Rationally Designed Peptoid Inhibitors of Amyloid-ß Oligomerization.

While plaques comprised of fibrillar Aß aggregates are hallmarks of Alzheimer's disease, soluble Aß oligomers present higher neurotoxicity. Thus, one therapeutic approach is to prevent the formation of Aß oligomers and reduce their associated harmful effects. We have proposed a peptoid mimic of the Aß hydrophobic KLVFF core as an ideal candidate aggregation inhibitor due to its ability to evade proteolytic degradation via repositioning of the side chain from the α-carbon to the amide nitrogen. This peptoid, JPT1, utilizes chiral sidechains to achieve a helical structure, while C-terminal addition of two phenylalanine residues places aromatic groups on two sides of the helix with spacing designed to facilitate interaction with amyloid ß-sheet structure. We have previously shown that JPT1 modulates Aß fibril formation. Here, we demonstrate that JPT1 also modulates Aß oligomerization, and we explore the role of the charge on the linker between the KLVFF mimic and the extended aromatic residues. Additionally, we demonstrate that peptoid-induced changes in Aß oligomerization correlate with attenuation of oligomer-induced nuclear factor-κB activation in SH-SY5Y human neuroblastoma cells. These findings support the therapeutic potential of peptoids to target early stages of Aß aggregation and impact the associated Aß-induced cellular response.

Timely Completion of Direct Access Colonoscopy Is Noninferior to Office Scheduled for Screening and Surveillance.

GOALS: We aimed to evaluate whether direct access colonoscopy (DAC) is noninferior to office-scheduled colonoscopy (OSC) for achieving successful colonoscopy. BACKGROUND: DAC may improve access to colonoscopy. We developed an algorithm assessing eligibility, risk for inadequate preparation, and need for nursing/navigator assistance. STUDY: This was a retrospective, single-center study of DAC and OSC patients from June 5, 2018, to July 31, 2019. Patients were 45 to 75 years old with an indication of screening or surveillance. A successful colonoscopy met 3 criteria: complete colonoscopy (cecum, anastomosis, or ileum), adequate preparation (Boston Score ≥2/segment), and performed <90 days from initial patient contact. Unsuccessful colonoscopy did not meet ≥1 criteria. Secondary end points included days to successful colonoscopy, preparation quality, polyp detection, and 10-year recall rate. Noninferiority against risk ratio value of 0.85 was tested using 1-sided alpha of 0.05. RESULTS: A total of 1823 DAC and 828 OSC patients were eligible. DAC patients were younger, with a greater proportion of black patients and screening indications. For the outcome of successful colonoscopy, DAC was noninferior to OSC (DAC vs. OSC: 62.7% vs. 57.1%, RR 1.16, 95% LCL 1.09, P=0.001). For DAC, days to colonoscopy were fewer, and likelihood of 10-year recall after negative screening greater. Boston Score and polyp detection were similar for groups. Black patients were less likely to achieve successful colonoscopy; otherwise, groups were similar. For unsuccessful colonoscopies, proportionally more DAC patients canceled or no-showed while more OSC patients scheduled >90 days. DAC remained noninferior to OSC at 180 days. CONCLUSIONS: DAC was noninferior to OSC for achieving successful colonoscopy, comparing similarly in quality and efficiency outcomes.

Respecting tribal voices in the development of a gestational diabetes risk reduction preconception counseling program for American Indian/Alaska Native adolescent females: a qualitative study.

BACKGROUND: American Indians and Alaska Natives (AI/AN) are disproportionately affected by adolescent obesity, adolescent pregnancy and gestational diabetes mellitus (GDM). GDM is associated with increased risk for perinatal death, obesity, and subsequent type 2 diabetes (T2D) for the offspring. Moreover, mothers with GDM are also at increased risk for T2D post-partum. Yet few lifestyle interventions exist to reduce GDM risk prior to pregnancy. We describe the process of adapting an existing validated preconception counseling intervention for AI/AN adolescent girls at-risk for GDM and their mothers. Perspectives and recommendations were gathered from a diverse array of stakeholders to assure the new program called Stopping GDM was culturally responsive and developed with tribal voices and perspectives represented. METHODS: We conducted focus groups and individual interviews with multiple AI/AN stakeholders (n = 55). Focus groups and interviews were digitally recorded, transcribed verbatim, and analyzed using a thematic content approach to construct cross-cutting themes across the focus groups and interviews. RESULTS: Four key themes emerged reflecting issues important to planning a reproductive health intervention: 1) Limited awareness, knowledge, and health education resources about GDM; 2) The importance of acknowledging traditional AI/AN values and the diversity of traditions and culture among AI/AN tribes; 3) The need to cultivate healthy decision-making skills and empower girls to make safe and healthy choices; and 4) Lack of communication about reproductive health between AI/AN mothers and daughters and between AI/AN women and health care professionals. CONCLUSION: Findings have been used to inform the cultural tailoring and adaptation of an existing preconception counseling program, originally designed for non-AI/AN adolescent girls with diabetes, for AI/AN adolescents at-risk for GDM in future pregnancies.

Examining the Performance of the MMPI-2-RF in a Sample of Pretransplant Military Veterans.

The present study aimed to describe the personality and psychopathology dimensions reported by veterans seeking organ transplantation, as well as to identify those dimensions associated with subsequent presurgical recommendations and transplant outcomes. Data were collected from 245 veterans undergoing a pretransplant psychological evaluation that included the MMPI-2-RF. Three treatment recommendations resulting from these evaluations, three recommendation adherence variables, and two transplant outcomes were extracted from electronic medical records. The sample's MMPI-2-RF scale scores were compared to the normative sample and two other presurgical samples and contrasted across subgroups defined by organ transplanted. Point-biserial correlations and logistic regression analyses examined associations between MMPI-2-RF scale scores and the eight measured outcomes. Results indicated that over-reporting, internalizing tendencies, negative emotionality, and a lack of positive emotions were uniquely predictive of mental health treatment recommendation, whereas somatic over-reporting, externalizing tendencies, and disinhibition were predictive of substance use treatment recommendation. Veterans who reported higher levels of activation were less likely to initiate mental health treatment. Finally, veterans with greater somatic preoccupation were less likely to be listed for organ transplant. More suspicious and mistrustful veterans were less likely to receive the transplant. These findings offer support for the role of the MMPI-2-RF in veteran pretransplant evaluations.

Universal Hepatitis B Vaccination in Adults Aged 19-59 Years: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

Hepatitis B (HepB) vaccines have demonstrated safety, immunogenicity, and efficacy during the past 4 decades (1,2). However, vaccination coverage among adults has been suboptimal, limiting further reduction in hepatitis B virus (HBV) infections in the United States. This Advisory Committee on Immunization Practices (ACIP) recommendation expands the indicated age range for universal HepB vaccination to now include adults aged 19-59 years. Removing the risk factor assessment previously recommended to determine vaccine eligibility in this adult age group (2) could increase vaccination coverage and decrease hepatitis B cases.

Using machine learning to predict heavy drinking during outpatient alcohol treatment.

BACKGROUND: Accurate clinical prediction supports the effective treatment of alcohol use disorder (AUD) and other psychiatric disorders. Traditional statistical techniques have identified patient characteristics associated with treatment outcomes. However, less work has focused on systematically leveraging these associations to create optimal predictive models. The current study demonstrates how machine learning can be used to predict clinical outcomes in people completing outpatient AUD treatment. METHOD: We used data from the COMBINE multisite clinical trial (n = 1383) to develop and test predictive models. We identified three priority prediction targets, including (1) heavy drinking during the first month of treatment, (2) heavy drinking during the last month of treatment, and (3) heavy drinking between weekly/bi-weekly sessions. Models were generated using the random forest algorithm. We used "leave sites out" partitioning to externally validate the models in trial sites that were not included in the model training. Stratified model development was used to test for sex differences in the relative importance of predictive features. RESULTS: Models predicting heavy alcohol use during the first and last months of treatment showed internal cross-validation area under the curve (AUC) scores ranging from 0.67 to 0.74. AUC was comparable in the external validation using data from held-out sites (AUC range = 0.69 to 0.72). The model predicting between-session heavy drinking showed strong classification accuracy in internal cross-validation (AUC = 0.89) and external test samples (AUC range = 0.80 to 0.87). Stratified analyses showed substantial sex differences in optimal feature sets. CONCLUSION: Machine learning techniques can predict alcohol treatment outcomes using routinely collected clinical data. This technique has the potential to greatly improve clinical prediction accuracy without requiring expensive or invasive assessment methods. More research is needed to understand how best to deploy these models.

Sexual minority disparities in opioid and benzodiazepine misuse among adults with opioid use disorder.

BACKGROUND AND OBJECTIVES: Sexual minority individuals demonstrate disparate rates of substance use. Research suggests that bisexual women are vulnerable to substance use disorders when compared to other sexual minority groups. This study explored differences in prevalence of past-year alcohol use disorder (AUD) with and without concurrent past-year opioid and/or benzodiazepine misuse. METHODS: The present study utilized responses from the National Survey on Drug Use and Health (NSDUH) public dataset between the years 2015-2019 (N = 16,002) to examine the association between sexual orientation and concurrent misuse of opioids and/or benzodiazepines among individuals with past-year AUD, stratified by sex. RESULTS: Bisexual females demonstrated higher rates of concurrent opioid and benzodiazepine use compared to all other groups. Although there was no association between sexual orientation and concurrent substance use patterns among males, female respondents with past-year AUD endorsing past-year misuse of opioids and benzodiazepines, both alone and in combination, were more likely to be bisexual compared to heterosexual. Lesbians were less likely to endorse concurrent misuse of opioids and benzodiazepines compared to bisexual females. DISCUSSION AND CONCLUSIONS: In a national sample, bisexual females demonstrated higher odds of risky concurrent substance use patterns. Identifying sexual minority individuals who exhibit elevated risk of co-occurring alcohol, opioid, and/or benzodiazepine misuse is an important step to targeted prevention efforts and allocation of resources to combat rising overdose deaths. SCIENTIFIC SIGNIFICANCE: For the first time, this study explored risky concurrent alcohol, opioid, and benzodiazepine misuse patterns among individuals of different sexual orientations.

Licit and illicit drug use across trimesters in pregnant women endorsing past-year substance use: Results from National Survey on Drug Use and Health (2009-2019).

PURPOSE: Given the health consequences, perinatal substance use is a significant public health concern, especially as substance use rates increase among women; ongoing data regarding the rates of substance use across trimesters of pregnancy is needed. METHODS: The present study utilized cross-sectional population-based data from the National Survey of Drug Use and Health (NSDUH) between 2009 and 2019. We aimed to explore both licit and illicit substance use assessed within each trimester among women endorsing past-year substance use. The NSDUH sample included 8,530 pregnant women. RESULTS: Perinatal substance use was less prevalent among women in later trimesters; however, past-month substance use was observed for all substances across trimesters. The prevalence of past-month licit substance use among pregnant women ranged from 5.77 to 22.50% and past-month illicit substance use ranged from 4.67 to 14.81%. In the second trimester, lower odds of past-month substance use were observed across tobacco, alcohol, and marijuana (odds ratios [ORs] ranging from 0.29 to 0.47), when compared to the first trimester. A similar lower rate of past-month substance use was observed in the third trimester compared to the first trimester, across tobacco, alcohol, and marijuana use, as well as cocaine, prescription pain medication, and tranquilizer use (ORs ranging from 0.02 to 0.42). The likelihood of polysubstance use was lower among women in the second and third trimesters compared to the first trimester (ORs ranging from 0.09 to 0.46). CONCLUSION: Findings indicate that a minority of women continue to use substances across all trimesters. This is especially true among women using licit substances and marijuana. These results highlight the need for improved interventions and improved access to treatment for these women.

Associations Between Rurality, pre-pregnancy Health Status, and Macrosomia in American Indian/Alaska Native Populations.

OBJECTIVES: To examine the relationships between pre-pregnancy diabetes mellitus (DM), gestational diabetes mellitus (GDM), pre-pregnancy body mass index (BMI) and county-level social determinants of health, with infant macrosomia within a sample of American Indian/Alaska Native (AI/AN) women receiving Indian Health Service (IHS) care. METHODS: The sample included women-infant dyads representing 1,136 singleton births from fiscal year 2011 (10/1/2019-9/30/2011). Data stemmed from the IHS Improving Health Care Delivery Data Project. Multivariate generalized linear mixed models were fitted to assess the association of macrosomia with pre-pregnancy health status and social determinants of health. RESULTS: Nearly half of the women in the sample were under age 25 years (48.6%), and most had Medicaid health insurance coverage (76.7%). Of those with a pre-pregnancy BMI measure, 66.2% were overweight or obese. Although few women had pre-pregnancy DM (4.0%), GDM was present in 12.8% of women. Most women had a normal term delivery (85.4%). Overweight, obesity, pre-pregnancy DM, and county-level rurality were all significantly associated with higher odds of infant macrosomia.

Sex Differences across Retrospective Transitions in Posttraumatic Stress and Substance Use Disorders.

Objectives: Concurrent substance use disorder (SUD) and posttraumatic stress disorder (PTSD) occur at high rates and are typically associated with poor treatment outcomes in both sexes. However, women have a propensity to cope with increased negative affect via substance use in comparison to men; thus, it is important to elucidate the sex-specific bidirectional relationships between SUD and PTSD to improve our understanding of concurrent SUD/PTSD in men and women. Methods: Using data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-Wave 3; n = 36,309), the present study evaluated the impact of sex on the relationship between past-year SUDs (new, remitted, ongoing), including alcohol and drug use, and retrospective transitions in new vs. absent and ongoing vs. remitted diagnoses of PTSD. Additionally, the impact of sex was explored in models examining past year PTSD (new, remitted, ongoing) and retrospective transitions in new vs. absent and ongoing vs. remitted diagnosis of SUDs. Diagnostic transitions were based on retrospective reporting. Results: Results indicated that new, remitted, and ongoing SUDs increase the likelihood of new PTSD diagnoses (OR range = 2.53-8.11; p < 0.05). Among individuals with ongoing drug use disorders (DUD), there were greater odds of ongoing PTSD (OR = 2.10, p < 0.01). When examining the relationship reciprocally, new, remitted, and ongoing PTSD increased the likelihood of new SUDs (OR range = 2.50-8.22; p < 0.05), and ongoing PTSD increased the likelihood of ongoing SUD and DUD (OR = 1.40, 1.70, respectively; p < 0.05). Sex-specific analyses revealed that the relationship between PTSD and SUDs varies between sexes, particularly among women. For instance, women with new PTSD had higher odds of SUDs, and women with ongoing PTSD were almost 2.5 times more likely to have an ongoing DUD. Women with a new PTSD diagnosis were more likely to be diagnosed with a new SUD (OR = 3.27) and an ongoing DUD (OR = 3.08). Conclusions: Results indicate a bidirectional relationship between PTSD and SUD that is in many instances larger in women. Thus, illustrating potential sex-specific differences in underlying mechanisms implicated in SUD/PTSD, warranting additional research.

Prevention of Hepatitis A Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices, 2020.

HEPATITIS A IS A VACCINE-PREVENTABLE, COMMUNICABLE DISEASE OF THE LIVER CAUSED BY THE HEPATITIS A VIRUS (HAV). THE INFECTION IS TRANSMITTED VIA THE FECAL-ORAL ROUTE, USUALLY FROM DIRECT PERSON-TO-PERSON CONTACT OR CONSUMPTION OF CONTAMINATED FOOD OR WATER. HEPATITIS A IS AN ACUTE, SELF-LIMITED DISEASE THAT DOES NOT RESULT IN CHRONIC INFECTION. HAV ANTIBODIES (IMMUNOGLOBULIN G [IGG] ANTI-HAV) PRODUCED IN RESPONSE TO HAV INFECTION PERSIST FOR LIFE AND PROTECT AGAINST REINFECTION; IGG ANTI-HAV PRODUCED AFTER VACCINATION CONFER LONG-TERM IMMUNITY. THIS REPORT SUPPLANTS AND SUMMARIZES PREVIOUSLY PUBLISHED RECOMMENDATIONS FROM THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) REGARDING THE PREVENTION OF HAV INFECTION IN THE UNITED STATES. ACIP RECOMMENDS ROUTINE VACCINATION OF CHILDREN AGED 12-23 MONTHS AND CATCH-UP VACCINATION FOR CHILDREN AND ADOLESCENTS AGED 2-18 YEARS WHO HAVE NOT PREVIOUSLY RECEIVED HEPATITIS A (HEPA) VACCINE AT ANY AGE. ACIP RECOMMENDS HEPA VACCINATION FOR ADULTS AT RISK FOR HAV INFECTION OR SEVERE DISEASE FROM HAV INFECTION AND FOR ADULTS REQUESTING PROTECTION AGAINST HAV WITHOUT ACKNOWLEDGMENT OF A RISK FACTOR. THESE RECOMMENDATIONS ALSO PROVIDE GUIDANCE FOR VACCINATION BEFORE TRAVEL, FOR POSTEXPOSURE PROPHYLAXIS, IN SETTINGS PROVIDING SERVICES TO ADULTS, AND DURING OUTBREAKS.

Identifying Relative Changes in Social Risk Factors: An Analytic Approach.

BACKGROUND: Individuals often report concurrent social risk factors such as food insecurity, unstable housing, and transportation barriers. Comparing relative changes between pairs of social risk factors may identify those that are more resistant to change. OBJECTIVE: The objective of this study was to develop a method to describe relative changes in pairs of social risk factors. RESEARCH DESIGN: This was a prospective cohort study. SUBJECTS: Participants in a randomized controlled trial of hypertension care in an Urban Indian Health Organization. MEASURES: We measured 7 social risk factors (housing, transportation, food, clothing, health care, utilities, and debts) at enrollment, 6, and 12 months among 295 participants in the trial. We hypothesized that pairwise comparisons could identify social risk factors that were less likely to change over time. We used conditional odds ratios (ORs) with 95% confidence intervals (CIs) to rank each pair. RESULTS: Food, clothing, health care, utilities, and debts had more changes between 0 and 6 months relative to housing (OR=2.3, 3.4, 4.7, 3.5, and 3.4, respectively; all 95% CI excluded 1.0). These same social risk factors also had more changes between baseline and 6 months relative to transportation (OR=2.8, 3.4, 4.9, 4.7, and 4.1, respectively; all 95% CI excluded 1.0). Changes in housing and transportation risk factors were comparable (OR=0.7, 95% CI: 0.4-1.4). Relative changes between 6 and 12 months were similar. CONCLUSIONS: Housing and transportation exhibited fewer relative changes than other social risk factors and might be more resistant to change. Awareness of the relationships between social risk factors can help define priorities for intervention.

Multi-level Diabetes Prevention and Treatment Interventions for Native People in the USA and Canada: a Scoping Review.

PURPOSE OF REVIEW: This scoping literature review seeks to answer the question "What is known in the existing literature about multi-level diabetes prevention and treatment interventions for Native people living in the United States and Canada?" RECENT FINDINGS: Multi-level interventions to prevent and/or treat chronic diseases, such as diabetes, promise to help individuals who experience health disparities related to social determinants of health. As described by the socio-ecological model, such interventions mobilize support through a combination of individual, interpersonal, organizational, community, and policy levels of activity. This review revealed little literature about multi-level diabetes prevention and/or treatment programs for US and Canada-based Native peoples. Ten interventions were identified; all focused on diabetes prevention; eight were specific to youth. Multi-level intervention design elements were largely individual-, school-, and community-based. Only three interventions included environmental or policy-level components.

The CAPACITI Decision-Support Tool for National Immunization Programs.

OBJECTIVES: Immunization programs in low-income and middle-income countries (LMICs) are faced with an ever-growing number of vaccines of public health importance recommended by the World Health Organization, while also financing a greater proportion of the program through domestic resources. More than ever, national immunization programs must be equipped to contextualize global guidance and make choices that are best suited to their setting. The CAPACITI decision-support tool has been developed in collaboration with national immunization program decision makers in LMICs to structure and document an evidence-based, context-specific process for prioritizing or selecting among multiple vaccination products, services, or strategies. METHODS: The CAPACITI decision-support tool is based on multi-criteria decision analysis, as a structured way to incorporate multiple sources of evidence and stakeholder perspectives. The tool has been developed iteratively in consultation with 12 countries across Africa, Asia, and the Americas. RESULTS: The tool is flexible to existing country processes and can follow any type of multi-criteria decision analysis or a hybrid approach. It is structured into 5 sections: decision question, criteria for decision making, evidence assessment, appraisal, and recommendation. The Excel-based tool guides the user through the steps and document discussions in a transparent manner, with an emphasis on stakeholder engagement and country ownership. CONCLUSIONS: Pilot countries valued the CAPACITI decision-support tool as a means to consider multiple criteria and stakeholder perspectives and to evaluate trade-offs and the impact of data quality. With use, it is expected that LMICs will tailor steps to their context and streamline the tool for decision making.

An online diabetes nutrition education programme for American Indian and Alaska Native adults with type 2 diabetes: perspectives from key stakeholders.

OBJECTIVE: To explore stakeholder perspectives regarding online diabetes nutrition education for American Indians and Alaska Natives (AI/AN) with type 2 diabetes (T2D). DESIGN: Qualitative data were collected through focus groups and interviews. Focus group participants completed a brief demographic and internet use survey. SETTING: Focus groups and community participant interviews were conducted in diverse AI/AN communities. Interviews with nationally recognised content experts were held via teleconference. PARTICIPANTS: Eight focus groups were conducted with AI/AN adults with T2D (n 29) and their family members (n 22). Community participant interviews were conducted with eleven clinicians and healthcare administrators working in Native communities. Interviews with nine content experts included clinicians and researchers serving AI/AN. RESULTS: Qualitative content analysis used constant comparative method for coding and generating themes across transcripts. Descriptive statistics were computed from surveys. AI/AN adults access the internet primarily through smartphones, use the internet for many purposes and identify opportunities for online diabetes nutrition education. CONCLUSIONS: Online diabetes nutrition education may be feasible in Indian Country. These findings will inform the development of an eLearning diabetes nutrition education programme for AI/AN adults with T2D.

Development and integration of a wound cleansing pathway into clinical practice.

Wound bed preparation has come into sharper focus over the past decade, with strategies identified to improve wound condition. This article focuses on implementing a wound cleansing policy and measuring, through audits, how this change affected rates of wound infection. From 2016 onwards, the Skin Integrity Team at Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust took steps to revise and improve wound care practices. This resulted in the introduction of a wound cleansing pathway incorporating a surfactant-based cleanser in place of saline, with subsequent staff training and other changes made to practice. This study details the steps taken to implement the new pathway, which brought a reduction in wound infections of 84.3% between 2017 and 2019.

Novel Aminoglycoside-Tolerant Phoenix Colony Variants of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen and is known to produce biofilms. We previously showed the emergence of colony variants in the presence of tobramycin-loaded calcium sulfate beads. In this study, we characterized the variant colonies, which survived the antibiotic treatment, and identified three distinct phenotypes-classically resistant colonies, viable but nonculturable colonies (VBNC), and phoenix colonies. Phoenix colonies, described here for the first time, grow out of the zone of clearance of antibiotic-loaded beads from lawn biofilms while there are still very high concentrations of antibiotic present, suggesting an antibiotic-resistant phenotype. However, upon subculturing of these isolates, phoenix colonies return to wild-type levels of antibiotic susceptibility. Compared with the wild type, phoenix colonies are morphologically similar aside from a deficiency in green pigmentation. Phoenix colonies do not recapitulate the phenotype of any previously described mechanisms of resistance, tolerance, or persistence and, thus, form a novel group with their own phenotype. Growth under anaerobic conditions suggests that an alternative metabolism could lead to the formation of phoenix colonies. These findings suggest that phoenix colonies could emerge in response to antibiotic therapies and lead to recurrent or persistent infections, particularly within biofilms where microaerobic or anaerobic environments are present.

Licensure of a Diphtheria and Tetanus Toxoids and Acellular Pertussis, Inactivated Poliovirus, Haemophilus influenzae Type b Conjugate, and Hepatitis B Vaccine, and Guidance for Use in Infants.

On December 21, 2018 the Food and Drug Administration (FDA) licensed a hexavalent combined diphtheria and tetanus toxoids and acellular pertussis (DTaP) adsorbed, inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib) conjugate (meningococcal protein conjugate) and hepatitis B (HepB) (recombinant) vaccine, DTaP-IPV-Hib-HepB (Vaxelis; MCM Vaccine Company),* for use as a 3-dose series in infants at ages 2, 4, and 6 months (1). On June 26, 2019, after reviewing data on safety and immunogenicity, the Advisory Committee on Immunization Practices (ACIP)† voted to include DTaP-IPV-Hib-HepB in the federal Vaccines for Children (VFC) program.§ This report summarizes the indications for DTaP-IPV-Hib-HepB and provides guidance for its use.

Recommendations from an expert panel of health professionals regarding a gestational diabetes risk reduction intervention for American Indian/Alaska Native Teens.

BACKGROUND: American Indian/Alaska Native (AI/AN) adolescents are at higher risk for gestational diabetes (GDM), type 2 diabetes, and pregnancy complications than the general population. OBJECTIVE: To inform cultural adaptation of a validated evidence-based intervention (VEBI) originally designed to deliver preconception counseling and diabetes education to non-AI/AN teens with diabetes. DESIGN: Qualitative data were collected using focus group and individual interview methods with health care professionals and experts (n = 16) in AI/AN health, GDM, adolescent health, and/or mother-daughter communication. A semistructured discussion guide elicited responses about provision of care for AI/AN girls at risk for GDM, experience with successful programs for AI/AN teens, comfort of mother/daughter dyads in talking about diabetes and reproductive health and reactions to video clips and booklet selections from the VEBI. All interviews were recorded and transcribed verbatim, and data analysis included inductive coding and identification of emergent themes. RESULTS: Providers felt teens and their moms would be comfortable talking about the VEBI topics and that teens who did not feel comfortable talking to their mom would likely rely on another adult female. Participants suggested including: AI/AN images/motifs, education with a community focus, and avoiding directive language. Concerns included: socioeconomic issues that affect AI/AN people such as: food and housing insecurity, abuse, and historical trauma. CONCLUSIONS: Perspectives from these participants have been used to guide the development of a culturally tailored GDM risk reduction program for AI/AN girls. This program will be available to health care providers who serve the AI/AN population.

Binding Interactions of Ergotamine and Dihydroergotamine to 5-Hydroxytryptamine Receptor 1B (5-HT1b) Using Molecular Dynamics Simulations and Dynamic Network Analysis.

Ergotamine (ERG) and dihydroergotamine (DHE), common migraine drugs, have small structural differences but lead to clinically important distinctions in their pharmacological profiles. For example, DHE is less potent than ERG by about 10-fold at the 5-hydroxytrptamine receptor 1B (5-HT1B). Although the high-resolution crystal structures of the 5-HT1B receptor with both ligands have been solved, the high similarity between these two complex structures does not sufficiently explain their activity differences and the activation mechanism of the receptor. Hence, an examination of the dynamic motion of both drugs with the receptor is required. In this study, we ran a total of 6.0 µs molecular dynamics simulations on each system. Our simulation data show the subtle variations between the two systems in terms of the ligand-receptor interactions and receptor secondary structures. More importantly, the ligand and protein root-mean-square fluctuations (RMSFs) for the two systems were distinct, with ERG having a trend of lower RMSF values, indicating it to be bound tighter to 5-HT1B with less fluctuations. The molecular mechanism-general born surface area (MM-GBSA) binding energies illustrate this further, proving ERG has an overall stronger MM-GBSA binding energy. Analysis of several different microswitches has shown that the 5-HT1B-ERG complex is in a more active conformation state than 5-HT1B-DHE, which is further supported by the dynamic network model, with reference to mutagenesis data with the critical nodes and the first three low-energy modes from the normal mode analysis. We also identify Trp3276.48 and Phe3316.52 as key residues involved in the active state 5-HT1B for both ligands. Using the detailed dynamic information from our analysis, we made predictions for possible modifications to DHE and ERG that yielded five derivatives that might have more favorable binding energies and reduced structural fluctuations.