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Abstract Background With an increasing proportion of older adults and the associated risk of Alzheimer’s Disease and Related Dementias (ADRD) around the globe, there is an urgent need to engage in ADRD risk reduction efforts. African American (AA) older adults in the U.S. are disproportionally impacted by ADRD compared to other races and ethnicities. Mindful walking integrates two potentially protective factors of ADRD by elevating mindfulness and physical activity (i.e., walking), resulting in a synergistic behavioral strategy that is feasible and safe for older adults. However, the efficacy of applying this intervention for cognitive health outcomes has not been evaluated using experimental designs. Methods This paper documents the goal and protocol of a community-based, mindful walking randomized controlled trial to examine the short- and longer-term efficacy on cognitive and other health-related outcomes in ADRD at-risk AA older adults. The study outcomes include various brain health determinants, including cognitive function, quality of life, psychological well-being, physical activity, mindfulness, sleep, and overall health status. In addition, the estimated costs of program implementation are also collected throughout the study period. This study will recruit 114 older adults (ages 60+ years) with elevated ADRD risk from the Midlands region of South Carolina. Older adults are randomly assigned to participate in 24 sessions of outdoor mindful walking over three months or a delayed mindful walking group (n=57 in each group). Participants in both groups follow identical measurement protocols at baseline, after 12 weeks, after 18 weeks, and after 24 weeks from baseline. The outcome measures are administered in the lab and in everyday settings. Costs per participant are calculated using micro-costing methods. The eliciting participant costs for mindful walking engagement with expected results are reported using the payer and the societal perspectives. Discussion This study will generate evidence regarding the efficacy of mindful walking on sustaining cognitive health in vulnerable older adults. The results can inform future large-scale effectiveness trials to support our study findings. If successful, this mindful walking program can be scaled up as a low-cost and viable lifestyle strategy to promote healthy cognitive aging in diverse older adult populations, including those at greatest risk. Trial registration ClinicalTrials.gov number NCT06085196 (retrospectively registered on 10/08/2023).

BackgroundThe concept of health literacy (HL) is constantly evolving, and social determinants of health (SDoH) have been receiving considerable attention in public health scholarship. Since a 1-size-fits-all approach for HL fails to account for multiple contextual factors and as a result poses challenges in improving literacy levels, there is a need to develop a deeper understanding of the current state of HL and digital health literacy (DHL) research. ObjectiveThis study examined scholars’ conceptualization and scope of work focused on HL and DHL. MethodsUsing a search string, investigators (N=2042) focusing on HL, DHL, or both were identified from the grantee websites of the National Institutes of Health RePORTER (RePORT Expenditures and Results) and the Canadian Institutes of Health Research. The investigators were emailed a survey via Qualtrics. Survey questions examined the focus of work; whether the investigators studied HL/DHL in combination with other SDoH; the frameworks, definitions, and approaches used; and research settings. We analyzed survey data using SPSS Statistics version 28 and descriptive analysis, including frequencies and percentages, was conducted. Chi-square tests were performed to explore the association between the focus of work, settings, and age groups included in the investigators’ research. ResultsA total of 193 (9.5%) of 2042 investigators responded to the online survey. Most investigators (76/153, 49.7%) were from public health, 83/193 (43%) reported their research focused on HL alone, 46/193 (23.8%) mentioned DHL, and 64/193 (33.2%) mentioned both. The majority (133/153, 86.9%) studied HL/DHL in combination with other SDoH, 106/135 (78.5%) conducted HL/DHL work in a community setting, and 100/156 (64.1%) reported not using any specific definition to guide their work. Digital tools (89/135, 65.9%), plain-language materials (82/135, 60.7%), and visual guides (56/135, 41.5%) were the top 3 approaches used. Most worked with adults (131/139, 94.2%) and all races and ethnicities (47/121, 38.8%). ConclusionsHL and DHL research largely considered SDoH. Multiple HL tools and approaches were used that support the examination and improvement of literacy and communication surrounding health care issues.

BackgroundThe sale of loose cigarettes or bidis can undermine the purpose of requiring health warning labels (HWLs) on cigarette packs and bidi bundles by diminishing their visibility and legibility. ObjectiveThis mixed-methods study aims to examine the association between purchase behavior (loose vs pack or bundle), HWL exposure, and responses to HWLs among Indian adults who smoke. MethodsData were analyzed from the 2018-2019 India Tobacco Control Policy Survey and from 28 in-depth interviews conducted with Indian adults who smoked in 2022. The Tobacco Control Policy Survey sample included tobacco users who bought cigarettes (n=643) or bidis (n=730), either loose or in packs or bundles at their last purchase. Ordinal regression models were fit separately for cigarettes and bidis, whereby HWL variables (noticing HWLs, reading and looking closely at HWLs, forgoing a cigarette or bidi because of HWLs, thinking about health risks of smoking, and thinking about quitting smoking cigarettes or bidis because of HWLs) were regressed on last purchase (loose vs packs or bundles). In-depth interviews with participants from Delhi and Mumbai who purchased loose cigarettes in the last month were conducted, and thematic analysis was used to analyze the interview data. ResultsSurvey findings indicated that about 74.3% (478/643) of cigarette users and 11.8% (86/730) of bidi users reported having bought loose sticks at their last purchase. Those who purchased loose cigarettes (vs packs) noticed HWLs less often (estimate –0.830, 95% CI –1.197 to –0.463, P

IntroductionBanning the sales of loose cigarettes is recommended by Article 16 of the World Health Organization – Framework Convention on Tobacco Control. This study aims to understand the perceptions of cigarette users and tobacco vendors regarding such a ban.MethodsUsing a systematic recruitment and interview protocol, we interviewed cigarette users (n = 28) and tobacco vendors (n = 28) from two Indian cities where sales of loose cigarettes were banned (Mumbai) or not banned (Delhi). Separate semi-structured interview guides were used for users and vendors. Interview questions focused on reasons for purchasing loose cigarettes, preference for buying and selling loose vs. packs, thoughts on the necessity of banning loose cigarettes, and the perceived impact of the policy ban for vendors and cigarette users. We performed thematic analysis and used NVivo for organizing transcript coding.ResultsThe main reasons users cited for purchasing loose cigarettes were financial constraints, social restrictions (fear of getting caught), and limiting cigarette consumption. In Mumbai, awareness of the existing ban was poor among both users and vendors. Those who were aware did not think the policy had been implemented. Users thought that loose cigarettes promoted smoking initiation and prevented them from quitting. Both users and vendors reported that a ban on loose cigarettes would reduce cigarette consumption and promote quit attempts as it would not be possible for everyone to purchase packs because of financial and social reasons.ConclusionUsers in both cities reported easy access to and widespread availability of loose cigarettes. Low awareness of the ban in Mumbai suggested inadequate enforcement. A country-wide ban on the sale of loose cigarettes could be highly effective in preventing smoking initiation and promoting quitting.

Abstract Objectives Periodontal disease is understood to be a result of dysbiotic interactions between the host and the biofilm, causing a unique reaction for each individual, which in turn characterizes their susceptibility. The objective of this study was to chronologically evaluate periodontal tissue destruction induced by systemic bacterial challenge in known susceptible (BALB/c) and resistant (C57BL/6) mouse lineages. Material and Methods Animals, 6–8 weeks old, were allocated into three experimental groups: Negative control (C), Gavage with sterile carboxymethyl cellulose 2%—without bacteria (Sham), and Gavage with carboxymethyl cellulose 2% + Porphyromonas gingivalis (Pg‐W83). Before infection, all animals received antibiotic treatment (sulfamethoxazole/trimethoprim, 400/80 mg/5 mL) for 7 days, followed by 3 days of rest. Microbial challenge was performed 3 times per week for 1, 2, or 3 weeks. After that, the animals were kept until the completion of 42 days of experiments, when they were euthanized. The alveolar bone microarchitecture was assessed by computed microtomography. Results Both C57BL/6 and BALB/c mice exhibited significant bone volume loss and lower trabecular thickness as well as greater bone porosity compared to the (C) and (Sham) groups after 1 week of microbial challenge (p

BackgroundNon-germinomatous germ cell tumors (NGGCT) accounts for one third of intracranial GCT. While the germinoma group have an excellent overall survival, the standard of practice for children with NGGCT is still under evaluation.AimsDescribe the results of the of the Brazilian consortium protocol.MethodsSince 2013, 15 patients with a diagnosis of NGGCT by histopathology and/or serum/cerebrospinal fluid (CSF) tumor markers, βHCG >200mlU/ml and/or positive alpha-fetoprotein were treated with neoadjuvant chemotherapy with carboplatin, cyclophosphamide and etoposide followed by ventricular radiotherapy (RTV) of 18Gy with boost (32Gy) to the primary site. Metastatic patients underwent craniospinal irradiation (CSI) and “slow responders” to the four initial cycles of CT, to autologous stem cell transplantation (ASCT) followed by CSI.ResultsMean age, 13.1 years. Thirteen males. Primary sites: pineal (n=12), suprasellar (n=2) and bifocal (n=1). Four patients were metastatic at diagnosis. Eight patients had CSF and/or serum alpha-fetoprotein levels > 1,000ng/ml. Tumor responses after chemotherapy demonstrated complete in six cases and partial in seven, with “second-look” surgery being performed in five cases, and two patients presenting viable lesions being referred to ASCT. The main toxicity observed was hematological grades 3/4. Two patients with metastatic disease, one with Down Syndrome and AFP > 1,000ng/ml and the other with choriocarcinoma and pulmonary metastases, developed progressive disease resulting in death, as well as two other patients without evidence of disease, due to endocrinological disorders. Event-free and overall survival at 2 and 5 years were 80% and 72.7%, respectively, with a mean follow-up of 48 months (range, 7-107).ConclusionsDespite the small number of patients, in our series, treatment with six cycles of chemotherapy and RTV with focal boost for localized disease (n=11) and ACST for identified slow responders (n=2) seem to be effective strategies contributing to the overall effort to improve outcomes of this group of patients.

We studied the effect of titanium dioxide (TiO2) nanoparticles (NPs) on dielectric behavior of Na[Formula: see text] ion-conducting salt-complexed polymer nanocomposite system formed from a binary polymer blend of poly(ethylene oxide) (PEO) and polyvinyl pyrrolidone (PVP), with the addition of both sodium metaperiodate (NaIO4) at concentration 10[Formula: see text]wt.% and TiO2 NPs of size ∼10[Formula: see text]nm, at concentrations 1, 2, 3, 4 and 5[Formula: see text]wt.%. Free standing nanocomposite PEO/PVP/NaIO4/TiO2 films (150[Formula: see text][Formula: see text]m) were characterized at room-temperature by analyzing their complex electrical impedance and dielectric spectra in the range 1[Formula: see text]Hz–1[Formula: see text]MHz. At the concentration of 3[Formula: see text]wt.% of TiO2 NPs, both ion conductivity and dielectric permittivity of the PEO/PVP/NaIO4/TiO2 ion-conducting dielectrics reach an enhancement by more than one order of magnitude as compared to nanoadditive-free case.

Abstract Background: The Centers for Disease Control and Prevention (CDC)-funded Cancer Prevention and Control Research Network (CPCRN) has been a leader in cancer-related dissemination & implementation (D&I) science. Given increased demand for D&I research, the CPCRN Scholars Program launched in 2021 to expand the number of practitioners, researchers, and trainees proficient in cancer D&I science methods. Methods: The evaluation was informed by a logic model and data collected through electronic surveys. Through an application process (baseline survey), we assessed scholars’ competencies in D&I science domains/subdomains, collected demographic data, and asked scholars to share proposed project ideas. We distributed an exit survey one month after program completion to assess scholars’ experience and engagement with the program and changes in D&I competencies. A follow-up survey was administered to alumni nine months post-program to measure their continued network engagement, accomplishments, and skills. Results: Three cohorts completed the program, consisting of 20, 17, and 25 scholars in Years 1-3, respectively. There was a significant increase in the total D&I competency scores for all three cohorts for 4 overarching domains and 43 subdomains (MPre = 1.38 MPost = 1.89). Differences were greatest for the domain of Practice-Based Considerations (0.50 mean difference) and Theory & Analysis (0.47 mean difference). Alumni surveys revealed that scholars appreciated access to D&I-focused webinars, toolkits, and training resources. 80% remain engaged with CPCRN workgroups and investigators. Conclusions: Program evaluation with scholars and alumni helped with ongoing quality assurance, introspection, and iterative program adaptation to meet scholars’ needs. This approach is recommended for large-scale capacity-building training programs.

This study aimed to evaluate laypersons’ esthetic perception of different dentogingival characteristics based on smile dynamics. Six voluntary models were selected, with only one presenting dentogingival characteristics within esthetic standards: white teeth, good alignment, and adequate gingival contour. Two videos were then produced. One video focused on the mouth, whereas the other focused on the entire face of the model, to ensure that the dynamics of the smile could be evaluated. For the evaluation, 200 laypeople were asked to rank the models from first to sixth place in their order of preference. Laypeople were required to justify their reasons for choosing the first and last places. The obtained data were subjected to descriptive and inferential statistical analyses. The results showed that smile and face dynamics influenced the perception of dentogingival characteristics and facial esthetics. No significant changes were observed. However, a gummy smile accompanied by dental alterations was observed in the video of the mouth and was masked by the facial set exposed in the video of the face. A diastema between the central incisors was decisive for negative evaluation of both the mouth and face. The standard model was rated as the most pleasing. Smiles and facial dynamics influence the perception of dentogingival characteristics. Smile and facial dynamics influence the perception of dentogingival alterations among Brazilian laypeople. Diastema is an alteration that interferes with the isolated evaluation of the lower third of the face and the facial set.

Objective: Radical prostatectomy is the recommended treatment for localized prostate cancer; however, it is an invasive procedure that can leave serious morbidity. Robot-assisted radical prostatectomy was introduced with the aim of reducing postoperative morbidity and facilitating rapid recovery compared to the traditional Walsh's open radical retropubic prostatectomy. Therefore, a protocol was developed to perform an open prostatectomy comparable to that performed by robotics, but without involving novel instrumentation. Methods: A total of 220 patients diagnosed with localized prostate cancer underwent radical prostatectomy. They were divided into two groups: anterograde technique (115 patients) and the retrograde method (105 patients). The study outcomes were observed 3 months after surgery. Results: No differences were found in terms of surgical time, hospital stay, and suction drainage. However, reduced bleeding was observed in the anterograde technique (p=0.0003), with rapid anastomosis duration (p=0.005). Among the patients, 60.9% undergoing the anterograde technique were continent 3 months after surgery compared to 42.9% treated by the retrograde method (p=0.007). Additionally, fewer complications in terms of the number (p=0.007) and severity (p=0.0006) were observed in the anterograde technique. Conclusion: The anterograde method displayed increased efficiency in reducing complications, compared to the retrograde technique.

Introduction: Cancer rates increase with age, and older cancer survivors have unique medical care needs, making assessment of health status and identification of appropriate supportive resources key to delivery of optimal cancer care. Comprehensive geriatric assessments (CGAs) help determine an older person’s functional capabilities as cancer care providers plan treatment and follow-up care. Despite its proven utility, research on implementation of CGA is lacking.Methods: Guided by a qualitative description approach and through interviews with primary care providers and oncologists, our goal was to better understand barriers and facilitators of CGA use and identify training and support needs for implementation. Participants were identified through Cancer Prevention and Control Research Network partner listservs and a national cancer and aging organization. Potential interviewees, contacted via email, were provided with a description of the study purpose. Eight semi-structured interviews were conducted via Zoom, recorded, and transcribed verbatim by a professional transcription service. The interview guide explored providers’ knowledge and use of CGAs. For codebook development, three representative transcripts were independently reviewed and coded by four team members. The interpretive process involved reflecting, transcribing, coding, and searching for and identifying themes.Results: Providers shared that, while it would be ideal to administer CGAs with all new patients, they were not always able to do this. Instead, they used brief screening tools or portions of CGAs, or both. There was variability in how CGA domains were assessed; however, all considered CGAs useful and they communicated with patients about their benefits. Identified facilitators of implementation included having clinic champions, an interdisciplinary care team to assist with implementation and referrals for intervention, and institutional resources and buy-in. Barriers noted included limited staff capacity and competing demands on time, provider inexperience, and misaligned institutional priorities.Discussion: Findings can guide solutions for improving the broader and more systematic use of CGAs in the care of older cancer patients. Uptake of processes like CGA to better identify those at risk of poor outcomes and intervening early to modify treatments are critical to maximize the health of the growing population of older cancer survivors living through and beyond their disease.

Stevia mash (SM), leaves of Stevia rebaudiana Bertoni plant, is an additive used in poultry that enhances growth and health. Objective: to determine the effect of 1 % SM on productive parameters, gut health, and the cecal microbiome in broilers between the first 15 and 21 days old. One hundred sixty male, 1-day-old broilers (48.5 ± 2.5 g) were divided into Control (C) without SM and Treated (T) with 1 % SM on diet, during 15/21 days. Each subgroup had eight broilers/five repetitions/treatment. At day 15 or 21, all broilers were dissected, Fabricius Bursa and Gut removed and processed for histomorphometry, followed by Villi Height/Crypt Deep (VH/CD) ratio. Conversion Index (CI) was determined. The V3-V4 region of 16S rRNA gene was amplified from DNA obtained from pooled cecal contents and sequenced on Illumina Miseq PE 2 × 250 platform. Sequence processing and taxonomic assignments were performed using the SHAMAN pipeline. Both T groups have better VH/CD Ratios than C groups (p ≤ 0.05). In guts, increased plasmatic and goblet cells number and thicker mucus layer were found in T15 and T21. All groups received SM showed early immunological maturity in Fabricius Bursa. IC was similar between all treatments. Faecalibacterium, Ruminococcus torques group, and Bacteroides were the major genera modulated by SM addition. At 15 and 21 days old, SM exerts a impact on diversity and evenness of the cecal microbiome. Conclusion: SM (1 %) produced early immunologic maturity on Fabricius Bursa, increased intestinal functionality, and modified the microbiota, increasing beneficial microbial genera and microbial diversity.

BackgroundAs telemedicine plays an increasing role in health care delivery, providers are expected to receive adequate training to effectively communicate with patients during telemedicine encounters. Teach-back is an approach that verifies patients’ understanding of the health care information provided by health care professionals. Including patients in the design and development of teach-back training content for providers can result in more relevant training content. However, only a limited number of studies embrace patient engagement in this capacity, and none for remote care settings. ObjectiveWe aimed to design and evaluate the feasibility of patient-centered, telehealth-focused teach-back training for family medicine residents to promote the use of teach-back during remote visits. MethodsWe codeveloped the POTENTIAL (Platform to Enhance Teach-Back Methods in Virtual Care Visits) curriculum for medical residents to promote teach-back during remote visits. A patient participated in the development of the workshop’s videos and in a patient-provider panel about teach-back. We conducted a pilot, 2-arm cluster, nonrandomized controlled trial. Family medicine residents at the intervention site (n=12) received didactic and simulation-based training in addition to weekly cues-to-action. Assessment included pre- and postsurveys, observations of residents, and interviews with patients and providers. To assess differences between pre- and postintervention scores among the intervention group, chi-square and 1-tailed t tests were used. A total of 4 difference-in-difference models were constructed to evaluate prepost differences between intervention and control groups for each of the following outcomes: familiarity with teach-back, importance of teach-back, confidence in teach-back ability, and ease of use of teach-back. ResultsMedical residents highly rated their experience of the teach-back training sessions (mean 8.6/10). Most residents (9/12, 75%) used plain language during training simulations, and over half asked the role-playing patient to use their own words to explain what they were told during the encounter. Postintervention, there was an increase in residents’ confidence in their ability to use teach-back (mean 7.33 vs 7.83; P=.04), but there was no statistically significant difference in familiarity with, perception of importance, or ease of use of teach-back. None of the difference-in-difference models were statistically significant. The main barrier to practicing teach-back was time constraints. ConclusionsThis study highlights ways to effectively integrate best-practice training in telehealth teach-back skills into a medical residency program. At the same time, this pilot study points to important opportunities for improvement for similar interventions in future larger-scale implementation efforts, as well as ways to mitigate providers’ concerns or barriers to incorporating teach-back in their practice. Teach-back can impact remote practice by increasing providers’ ability to actively engage and empower patients by using the features (whiteboards, chat rooms, and mini-views) of their remote platform.

PURPOSEUnderstanding the epidemiological profile of young patients with breast cancer (BC) is crucial for devising effective control strategies. However, data on Brazilian patients with BC, particularly concerning the association with pathogenic germline mutations, are limited. This retrospective cross-sectional study seeks to shed light on the epidemiological and genetic profiles of young patients with BC in Brazil, with a specific focus on the correlation between germline mutations and clinical outcomes.METHODSWe analyzed medical records from two institutions in Minas Gerais, Brazil, focusing on young patients with BC diagnosed from January 2012 to December 2020. The collected variables included sociodemographic profile, tumor characteristics, mutational status, follow-up duration, and time from diagnosis to death.RESULTSThe findings highlight high rates of genetic mutations, more aggressive tumor characteristics, and the necessity for more radical surgical interventions in patients with mutations.CONCLUSIONIn general, young patients with BC in Brazil present an unfavorable prognosis, emphasizing the need for early diagnosis and personalized treatment strategies.

Focal liver lesions are common, with a prevalence up to 20%. The lesions must be evaluated in context of risk factors associated with malignancy. Risk factors include age >40 years, known current or past malignancy, presence of liver cirrhosis or chronic liver disease (i.e. suspected by elevated liver elastography measurement ≥8 kPa or FIB-4 score ≥1.3), unintentional weight loss, fever or night sweats, newly detected focal liver lesions, documented growth of focal liver lesions, current or past use of androgens (e.g. testosterone, oxymetholone, danazol), increased serum tumour markers (i.e. alpha-fetoprotein, carbohydrate antigen 19-9 [CA19-9], carcinoembryonic antigen [CEA]) and family history of malignancy. In patients without risk factors of malignancy, regional (non-)fatty changes, simple liver cysts and typical haemangiomas can be diagnosed by conventional ultrasound (without contrast). Conventional ultrasound Doppler is recommended to rule out vascular malformations such as portosystemic shunts. In all other cases of focal liver lesions, contrast-enhanced imaging is indicated for differentiation in benign and malignant dignity. Contrast-enhanced ultrasound (CEUS) as a first diagnostic step and contrast-enhanced magnetic resonance imaging (MRI) are accurate tests to diagnose haemangioma and focal nodular hyperplasia. Hepatocellular adenoma is diagnosed by contrast-enhanced MRI and/or histology. “Wash out” on CEUS is highly suspicious for a malignant focal liver lesion. Additional investigations aimed at identifying the primary tumour, as well as staging-computed tomography, MRI and/or histology may be necessary and should be decided on a case-by-case basis. A biopsy of focal liver lesions is indicated in cases of unclear dignity, malignant aspect and focal liver lesions of unclear origin as well as for guiding surgical and oncological management.

BackgroundResearch clearly demonstrates social determinants of health (SDOH) impact health outcomes. Provider consideration of patient SDOH in prevention and treatment planning is critical for improved health care quality and health equity. Despite awareness of the connections between SDOH and improved population health, research demonstrates few providers document patient SDOH. ObjectiveThis qualitative study aimed to better understand the barriers and facilitators of SDOH assessment, documentation, and referral in different health care settings and roles. MethodsIndividual semistructured interviews were conducted with practicing health care providers in South Carolina between August 25, 2022, and September 2, 2022. Participants were recruited via community partners’ web-based newsletters or listservs using a purposive sampling design. An interview guide with 19 questions was used to explore the following research question: How do SDOH impact patient health and what are the facilitators and barriers experienced by multidisciplinary health care providers assessing and documenting patient SDOH? ResultsParticipants (N=5) included a neonatal intensive care unit registered nurse, a nurse practitioner, a certified nurse midwife, a family and preventive medicine physician, and a counselor (licensed clinical social worker) with careers spanning 12 to 32 years. Participant responses are presented according to the following 5 themes: participants’ understanding of SDOH for the patient population, assessment and documentation practices, referrals to other providers and community-based resources, barriers and facilitators of SDOH assessment and documentation, and SDOH assessment and documentation training preferences. Overall, participants were aware of the importance of including patient SDOH in assessment and intervention but noted a variety of institutional and interpersonal barriers to assessment and documentation, including time constraints, perceptions of stigma around discussion of SDOH, and limited referral protocols. ConclusionsIncentivizing inclusion of patient SDOH in health care must be facilitated from the top down, so assessment and documentation can be universally implemented in a pragmatic way that works for providers in a variety of roles and settings for the betterment of health care quality, health equity, and improved population health outcomes. Partnering with community organizations can serve to augment health care organizations’ resource and referral availability for addressing patients’ social needs.

Background The Framingham 10‐year cardiovascular disease risk score, which is based on age, sex, smoking, total cholesterol, high‐density lipoprotein‐cholesterol, blood pressure, and diabetes, has been found to be associated with cognitive health, but these findings have not been validated in a representative sample in the United States. We aimed to examine the associations of Framingham risk score with cognitive function among older adults in a nationally representative sample, as well as by race or ethnicity, education, and family income. Methods and Results A total of 2254 older adults ≥60 years (57% female, 79% non‐Hispanic White) in the National Health and Nutrition Examination Survey 2011 to 2014 were included in the final sample for analysis. All components of the Framingham risk score were obtained with questionnaire or measured in the laboratory. Cognitive function was examined using the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Task (immediate and delayed memory), Digit Symbol Substitution Test, and Animal Fluency Test. Multivariable linear regression models were used to assess the associations between Framingham risk score and test‐specific and global cognition Z scores. Each incremental 5% in Framingham 10‐year cardiovascular disease risk was associated with lower Z scores for Digit Symbol Substitution Test (β=−0.06 [95% CI, −0.09 to −0.03]), delayed memory (β=−0.05 [95% CI, −0.08 to −0.01]), immediate memory (β=−0.07 [95% CI, −0.10 to −0.03]), and global cognition (β=−0.05 [95% CI, −0.09 to −0.02]). Socioeconomic status, particularly race or ethnicity and monthly income levels, were strong effect measure modifiers of the associations. Conclusions Lower cardiovascular risk factors are associated with better cognitive function.

Like cancer, Alzheimer’s disease and related dementias (ADRD) comprise a global health burden that can benefit tremendously from the power of disease registry data. With an aging population, the incidence, treatment, and mortality from ADRD is increasing and changing rapidly. In the same way that current cancer registries work toward prevention and control, so do ADRD registries. ADRD registries maintain a comprehensive and accurate registry of ADRD within their state, provide disease prevalence estimates to enable better planning for social and medical services, identify differences in disease prevalence among demographic groups, help those who care for individuals with ADRD, and foster research into risk factors for ADRD. ADRD registries offer a unique opportunity to conduct high-impact, scientifically rigorous research efficiently. As research on and development of ADRD treatments continue to be a priority, such registries can be powerful tools for conducting observational studies of the disease. This perspectives piece examines how established cancer registries can inform ADRD registries’ impact on public health surveillance, research, and intervention, and inform and engage policymakers.

PURPOSEThis prospective Brazilian single-arm trial was conducted to determine response to chemotherapy and survival after response-based radiotherapy in children with intracranial germinomas, in the setting of a multi-institutional study in a middle-income country (MIC) with significant disparity of subspecialty care.PATIENTS AND METHODSSince 2013, 58 patients with histologic and/or serum and CSF tumor marker evaluations of primary intracranial germ cell tumors were diagnosed; 43 were germinoma with HCGβ levels ≤200 mIU/mL and five between 100 and 200 mIU/mL. The treatment plan consisted of four cycles of carboplatin and etoposide followed by 18 Gy whole-ventricular field irradiation (WVFI) and primary site(s) boost up to 30 Gy; 24 Gy craniospinal was prescribed for disseminated disease.RESULTSMean age 13.2 years (range, 4.7-25.5 years); 29 were males. Diagnosis was made by tumor markers (n = 6), surgery (n = 25), or both (n = 10). Two bifocal cases with negative tumor markers were treated as germinoma. Primary tumor location was pineal (n = 18), suprasellar (n = 14), bifocal (n = 10), and basal ganglia/thalamus (n = 1). Fourteen had ventricular/spinal spread documented by imaging studies. Second-look surgery occurred in three patients after chemotherapy. Thirty-five patients achieved complete responses after chemotherapy, and eight showed residual teratoma/scar. Toxicity was mostly grade 3/4 neutropenia/thrombocytopenia during chemotherapy. At a median follow-up of 44.5 months, overall and event-free survivals were 100%.CONCLUSIONThe treatment is tolerable, and WVFI dose reduction to 18 Gy preserves efficacy; we have demonstrated the feasibility of successfully conducting a prospective multicenter trial in a large MIC despite resource disparity.

Abstract Purpose The aim of this study was to develop a patient decision aid (pDA) that could support patients with breast cancer (BC) in making an informed decision about breast reconstruction (BR) after mastectomy. Methods The development included four stages: (i) Establishment of a multidisciplinary team; (ii) Needs assessment consisting of semi‐structured interviews in patients and a survey among healthcare professionals (HCPs); (iii) Creation of content, design and technical system; and (iv) Acceptability and usability testing using a think‐aloud approach in patients and interviews among HCPs and representatives of the Dutch Breast Cancer Patient Organization. Results From the needs assessment, three themes were identified: Challenging period to make a decision, Diverse motivations for a personal decision and Information needed to make a decision about BR. HCPs valued the development of a pDA, especially to prepare patients for consultation. The pDA that was developed contained three parts: first, a consultation sheet for oncological breast surgeons to introduce the choice; second, an online tool including an overview of reconstructive options, the pros and cons of each option, information on the consequences of each option for daily life, exercises to clarify personal values and patient stories; and third, a summary sheet with patients’ values, preferences and questions to help inform and guide the discussion between the patient and her plastic surgeon. The pDA was perceived to be informative, helpful and easy to use by patients and HCPs. Conclusion Consistent with information needs, a pDA was developed to support patients with BC who consider immediate BR in making an informed decision together with their plastic surgeon. Patient or Public Contribution Patients participated in the needs assessment and in acceptability and usability testing.

ObjectiveTo identify trends in the prevalence of mild cognitive impairment (MCI) and dementia, and to determine risk factors associated with the early detection of dementia among U.S. middle-aged and older adults.MethodsWe used 10-year nationally representative longitudinal data from the Health and Retirement Study (HRS) (2006–2016). Adults aged 55 years or older were included to examine the trend. To identify the associated factors, adults aged 55 years or older in 2006 who developed MCI or dementia in subsequent waves until the 2016 wave were included. Early and late detection of dementia were identified using the Langa-Weir classification of cognitive function. Multivariate logistic regression models were used to identify factors associated with the early detection of dementia.ResultsThe sample size for the analysis of the prevalence of MCI and dementia ranged from 14,935 to 16,115 in the six survey years, and 3,729 individuals were identified to determine associated factors of the early detection of dementia. Among them, participants aged 65 years or older accounted for 77.9%, and male participants accounted for 37.2%. The 10-year prevalence of MCI and dementia was 14.5 and 6.6%, respectively. We also found decreasing prevalence trends in MCI (from 14.9 to 13.6%) and dementia (from 7.4 to 6.0%) overall in the past decade. Using logistic regression controlling for the year, non-Hispanic black (MCI: OR = 2.83, P < 0.001; dementia: OR = 2.53, P < 0.001) and Hispanic (MCI: OR = 2.52, P < 0.001; dementia: OR = 2.62, P < 0.001) had a higher prevalence of both MCI and dementia than non-Hispanic white participants. In addition, men had a lower prevalence of MCI (OR = 0.94, P = 0.035) and dementia (OR = 0.84, P < 0.001) compared to women. Associated factors of the early detection of dementia include age, gender, race, educational attainment, stroke, arthritis diseases, heart problems, and pensions.ConclusionThis study found a decreasing trend in the prevalence of MCI and dementia in the past decade and associated racial/ethnic and gender disparities among U.S. middle-aged and older adults. Healthcare policies and strategies may be needed to address health disparities in the prevalence and take the associated factors of the early detection of dementia into account in clinical settings.

The Cuvier's beaked whale (CBW; Ziphius cavirostris) is a cosmopolitan marine mammal found in deep tropical and temperate waters of all oceans. CBW strandings have been recorded sporadically in Brazil; however, there is lack of information available regarding their causes of stranding and/or death. Herein, we report the epidemiologic, pathologic, morphologic parasitologic features and molecular identification of arterial and renal crassicaudiasis by Crassicauda sp. in three geographically and chronologically distant CBW stranded off Brazil. CBW-1 was an adult male stranded dead in Rio Grande do Sul State. CBW-2 was an adult female that stranded alive in Sergipe State and died shortly after. CBW-3 was and adult male that stranded dead in Santa Catarina State. The most relevant pathologic findings in these three CBW were severe, chronic proliferative mesenteric and caudal aortic endarteritis and chronic granulomatous and fibrosing interstitial nephritis with renicular atrophy and loss, and numerous intralesional Crassicauda sp. nematodes. Furthermore, CBW-1 had concomitant gram-negative bacterial pneumonia and pulmonary and hepatic thromboembolism. Morphologic analysis of renal adult nematodes identified Crassicauda sp. in the three CBW. Molecular analyses targeting the 18S and ITS-2 ribosomal loci of renal nematodes in CBW-2 and CBW-3 identified C. anthonyi. It is believed that severe arterial and renal crassicaudiasis likely resulted or contributed significantly to morbidity and death of these animals. These results expand the known geographical range of occurrence of crassicaudiasis in CBW. Specifically, the present study provides the first accounts of arterial and renal crassicaudiasis in CBW off the southern hemisphere, specifically in CBW off Brazil, and to the authors' knowledge, it is the first record of C. anthonyi in the southern Atlantic Ocean.

Improving health literacy is a national public health priority. Given the context of the COVID-19 pandemic, it is even more critical for health and medical information to be clear and understandable for patients and their families. Clinic-based programs to improve health literacy need to be pragmatic, feasible, and helpful for the implementing clinic and patients. This paper describes the development, implementation, and evaluation of a pragmatic, clinic-based health literacy intervention in a safety-net clinic that serves uninsured and indigent patients. Study methods are guided by a previous pilot study and components recommended for pragmatic interventions. An electronic readiness assessment was distributed to out-patient clinics affiliated with a statewide hospital association. The AskMe3 tool was used for the intervention as it is evidence informed and relatively easy to implement. Implementation included ongoing dialogue between the clinic and the academic research team. Within the implementing clinic, data collected from patients via verbally administered questionnaires was analyzed using descriptive statistics and chi-squares. Interview data collected from the clinic director was analyzed qualitatively for themes. The implementing clinic had some of the lowest average scores of the 34 clinics who participated in the initial readiness assessment. Despite this, they were able to successfully implement the health literacy intervention during a global pandemic. Eighty-eight participants completed patient questionnaires at this clinic. Most patients (96%) agreed the AskMe3 questions helped them talk with the doctor or nurse at their current appointment. Most (99%) also perceived the AskMe3 tool to be very helpful when used in a clinical setting. The clinic director offered that the staff initially thought the intervention would be difficult to implement. However, implementation by clinic volunteers with encouragement and prioritization of health literacy by the clinic director contributed to success. When considering interventions for clinical settings, a pragmatic approach can help with selection and implementation of a program that fits with the realities on the ground. Further, frequent technical assistance can help resolve implementation barriers. Interventions utilizing tools such as AskMe3, because of their simplicity, allow creative solutions to capacity issues for clinics who see a need for health literacy improvements.

Laurencia seaweed species synthesize a broad range of secondary metabolites, mainly terpenes (e.g., elatol), exhibiting diverse ecological roles, such as defense against fouling and herbivores. Recently, an intricate cellular machinery was described concerning terpenes biosynthetic pathways, storage inside corps en cerise (CC), and regulated exocytosis in these species. But for seaweeds in general, the proteins involved in transmembrane transport of secondary metabolites remain unknown. Assays with Rhodamine-123 and cyclosporine A (CSA) revealed the presence of ABC transporters in CC membrane of Laurencia dendroidea. In vivo incubation assays with CSA resulted in CC morphological changes, reduced intracellular elatol concentrations, and increased biofouling cover on the seaweed surface. Cultivation assays in the presence of a marine pathogenic bacteria induced the expression of ABC proteins belonging to the subfamilies ABCB, ABCD, ABCF, and ABCG. The latter subfamily is known to be associated with the transport of plant terpenes. Our results shed new light on the role of ABC proteins in key mechanisms of the defensive system in seaweeds against fouling and herbivory.

ABSTRACT: Oral diseases are limiting to health, welfare, and conservation practices, especially in the case of endangered animals. In this retrospective study, a survey on oral health-related conditions noted in the clinical records for 261 deer comprised in an ex situ population of the Marsh Deer Conservation Center (CCCP) over 30 years (1990-2020) was carried out. Of these, 49 (18.77%) marsh deer (31 females - 63.27% and 18 males - 36.73%) had clinical oral affections; the affected deer’s mean age was 8.9 years. Logistic regression analysis was performed, and the variable age was significantly associated with the presence of dental affections. Thus, with a change in the age category, a deer had eight times the chance of manifesting oral affections; therefore, age can be considered a risk factor for the manifestation of oral affections in the species. Increased facial volume (65.3%), accumulation of food in the mouth (36.7%), tooth loss (22.4%), fistulas (22.4%), mucosal or palatal lesions (22.4%), tooth wear (20.4%), and tooth root exposure (18.3%) were the most frequently recorded lesions. The relatively high occurrence of oral affections in Blastocerus dichotomus reiterates the importance of oral health care when deer are kept in human care.

Mayaro virus (MAYV) is an emerging arbovirus in Central and South America that is transmitted by mosquitoes and causes arthritogenic disease. Here, the authors present the 4.4 Å resolution cryo-EM structure of MAYV and describe specific features of the virus, which could be exploited for the design of MAYV-specific diagnostics and therapeutics.

Until December 2021, the COVID-19 pandemic has caused more than 5.5 million deaths. Vaccines are being deployed worldwide to mitigate severe disease and death, but continued transmission and the emergence of SARS-CoV-2 variants indicate that specific treatments against COVID-19 are still necessary. We screened 400 compounds from the Medicines for Malaria Venture (MMV) Pathogen Box seeking for molecules with antiviral activity against SARS-CoV-2 by using a high-throughput screening (HTS) infection assay in Vero CCL81 cells. On resupply of 15 selected hit compounds, we confirmed that 7 of them presented a dose-dependent cytoprotective activity against SARS-CoV-2-induced cytopathic effect (CPE) in the micromolar range. They were validated in low-throughput infection assays using four different cell lines, including the human lung Calu-3 cell line. MMV000063, MMV024937, MMV688279, and MMV688991 reduced viral load in cell culture, assessed by RT-qPCR and viral plaque assay, while MMV688279 and MMV688991 (also known as nitazoxanide) were the most promising, reducing SARS-CoV-2 load by at least 100-fold at 20 µM in almost all cell types tested. Our results indicate that active anti-SARS-CoV-2 molecules exist within the repertoire of antiviral, antiparasitic and antimicrobial compounds available to date. Although the mode of action by which MMV688279 and MMV688991 reduce SARS-CoV-2 replication is yet unknown, the fact that they were active in different cell types holds promise not only for the discovery of new therapeutic targets, but also for the development of novel antiviral medicines against COVID-19.

Recognition of the impact of social determinants of health (SDoH) on healthcare outcomes, healthcare service utilization, and population health has prompted a global shift in focus to patient social needs and lived experiences in assessment and treatment. The International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) provides a list of non-billable “Z codes” specific to SDoH for use in electronic health records. Using population-level analysis, this study aims to examine clinical application of Z codes in South Carolina before and during the COVID-19 pandemic. The study population consists of South Carolina residents who had a healthcare visit and had their COVID-19 test result reported to the state's Department of Health and Environmental Control before January 14, 2021. Of the 1,190,531 individuals in the overall sample, Z codes were used only for 14,665 (1.23%) of the patients, including 2,536 (0.97%) COVID-positive patients and 12,129 (1.30%) COVID-negative patients. Compared with hospitals that did not use Z codes, those that did were significantly more likely to have higher bed capacity (p = 0.017) and to be teaching hospitals (p = 0.03), although this was significant only among COVID-19 positive individuals. Those at inpatient visits were most likely to receive Z codes (OR: 5.26; 95% CI: 5.14, 5.38; p < 0.0001) compared to those at outpatient visits (OR: 0.07; 95%CI: 0.06, 0.07; p < 0.0001). There was a slight increase of Z code use from 2019 to 2020 (OR: 1.33, 95% CI: 1.30, 1.36; p < 0.0001), which was still significant when stratified by facility type across time. As one of the first studies to examine Z code use among a large patient population, findings clearly indicate underutilization by providers. Additional study is needed to understand the potentially long-lasting health effects related to SDoH among underserved populations.

Abstract Harassment is a common problem in many institutions, including academic ones. It creates invisible barriers for attracting and maintaining women and other minorities at academia. In this work, we quantify and qualify this problem in one of the biggest universities of Brazil, the Federal University of Rio Grande do Sul (UFRGS). We applied a spontaneously-responded survey to 25% of its professors, 20% of its staff and 12.5% of its students. Our results present that sexual and moral harassment are very frequent in UFRGS and are not distributed homogeneously among all groups: women, black+parda, and non-heterosexual people are the most common victims. Moreover, the staff has higher percentage of moral harassment victims. We also unvealed an important problem of under-notification, where only around 10% of these cases are reported. We show that victims are afraid of reporting or do not believe in the institutional channels of reporting proposed by the university. We then discuss which type of events are perceived as harassment and the frequency at which they happen with different genders. We finalize the paper with a discussion of our results and recommendations to improve this scenario.

Abstract Background Individuals’ stress in responding to the current COVID-19 pandemic may be exacerbated by information uncertainty driven by inconsistent, unverified, and conflicting news from various sources. The current study aims to test if information uncertainty during the COVID-19 outbreak was related to acute stress disorder (ASD) over and above other psychosocial stressors. Methods An anonymous online survey was conducted with 7800 college students throughout China from January 31 through February 11, 2020. Existing scales were modified to measure ASD and six potential stressors including information uncertainty during the COVID-19 outbreak. Hierarchical regression analysis was conducted to assess the unique association of information uncertainty with ASD. To minimize the effect of large sample size and also to get a sense of whether the effects of information uncertainty were similar to people at the center of the epidemic, we repeated the hierarchical regression among 10% of the students who were randomly selected from the entire sample (“10% random sample”; n = 780) and 226 students from Hubei Province where the outbreak started. Results Information uncertainty was highly prevalent among the respondents (64%). It was significantly associated with ASD beyond other key variables and potential stressors across three samples. In the hierarchical regression among the entire sample, demographic variables accounted for 9.4% of the variance in ASD. The other five stressors added 5.1% of the variance. The information uncertainty (β = .159; p

The interannual variability and trends of sea surface temperature (SST) around southern South America are studied from 1982 to 2017 using monthly values of the Optimally Interpolation SST version 2 gridded database. Mid-latitude (30°–50°S) regions in the eastern South Pacific and western South Atlantic present moderate to intense warming (~0.4°C decade−1), while south of 50°S the region around southern South America presents moderate cooling (~ −0.3°C decade−1). Two areas of statistically significant trends of SST anomalies (SSTa) with opposite sign are found on the Patagonian Shelf over the southwest South Atlantic: a warming area delimited between 42 and 45°S (Northern Patagonian Shelf; NPS), and a cooling area between 49 and 52°S (Southern Patagonian Shelf; SPS). Between 1982 and 2017 the warming rate has been 0.15 ± 0.01°C decade−1 representing an increase of 0.52°C at NPS, and the cooling rate has been –0.12 ± 0.01°C decade−1 representing a decrease of 0.42°C at SPS. On both regions, the largest trends are observed during 2008–2017 (0.35 ± 0.02°C decade−1 at NPS and –0.27 ± 0.03°C decade−1 at SPS), while the trends in 1982–2007 are non-significant, indicating the record-length SSTa trends are mostly associated with the variability observed during the past 10 years of the record. The spectra of the records present significant variance at interannual time scales, centered at about 80 months (~6 years). The observed variability of SSTa is studied in connection with atmospheric forcing (zonal and meridional wind components, wind speed, wind stress curl and surface heat fluxes). During 1982–2007, the local meridional wind explains 25–30% of the total variance at NPS and SPS on interannual time scales. During 2008–2017, the SSTa at NPS is significantly anticorrelated with the local zonal wind (r = –0.85), while at SPS it is significantly anticorrelated with the meridional wind (r = –0.61). Our results show that a substantial fraction of the interannual variability of SSTa around southern South America can be described by the first three empirical orthogonal function (EOF) modes which explain 28, 16, and 12% of the variance, respectively. The variability of the three EOF principal components time series is associated with the combined variability of El Niño–Southern Oscillation, the Interdecadal Pacific Oscillation and the Southern Annular Mode.

PurposesMost molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches.Patients and MethodsWe collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes.ResultsPAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors.ConclusionsThis is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America.Clinical Trial RegistrationClinicalTrials.gov (Identifier: NCT02326857).

St. Meinrad Seminary and School of Theology, a seminary located in southern Indiana, was founded in 1857 by monks of the Benedictine order of Einsiedeln in Switzerland. The seminary has since been devoted to the education of faith leaders—priests, deacons, and graduate lay students. Due to the growth of underserved Latino populations in the Midwest region of the United States, there is a need to prepare future faith leaders to serve Latino congregations. This work provides an exploration into the ways in which language learning collaborations based on Benedictine hospitality can cultivate community. It outlines a Benedictine pedagogy of community that is threefold. First, given the importance of language to communicate with members of Latino communities in the United States, the cultivation of community is understood in terms of the world readiness standards of the American Council on the Teaching of Foreign Languages (ACTFL). Second, because Benedictine monasteries were founded on the value of hospitality, these interactions are imbued with Benedictine hospitality. Third, it is argued that Benedictine communities are contexts in which the liminal intertwines with the liminoid, resulting in fertile ground for the creation of what we call liminal/liminoid encounters that have the potential to level asymmetric power relations and lead to meaningful dialogue. The final section shows how this Benedictine pedagogy of community is enacted in one specific Spanish language learning immersion that takes place at a sister Benedictine Monastery abroad, Our Lady of Angels, in Cuernavaca, Mexico. It also provides a small sample of seven students’ responses to two critical questions from a survey questionnaire. Even though this small qualitative sample is not generalizable, it helps illuminate how these interactions may lead to the development of cultural sensitivity, of a sense of community, between students and members of this language learning immersion abroad. Responses indicate that students who participated in this program for at least eight weeks exhibit an interest in continuing to interact and collaborate in multicultural communities as well as a willingness to learn the target language beyond this experience.

Collaborative Online International Learning (COIL) is a teaching and learning approach whereby entire courses or modules are co-developed and team taught by instructors from different institutions for students of both institutions. Since 2006, the approach has been gaining in mass appeal; however, considering our present-day global coronavirus pandemic, COILs have a renewed relevance in academia. Faculty from the University of South Carolina (United States) and Coventry University (England) embarked on a COIL partnership yielding a valuable experience that can serve as a model for other institutions that are interested in developing innovative and cross-cultural distance learning opportunities. The purpose of this paper is to explain how the institutional partnership emerged, describe the course content, and provide lessons that our team learned through the COIL development and implementation process. Our experience as a first-time COIL partnership is a model for others to consider as the landscape for the academic enterprise expands the confines of brick-and-mortar institutions.

Objectives: As the United States (U.S.) population rapidly ages, the incidence of Alzheimer's Disease and Related Dementias (ADRDs) is rising, with racial/ethnic minorities affected at disproportionate rates. Much research has been undertaken to test, sequence, and analyze genetic risk factors for ADRDs in Caucasian populations, but comparatively little has been done with racial/ethnic minority populations. We conducted a scoping review to examine the nature and extent of the research that has been published about the genetic factors of ADRDs among racial/ethnic minorities in the U.S.Design: Using an established scoping review methodological framework, we searched electronic databases for articles describing peer-reviewed empirical studies or Genome-Wide Association Studies that had been published 2005–2018 and focused on ADRD-related genes or genetic factors among underrepresented racial/ethnic minority population in the U.S.Results: Sixty-six articles met the inclusion criteria for full text review. Well-established ADRD genetic risk factors for Caucasian populations including APOE, APP, PSEN1, and PSEN2 have not been studied to the same degree in minority U.S. populations. Compared to the amount of research that has been conducted with Caucasian populations in the U.S., racial/ethnic minority communities are underrepresented.Conclusion: Given the projected growth of the aging population and incidence of ADRDs, particularly among racial/ethnic minorities, increased focus on this important segment of the population is warranted. Our review can aid researchers in developing fundamental research questions to determine the role that ADRD risk genes play in the heavier burden of ADRDs in racial/ethnic minority populations.

Objective: To examine content and readability of COVID-19 information on outpatient clinic websites in South Carolina.Participants: Thirty-three outpatient clinic websites.Methods: Using a multi-step search strategy, we located three COVID-19 information content sections from each website. Descriptive statistics were calculated for content section characteristics (focus, information source, target population/race, presence of graphics, mobilizing information). Flesch Reading Ease (FRE), Flesch Kincaid Grade Level (FKGL), and Simple Measure of Gobbledygook (SMOG) were used to calculate reading levels. Mann Whitney U and Kruskal Wallis tests were performed to examine readability levels by clinic type (primary care vs. specialty) and content section characteristics.Results: Twenty-six clinics offered COVID-19 information; 70 content sections across all 26 clinics were analyzed. Sections focused on COVID-19 clinic policies (48.4%), prevention (22.6%), testing (19.4%), and symptoms (9.7%). 93.5% lacked target population, 41.9% provided no information source, 38.7% had no graphics, and none mentioned racial/ethnic groups. MFRE = 54.3, MFKGL = 9.9, MSMOG = 9.5.Conclusion: COVID-19 information focused mainly on clinic policy and was written at a ninth-grade skill level. Findings suggest there is opportunity for clinics to update their online content to convey more plain language and sourced information, especially for high-risk groups.

Sinorhizobium meliloti contains the negatively charged phosphatidylglycerol and cardiolipin as well as the zwitterionic phosphatidylethanolamine (PE) and phosphatidylcholine (PC) as major membrane phospholipids. In previous studies we had isolated S. meliloti mutants that lack PE or PC. Although mutants deficient in PE are able to form nitrogen-fixing nodules on alfalfa host plants, mutants lacking PC cannot sustain development of any nodules on host roots. Transcript profiles of mutants unable to form PE or PC are distinct; they differ from each other and they are different from the wild type profile. For example, a PC-deficient mutant of S. meliloti shows an increase of transcripts that encode enzymes required for succinoglycan biosynthesis and a decrease of transcripts required for flagellum formation. Indeed, a PC-deficient mutant is unable to swim and overproduces succinoglycan. Some suppressor mutants, that regain swimming and form normal levels of succinoglycan, are altered in the ExoS sensor. Our findings suggest that the lack of PC in the sinorhizobial membrane activates the ExoS/ChvI two-component regulatory system. ExoS/ChvI constitute a molecular switch in S. meliloti for changing from a free-living to a symbiotic life style. The periplasmic repressor protein ExoR controls ExoS/ChvI function and it is thought that proteolytic ExoR degradation would relieve repression of ExoS/ChvI thereby switching on this system. However, as ExoR levels are similar in wild type, PC-deficient mutant and suppressor mutants, we propose that lack of PC in the bacterial membrane provokes directly a conformational change of the ExoS sensor and thereby activation of the ExoS/ChvI two-component system.

A quantitative understanding of aggregation mechanisms leading to the formation of composites of inorganic nanoparticles (NPs) and proteins in aqueous media is of paramount interest for colloid chemistry. In particular, the interactions between silica (SiO2) NPs and lysozyme (LZM) have attracted attention, because LZM is well-known to adsorb strongly to silica NPs, while at the same time preserving its enzymatic activity. The inherent nature of the aggregation processes leading to NP–LZM composites involves structural changes at length scales from few to at least hundreds of nanometres but also time scales much smaller than one second. To unravel these we used in situ synchrotron-based small-angle X-ray scattering (SAXS) and followed the subtle interparticle interactions in solution at a time resolution of 50 ms/frame (20 fps). We show that if the size of silica NPs (ca. 5 nm diameter) is matched by the dimensions of LZM, the evolving scattering patterns contain a unique structure-factor contribution originating from the presence of LZM. We developed a scattering model and applied it to analyse this structure function, which allowed us to extract structural information on the deformation of lysozyme molecules during aggregation, as well as to derive the mechanisms of composite formation.

Alzheimer's disease and related dementias (ADRD) are at the forefront of the United States (US) public health agenda due to their tremendous human and financial burden. Further, disproportionately high ADRD rates among racial/ethnic minorities require incorporating the unique perspectives of racially and ethnically diverse scientists, which will necessitate diversifying the scientific workforce that investigates disparities in aging. The purpose of this paper is to describe the training and mentorship initiatives of the National Institute on Aging (NIA)-funded Carolina Center on Alzheimer's Disease and Minority Research, emphasizing lessons learned from our engagement with underrepresented minority and minoritized (URM) Scientists. We highlight three aims of the Center's training and mentorship component: (1) Fund pilot projects for URM Scientists conducting research on sociocultural, behavioral, and environmental factors that influence ADRD-related health disparities; (2) Provide mentorship to build the research capacity of Center Scientists; and (3) Offer research education in Health Disparities and Minority Aging Research to Center Scientists and interested researchers at all partner institutions. Our experience may be a practical resource for others developing interdisciplinary training programs to increase the pipeline of URM Scientists conducting ADRD research.

Marine natural products have emerged as an important source for drug development, notably in the field of anticancer therapy. Still, the limited effectiveness of current therapies for central nervous system tumors indicates the need to identify new therapeutic targets and also novel pharmacological agents. In this context, proteasome inhibitors are appearing as a promising new treatment for these diseases. Herein, cytotoxic extracts produced by four marine bacteria recovered from the Brazilian endemic ascidian Euherdmania sp. were screened to evaluate their potential as proteasome inhibitors. The extract from marine Streptomyces sp. BRA-346 was selected for further investigation due to the potent proteasome inhibitory activity it displayed. Bioassay-guided fractionation led to an enriched fraction (proteasome inhibition IC50 = 45 ng/mL), in which the presence of dihydroeponemycin (DHE), known for its proteasome inhibitory effect, and related compounds were annotated by mass spectrometry and further confirmed by comparison with DHE standard. Both DHE and the epoxyketone-containing fraction were evaluated in glioma cell lines, displaying high cytotoxicity in HOG and T98G cells (GI50 of 1.6 and 1.7 ng/mL for DHE, and 17.6 and 28.2 ng/mL for the BRA-346 fraction, respectively). Additional studies showed that the epoxyketone-containing fraction (at GI50 levels) led to an accumulation of ubiquitinated proteins and up-regulation of genes related to ER-stress response, suggesting treated cells are under proteasome inhibition. DHE induced similar effects in treated cells but at concentrations 25 times its GI50, suggesting that the other epoxyketone compounds in the bacteria extract derived fraction may contribute to enhance proteasome inhibition and further cellular effects in glioma cells. These findings revealed the molecular pathways modulated by this class of compounds in glioma cells and, moreover, reinforced the potential of this marine bacteria in producing a cocktail of structurally-related compounds that affect the viability of glioma cells.

Abstract Natural Sapajus libidinosus populations are in continuous decline due to fragmentation, habitat loss, and the illegal pet trade. They live in Caatinga scrub forests, which already lost over 50% of their original cover. The lack of studies on S. libidinosus population genetics means that we do not know how they are being affected by this striking habitat loss and other anthropogenic disturbances. Polymorphic markers are not available for the study of S. libidinosus diversity and population genetics. Thus, here we aimed to test the transferability of 14 microsatellite markers to S. libidinosus. These microsatellites were previously isolated from Cebus capucinus (white-faced capuchin), species belonging to the same subfamily (Cebinae) as the study species. We found that six of the tested microsatellite markers (tetra-nucleotide) were cross-amplified in our target species. All loci were polymorphic. The number of alleles varied from 4 to 7, and the expected heterozygosity ranged from 0.588 to 0.869. The microsatellite markers transferred to S. libidinosus and characterised in our study will be valuable tools to evaluate the genetic variability of both wild and captive populations. They will considerably reduce the costs of microsatellite isolations, helping to prioritise currently limited research and conservation budgets in Brazil.

The identification of endogenous metabolites has great potential for understanding the underlying tissue processes occurring in either a homeostatic or a diseased state. The application of gas chromatography-mass spectrometry (GC-MS)-based metabolomics on musculoskeletal tissue samples has gained traction. However, limited comparison studies exist evaluating the sensitivity, reproducibility, and robustness of the various existing extraction protocols for musculoskeletal tissues. Here, we evaluated polar metabolite extraction from bone and muscle of mouse origin. The extraction methods compared were (1) modified Bligh–Dyer (mBD), (2) low chloroform (CHCl3)-modified Bligh–Dyer (mBD-low), and (3) modified Matyash (mMat). In particular, the central carbon metabolites (CCM) appear to be relevant for musculoskeletal regeneration, given their role in energy metabolism. However, the sensitivity, reproducibility, and robustness of these methods for detecting targeted polar CCM remains unknown. Overall, the extraction of metabolites using the mBD, mBD-low, and mMat methods appears sufficiently robust and reproducible for bone, with the mBD method slightly bettering the mBD-low and mMat methods. Furthermore, mBD, mBD-low, and mMat were sufficiently sensitive in detecting polar metabolites extracted from mouse muscle; however, they lacked repeatability. This study highlights the need for a re-thinking, towards a tissue-specific optimization of methods for metabolite extractions, ensuring sufficient sensitivity, repeatability, and robustness.

Abstract Plant-derived molluscicides have been indicated as biodegradable and low-cost strategies for control of Biomphalaria spp., intermediate host for the Schistosoma. This study evaluated whether the crude ethanolic extract of the Persea americana stem bark has molluscicidal activity against embryos, newly-hatched and adults of Biomphalaria glabrata. The extract was obtained, characterized and its toxicity analyzed by snail embryotoxicity test (144 h) and acute toxicity test with newly-hatching and adult snails (96 h). Results showed the presence of flavonoids, anthraquinone heterosides, coumarins and tannins in the crude ethanolic extract, which showed molluscicidal activity against all life cycle stages of B. glabrata. The LC50 for embryos, newly-hatched and adults were 27.06, 30.60 and 55.55 ppm, respectively. Embryos exposed to the extract at 50 ppm showed hatching inhibition and at 6.2 and 25 ppm had the highest rates of morphological alterations, such as shell malformations and coagulation of the perivitelline substance. Adult snails exposed to the extract at 75 ppm showed a peak of behavioral changes, such as lethargy and shell reclusion, in addition to answers like hemolymph release in most concentrations. Further studies are required, prioritizing toxicity testing on non-target organisms and further elucidation of the active molecules.

Limited health literacy is associated with poor patient health outcomes and increased hospitalization rates. Patient-provider communication plays an important role in patient health literacy and the understanding of medical terminology. This study demonstrates how a collaboration between clinical, academic, and community partners was instrumental in the design and implementation of a clinic readiness assessment and a clinic-based pilot intervention to encourage patient-provider communication and improve patient health literacy. A state hospital association, academic research team, and community adult literacy center director collaborated to develop a 60-item clinic readiness assessment and an evidence-informed pilot intervention. The clinic readiness assessment captured clinics’ motivation and capacity for pilot implementation and providers’ current communication strategies. The intervention centered around AskMe3™ educational materials and involved 2 patient visits (initial and follow-up visits). Data collection instruments for the intervention were administered verbally and included questions about patient demographics and communication needs, and a single-item health literacy measure. Descriptive statistics (frequencies/percentages) were used to analyze results from the clinic readiness assessment and pilot intervention. Establishment of the partnership, and collaborative, iterative development of the clinic readiness assessment and pilot intervention are described. This pilot project resulted in important lessons learned which led to critical modifications that will inform future expansion of the intervention. Collaboration between healthcare leaders, researchers, and community partners is recommended for developing clinic-based health literacy initiatives.

Bacillus amyloliquefaciens MEP218 is an autochthonous bacterial isolate with antibacterial and antifungal activities against a wide range of phytopathogenic microorganisms. Cyclic lipopeptides (CLP), particularly fengycins, produced by this bacterium; are the main antimicrobial compounds responsible for the growth inhibition of phytopathogens. In this work, the CLP fraction containing fengycins with antibacterial activity was characterized by LC-ESI-MS/MS. In addition, the antibacterial activity of these fengycins was evaluated on the pathogens Xanthomonas axonopodis pv. vesicatoria (Xav), a plant pathogen causing the bacterial spot disease, and Pseudomonas aeruginosa PA01, an opportunistic human pathogen. In vitro inhibition assays showed bactericidal effects on Xav and PA01. Atomic force microscopy images revealed dramatic alterations in the bacterial surface topography in response to fengycins exposure. Cell damage was evidenced by a decrease in bacterial cell heights and the loss of intracellular content measured by potassium efflux assays. Furthermore, the viability of MRC-5 human normal lung fibroblasts was not affected by the treatment with fengycins. This study shows in vivo evidence on the less-known properties of fengycins as antibacterial molecules and leaves open the possibility of using this CLP as a novel antibiotic.

The uptake transporter NaCT (gene symbol SLC13A5) is expressed in liver and brain and important for energy metabolism and brain development. Substrates include tricarboxylic acid cycle intermediates, e.g., citrate and succinate. To gain insights into the substrate spectrum of NaCT, we tested whether arginine and the cardioactive L-arginine metabolites asymmetric dimethylarginine (ADMA) and L-homoarginine are also transported by human and mouse NaCT/Nact. Using HEK293 cells overexpressing human or mouse NaCT/Nact we characterized these substances as substrates. Furthermore, inhibition studies were performed using the arginine derivative symmetric dimethylarginine (SDMA), the NaCT transport inhibitor BI01383298, and the prototypic substrate citrate. Arginine and the derivatives ADMA and L-homoarginine were identified as substrates of human and mouse NaCT. Transport of arginine and derivatives mediated by human and mouse NaCT were dose-dependently inhibited by SDMA. Whereas BI01383298 inhibited only human NaCT-mediated citrate uptake, it inhibits the uptake of arginine and derivatives mediated by both human NaCT and mouse Nact. In contrast, the prototypic substrate citrate inhibited the transport of arginine and derivatives mediated only by human NaCT. These results demonstrate a so far unknown link between NaCT/Nact and L-arginine and its cardiovascular important derivatives.

Ubiquitin and ubiquitin-like modifiers such as SUMO play important roles in several cellular pathways that can become deregulated in cancer. Here the authors describe the structural basis for inhibition of SUMO E1 ligase by the small molecule COH000.