Transcriptional control of a metabolic switch regulating cellular methylation reactions is part of a common response to stress in divergent bee species.

Recent global declines in bee health have elevated the need for a more complete understanding of the cellular stress mechanisms employed by diverse bee species. We recently uncovered the biomarker lethal (2) essential for life [l(2)efl] genes as part of a shared transcriptional program in response to a number of cell stressors in the western honey bee (Apis mellifera). Here, we describe another shared stress-responsive gene, glycine N-methyltransferase (Gnmt), which is known as a key metabolic switch controlling cellular methylation reactions. We observed Gnmt induction by both abiotic and biotic stressors. We also found increased levels of the GNMT reaction product sarcosine in the midgut after stress, linking metabolic changes with the observed changes in gene regulation. Prior to this study, Gnmt upregulation had not been associated with cellular stress responses in other organisms. To determine whether this novel stress-responsive gene would behave similarly in other bee species, we first characterized the cellular response to endoplasmic reticulum (ER) stress in lab-reared adults of the solitary alfalfa leafcutting bee (Megachile rotundata) and compared this with age-matched honey bees. The novel stress gene Gnmt was induced in addition to a number of canonical gene targets induced in both bee species upon unfolded protein response (UPR) activation, suggesting that stress-induced regulation of cellular methylation reactions is a common feature of bees. Therefore, this study suggests that the honey bee can serve as an important model for bee biology more broadly, although studies on diverse bee species will be required to fully understand global declines in bee populations.

Neighborhood ethnic density and disparities in proximal blood donation opportunities.

BACKGROUND: Despite being the largest racial/ethnic minority group in the United States, Hispanic/Latinos (H/L) are significantly underrepresented among blood donors. A lack of proximal blood donation opportunities may be one factor contributing to these disparities. However, few studies have investigated this possibility. STUDY DESIGN AND METHODS: Proprietary data on mobile blood collections in Maricopa County, Arizona, were gathered for the period of January 01, 2022 to April 30, 2022 and paired with census tract information using ArcGIS. Maricopa County encompasses the city of Phoenix with a total population of approximately 4.5 million people, including 1.5 million H/L residents. Blood drive count was regressed on H/L ethnic density and total population, and model estimates were exponentiated to obtain odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: During the specified period, approximately 27,000 red blood cell units were collected through mobile drives. Consistent with expectations, when controlling for total neighborhood population, each 10% increase in H/L ethnic density lowered the odds of having a blood drive in the corresponding neighborhood by 12% (OR = 0.88, 95% CI (0.83, 0.92), p < .001). DISCUSSION: These findings provide initial evidence of fewer proximal donation opportunities in areas with greater H/L population density which may contribute to H/L underrepresentation in blood donation and the need for more inclusive collection efforts. Improved access to blood collection is modifiable and could help to increase the overall blood supply, enhance the ability to successfully match specific blood antigen needs of an increasingly diverse population, and bring about a more resilient blood system.

The Vaginal Microbiota, Human Papillomavirus Infection, and Cervical Carcinogenesis: A Systematic Review in the Latina Population.

BACKGROUND: Latina women experience disproportionately higher rates of HPV infection, persistence, and progression to cervical dysplasia and cancer compared to other racial-ethnic groups. This systematic review explores the relationship between the cervicovaginal microbiome and human papillomavirus infection, cervical dysplasia, and cervical cancer in Latinas. METHODS: The review abides by the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, EMBASE, and Scopus databases were searched from January 2000 through November 11, 2022. The review included observational studies reporting on the cervicovaginal microbiota in premenopausal Latina women with human papillomavirus infection, cervical dysplasia, and cervical cancer. RESULTS: Twenty-five articles were eligible for final inclusion (N = 131,183). Forty-two unique bacteria were reported in the cervicovaginal microbiome of Latinas. Seven bacteria: Lactobacillus crispatus, Lactobacillus iners, Chlamydia trachomatis, Prevotella spp., Prevotella amnii, Fusobacterium spp. and Sneathia spp. were enriched across multiple stages of cervical carcinogenesis in Latinas. Therefore, the total number of reported bacteria includes four bacteria associated with the healthy state, 16 bacteria enriched in human papillomavirus outcomes, 24 unique bacteria associated with abnormal cytology/dysplasia, and five bacteria associated with cervical cancer. Furthermore, three studies reported significantly higher alpha and beta diversity in Latinas with cervical dysplasia and cancer compared to controls. Lactobacillus depletion and an increased abundance of L. iners in Latinas compared to non-Latinas, regardless of human papillomavirus status or lesions, were observed. CONCLUSIONS: The identification of 42 unique bacteria and their enrichment in cervical carcinogenesis can guide future cervicovaginal microbiome research to better inform cervical cancer prevention strategies in Latinas.

Benefits of metabolic surgery on macrovascular outcomes in adult patients with type 2 diabetes: a systematic review and meta-analysis.

Type 2 diabetes (T2D) is a chronic metabolic disorder that affects millions of individuals associated with an increased risk of mortality and macrovascular complications. We aimed to synthesize the benefit of metabolic surgery (MS) on macrovascular outcomes in adult patients with T2D.We included both cohort studies and randomized controlled trials (RCTs) that evaluated MS added to medical therapy compared with medical therapy alone in the treatment of adult patients with T2D. Studies must have evaluated the incidence of any macrovascular complication of the disease for a period of at least 6 months. We performed our search using PubMed, Scopus, EMBASE, Web of Science, and COCHRANE Central database which was performed from inception date until March 2022. The trial protocol was previously registered at PROSPERO (CRD42021243739). A total of 6338 references were screened throughout the selection process from which 16 studies involving 179,246 participants fulfilled inclusion criteria. MS reduced the risk of any cardiovascular event by 44% (relative risk .56 [95% CI, .42-.75]; P = < .001), myocardial infarction by 54% (.46 [95% CI, .26-.83]; P = .009), coronary artery disease by 40% (.60 [95% CI, .42-.85]; P = .004) and heart failure by 71% (.29 [95% CI, .14-.61]; P = .001). It also provided a risk reduction of stroke by 29% (.71 [95% CI, .51-.99]; P = .04) and 38% (.62 [95% CI, .46-.85]; P = .001) for cerebrovascular events. On mortality, MS yields a risk reduction of 55% (.45 [95% CI, .36-.57]; P <.001) in overall mortality and 69% in cardiovascular mortality (relative risk .31 [95% CI, .22-.42]; P < .001). Peripheral vascular disease risk was also reduced. MS in adult patients with T2D can reduce the risk of mortality and of any macrovascular outcomes. However, there is a need for the planning of randomized clinical trials to further analyze and confirm the results.

Harms of third- and fourth-generation combined oral contraceptives in premenopausal women: A systematic review and meta-analysis.

We assessed the available evidence regarding adverse effects on surrogate and patient-important health outcomes of third- and fourth-generation combined oral contraceptives among premenopausal women. We performed a systematic review and meta-analysis including randomized controlled trials and observational studies comparing third- and fourth-generation combined oral contraceptives with other generation contraceptives or placebo. Studies that enrolled women aged 15 to 50 years, with at least three cycles of intervention and 6 months of follow-up were included. A total of 33 studies comprising 629,783 women were included. Low-density lipoprotein cholesterol levels were significantly lower in fourth-generation oral contraceptives (mean differences (MD): -0.24 mmol/L; [95% CI -0.39 to -0.08]), while total cholesterol was significantly increased in levonorgestrel users when compared to third-generation oral contraceptives (MD: 0.27 mmol/L; [95% CI 0.04 to 0.50]). A decreased arterial thrombosis incidence was shown in fourth-generation oral contraceptive users, as compared to levonorgestrel (incidence rate ratio (IRR): 0.41; [95% CI 0.19 to 0.86]). No difference was found in the occurrence of deep venous thrombosis between fourth-generation oral contraceptives and levonorgestrel users (IRR: 0.91; [95% CI 0.66 to 1.27]; p = 0.60; I2 = 0%). Regarding the remaining outcomes, data were heterogeneous and showed no clear difference. In premenopausal women, the use of third- and fourth-generation oral contraceptives is associated with an improved lipid profile and lower risk of arterial thrombosis. Data were inconclusive regarding the rest of outcomes assessed. This review was registered in PROSPERO with CRD42020211133.

A phase 2 study of neoadjuvant chemotherapy plus durvalumab in resectable locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Patients with locally advanced head and neck squamous cell cancer (HNSCC) are treated with surgery followed by adjuvant (chemo) radiotherapy or definitive chemoradiation, but recurrence rates are high. Immune checkpoint blockade improves survival in patients with recurrent/metastatic HNSCC; however, the role of chemo-immunotherapy in the curative setting is not established. METHODS: This phase 2, single-arm, multicenter study evaluated neoadjuvant chemo-immunotherapy with carboplatin, nab-paclitaxel, and durvalumab in patients with resectable locally advanced HNSCC. The primary end point was a hypothesized pathologic complete response rate of 50%. After chemo-immunotherapy and surgical resection, patients received study-defined, pathologic risk adapted adjuvant therapy consisting of either durvalumab alone (low risk), involved field radiation plus weekly cisplatin and durvalumab (intermediate risk), or standard chemoradiation plus durvalumab (high risk). RESULTS: Between December 2017 and November 2021, 39 subjects were enrolled at three centers. Oral cavity was the most common primary site (69%). A total of 35 of 39 subjects underwent planned surgical resection; one subject had a delay in surgery due to treatment-related toxicity. The most common treatment-related adverse events were cytopenias, fatigue, and nausea. Post treatment imaging demonstrated an objective response rate of 57%. Pathologic complete response and major pathologic response were achieved in 29% and 49% of subjects who underwent planned surgery, respectively. The 1-year progression-free survival was 83.8% (95% confidence interval, 67.4%-92.4%). CONCLUSIONS: Neoadjuvant carboplatin, nab-paclitaxel, and durvalumab before surgical resection of HNSCC were safe and feasible. Although the primary end point was not met, encouraging rates of pathologic complete response and clinical to pathologic downstaging were observed.

Circulating tumor HPV DNA as an alternative method to determine HPV status in oropharyngeal squamous cell carcinoma.

Human Papilloma Virus (HPV) testing is mandatory for all newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC) due to its importance for prognostication and aiding in treatment decision making. Fine needle aspiration (FNA) is a widely used and accepted diagnostic tool for OPSCC. Although FNA can accurately determine histological diagnosis, results are often indeterminate or lack insufficient samples for HPV testing. For samples with an indeterminant FNA, we propose an alternate method for determining HPV status using circulating tumor tissue modified HPV DNA (ctHPVDNA). We report three cases that confirmed HPV status using ctHPVDNA following an indeterminate FNA. If validated, this non-invasive assay could prevent the need for repeat FNAs or operative biopsies for the sole purpose of determining HPV status.

Patient-Reported Receipt of Oncology Clinician-Delivered Brief Tobacco Treatment (5As) Six Months following Cancer Diagnosis.

INTRODUCTION: Smoking after a cancer diagnosis represents a modifiable health risk. It is recommended that oncology clinicians address tobacco use among their patients using the 5As brief model: Asking about use, Advising users to quit, Assessing willingness to quit, Assisting in quit attempts (counseling and medication), and Arranging follow-up. However, cross-sectional studies have found limited adoption of 5As (especially Assist and Arrange) in oncology settings. Further investigation is needed to understand changes in, and factors associated with, 5As delivery over time. METHODS: Patients recently diagnosed with cancer and reporting current smoking (N = 303) enrolled in a smoking cessation clinical trial and completed three longitudinal surveys; at pre-intervention baseline and 3- and 6-month follow-up post-enrollment. Patient-level correlates of 5As receipt at baseline, 3 months, and 6 months were identified using multilevel regression models. RESULTS: At baseline, patient-reported rates of 5As receipt from oncology clinicians ranged from 85.17% (Ask) to 32.24% (Arrange). Delivery declined from baseline to 6-month follow-up for all 5As, with the largest declines observed for Ask, Advise, Assess, and Assist-Counseling. Diagnosis of a smoking-related cancer was associated with greater odds of 5As receipt at baseline but lower odds at 6-month follow-up. At each time point, female gender, religiosity, advanced disease, cancer-related stigma, and smoking abstinence were associated with lower odds of 5As receipt, while reporting a recent quit attempt prior to enrollment was associated with higher odds of 5As receipt. CONCLUSION: Oncology clinicians' 5As delivery declined over time. Clinician delivery of the 5As varied based on patients' sociodemographics, clinical and smoking characteristics, and psychosocial factors.

Examining Between-Group Differences in Social Network Density and High-Sensitivity C-Reactive Protein in Older Adults: Implications for the Hispanic Mortality Paradox.

OBJECTIVE: Hispanic/Latino(x) and African American/Black older adults experience disproportionate cardiometabolic disease burdens when compared with their non-Hispanic White counterparts. Sources of resilience such as social networks have been found to mitigate the risk of this disease and its end points like high-sensitivity C-reactive protein (hs-CRP). However, little is known about the social network infrastructure among these groups. Moreover, existing work has largely ignored the degree to which members of one's network are connected to one another (network density), which may be important for navigating structural barriers within interdependent groups. The objective of this study was to understand the association between network density and 5-year hs-CRP (blood spot) and whether this association was moderated by race-ethnicity. METHODS: A subsample of Hispanic/Latino(x), African American/Black, and non-Hispanic White older adults ( N = 1431) from the National Social Life Health and Aging Project was used. Multivariable regression was used to estimate the association between network density and its interaction with race-ethnicity, with hs-CRP 5 years later. RESULTS: Although no main effect of network density on 5-year hs-CRP was found, results revealed a significant network density by race-ethnicity interaction (Wald χ2 (2, 1242) = 3.31, p = .037). Simple slopes analyses revealed that Hispanic/Latino(x) older adults with high network density had significantly lower hs-CRP levels when compared with their same-ethnic counterparts with low network density ( b = -0.73, standard error = 0.31, 95% confidence interval = -1.33 to -0.13, p = .018). CONCLUSIONS: Results demonstrate population-level differences in social network structure and differential associations of this infrastructure with health. Implications for the Hispanic Mortality Paradox are discussed.

Affective Experience and Regulation via Sleep, Touch, and "Sleep-Touch" Among Couples.

Touch associated with sleep (sleep-touch; reported physical contact during or shortly before/after sleep) is underexplored as a distinct contributor to affect regulatory processes associated with adult sleep. Given the affect-regulating effects of interpersonal touch, we theorized that among healthy co-sleeping adults, sleep-touch would add to sleep-related effects on affective "resetting," resulting in the experience of calmer, more regulated states. We studied 210 married heterosexual couples (aged 20-67 years, 79% non-Hispanic white, 13% Latinx) assigned 14 days of twice-daily (morning/evening) sleep/mood diaries. Multilevel daily (within-couple) mediation analyses showed that as hypothesized, more reported sleep-touch was associated with happier/calmer and less angry/irritable morning mood. In turn, happier/calmer mood was associated with greater enjoyment of time with spouse (for both spouses). Sleep-touch also was linked directly to both evening positive spousal events and enjoyment ratings. Sleep-touch was associated indirectly with fewer negative spousal events and less spouse-related stress via less angry/irritable morning mood (both spouses). Further, wives' sleep-touch was related to happier/calmer husband mood and evening enjoyment; husbands' sleep-touch was unrelated to wives' reports. All associations with sleep-touch were present while accounting for subjective sleep quality, prior evening mood, non-sleep-related physical affection, day in study, and weekend versus weekday. We speculate that among relatively healthy satisfied couples, physical touch during and surrounding sleep may add to sleep's restorative and affect-regulatory functions, suggesting a pathway through which co-sleeping can improve affect regulation and ultimately relationships and health.

Intensive vs. conventional blood pressure goals in older patients with type 2 diabetes: a systematic review and meta-analysis.

PURPOSE: Assess the effect of intensive vs conventional blood pressure goals on patient-important outcomes in older adults with type 2 diabetes. METHODS: A comprehensive search was performed using electronic databases. Randomized controlled trials comparing intensive vs conventional blood pressure goals in adults over 60 years of age with type 2 diabetes were included. Events were evaluated using a modified Mantel-Haenszel meta-analysis with Peto's method. Study selection and data extraction were performed independently and in duplicate. RESULTS: Seven trials were included. A 19% risk reduction (OR 0.81; 95% CI 0.69-0.95; I2 = 8%; p = 0.35) in the occurrence of major adverse cardiovascular events (MACE) and 37% risk reduction (OR 0.63; 95% CI 0.51-0.79; I2 = 0%; p = 0.56) in the occurrence of fatal or non-fatal stroke was documented in the intensive treatment group. There were no differences in the occurrence of all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and peripheral vascular disease. Data regarding treatment adverse effects and microvascular outcomes was scarce. CONCLUSIONS: Intensive blood pressure goals in older patients with diabetes were associated with a lower risk of stroke and MACE, but not with all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and peripheral vascular disease.

Including General Audiences in a Virtual Scientific Dementia Conference: Will They Get Anything From It?

BACKGROUND: Study participants, patients, and care partners are key stakeholders in research and have asked for greater inclusion in the dissemination of scientific learning. However, the participation of general audiences in scientific conferences dedicated to Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) is not widely supported or studied. OBJECTIVE: Our objectives were to evaluate the interest, level of engagement, and impact of including general audiences in a virtual dementia conference. METHODS: A diverse group of lay participants, identified via community-based health advocacy groups and research centers, were invited to attend the 2021 Alzheimer's Association International Conference (AAIC), with optional small-group discussions. Participants received complimentary access to all scientific sessions and were supported via navigation tips, recommended sessions, and a glossary of frequently used terms and acronyms. RESULTS: Lay participants demonstrated a high level of engagement, even among those that were research-naïve, attending virtual sessions for an average of 11.7 hours across the five days and recommending a variety of sessions to each other on topics extending from prevention of dementia to new therapies and care. Most participants said they would attend the conference again and rated the quality of interaction as high, while requesting more opportunities to engage directly with researchers. CONCLUSION: General audiences, in particular research participants, are advocating for greater participation in scientific conferences. This program can serve as a model to accomplish inclusion; thereby acknowledging their invaluable contribution to science.

Trends of sources of clinical research funding from 1990 to 2020: a meta-epidemiological study.

Evidence has raised concerns regarding the association between funding sources and doubtful data. Our main outcome was to analyze trends on funding sources in articles published from 1990 to 2020 in the more influential journals of internal and general medicine. In this meta-epidemiological study, we included peer-reviewed studies from the 10 highest impact journals in general and internal medicine published between January 1990 and February 2020 based on published original research according to the 2018 InCites Journal of Citation Reports, these consisted of the following: The New England Journal of Medicine, The Lancet, JAMA, BMJ, JAMA Internal Medicine, Annals of Internal Medicine, PLOS Medicine, Cachexia, BMC Medicine, and Mayo Clinic Proceedings Two reviewers working in duplicate extracted data regarding year of publication, study design, and sources of funding. In total, 496 articles were found; of these, 311 (62.7%) were observational studies, 167 (33.7%) were experimental, and 16 (3.2%) were secondary analyses. Percentages of grant sources through the years were predominantly from government (60%), industry (23.83%), and non-governmental (16.06%) organizations. The percentage of industry subsidies tended to decrease, but this was not significant in a linear regression model (r=0.02, p≥0.05). Government and non-government funding sources showed a trend to decrease in the same univariate analysis with both significant associations (r=0.21, p≤0.001 and r=0.10, p≤0.001, respectively). The main funding source in medical research has consistently been government aid. Despite previous reported data, no association was found between the source of funding and statistically significant results favoring study authors' hypothesis.