence-based informational campaigns. Efforts must focus on enhancing mental healthcare access, reducing stigma, and supporting individuals with co-occurring conditions amidst this evolving COVID-19 health crisis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Institutional Review Board of Baylor College of Medicine issued approval H-50771. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mejia et al.)

Substance misuse and substance use disorder continue to be major causes of morbidity and mortality, and family physicians are well positioned to provide evidence-based prevention and management for these conditions. Of people 12 years and older, 13% reported using a nonprescribed controlled substance in the past month, and 24% had at least one episode of binge drinking of alcohol, defined as five or more drinks for men and four or more drinks for women on one occasion. Benzodiazepines are used by 12% of the U.S. population. Clinicians should incorporate standardized screening and brief intervention for use of alcohol and other substances into routine care of adult patients, as well as referral to specialized treatment services when indicated. Use of nonstigmatizing, person-first language has been shown to positively affect care for patients with substance use disorders. Alcohol screening and brief intervention have been shown to reduce excessive drinking by 40% in patients at 6 months postintervention. Office-based treatment of alcohol use disorder with medications approved by the U.S. Food and Drug Administration, such as acamprosate and naltrexone, remains underutilized, presenting another opportunity for family physicians to positively affect the health of their patients and communities. With elimination of the X-waiver, any clinician with Schedule III prescriptive authority can treat opioid use disorder with buprenorphine in their office-based practice. Opioid overdose education and naloxone coprescribing are other tools family physicians can employ to combat the overdose crisis.

EB1 is a key cellular protein that delivers regulatory molecules throughout the cell via the tip-tracking of growing microtubule plus-ends. Thus, it is important to understand the mechanism for how EB1 efficiently tracks growing microtubule plus-ends. It is widely accepted that EB1 binds with higher affinity to GTP-tubulin subunits at the growing microtubule tip, relative to GDP-tubulin along the microtubule length. However, it is unclear whether this difference in affinity alone is sufficient to explain the tip-tracking of EB1 at growing microtubule tips. Previously, we found that EB1 binds to exposed microtubule protofilament-edge sites at a ~70 fold faster rate than to closed-lattice sites, due to diffusional steric hindrance to binding. Thus, we asked whether rapid protofilament-edge binding could contribute to efficient EB1 tip tracking. A computational simulation with differential EB1 on-rates based on closed-lattice or protofilament-edge binding, and with EB1 off-rates that were dependent on the tubulin hydrolysis state, robustly recapitulated experimental EB1 tip tracking. To test this model, we used cell-free biophysical assays, as well as live-cell imaging, in combination with a Designed Ankyrin Repeat Protein (DARPin) that binds exclusively to protofilament-edge sites, and whose binding site partially overlaps with the EB1 binding site. We found that DARPin blocked EB1 protofilament-edge binding, which led to a decrease in EB1 tip tracking on dynamic microtubules. We conclude that rapid EB1 binding to microtubule protofilament-edge sites contributes to robust EB1 tip tracking at the growing microtubule plus-end., Competing Interests: SG, JH, RG, TR, MM, MG No competing interests declared, (© 2024, Gonzalez et al.)

To achieve understanding and best care, screening and treating patients should consider the patient's social environment. Social and behavioral factors influence both positive and negative health behaviors that influence mental and physical health. Primary care providers continually navigate barriers faced by patients and seek solutions that take into consideration social and behavioral factors. The role of the PCP begins with an understanding of common barriers and community resources, then by assessing and responding to the patient's own challenges, and finally by advocating in the clinic and public for changes to the underlying social and structural causes of morbidity and mortality., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Early life adversity predicts shorter adult lifespan in several animal taxa. Yet, work on long-lived primate populations suggests the evolution of mechanisms that contribute to resiliency and long lives despite early life insults. Here, we tested associations between individual and cumulative early life adversity and lifespan on rhesus macaques at the Cayo Santiago Biological Field Station using 50 years of demographic data. We performed sex-specific survival analyses at different life stages to contrast short-term effects of adversity (i.e., infant survival) with long-term effects (i.e., adult survival). Female infants showed vulnerability to multiple adversities at birth, but affected females who survived to adulthood experienced a reduced risk later in life. In contrast, male infants showed vulnerability to a lower number of adversities at birth, but those who survived to adulthood were negatively affected by both early life individual and cumulative adversity. Our study shows profound immediate effects of insults  on female infant cohorts and suggests that affected female adults are more robust. In contrast, adult males who experienced harsh conditions early in life showed an increased mortality risk at older ages as expected from hypotheses within the life course perspective. Our analysis suggests sex-specific selection pressures on life histories and highlights the need for studies addressing the effects of early life adversity across multiple life stages., Competing Interests: We declare no conflict of interest., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

During mitosis, sister chromatids are stretched apart at their centromeres via their attachment to oppositely oriented kinetochore microtubules. This stretching generates inwardly directed tension across the separated sister centromeres. The cell leverages this tension signal to detect and then correct potential errors in chromosome segregation, via a mechanical tension signaling pathway that detaches improperly attached kinetochores from their microtubules. However, the sequence of events leading up to these detachment events remains unknown. In this study, we used microfluidics to sustain and observe low-tension budding yeast metaphase spindles over multiple hours, allowing us to elucidate the tension history prior to a detachment event. We found that, under conditions in which kinetochore phosphorylation weakens low-tension kinetochore-microtubule connections, the mechanical forces produced via the dynamic growth and shortening of microtubules is required to efficiently facilitate detachment events. Our findings underscore the critical role of robust kinetochore microtubule dynamics in ensuring the fidelity of chromosome segregation during mitosis., (© 2023 Parmar et al.)

Anxiety disorders are the most common psychiatric conditions in children and adolescents, affecting nearly 1 in 12 children and 1 in 4 adolescents. Anxiety disorders include specific phobias, social anxiety disorder, separation anxiety disorder, agoraphobia, panic disorder, and generalized anxiety disorder. Risk factors include parental history of anxiety disorders, socioeconomic stressors, exposure to violence, and trauma. The U.S. Preventive Services Task Force recommends screening for anxiety disorders in children eight years and older; there is insufficient evidence to support screening in children younger than eight years. Symptoms of anxiety disorders in children and adolescents are similar to those in adults and can include physical and behavioral symptoms such as diaphoresis, palpitations, and tantrums. Care should be taken to distinguish symptoms of a disorder from normal developmental fears and behaviors, such as separation anxiety in infants and toddlers. Several validated screening measures are useful for initial assessment and ongoing monitoring. Cognitive behavior therapy and selective serotonin reuptake inhibitors are the mainstay of treatment and may be used as monotherapies or in combination. Prognosis is improved with early intervention, caretaker support, and professional collaboration.

Objective: Medical students are vulnerable to stress and depression during medical school and the COVID-19 pandemic may have exacerbated these issues. This study examined whether the risk of depression was associated with COVID-19 pandemic-related medical school communication., Methods: A 144 - item pilot cross-sectional online survey of medical students in the US, was carried out between September 1, 2020 and December 31, 2020. Items on stress, depression, and communication between students and their medical schools were included. This study examined associations of student perceptions of universities' communication efforts and pandemic response with risk of developing depression., Results: The sample included 212 students from 22 US states. Almost 50% (48.6%) were at risk of developing depression. Students felt medical schools transitioned well to online platforms, while the curriculum was just as rigorous as in-person courses. Students at risk of developing depression reported communication was poor more frequently compared to students at average risk. Students at risk of depression were also more than 3 times more likely to report their universities' communication about scholarships or other funding was poor in adjusted analyses., Conclusion: Universities communicated well with medical students during the pandemic. However, this study also highlights the need for ongoing efforts to address student mental health by medical schools.

Kinesin-14 molecular motors represent an essential class of proteins that bind microtubules and walk toward their minus-ends. Previous studies have described important roles for Kinesin-14 motors at microtubule minus-ends, but their role in regulating plus-end dynamics remains controversial. Kinesin-14 motors have been shown to bind the EB family of microtubule plus-end binding proteins, suggesting that these minus-end-directed motors could interact with growing microtubule plus-ends. In this work, we explored the role of minus-end-directed Kinesin-14 motor forces in controlling plus-end microtubule dynamics. In cells, a Kinesin-14 mutant with reduced affinity to EB proteins led to increased microtubule lengths. Cell-free biophysical microscopy assays were performed using Kinesin-14 motors and an EB family marker of growing microtubule plus-ends, Mal3, which revealed that when Kinesin-14 motors bound to Mal3 at growing microtubule plus-ends, the motors subsequently walked toward the minus-end, and Mal3 was pulled away from the growing microtubule tip. Strikingly, these interactions resulted in an approximately twofold decrease in the expected postinteraction microtubule lifetime. Furthermore, generic minus-end-directed tension forces, generated by tethering growing plus-ends to the coverslip using λ-DNA, led to an approximately sevenfold decrease in the expected postinteraction microtubule growth length. In contrast, the inhibition of Kinesin-14 minus-end-directed motility led to extended tip interactions and to an increase in the expected postinteraction microtubule lifetime, indicating that plus-ends were stabilized by nonmotile Kinesin-14 motors. Together, we find that Kinesin-14 motors participate in a force balance at microtubule plus-ends to regulate microtubule lengths in cells., Competing Interests: The authors declare no competing interest.

Background: While prior research has informed how cigarette smokers understand and apply the term addiction, little is known about how this term is used by cigarillo smokers. This is an important area of study given the decline in cigarette use and increase in cigar product consumption., Purpose/objectives: This paper examines how cigarillo smokers self-identify in terms of addiction and the association of this identification with tobacco use, quitting experiences, and level of nicotine dependence., Methods: Transcripts from semi-structured interviews conducted in 2015-2016 with 57 participants (aged 14-28) about cigarillo use and beliefs were analyzed using a phenomenological approach to examine themes around addiction and cessation experiences. Analyses were limited to participants endorsing having a habit. Quantitative analyses were conducted to assess associations with demographics, tobacco use, addiction, cessation, and nicotine dependence for two groups: participants endorsing having an addiction to cigarillos and those who did not., Results: All participants described the term addiction similarly. Participants with an addiction had significantly higher nicotine dependence and self-rating of addiction than those without an addiction. Although most quitting experiences did not differ between the two groups, participants who did not identify as addicted felt that they could quit smoking cigarillos at any time., Conclusions: Variations in identification with addiction are not associated with differences in definitions, use and quit experiences. Understanding self-perceptions of addiction can inform targeted communication to encourage cessation and the use of cessation resources., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Adversity early in life can shape the reproductive potential of individuals through negative effects on health and life span. However, long-lived populations with multiple reproductive events may present alternative life history strategies to optimize reproductive schedules and compensate for shorter life spans. Here, we quantify the effects of major hurricanes and density dependence as sources of early-life ecological adversity on Cayo Santiago rhesus macaque female reproduction and decompose their effects onto the mean age-specific fertility, reproductive pace, and lifetime reproductive success (LRS). Females experiencing major hurricanes exhibit a delayed reproductive debut but maintain the pace of reproduction past debut and show a higher mean fertility during prime reproductive ages, relative to unaffected females. Increasing density at birth is associated to a decrease in mean fertility and reproductive pace, but such association is absent at intermediate densities. When combined, our study reveals that hurricanes early in life predict a delay-overshoot pattern in mean age-specific fertility that supports the maintenance of LRS. In contrast to predictive adaptive response models of accelerated reproduction, this long-lived population presents a novel reproductive strategy where females who experience major natural disasters early in life ultimately overcome their initial reproductive penalty with no major negative fitness outcomes. Density presents a more complex relation with reproduction that suggests females experiencing a population regulated at intermediate densities early in life will escape density dependence and show optimized reproductive schedules. Our results support hypotheses about life history trade-offs in which adversity-affected females ensure their future reproductive potential by allocating more energy to growth or maintenance processes at younger adult ages., Competing Interests: We declare no conflict of interest., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

In the failing heart, the cardiac myocyte microtubule network is remodeled, which contributes to cellular contractile failure and patient death. However, the origins of this deleterious cytoskeletal reorganization are unknown. We now find that oxidative stress, a condition characteristic of heart failure, leads to cysteine oxidation of microtubules. Our electron and fluorescence microscopy experiments revealed regions of structural damage within the microtubule lattice that occurred at locations of oxidized tubulin. The incorporation of GTP-tubulin into these damaged, oxidized regions led to stabilized "hot spots" within the microtubule lattice, which suppressed the shortening of dynamic microtubules. Thus, oxidative stress may act inside of cardiac myocytes to facilitate a pathogenic shift from a sparse microtubule network into a dense, aligned network. Our results demonstrate how a disease condition characterized by oxidative stress can trigger a molecular oxidation event, which likely contributes to a toxic cellular-scale transformation of the cardiac myocyte microtubule network., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Cancer among infants (<1 year old) has unique epidemiologic, clinical, and genetic characteristics compared with cancer in older children. Nonetheless, data on secular trends in infant cancer incidence and survival in the United States is sparse., Methods: Population-based data from nine areas of the Surveillance Epidemiology and End Results (SEER) were used to estimate the incidence, average annual percentage change (APC) for trends, and survival of malignant neoplasm among infants from 1975 to 2014. Data were stratified by gender, race, registry, and cancer type., Results: There were 3437 new infant cancer cases with an overall incidence of 23.6/100 000. Neuroblastoma was the most common infant malignancy (6.5/100 000), followed by leukemia (3.8/100 000), and brain and central nervous system tumors (3.3/100 000). The incidence rate increased significantly from 1975 to 2014 (APC 0.68; 95% CI 0.30-1.06; P < .05). Variations in overall incidence rates were uneven across SEER registry geographic areas, with the lowest rates among both males and females in New Mexico. Relative to other racial distribution, infant cancer rates were highest among Whites. The relative survival rates improved over time for all tumors except for renal, sarcomas, and germ cells and were not significantly different by gender or race., Conclusions: Cancer incidence among infants increased over time largely driven by leukemia, germ cell, and sarcoma mainly among male infants. The overall survival for infant cancer has improved over the past 40 years, especially since 1990 for hepatic tumors, lymphoma, and leukemia. Further research is needed to explore the potential impacts of genetic, environmental, and perinatal factors for possible explanations for these increased cancer incidence trends., (© 2021 Wiley Periodicals LLC.)

Background: Giardia duodenalis is a gastrointestinal protozoan causing 184 million cases of giardiasis worldwide annually. Detection is by microscopy or coproantigen assays, although sensitivity is often compromised by intermittent shedding of cysts or trophozoites, or operator expertise. Therefore, for enhanced surveillance field-applicable, point-of-care (POC), molecular assays are needed. Our aims were to: (i) optimise the recombinase polymerase amplification (RPA) assay for the isothermal amplification of the G. duodenalis β-giardin gene from trophozoites and cysts, using published primer and probes; and (ii) perform a pilot field validation of RPA at a field station in a resource-poor setting, on DNA extracted from stool samples from schoolchildren in villages around Lake Albert, Uganda. Results were compared to an established laboratory small subunit ribosomal RNA (SSU rDNA) qPCR assay with additional testing using a qPCR targeting the triose phosphate isomerase (tpi) DNA regions that can distinguish G. duodenalis of two different assemblages (A and B), which are human-specific., Results: Initial optimisation resulted in the successful amplification of predicted RPA products from G. duodenalis-purified gDNA, producing a double-labelled amplicon detected using lateral flow strips. In the field setting, of 129 stool samples, 49 (37.9%) were positive using the Giardia/Cryptosporidium QuikChek coproantigen test; however, the RPA assay when conducted in the field was positive for a single stool sample. Subsequent molecular screening in the laboratory on a subset (n = 73) of the samples demonstrated better results with 21 (28.8%) RPA positive. The SSU rDNA qPCR assay resulted in 30/129 (23.3%) positive samples; 18 out of 73 (24.7%) were assemblage typed (9 assemblage A; 5 assemblage B; and 4 mixed A+B). Compared with the SSU rDNA qPCR, QuikChek was more sensitive than RPA (85.7 vs 61.9%), but with similar specificities (80.8 vs 84.6%). In comparison to QuikChek, RPA had 46.4% sensitivity and 82.2% specificity., Conclusions: To the best of our knowledge, this is the first in-field and comparative laboratory validation of RPA for giardiasis in low resource settings. Further refinement and technology transfer, specifically in relation to stool sample preparation, will be needed to implement this assay in the field, which could assist better detection of asymptomatic Giardia infections.

Background: Since 1979, mortality from hepatocellular cancer (HCC) has doubled in the United States (US). Lifesaving drugs, prohibitively expensive for some, were approved and marketed to treat hepatitis C virus (HCV), a major risk factor for HCC, beginning in 1997. After the prior introduction of other lifesaving innovations, including active retroviral drug therapy for human immunodeficiency virus and surfactant for respiratory distress syndrome of the newborn, racial inequalities in their mortalities increased in the US. In this descriptive study, we explored racial inequalities in mortality from HCC before and after licensure of HCV drugs in the US., Methods: The US Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research (WONDER) were used to describe HCC mortality rates from 1979 to 2016 in those 55 years of age and older, because they suffer the largest disease burden. Joinpoint regression was used to analyze trends. To estimate excess deaths, we applied White age-sex-specific rates to corresponding Black populations., Findings: From 1979 to 1998, racial inequalities in mortality from HCC in the US were declining but from 1998 to 2016 racial inequalities steadily increased. From 1998 to 2016, of the 16,770 deaths from HCC among Blacks, the excess relative to Whites increased from 27.8% to 45.4%, and the trends were more prominent in men. Concurrently, racial inequalities in mortality decreased for major risk factors for HCC, including alcohol, obesity and diabetes., Interpretation: These descriptive data, useful to formulate but not test hypotheses, demonstrate decreasing racial inequalities in mortality from HCC which were followed by increases after introduction of lifesaving drugs for HCV in the US. Among many plausible hypotheses generated are social side effects, including unequal accessibility, acceptability and/or utilization. Analytic epidemiological studies designed a priori to do so are necessary to test these and other hypotheses., Competing Interests: RSL, MCM, JLS, SJG, MHA, BAH, RJZ report no conflicts., (© 2020 The Author(s).)

Background: Patients with substance use disorders (SUDs) are more likely to experience serious health problems, high healthcare utilization, and premature death. However, little is known about the contribution of SUDs to medical 30-day readmission risk. We examined the association between SUDs and 30-day all cause readmission among non-pregnant adult in-patients in the US. Methods: We conducted a retrospective study using 2010-2014 data from the Nationwide Readmissions Database. Our primary focus was on opioid use compared to stimulant use (cocaine and amphetamine) identified by ICD-9-CM diagnosis codes in index hospitalizations. Multivariable logistic regression models were used to estimate adjusted odds ratios and 95% CI representing the association between substance use and 30-day readmission, overall and stratified by the principal reason for the index hospitalization. Results: Nearly 118 million index hospitalizations were included in the study, 4% were associated with opioid or stimulant use disorder. Readmission rates for users (19.5%) were higher than for nonusers (15.7%), with slight variation by the type of substance used: cocaine (21.8%), opioid (19.0%), and amphetamine (17.5%). After adjusting for key demographic, socioeconomic, clinical, and health system characteristics, SUDs and stimulant use disorders increased the odds of 30-day all-cause readmission by 20%. Conclusions: Reducing the frequency of inpatient readmission is an important goal for improving the quality of care and ensuring proper transition to residential/outpatient care among patients with SUDs. Differences between groups may suggest directions for further investigation into the distinct needs and challenges of hospitalized opioid- and other drug-exposed patients.

The U.S. Preventive Services Task Force recommends that clinicians adopt universal alcohol screening and brief intervention as a routine preventive service for adults, and efforts are underway to support its widespread dissemination. The likelihood that healthcare systems will sustain this change, once implemented, is under-reported in the literature. This article identifies factors that were important to postimplementation sustainability of an evidence-based practice change to address alcohol misuse that was piloted within three diverse primary care organizations. The Centers for Disease Control and Prevention funded three academic teams to pilot and evaluate implementation of alcohol screening and brief intervention within multiclinic healthcare systems in their respective regions. Following the completion of the pilots, teams used the Program Sustainability Assessment Tool to retrospectively describe and compare differences across eight sustainability domains, identify strengths and potential threats to sustainability, and make recommendations for improvement. Health systems varied across all domains, with greatest differences noted for Program Evaluation, Strategic Planning, and Funding Stability. Lack of funding to sustain practice change, or data monitoring to promote fit and fidelity, was an indication of diminished Organizational Capacity in systems that discontinued the service after the pilot. Early assessment of sustainability factors may identify potential threats that could be addressed prior to, or during implementation to enhance Organizational Capacity. Although this study provides a retrospective assessment conducted by external academic teams, it identifies factors that may be relevant for translating evidence-based behavioral interventions in a way that assures that they are sustained within healthcare systems.

Alcohol, tobacco, marijuana, and other substance use by adolescents can have a serious impact on their health and well-being according to the American Academy of Pediatrics (AAP, 2016). School social workers (SSW) are trained to conduct assessments and interventions with adolescents and families to improve their functioning and academic performance (National Association of Social Workers [NASW], 2003). Also, substance abuse prevention, identification, brief intervention, and referral to treatment are supported by the profession's standards for working with adolescents (NASW, 2003). For SSW interested in incorporating these services into their work, this practice highlights column describes the importance and principles of conducting adolescent screening, brief intervention, and referral to treatment (SBIRT) for substance use. Highlights are drawn from Substance Use Screening and Intervention Implementation Guide: No Amount of Substance Use Is Safe for Adolescents (hereinafter, AAP Guide), a guide developed through a cooperative agreement between AAP and Centers for Disease Control and Prevention (CDC) (AAP, 2016).

Objective: To examine high school youths' perceptions of health risks, and personal and parental attitudes toward cigarette, cigar, and marijuana use among youth who use or modify cigars., Participants: The 2013 Cuyahoga County Youth Risk Behavior Survey used a two-stage cluster sample design to randomly sample public high schools and classrooms. Students in selected classrooms were eligible; 16,855 students completed the survey., Main Outcome Measures: This study examines the association between risk perceptions of and youths' personal and parental attitudes toward smoking cigarettes, cigars, and marijuana with current use of cigars, cigarillos or little cigars (CCLCs) or modified CCLCs (ie, freaking or blunting)., Results: 23.5% of youth reported current use of CCLCs in some way; 11.0% reported current freaking and 18.5% reported current blunt use. CCLC users tended to be male and Black. Perceiving all smoking behaviors as risky, wrong, or wrong by parents reduced odds of using CCLCs. After multivariate analysis, Blacks had increased odds of using CCLCs if they perceived smoking cigarettes as harmful, which was not found among other race/ethnicity categories. Having parents who believed that smoking CCLCs is wrong increased the odds of youth freaking or blunting among all CCLC users. Odds of blunting was greater for those who believed CCLCs were more risky among all CCLC users., Conclusions: Findings suggest that CCLC users may think cigars are safer than cigarettes, and that modifiers may think their use is safer and more in line with their parents' views than non-modified CCLCs., Competing Interests: Competing Interests: None declared.

Background: Little is known about how adolescents who smoke both cigarettes and cigar products obtain and use these products. This study sought to explore cigarette and cigar acquisition and situational use among high school smokers., Methods: Data are drawn from the 2011 Cuyahoga County Youth Risk Behavior Survey. Analysis was limited to youth who smoke cigarettes as well as cigars, cigarillos, and little cigars (CCLC) in the past month (N = 649). Consumption of both products was calculated and used to create four subtypes of users based on high or low use of each product (Dual High, Dual Low, High CCLC/Low Cigarette, and Low CCLC/High Cigarette users). Current users were asked to identify situations in which they use cigarettes and CCLCs and ways in which they obtain these products. Data were analyzed overall and by user subtype., Results: Youth reported acquiring cigarettes and CCLC in similar ways, although youth were more likely to take cigarettes from family members than CCLC (11.1% vs. 4.8%). Several differences were observed between cigarettes and CCLC for situational use. While both products are frequently used in social situations (e.g., with friends), cigarettes were more likely to be used in solitary situations (e.g., before bed). Further, significant differences were observed among the four user subtypes., Conclusions: Study results highlight important, nuanced differences regarding how young multi-tobacco users obtain and the situational use of such products. Importantly, these findings vary by user subtype, informing future interventions to prevent and reduce smoking among the most vulnerable subgroups of youth., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Prevalence of cigar use has been increasing among youth. Research indicates that youth are modifying cigar products either by "freaking" (ie, removing the filter paper) or "blunting" (removing the tobacco and supplementing or replacing with marijuana), yet little is known about youth who engage in this behavior. Thus, this study examines demographic and concurrent substance use behaviors of youth who modify cigars., Methods: Data from the 2013 Cuyahoga County Youth Risk Behavior survey were examined (n = 16 855). The survey collected data on demographics, cigar product use, cigar modification behaviors, and current cigarette, hookah and marijuana use. Responses to cigar product use items were used to create a composite to classify youth in one of eight unique user categories. Univariate and bivariate statistics were calculated using SPSS complex samples procedures., Results: Overall, 15.2% reported current cigar product use, 11.0% reported current freaking, and 18.5% reported current blunt use; taken together, 25.3% of respondents reported any current use of a cigar product. When examined by user category, of those who endorsed any cigar product use, cigars, cigarillos, and little cigars use only was most endorsed (26.3%), followed by Blunt only (25.2%) and all three (ie, cigars, cigarillos, and little cigars, freaking, and blunting; 17.4%)., Conclusion: A substantial proportion of high school youth who report using cigar products are modifying them in some way, with nearly half freaking and nearly two-thirds blunting. Given the FDA Center for Tobacco products recent extension of its regulatory authority to include cigar products, it is imperative to understand more about the prevalence of and reasons for cigar modification behaviors., Implications: Although the FDA has recently enacted regulatory authority over cigar products, little is known about cigar product modification. This is the first study to concurrently examine two unique cigar modification behaviors, "freaking" (ie, removing the filter paper) and "blunting" (removing the tobacco and supplementing or replacing with marijuana). A significant proportion of high school youth are modifying cigar products to be used as a tobacco product and as a mechanism to smoke marijuana. More research is needed to understand these behaviors to prevent and reduce the use of cigar products among youth., (© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Parental perceptions of their children's weight status may limit their willingness to participate in or acknowledge the importance of early interventions to prevent childhood obesity. This study aimed to examine potential differences in Hispanic mothers' and fathers' perceptions of childhood obesity, lifestyle behaviors and communication preferences to inform the development of culturally appropriate childhood obesity interventions. A qualitative study using focus groups was conducted. Groups (one for mothers and one for fathers) were composed of Hispanic parents (n = 12) with at least one girl and one boy (≤ 10 years old) who were patients at a pediatric clinic in Tennessee, USA. Thirteen major themes clustered into four categories were observed: (i) perceptions of childhood obesity/children's weight; (ii) parenting strategies related to children's dietary behaviors/physical activity; (iii) perceptions of what parents can do to prevent childhood obesity and (iv) parental suggestions for partnering with child care providers to address childhood obesity. Mothers appeared to be more concerned than fathers about their children's weight. Fathers expressed more concern about the girls' weight than boys'. Mothers were more likely than fathers to congratulate their children more often for healthy eating and physical activity. Parents collectively expressed a desire for child care providers (e.g. caregivers, teachers, medical professionals and food assistance programs coordinators) to have a caring attitude about their children, which might in turn serve as a motivating factor in talking about their children's weight. Parental perceptions of their children's weight and healthy lifestyle choices are of potential public health importance since they could affect parental participation in preventive interventions., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Information on the burden and risk factors for diabetes-depression comorbidity in the US is sparse. We used data from the largest all-payer, nationally-representative inpatient database in the US to estimate the prevalence, temporal trends, and risk factors for comorbid depression among adult diabetic inpatients., Methods: We conducted a retrospective analysis using the 2002-2014 Nationwide Inpatient Sample databases. Depression and other comorbidities were identified using ICD-9-CM codes. Logistic regression was used to investigate the association between patient characteristics and depression., Results: The rate of depression among patients with type 2 diabetes increased from 7.6% in 2002 to 15.4% in 2014, while for type 1 diabetes the rate increased from 8.7% in 2002 to 19.6% in 2014. The highest rates of depression were observed among females, non-Hispanic whites, younger patients, and patients with five or more chronic comorbidities., Conclusions: The prevalence of comorbid depression among diabetic inpatients in the US is increasing rapidly. Although some portion of this increase could be explained by the rising prevalence of multimorbidity, increased awareness and likelihood of diagnosis of comorbid depression by physicians and better documentation as a result of the increased adoption of electronic health records likely contributed to this trend., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Substance use affects people of all ages, cultures, and socioeconomic levels. Most underserved populations have lower rates of substance use than the general population in a given society, excluding tobacco use. The impact of substance use is more severe, however, in the underserved, with higher rates of incarceration, job loss, morbidity, and mortality. Innovative solutions are being developed to address these differences. Working together, underserved patients with substance use problems can be helped on their journeys toward health and wholeness., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Little cigar and cigarillo (LCC) use has received increased attention, but research on their modification is limited. Qualitative interviews with 17 young adult African American male LCC users investigated tobacco use behaviors and patterns, including LCC modification. The modification of LCCs for use as blunts emerged as a very prominent aspect of LCC users' tobacco use. Four subthemes regarding marijuana and blunt use are explored in this article, including participants' explanations of how blunts are made and used, concurrent use of marijuana and tobacco, perceptions and reasons for smoking marijuana and blunts, and perceptions of the risks of blunt use.

Background: Among Hispanics, chronic liver disease and cirrhosis are among the leading causes of death despite generally lower alcohol consumption rates. Moreover, recent national studies have suggested temporal changes in Hispanic consumption and alcohol mortality, which raises the question of whether Hispanic white disparities in alcohol-related mortality are also changing over time. This study aimed to describe temporal trends of alcohol-related mortality between Hispanics and non-Hispanic (NH) whites in the United States from 1999 to 2014 and to assess county-level sociodemographic characteristics that are associated with racial/ethnic disparities in age-adjusted alcohol-related mortality., Methods: We conducted a population-based, cross-sectional, ecologic study using multiple cause-of-death mortality data linked, at the county level, to census data from the American Community Survey., Results: Overall, 77% of alcohol-related deaths were among men, and Hispanic men had the highest age-adjusted alcohol-related mortality rate (41.6 per 100,000), followed by NH white men (34.8), NH white women (10.8), and Hispanic women (6.7). Whereas the relative gap in alcohol-related mortality between NH white and Hispanic women increased from 1999 to 2014, the disparity between NH white and Hispanic men that was pronounced in earlier years was eliminated by 2012. From 2007 to 2014, when the race/ethnic disparity among men was decreasing, county-specific Hispanic:NH white age-adjusted mortality ratios (AAMRs) ranged from 0.29 to 2.64. Lower Hispanic rates were associated with large metropolitan counties, and those counties that tended to have Hispanic populations were less acculturated, as evidenced by their higher rates of being foreign-born, non-U.S. citizens or citizens through naturalization, and a higher proportion that do not speak English "very well.", Conclusions: Since 1999, whereas the increasing mortality rate among whites is leading to a widening gap among women, mortality differences between Hispanic and white men have been eliminated. The understanding of contextual factors that are associated with disparities in alcohol-related mortality may assist in tailoring prevention efforts that meet the needs of minority populations., (Copyright © 2016 by the Research Society on Alcoholism.)

Aims: Type 2 diabetes mellitus (T2DM) is often complicated by infections leading to hospitalization, increased morbidity, and mortality. Not much is known about the impact of Clostridium difficile infection (CDI) on health outcomes in hospitalized patients with T2DM. We estimated the prevalence and temporal trends of CDI; evaluated the associations between CDI and in-hospital mortality, length of stay (LOS), and the costs of inpatient care; and compared the impact of CDI with that of other infections commonly seen in patients with T2DM., Methods: We conducted a cross-sectional analysis using data from the Nationwide Inpatient Sample among patients ⩾18years with T2DM and generalized linear regression was used to analyze associations and jointpoint regression for trends., Results: The prevalence of CDI was 6.8 per 1000 hospital discharges. Patients with T2DM and CDI had increased odds of in-hospital mortality (OR, 3.63; 95% CI 3.16, 4.17). The adjusted mean LOS was higher in patients with CDI than without CDI (11.9 vs. 4.7days). That translated to average hospital costs of $23,000 and $9100 for patients with and without CDI, respectively. The adjusted risk of mortality in patients who had CDI alone (OR 3.75; 95% CI 3.18, 4.41) was similar to patients who had CDI in addition to other common infections (OR 3.25; 95% CI 2.58, 4.10)., Conclusion: CDI is independently associated with poorer health outcomes in patients with T2DM. We recommend close surveillance for CDI in hospitalized patients and further studies to determine the cost effectiveness of screening for CDI among patients with T2DM., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Preoperative imaging to assess response to neoadjuvant chemotherapy in breast cancer is routine but no single imaging modality is standard of practice. Our hypothesis is that ultrasound (US) is comparable to magnetic resonance imaging (MRI) in the prediction of residual disease., Methods: A single-institution, Institutional Review Board-approved prospective trial of primary invasive ductal breast cancer patients receiving neoadjuvant chemotherapy enrolled women from 2008 to 2012. Two-dimensional (2D) and three-dimensional (3D) US, as well as MRI images of pre- and post-neoadjuvant tumors were obtained. Skin involvement or inadequate images were excluded. Residual tumor on imaging was compared with surgical pathology. Differences of tumor volume on imaging and pathology were compared using the non-parametric Wilcoxon signed-rank test. US to MRI agreement was determined by the kappa coefficient. Tumor volumes in estrogen receptor (ER), progesterone receptor (PR), and Her2neu subgroups were compared using the Kruskal-Wallis test. ER/PR staining <5 % was considered negative; Her2neu status was determined by in situ hybridization., Results: Forty-two patients were enrolled in the study; 39 had evaluable post-treatment data. Four patients were Her2neu positive, and 17 (46 %) patients had triple-negative tumors. Among 11 (28 %) patients with pathologic complete response (pCR), US correctly predicted pCR in six (54.5 %) patients compared with eight (72.7 %) patients when MRI was used. This is a substantial agreement between US and MRI in predicting pCR (kappa = 0.62). There was no difference between 2D and 3D US modalities. For the 39 patients, US and MRI had no significant difference in volume estimation of pathology, even stratified by receptor status., Conclusion: The estimation of residual breast tumor volume by US and MRI achieves similar results, including prediction of pCR.

Alcohol consumption during pregnancy can result in birth defects known as fetal alcohol spectrum disorders. This study examined whether 1-h training sessions on alcohol screening, brief intervention, diagnoses, and treatment of fetal alcohol spectrum disorders could increase practical knowledge and confidence in nurses and student nurses. Data were collected from 420 nurses (n = 95) and student nurses (n = 325) in the southeastern United States, from 2009 to 2011. Pre- and post-test data were analyzed using chi-square tests and t-tests. The post-training response rate was 84%. Nurses were more likely to know what constitutes binge drinking, facial abnormalities associated with fetal alcohol syndrome, and criteria for diagnosis. Nurses were also more confident in educating about effects of prenatal alcohol use, identifying fetal alcohol spectrum disorders and utilizing resources. Training materials may need to be improved and/or longer training programs developed for student nurses, and nursing school programs should place more emphasis on educating and preparing student nurses regarding this topic area., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The activity in accelerator development for accelerator-based BNCT (AB-BNCT) both worldwide and in Argentina is described. Projects in Russia, UK, Italy, Japan, Israel, and Argentina to develop AB-BNCT around different types of accelerators are briefly presented. In particular, the present status and recent progress of the Argentine project will be reviewed. The topics will cover: intense ion sources, accelerator tubes, transport of intense beams, beam diagnostics, the (9)Be(d,n) reaction as a possible neutron source, Beam Shaping Assemblies (BSA), a treatment room, and treatment planning in realistic cases., (© 2013 Elsevier Ltd. All rights reserved.)

We describe the present status of an ongoing project to develop a Tandem-ElectroStatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based (AB)-BNCT. The project final goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the (7)Li(p,n)(7)Be reaction. The machine currently being constructed is a folded TESQ with a high-voltage terminal at 0.6 MV. We report here on the progress achieved in a number of different areas., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A facility for the irradiation of a section of patients' explanted liver and lung was constructed at RA-3 reactor, Comisión Nacional de Energía Atómica, Argentina. The facility, located in the thermal column, is characterized by the possibility to insert and extract samples without the need to shutdown the reactor. In order to reach the best levels of security and efficacy of the treatment, it is necessary to perform an accurate dosimetry. The possibility to simulate neutron flux and absorbed dose in the explanted organs, together with the experimental dosimetry, allows setting more precise and effective treatment plans. To this end, a computational model of the entire reactor was set-up, and the simulations were validated with the experimental measurements performed in the facility., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Gastroesophageal cancer remains a leading cause of cancer deaths and is uniformly fatal in patients presenting with metastases and recurrence. This study sets out to determine the effect of a third-generation, replication-competent, oncolytic herpes simplex type 1 virus containing transgenes encoding for a fusogenic membrane glycoprotein and Fcy::Fur, against gastroesophageal cancer., Methods: The cytotoxic effect of the virus was tested on human gastroesophageal cancer cell lines OCUM-2MD3, MKN-45, AGS, MKN-1, MKN-74, and BE-3 at sequential multiplicities of infection (MOI). Cytotoxicity was measured using a lactate dehydrogenase assay. Viral replication was tested by serially diluting supernatants from viral infections and titering on VERO cells via standard plaque assay. Correlations of cytotoxicity and viral replication were also investigated., Results: All cell lines were susceptible to viral infection and demonstrated a dose-dependent effect, with greater and faster cytotoxicity at higher MOIs. Viral replication was supported in the cell lines tested, with peak titers by d 5, some supporting as high as >40,000× amplification. Cell lines with longer doubling times (>30 h) also achieved higher viral titers at a MOI of 0.1. Cell lines with shorter doubling times achieved 50% cell kill in fewer days, with an average of 2.3 d for cell lines with doubling times under 30 h compared with 4.4 d for cell lines with doubling times over 30 h., Conclusion: These results suggest that this third-generation oncolytic herpesvirus can effectively infect and lyse gastroesophageal cancer cells and may provide a novel therapy against gastroesophageal cancer., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Malignant pleural mesothelioma is a highly aggressive tumor. Alternative treatment strategies such as oncolytic viral therapy may offer promising treatment options in the future. In this study, the oncolytic efficacy and induction of tumor remission by a genetically engineered Newcastle disease virus [NDV; NDV(F3aa)-GFP; GFP, green fluorescent protein] in malignant pleural mesothelioma is tested and monitored by bioluminescent tumor imaging. The efficacy of NDV(F3aa)-GFP was tested against several mesothelioma cell lines in vitro. Firefly luciferase-transduced MSTO-211H* orthotopic pleural mesothelioma tumor-bearing animals were treated with either single or multiple doses of NDV(F3aa)-GFP at different time points (days 1 and 10) after tumor implantation. Tumor burden was assessed by bioluminescence imaging. Mesothelioma cell lines exhibited dose-dependent susceptibility to NDV lysis in the following order of sensitivity: MSTO-211H > MSTO-211H* > H-2452 > VAMT > JMN. In vivo studies with MSTO-211H* cells showed complete response to viral therapy in 65% of the animals within 14 days after treatment initiation. Long-term survival in all of these animals was >50 days after tumor installation (control animals, <23 d). Multiple treatment compared with single treatment showed a significantly better response (P = 0.005). NDV seems to be an efficient viral oncolytic agent in the therapy of malignant pleural mesothelioma in an orthotopic pleural mesothelioma tumor model.