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Radiation induced cholecystitis is a known but rare complication of Yttrium90 (Y90) radioembolization of hepatic tumors due to nontarget embolization. Many documented cases of radiation induced cholecystitis have been treated with cholecystectomy, which is significant given the typical patient population undergoing radioembolization tends to be of higher surgical risk. Here, we present a case of a 68 year old male who developed radiation induced cholecystitis status post hepatic radioembolization that resolved with conservative management alone. This case highlights that radiation induced cholecystitis may be successfully and safely treated conservatively.

Lifestyle factors and their impact on cancer prevention, prognosis, and survivorship are increasingly recognized in the medical literature. Lifestyle factors are primarily defined here as diet and physical activity. We conducted a narrative review of the primary published data, including randomized controlled trials and prospective studies, on the impact of primary lifestyle factors on oncogenesis and clinical outcomes in the preventative and survivorship setting. First, we discuss the oncogenic mechanisms behind primary lifestyle factors (diet, physical activity and, within these 2, obesity). Then, we discuss the impact of adherence to lifestyle guidelines and dietary patterns on cancer incidence based on primary data. Owing to the plethora of published literature, to summarize the data in a more efficient manner, we describe the role of physical activity on cancer incidence using summative systematic reviews. We end by synthesizing the primary data on lifestyle factors in the survivorship setting and conclude with potential future directions. In brief, the various large-scale studies investigating the role diet and physical activity have reported a beneficial effect on cancer prevention and survivorship. Although the impact of single lifestyle factors on cancer incidence risk reduction is generally supported, holistic approaches to address the potential synergistic impact of multiple lifestyle factors together in concert is limited. Future research to identify the potentially synergistic effects of lifestyle modifications on oncogenesis and clinical outcomes is needed, particularly in cancer subtypes beyond colorectal and breast cancers.

Background: Gastrointestinal conditions are common in hospitalized patients. Decreased mobility, dietary changes, medications and their underlying illness may alter patients’ bowel movements. It’s important for health care providers to be aware of patient’s bowel habits, especially for early identification of Clostridiodies difficile infection (CDI). Prior research has shown that patient modesty may be a barrier to discussing bowel habits with nurses and providers. This can lead to delay in diagnosis of CDI, lack of timely isolation and possible misclassification of community onset CDI cases as hospital onset (HO-CDI). Methods: A Bowel Habits Assessment Tool (BHAT) was developed to assist health care providers in learning skills to assess and document patient bowel habits accurately. The tool provides a structured approach to help clinicians gather relevant information, identify abnormalities, and promote effective communication with patients. The tool was developed by an infectious disease physician and modeled on existing tools utilized to take a sexual history. A team of infectious disease physicians, nurses and a gastroenterologist reviewed the tool and provided feedback. See Table 1. The tool was introduced as a pilot program at a 180 bed academically affiliated Veterans Affairs Hospital. Micro educational sessions were held to provide education about the importance of a bowel habit history, introduce the tool and teach its use in clinical care. The teaching sessions were led by an Infectious Disease physician and a nurse infection preventionist. An anonymous pre and post survey employing a 5-point Likert scale was administered to participants. All participation was voluntary. This project was reviewed and approved as a Quality Improvement by the VA Research Office, Eastern Colorado Health Care System. Results: Twenty nine healthcare personnel participated in the pilot. Participants included nurses (13), resident physicians (13), medical students (2) and nursing assistants (1). 59% of participants stated that they strongly agree with the statement “I am comfortable discussing patient’s bowel habits” on the pre-survey. (Question 1). This increased to 73% after the BHAT educational session. The mean difference between pre and post survey responses for question one was 0.45 (CI 0.08761 to 0.8089, p= 0.0167). All participants found the BHAT related to their work and useful, with 41% strongly agreeing and 52% somewhat agreeing that the BHAT was useful. See figure 1: Survey Responses. Conclusions: The effectiveness of a bowel habit assessment tool was demonstrated using a pre and post survey. BHAT improved clinicians comfort level discussing patient’s bowel habits.

Abstract Efficiently managing agricultural irrigation is vital for food security today and into the future under climate change. Yet, evaluating agriculture’s hydrological impacts and strategies to reduce them remains challenging due to a lack of field-scale data on crop water consumption. Here, we develop a method to fill this gap using remote sensing and machine learning, and leverage it to assess water saving strategies in California’s Central Valley. We find that switching to lower water intensity crops can reduce consumption by up to 93%, but this requires adopting uncommon crop types. Northern counties have substantially lower irrigation efficiencies than southern counties, suggesting another potential source of water savings. Other practices that do not alter land cover can save up to 11% of water consumption. These results reveal diverse approaches for achieving sustainable water use, emphasizing the potential of sub-field scale crop water consumption maps to guide water management in California and beyond.

Abstract Background Hypercalcemia has been associated with hypergastrinemia in humans. Hypergastrinemia could be responsible for gastrointestinal (GI) signs in dogs with primary hyperparathyroidism (PHPT). Hypothesis/Objectives (a) Determine whether hypergastrinemia occurs in dogs with PHPT, (b) assess for potential correlations among ionized calcium (iCa), parathyroid hormone (PTH), and serum gastrin concentrations, and (c) determine whether gastrin concentrations decrease after management of PHPT. Animals Phase 1: 151 client‐owned dogs at the time of PHPT diagnosis, Phase 2: 24 dogs that underwent treatment for PHPT. Methods Dogs with azotemia, concurrent disease, or those receiving acid suppressants were excluded. Twenty‐four treated dogs had baseline and repeat quantification of serum gastrin, PTH, and iCa concentrations 4 weeks after treatment. The effect of treatment on gastrin, iCa, and PTH concentrations was assessed using Wilcoxon signed rank sum tests. Fisher exact testing was used to compare the proportion of dogs with hypergastrinemia in dogs with and without GI signs. Results Twenty‐seven of 151 PHPT dogs (17.9%) had increased pre‐treatment serum gastrin concentrations (median, 45.0 ng/L; interquartile range [IQR], 20.0 ng/L). Gastrin concentrations were not correlated with iCa (P = .92) or PTH (P = .60). Treatment of PHPT decreased PTH (P

ABSTRACTHigh levels of COVID-19 vaccine hesitancy have been reported among Black and Latinx populations, with lower vaccination coverage among racialized versus White sexual and gender minorities. We examined multilevel contexts that influence COVID-19 vaccine uptake, barriers to vaccination, and vaccine hesitancy among predominantly racialized sexual and gender minority individuals. Semi-structured online interviews explored perspectives and experiences around COVID-19 vaccination. Interviews were recorded, transcribed, uploaded into ATLAS.ti, and reviewed using thematic analysis. Among 40 participants (mean age, 29.0 years [SD, 9.6]), all identified as sexual and/or gender minority, 82.5% of whom were racialized. COVID-19 vaccination experiences were dominated by structural barriers: systemic racism, transphobia and homophobia in healthcare and government/public health institutions; limited availability of vaccination/appointments in vulnerable neighborhoods; absence of culturally-tailored and multi-language information; lack of digital/internet access; and prohibitive indirect costs of vaccination. Vaccine hesitancy reflected in uncertainties about a novel vaccine amid conflicting information and institutional mistrust was integrally linked to structural factors. Findings suggest that the uncritical application of “vaccine hesitancy” to unilaterally explain undervaccination among marginalized populations risks conflating structural and institutional barriers with individual-level psychological factors, in effect placing the onus on those most disenfranchised to overcome societal and institutional processes of marginalization. Rather, disaggregating structural determinants of vaccination availability, access, and institutional stigma and mistrust from individual attitudes and decision-making that reflect vaccine hesitancy, may support 1) evidence-informed interventions to mitigate structural barriers in access to vaccination, and 2) culturally-informed approaches to address decisional ambivalence in the context of structural homophobia, transphobia, and racism.

Abstract The mechanisms leading to changes in mesoscale chromatin organization during cellular aging are unknown. Here, we used transcriptional activator-like effectors, RNA-seq and superresolution analysis to determine the effects of genotoxic stress on oocyte chromatin structure. Major satellites are organized into tightly packed globular structures that coalesce into chromocenters and dynamically associate with the nucleolus. Acute irradiation significantly enhanced chromocenter mobility in transcriptionally inactive oocytes. In transcriptionally active oocytes, irradiation induced a striking unfolding of satellite chromatin fibers and enhanced the expression of transcripts required for protection from oxidative stress (Fermt1, Smg1), recovery from DNA damage (Tlk2, Rad54l) and regulation of heterochromatin assembly (Zfp296, Ski-oncogene). Non-irradiated, senescent oocytes exhibit not only high chromocenter mobility and satellite distension but also a high frequency of extra chromosomal satellite DNA. Notably, analysis of biological aging using an oocyte-specific RNA clock revealed cellular communication, posttranslational protein modifications, chromatin and histone dynamics as the top cellular processes that are dysregulated in both senescent and irradiated oocytes. Our results indicate that unfolding of heterochromatin fibers following acute genotoxic stress or cellular aging induced the formation of distended satellites and that abnormal chromatin structure together with increased chromocenter mobility leads to chromosome instability in senescent oocytes.

Background: While the majority of reproductive-aged females will experience pelvic pain during their lives, biological mechanisms underlying pelvic pain are not well understood. We investigated associations between pelvic pain symptoms and oxidative stress among people with and without surgically-confirmed endometriosis. Methods: Using an enzyme-linked immunosorbent assay, we measured 8-Hydroxy-2’-deoxyguanosine (8-OHdG) in urine samples and corrected for creatinine levels in 434 surgically-confirmed endometriosis participants compared to 605 participants never diagnosed with endometriosis. At enrollment, participants reported details of their pelvic pain symptoms. Linear regression was used to compute geometric mean (GM) creatinine-corrected 8-OHdG levels with 95% confidence intervals (CI) among all participants and those with and without endometriosis separately, adjusting for potential confounders. Interactions by surgically-confirmed endometriosis status were tested by Wald statistics. Results: No trends in 8-OHdG were observed among those with or without endometriosis for severity or frequency of dysmenorrhea, acyclic pelvic pain, dyspareunia or pain with bowel movements. Among endometriosis participants, lower 8-OHdG levels were observed for participants with any white, blue/black, or brown lesions (GM=76.7 versus 82.9 ng/mg; p=0.10), which was primarily driven by lower levels of 8-OHdG for any blue/black lesions (GM=72.8 versus 81.6 ng/mg; p=0.05). Conclusion: While no associations were observed between 8-OHdG and pelvic pain symptoms, future research is needed to assess how other pathways of oxidative damage, e.g. through proteins or lipids, may affect endometriosis-associated symptoms. Additionally, further research is needed to understand differences in oxidative stress among endometriosis lesion sub-phenotypes.

This study aimed to examine the potential predictors of improvement in mental health outcomes following participation in an intensive non-surgical outpatient weight management program (WMP) in an Australian public hospital. This was a retrospective cohort study of all adults with Class 3 obesity (BMI ≥ 40 kg/m2) who enrolled in the WMP from March 2018 to June 2021. The participants completed the Eating Disorder Examination Questionnaire Short Version (EDE-QS), Kessler-10 Psychological Distress Scale, and 36-Item Short-Form Survey (SF-36) at baseline and 12-month follow-up. A total of 115 patients completed 12 months in the WMP and were included in the study, with 76.5% being female, a mean ± SD age at baseline of 51.3 ± 13.8 years, a weight of 146 ± 26 kg, and a BMI of 51.1 ± 8.6 kg/m2. The participants lost an average of 8.6 ± 0.2 kg over 12 months, and greater weight loss at follow-up was significantly associated with improved global EDE-QS scores, psychological distress, and improved mental health quality of life. However, improvements in most mental health outcomes were not predicted by weight loss alone. Notably, a lower eating disorder risk at baseline was associated with less psychological distress at follow-up and greater weight loss at follow-up. Our results also found an association between reduced psychological distress and reduced binge eating frequency. These findings support the inclusion components of obesity interventions that target the psychological correlates of obesity to support improved outcomes in people with Class 3 obesity. Future studies should aim to identify which aspects of the WMP helped improve people’s psychological outcomes.

Functional MRI is a well-established tool used for pre-surgical planning to help the neurosurgeon have a roadmap of critical functional areas that should be avoided, if possible, during surgery to minimize morbidity for patients with brain tumors (though this also has applications for surgical resection of epileptogenic tissue and vascular lesions). This article reviews the locations of secondary language centers within the brain along with imaging findings to help improve our confidence in our knowledge on language lateralization. Brief overviews of these language centers and their contributions to the language networks will be discussed. These language centers include primary language centers of “Broca’s Area” and “Wernicke’s Area”. However, there are multiple secondary language centers such as the dorsal lateral prefrontal cortex (DLPFC), frontal eye fields, pre- supplemental motor area (pre-SMA), Basal Temporal Language Area (BTLA), along with other areas of activation. Knowing these foci helps to increase self-assurance when discussing the nature of laterality with the neurosurgeon. By knowing secondary language centers for language lateralization, via fMRI, one can feel confident on providing neurosurgeon colleagues with appropriate information on the laterality of language in preparation for surgery.

Abstract Introduction Mental health and substance abuse issues are increasing among HIV-positive people, and it negatively impacts health outcomes like engagement, retention in HIV care, and adherence to ART. Thus, national ART programs must include mental health management. The scoping review sought to map evidence on the efficacy of combining HIV and mental health care. Methods The Arksey and O’Malley methodological framework was used to map the existing research on integrating HIV and mental health services to identify knowledge gaps. Two independent reviewers screened articles for inclusion. Studies on HIV-mental health integration were considered. We searched numerous sources, extracted data, and summarized publications by integration model and patient outcomes. Results Twenty-nine articles met the criteria for this scoping review. Twenty-three studies were from high-income countries, with only six from low and middle-income countries in Africa (Zimbabwe 1, Uganda 3, South Africa 1, and Tanzania 1). Most of the literature discussed single-facility integration although multi-facility and integrated care through a case manager was researched as well. There was a reduction in depression, alcohol use, increased social function, decreased self-reported stigma, decreased psychiatric symptoms, and improved mood in PLHIV who received cognitive behavioral therapy in settings implementing integrated care. When providing integrated mental health services to PLHIV, healthcare workers reported feeling more comfortable discussing mental illness. Personnel in the mental health field reported less stigma and increased PLHIV referrals for mental health services due to integrated HIV and mental health care. Conclusion According to the research, integrating mental health services into HIV care improves the diagnosis and treatment of depression and other mental disorders related to substance abuse in PLHIV.

Background: Cancer cells remodel their local physical environment through processes of matrix reorganisation, deposition, stiffening and degradation. Urokinase-type plasminogen activator (uPA), which is encoded by the PLAU gene, is an extracellular proteolytic enzyme known to be involved in cancer progression and tumour microenvironment (TME) remodelling. Perturbing uPA therefore has a strong potential as a mechano-based cancer therapy. This work is a bioengineering investigation to validate whether 1) uPA is involved in matrix degradation and 2) preventing matrix degradation by targeting uPA can reduce cancer cell invasion and metastasis. Methods: To this aim, we used an engineered 3D in vitro model, termed the tumouroid, that appropriately mimics the tumour’s native biophysical environment (3 kPa). A CRISPR-Cas9 mediated uPA knockout was performed to introduce a loss of function mutation in the gene coding sequence. Subsequently, to validate the translational potential of blocking uPA action, we tested a pharmacological inhibitor, UK-371,801. The changes in matrix stiffness were measured by atomic force microscopy (AFM). Invasion was quantified using images of the tumouroid, obtained after 21 days of culture. Results: We showed that uPA is highly expressed in invasive breast and colorectal cancers, and these invasive cancer cells locally degrade their TME. PLAU (uPA) gene knock-out (KO) completely stopped matrix remodelling and significantly reduced cancer invasion. Many invasive cancer gene markers were also downregulated in the PLAU KO tumouroids. Pharmacological inhibition of uPA showed similarly promising results, where matrix degradation was reduced and so was the cancer invasion. Conclusion: This work supports the role of uPA in matrix degradation. It demonstrates that the invasion of cancer cells was significantly reduced when enzymatic breakdown of the TME matrix was prevented. Collectively, this provides strong evidence of the effectiveness of targeting uPA as a mechano-based cancer therapy.

Introduction Recent findings suggest that general anesthesia with endotracheal intubation (GA) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) who receive mechanical thrombectomy (MT) is associated with similar outcomes to conscious sedation (CS). [1][2] However, these trials involved stroke specific GA protocols in which immediate, post‐operative extubation was emphasized. In this study, we investigated outcomes of MT in AIS due to LVO as a function of the timing of extubation and explored variables that could delay extubation. Methods We performed a retrospective analysis of collected data gathered during a 5‐year period (2018‐2022) for all our patients with AIS due to LVO who received MT. We analyzed the stroke outcomes and complications between patients who had received GA and those who had received CS. We also investigated the relationships between associated pulmonary risk factors, timing of extubation, and tracheostomy, on the outcomes of stroke. Results A total of 242 patients were included in our study. 83 patients received GA and 159 patients received CS. Our study shows CS in MT had a 2.74 (95% CI = 1.21‐6.22) higher odds of having a final TICI rating of 0‐2a compared to those who had GA. A logistic regression model was fitted that included NIHSS prior to MT; in this analysis, patients who received GA had 2.71 times higher odds of reaching TICI 2b or higher (OR = 2.71, 95% CI = 1.19‐6.17). NIHSS was not a significant predictor of recanalization in our patients. Patients extubated in the IR suite vs. elsewhere (excluding patients who were not extubated in hospital) had 3.82 (95% CI = 1.03‐14.18) times higher odds of having an excellent mRS at 90 days (n=65). Those extubated late had higher odds of transitioning to comfort care (OR=4.50, 95% CI = 1.52‐13.31, p=0.004), and 90‐day mortality (OR=5.49, 95% CI = 1.71‐17.65, p=0.002). Those who were extubated early had a lower NIHSS post MT (mean = 10.89 vs 19.18), t=‐5.79, p

A spontaneous adrenal hemorrhage is a rare complication occurring in the setting of interventional radiology procedures. Here, we present the case of a 73-year-old male who underwent CT-guided drainage of a periduodenal collection. During the procedure, he developed sudden onset left back pain and hypertension, which revealed a left adrenal gland hemorrhage on CT imaging. Potential mechanisms for this complication include a physiological stress response, procedure-associated hypercoagulability, and direct trauma to the adrenal gland. Moreover, an adrenal hemorrhage should be monitored closely as it can lead to severe clinical consequences requiring treatment with IV analgesics and antihypertensives.

Many commercially available biologics, previously delivered only intravenously, are being re-formulated for subcutaneous delivery to improve patient access and compliance. However, due to inherent solubility limitations, large volume injections (more than 2 mL) are typically required. Different strategies are being explored to improve the tolerability of such injections, including the co-formulation with hyaluronidase and/or implementing different needle designs. While there have been separate reports of measuring injection forces and using imaging to track injection delivery and tissue response, there is no current set of methods to simultaneously characterize the injection delivery (bleb) and measure injection pressures. In this study we describe the development of Computed Tomography imaging methods in minipigs to characterize the morphology of the bleb following injection, along with inline pressure measurements to assess subcutaneous pressure during injection using two different injection volumes, 4.5 mL and 9 mL. We show that these parameters change with injection volume, and that inclusion of hyaluronidase in the injection increases bleb dispersion and reduces skin distention while also lowering the injection pressure. This method will likely be a valuable tool for assessing and comparing different injection delivery methods and formulations.

South Asian gay, bisexual, and other men who have sex with men (GBMSM) in the United States are subsumed under the broad, heterogeneous category of Asian GBMSM in national surveillance systems. Disaggregated data on their rates of HIV and sexually transmitted infection (STI) testing are not publicly reported. This is problematic as the diversity of ancestries, cultures, and customs across subgroups of Asian GBMSM may contribute to differential HIV and STI testing experiences. To address this deficit in knowledge, 115 South Asian GBMSM recruited through social media advertising and peer referral were surveyed about their patterns of HIV and STI testing. In the past 6 months, almost two-thirds ( n = 72, 62.61%) had two or more male sex partners, and more than a quarter ( n = 33, 28.70%) had condomless anal sex with two or more male partners. In the past year, more than one in four ( n = 32, 27.83%) had not been tested for HIV, and more than two in five ( n = 47, 40.87%) had not been tested for STIs. The prevalence of past-year HIV and STI testing was lower among participants aged ≥35 years and those who had never used pre-exposure prophylaxis. Participants who were partnered were less likely to have been tested for HIV, and those who were born outside the United States were less likely to have been tested for STIs in the past year. Findings highlight gaps in domestic HIV- and STI-prevention efforts with respect to adequately engaging South Asian GBMSM and suggest that some segments of this subgroup may benefit from targeted outreach.

Objectives To produce and evaluate a novel virtual reality (VR) training for public health emergency responders.Design Following a VR training designed to test key public health emergency responder competencies, a prospective cohort of participants completed surveys rating self-assessed skill levels and perceptions of training methods.Setting The VR training sessions were administered in a quiet room at the US Centers for Disease Control and Prevention (CDC), Atlanta, Georgia.Participants All participants volunteered from a list of CDC emergency international surge responders.Outcome measures Perceived impact of the training on responder skills was self-reported via a Likert 5-point scale questionnaire. Assessments were modelled according to the Expanded Technology Acceptance Model measuring participant perceived usefulness of and intention to use the new technology. Inductive coding of qualitative feedback resulted in the identification of central themes.Results From November 2019 to January 2020, 61 participants were enrolled. Most (98%) participants self-rated above neutral for all skills (mean 4.3; range 1.21–5.00). Regression modelling showed that the perceived ease of use of the VR and ability to produce demonstrable results as likely drivers of further use. Participants agreed that others would benefit from the training (97%), it was representative of actual response scenarios (72%) and they would use lessons learnt in the field (71%). Open-response feedback highlighted feeling being immersed in the training and its utility for public health responders.Conclusions At a time when a trained emergency public health workforce is a critical need, VR may be an option for addressing this gap. Participants’ impressions and feedback, in the setting of their high skill level and experience, highlighted the utility and benefit of using VR to deliver training. Further research is needed to determine skill acquisition through VR training among a pool of future responders with limited to no response experience.

Introduction: Integrative Medicine (IM) use and efficacy is poorly defined in those with plasma cell disorders (PCD). A 69-question survey on the subject was hosted on HealthTree.org for 3 months. Method: The survey included questions about complementary practice use, PHQ-2 score, quality of life, and more. Mean outcome values were compared between IM users and non-users. Proportions of supplement users and IM patients were compared between patients currently on myeloma specific treatment and patients not currently on treatment. Results: The top 10 IM modalities reported among 178 participants were aerobic exercise (83 %), nutrition (67 %), natural products (60 %), strength exercise (52 %), support groups (48 %), breathing exercises (44 %), meditation (42 %), yoga (40 %), mindfulness-based stress reduction (38 %), and massage (38 %). The survey showed most patients participated in IM modalities, though they felt uncomfortable discussing them with their oncologist. Participant characteristics were compared between groups (users and non-users) using two-sample t-tests and chi-square tests. Use of vitamin C (3.6 vs. 2.7; p = 0.01), medical marijuana (4.0 vs. 2.9; p = 0.03), support groups (3.4 vs. 2.7; p = 0.04), and massage (3.5 vs. 2.7; p = 0.03) were associated with a higher quality of life scores on MDA-SI MM. There were no other significant associations between supplement use or IM practices and the MDA-SI MM, brief fatigue inventory, or PHQ-2. Conclusion: This study provides a foundation in the understanding of IM use in PCD, but more research is needed to evaluate individual IM interventions and their efficacy.

Recent studies have reported several beneficial effects of natural compounds on cancerous cells, highlighting their use for future treatments. These preliminary findings have encouraged experiments with natural substances, such as plant extracts, to examine both cytotoxic and mitogenic effects and find alternative treatments for diseases such as breast cancer. This study examines the effects of microwave-assisted and ethanol maceration of marjoram (Origanum majorana) on MCF-7 breast cancer cell lines and normal breast tissue cell lines used as controls. Marjoram extracts displayed a cytotoxic effect on the MCF-7 cell lines and a mitogenic effect on the control cell lines at the MTS test. The metabolic profiles of MCF-7 and control cell lines were also assessed using the Biolog Phenotype Mammalian Metabolic (PM-M) platform and revealed statistically significant differences in the utilization of energy sources, metabolic activity in the presence of certain ionic species, and responses to metabolic effectors, such as stimulant/catabolic compounds and steroid hormones. Exposure to marjoram extracts exerted positive effects on the MCF-7 cells on the abnormal utilization of energy sources and the responses to metabolic effectors, while no major effects were detected on control cells. These effects were compared to the metabolic impact of the chemotherapeutic agent doxorubicin, which showed profound cytotoxic effects on both cancerous and normal breast cells. In conclusion, our in vitro evidence indicates that marjoram extracts are a promising alternative to chemotherapy in breast cancer since they can successfully eliminate cancerous cells by affecting their metabolic capacity to proliferate without inducing noticeable adverse effects on normal breast tissue.

Proteasome inhibitors are the cornerstone of multiple myeloma treatment, but challenges still remain despite the increased survival rates. We conducted a review on the role of curcumin, a natural product, as an adjunct to bortezomib and carfilzomib in preclinical multiple myeloma models. Four studies reviewed showed enhanced anticancer effects when curcumin was combined with bortezomib compared to either treatment alone. Two additional studies showed similar results with carfilzomib. Synergistic mechanisms include inhibition of NF-kB, IL-6-induced signaling pathways, JNK pathway modulation, and increased cell cycle arrest.

This study examined the real-world use of nivolumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This was a multinational retrospective study (VOLUME) assessing treatment effectiveness and safety outcomes and a prospective study (VOLUME-PRO) assessing HRQoL and patient-reported symptoms. There were 447 and 51 patients in VOLUME and VOLUME-PRO, respectively. Across both studies, the median age was 64.0 years, 80.9% were male, and 52.6% were former smokers. Clinical outcomes of interest included real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). The median rwOS was 9.2 months. Among patients with at least one assessment, 21.7% reported their best response as ‘partial response’, with 3.9% reporting ‘complete response’. The median duration of response (DoR) and median rwPFS were 11.0 months and 3.9 months, respectively. At baseline, VOLUME-PRO patients reported difficulties relating to fatigue, physical and sexual functioning, dyspnea, nausea, sticky saliva, dry mouth, pain/discomfort, mobility, and financial difficulties. There were improvements in social functioning and financial difficulties throughout the study; however, no other clinically meaningful changes were noted. No new safety concerns were identified. This real-world, multinational, multicenter, retrospective and prospective study supports the effectiveness and safety of nivolumab for R/M SCCHN patients.

Abstract The histone H3 variant H3.3, encoded by two genes H3-3A and H3-3B, can replace canonical isoforms H3.1 and H3.2. H3.3 is important in chromatin compaction, early embryonic development, and lineage commitment. The role of H3.3 in somatic cancers has been studied extensively, but its association with a congenital disorder has emerged just recently. Here we report eleven de novo missense variants and one de novo stop-loss variant in H3-3A (n = 6) and H3-3B (n = 6) from Baylor Genetics exome cohort (n = 11) and Matchmaker Exchange (n = 1), of which detailed phenotyping was conducted for 10 individuals (H3-3A = 4 and H3-3B = 6) that showed major phenotypes including global developmental delay, short stature, failure to thrive, dysmorphic facial features, structural brain abnormalities, hypotonia, and visual impairment. Three variant constructs (p.R129H, p.M121I, and p.I52N) showed significant decrease in protein expression, while one variant (p.R41C) accumulated at greater levels than wild-type control. One H3.3 variant construct (p.R129H) was found to have stronger interaction with the chaperone death domain-associated protein 6.

Abstract Background Transgender (trans) women face constrained access to gender-affirming HIV prevention and care. This is fueled in part by the convergence of limited trans knowledge and competency with anti-trans and HIV-related stigmas among social and healthcare providers. To advance gender-affirming HIV service delivery we implemented and evaluated ‘Transgender Education for Affirmative and Competent HIV and Healthcare (TEACHH)’. This theoretically-informed community-developed intervention aimed to increase providers’ gender-affirming HIV prevention and care knowledge and competency and reduce negative attitudes and biases among providers towards trans women living with and/or affected by HIV. Methods Healthcare and social service providers and providers in-training (e.g., physicians, nurses, social workers) working with trans women living with and/or affected by HIV (n = 78) participated in a non-randomized multi-site pilot study evaluating TEACHH with a pre-post-test design. Pre- and post-intervention surveys assessed participant characteristics, intervention feasibility (e.g., workshop completion rate) and acceptability (e.g., willingness to attend another training). Paired sample t-tests were conducted to assess pre-post intervention differences in perceived competency, attitudes/biases, and knowledge to provide gender-affirming HIV care to trans women living with HIV and trans persons. Results The intervention was feasible (100% workshop completion) and acceptable (91.9% indicated interest in future gender-affirming HIV care trainings). Post-intervention scores indicated significant improvement in: 1) knowledge, attitudes/biases and perceived competency in gender-affirming HIV care (score mean difference (MD) 8.49 (95% CI of MD: 6.12–10.86, p

Abstract Background Osteoarthritis (OA) subsequent to acute joint injury accounts for a significant proportion of all arthropathies. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitor cells classically known for potent immune-suppressive activity; however, MDSCs can also differentiate into osteoclasts. In addition, this population is known to be expanded during metabolic disease. The objective of this study was to determine the role of MDSCs in the context of OA pathophysiology. Methods In this study, we examined the differentiation and functional capacity of MDSCs to become osteoclasts in vitro and in vivo using mouse models of OA and in MDSC quantitation in humans with OA pathology relative to obesity status. Results We observed that MDSCs are expanded in mice and humans during obesity. MDSCs were expanded in peripheral blood of OA subjects relative to body mass index and in mice fed a high-fat diet (HFD) compared to mice fed a low-fat diet (LFD). In mice, monocytic MDSC (M-MDSC) was expanded in diet-induced obesity (DIO) with a further expansion after destabilization of the medial meniscus (DMM) surgery to induce post-traumatic OA (PTOA) (compared to sham-operated controls). M-MDSCs from DIO mice had a greater capacity to form osteoclasts in culture with increased subchondral bone osteoclast number. In humans, we observed an expansion of M-MDSCs in peripheral blood and synovial fluid of obese subjects compared to lean subjects with OA. Conclusion These data suggest that MDSCs are reprogrammed in metabolic disease, with the potential to contribute towards OA progression and severity.

Abstract Introduction Transgender (trans) and nonbinary people (TNB) are disproportionately impacted by HIV. HIV testing is critical to engage TNB people in HIV prevention and care. Yet, scant literature has examined social and structural factors associated with HIV testing among TNB people of diverse genders and in geographies with potentially lower trans acceptance. We: (1) characterized the prevalence of never having been tested for HIV; and (2) identified associated factors, among TNB people in Michigan, United States. Methods Data were from a community‐based participatory cross‐sectional survey (n = 539 sexually experienced TNB people). The prevalence of never having had an HIV test was reported overall and compared across socio‐demographic, clinical, social and structural factors using bivariable and multivariable logistic regression analyses. Results and discussion Approximately one‐quarter (26.2%) of participants had never had an HIV test (20.8% transfeminine; 30.0% transmasculine; 17.8% nonbinary assigned male at‐birth; and 32.0% nonbinary assigned female at‐birth). In a multivariable socio‐demographic model, older age (adjusted odds ratio [aOR] for 1‐year increase: 0.93, 95% CI: 0.90, 0.96, p

Abstract Background Drug checking uses chemical analytical technologies to analyze drugs from the unregulated market to reduce substance use-related risks. We aim to examine the frequency of third party use of a community drug checking service to explore the potential for harm reduction to extend beyond the individual into the community, increase service accessibility, and to contribute to upstream interventions in the supply. Methods Over 31 months, data were collected from a point-of-care drug checking service operated in Victoria, Canada. Through the implementation of survey questions at the intake of the service, data were collected about whether the drug check was for the individual, to sell, and/or for others. Results Just over half (52%) of service users were checking for reasons that extended beyond individual use. When checking for others, friends were the most common response, representing 52% of responses, and outreach/support workers checking for others was the second most at 32%. Twelve percent of service users reported checking to sell or for a supplier. Conclusions Third party checking is a frequent, and important aspect of drug checking services, which through facilitating community engagement and increasing accessibility, has expanded the reach of interventions beyond individuals to reduce risks within the unregulated market. Therefore, drug checking as an overdose response should be responsive and accessible for those using the service on the behalf of others.

Young people are not consistently or adequately valued by other global and community actors as contributing members and leaders. Given the current political context of democratic backsliding, school closures, and social distancing caused by the COVID-19 pandemic, young people are facing increased barriers to developing their democratic identities, learning how to be active citizens, and exercising their rights to participate in civic and political life. Now more than ever, development practitioners and the international community need to shift their approach to engaging young people in democracy and governance programs from one that views them as recipients to one that treats young people as partners and considers the unique environments in which they live. This paper argues that civic education programs that apply a positive youth development (PYD) approach can inform and shape how young people develop democratic identities and habits and directly link these identities and behaviors to building and sustaining democracies. The paper illuminates good practices and lessons learned through an exploration of global civic education programs demonstrating the utility of a PYD approach. The final section identifies areas to consider for the expansion and future of civic education programs to ensure their effectiveness and better link them to the Sustainable Development Goals.

To inform women of the Navajo Nation of safety measures implemented to minimize COVID-19 virus exposure during screening and treatment procedures at Navajo Nation based health care facilities, the Navajo Nation Breast and Cervical Cancer Prevention Program (NNBCCPP) and the University-based Partnership for Native American Cancer Prevention Program (NACP) collaborated to develop a podcast to describe the continued availability of services. During the COVID-19 pandemic, women of all ages and ethnicities in the US needing breast and cervical cancer prevention screenings and treatment, have been hesitant to seek services given the advice to avoid crowded spaces and maintain physical distancing. Epidemiological trends indicate that proactive, intensive strategies are needed in Native American communities for early detection and treatment to support early cancer diagnosis and improve cancer survival. The NNBCCPP and Northern Arizona University (NAU) through the National Institute of Health's National Cancer Institute funded NACP had a nascent partnership prior to the onset of COVID-19 pandemic. This partnership relied on face-to-face interaction to allow for informal social interaction, facilitate clear communication and support continued trust building. To adhere to federal, state and tribal recommendations to minimize gatherings and to stay in-place to minimize the spread of the virus, the Navajo Nation and NAU restricted, and in most cases would not approve employee travel for partnership meetings. The plans to develop a podcast necessitated bringing additional members into the collaboration who were unfamiliar to the original partners and due to travel restrictions, required all interactions to be remote. This expanded group met virtually to develop a script, record and edit the podcast. More importantly, group members had to build and maintain trust over months of communicating via a teleconference video platform. This collaborative addressed challenges related to unstable Internet connections and periodic stay-at-home policies; thus, these emerging partners had to modify social and professional communication to respect and accommodate the stress and uncertain circumstances created by the pandemic on the citizens and employees of Navajo Nation. This case study describes strategies used to maintain and respect all members of the partnership.

We examined how the relationship between maternal education and child health varies across women’s status and safety using pooled Demographic and Health Survey data from 24 sub-Saharan African countries. While maternal education was associated with less child stunting, wasting, and underweight, the effect of maternal education on stunting and underweight was attenuated among women who experienced high levels of intimate partner violence (IPV). Further, the positive influence of maternal education on stunting and underweight was less pronounced among women who lived in communities with higher levels of IPV, even after controlling for women’s own IPV. This suggests that the returns of maternal education may be dampened in the presence of IPV. The fact that this link operates at both individual and community levels underscores how gender norms, patriarchy, and gender-based violence stifle progress on children’s health. The results also demonstrate how the UN Sustainable Development Goals strengthening maternal education, improving child health, and reducing intimate partner violence must be jointly pursued and the importance of considering how child health outcomes may be tempered by context.

Abstract Within an animal species, the body sizes of individuals at higher latitudes are often different from individuals at lower latitudes. For homeothermic species that maintain a relatively constant body temperature, such as mammals and birds, individuals at higher latitudes tend to be larger. For ectothermic species, such as insects, that do not retain their own body heat and which often do not maintain a relatively constant body temperature, patterns of body size with latitude are highly variable. This has led some authors to contend that patterns in even closely related species cannot be expected to be similar. Indeed, to our knowledge, no studies of invertebrates have found that more closely related species have more similar relationships between body size and latitude. Further, no studies have investigated the potential influence of diet quality on interspecific differences in these clines. We measured wing lengths of specimens (N = 1753) in eight lycaenid butterfly species and one species of the sister family, Riodinidae to determine if more closely related species have similar latitudinal trends. We also estimated the mean nitrogen content of caterpillars’ hosts to investigate whether this often‐limiting nutrient influences the strength and direction of latitudinal clines in body size. We found that four species are significantly smaller at higher latitudes, an additional species is marginally smaller at higher latitudes (p

La privación de sueño es la condición de insuficiencia de sueño, pudiendo ser crónica o aguda. Se investigó el efecto de la privación del sueño en el desempeño académico, mediante la aplicación de una encuesta. Específicamente, se investigó: cómo afecta el no dormir al rendimiento universitario. Para lograr esto, también se identificaron las partes del cerebro que se relacionan al sueño y describen las consecuencias causadas por la falta de sueño. Además, se analiza el patrón de sueño en los individuos universitarios. Dentro de los resultados se evaluó la veracidad de la hipótesis propuesta, que entre más tiempo de descanso tienen los estudiantes, mejores son los resultados en sus estudios. Sin embargo, los resultados de la investigación arrojaron que los estudiantes que duermen menos tiempo de igual manera consiguen mantener resultados aceptables. El rendimiento de la mayoría de los estudiantes universitarios no se ve alterado de gran manera por la privación de sueño, pero es mejor tener buenos hábitos de sueño, para poder evitar enfermedades que pueden adquirir en un futuro.

Los juegos de estrategia siempre han sido muy gustados por las personas. Juegos como el ajedrez y las damas, por mencionar algunos muy jugados. Han creado rivalidad entre jugadores y hasta se han convertido en deportes jugados por profesionales. Con el surgir de la inteligencia artificial se abre una nueva ventana para probar si las computadoras pueden superar a los humanos. De estas ideas han surgido algoritmos que buscan solucionar problemas a través de diferentes estrategias. En este artículo se estudiaron los algoritmos de minimax y alfa-beta, su definición, funcionalidad y complejidad. Estos algoritmos se implementaron en la emulación del juego de Lara Croft Go, que fue programado en el lenguaje de Java utilizando el IDE de NetBeans. La aplicación consiste en un juego donde un humano se enfrenta a una IA que fue programada con ambos algoritmos y se define por diferentes factores, quien es el mejor resolviendo el juego. La recolección de los datos es definida por los movimientos que realice cada algoritmo para completar los niveles y la cantidad de estados que genere en la búsqueda de la solución. Basados en los datos recopilados durante la ejecución de los algoritmos, se demuestra que el algoritmo más eficiente en la búsqueda de la solución de los niveles implementados es el algoritmo de búsqueda Alfa-Beta, ya que genera menos estados, por lo tanto, evalúa menos nodos y llega a una solución en un tiempo menor que el algoritmo de búsqueda Minimax.

BackgroundMyeloproliferative neoplasms (MPNs) are a group of myeloid malignancies associated with significant symptom burden. Despite pharmacological advances in therapies, inadequate management of MPN symptoms results in reduced quality of life. ObjectiveThis study aims to determine the feasibility of a 12-week global wellness mobile app intervention in decreasing MPN symptom burden. The University of Arizona Andrew Weil Center for Integrative Medicine’s global wellness mobile app, My Wellness Coach (MWC), guides patients to improve their health and well-being through facilitating behavior changes. MethodsOf the 30 patients enrolled in a 12-week intervention, 16 (53%) were retained through the final assessment. Feasibility was assessed by the ease of recruitment, participant adherence, and mobile app acceptability. App acceptability was measured using the user version of the Mobile Application Rating Scale. MPN symptom burden was measured at baseline and 12 weeks after the intervention. ResultsRecruitment was efficient, with the participant goal reached within a 60-day period, suggestive of a demand for such an intervention. Adherence was less than the target within study design (75%), although similar to mobile device app use in other studies (53%). The app was deemed acceptable based on the mean user version of the Mobile Application Rating Scale 3-star rating by participants. Finally, there were statistically significant improvements in several MPN symptoms, quality of life, and total score on the Myeloproliferative Neoplasm Symptom Assessment Form surveys. ConclusionsOur 12-week intervention with the MWC app was feasible and was associated with a decrease in MPN symptom burden. Further investigation of the MWC app for use as a self-management strategy to reduce the symptom burden in patients with MPN is warranted.

Objectives: Women of all genders, including cisgender (cis) and transgender (trans) women, experience social and structural drivers of HIV inequities and pervasive barriers to HIV care. Yet, little is known about how HIV care providers address gender diversity in health care. Through a critical feminist lens informed by intersectionality theory, medical anthropology, and critical sociology, we explored (1) how do HIV care providers describe women living with HIV’s care needs and barriers; (2) what are their perspectives on optimal HIV care for women; and (3) to what extent do these conceptualizations include/exclude trans women. Methods: Utilizing a community-based exploratory qualitative study design, we conducted 60–90 minute semi-structured individual interviews from March 2019–April 2020 with eight HIV care providers ( n = 4 social service providers; n = 4 physicians) practicing across seven counties representative of rural, suburban, and urban Michigan, United States. Data were analyzed utilizing a reflexive thematic approach. Results: Three overarching themes emerged: (1) Emphasis on (different) clinical needs: key considerations in cis and trans women’s HIV care; (2) Recognition of the structural: barriers to HIV care affecting women of all genders; and (3) Proposed solutions: piecing together individual, social, and organizational interventions to increase access to HIV care that may benefit women living with HIV of all genders but are disproportionately framed as being for cis women. While HIV care providers recognized both cis and trans women living with HIV’s clinical care needs and structural barriers to care, they rarely envisioned optimal HIV care inclusive of gender affirmation and structural interventions. Conclusions: Findings suggest that HIV care providers can avoid reducing gender to biology and making assumptions about reproductive care needs, endocrinological care needs, caregiving responsibilities, and other life circumstances; provide gender-affirming medical care; and address structural barriers to HIV care to enhance intersectional and structurally focused gender-affirming—that is, trans-inclusive—women-centered HIV care.

Many lesbian, gay, bisexual, transgender (trans), queer, and other sexual and gender minority (LGBTQ+) people desire to conceive children. Yet, LGBTQ+ peoples' experiences are scant in reproductive health literature, particularly around pregnancy loss-a stigmatized and distressing pregnancy outcome. Informed by minority stress theory, this qualitative study aimed to explore the experiences of multi-level stigma and resilience among LGBTQ+ people in the context of conception, pregnancy, and loss. Seventeen semi-structured individual interviews (25-70 minutes) were conducted (2019) with a purposive sample of LGBTQ+ people in the United States (U.S.) who had experienced pregnancy loss (n = 14) or in an intimate partnership in which a pregnancy was lost (n = 3) in the last two years. Transcribed interviews were analyzed thematically. Participants described the profound sadness of pregnancy loss due to unique challenges of LGBTQ+ conception. Multiple types of stigma manifested at intrapersonal (e.g., anticipated sexual stigma upon disclosure), interpersonal (e.g., unsolicited advice about conception decisions), and structural levels (e.g., differential requirements to access conception compared to heterosexual/cisgender couples). Resilience was also seen individually (e.g., purposeful disclosure of conception, pregnancy, and loss), relationally (e.g., connecting with other LGBTQ+ community members), and collectively (e.g., creating/engaging in LGBTQ+-specific conception, pregnancy, and loss online spaces). LGBTQ+ people experience minority stressors of multi-level stigmatization throughout the pregnancy process, which limits their access to social support after experiencing pregnancy loss. However, individual, relational, and collective resilience strategies abound in response. Thus, minority stress theory can also be applied to recognize strengths-based and affirming approaches to reproductive healthcare for LGBTQ+ people.

Abstract Introduction Marijuana is a commonly used drug in the United States. Many states have legalized the recreational use of marijuana. The effects of marijuana on mental health are unknown. Methods In this prospective survey study, eligible participants included ED patients age 18 and older, who had ever used recreational marijuana. A survey instrument was developed, piloted, and revised. Data collected included reasons for marijuana use, marijuana's perceived effectiveness, and history of mental health conditions, including depression, anxiety, and suicidal thoughts. Results Among 303 participants (86% response rate), the median age of first marijuana use was 16 ([IQR 14, 19], range 6–65). The most commonly cited reasons for marijuana use included recreational use (70%; n = 211), to treat anxiety (30%; n = 89), to treat pain (25%; n = 74), and to treat depression (17%; n = 51). Mental health issues were common in the study population. A majority of patients reported anxiety in the last 30 days (59%; n = 176), and a significant minority of patients reported serious depression in the last 30 days (46%; n = 137). Some patients reported suicidal thoughts in the last 30 days (9%; n = 29). Participants who used marijuana more frequently reported more days of anxiety (median 15.5, compared to 1; P = 0.001). Among participants with mental health conditions, most began using marijuana before the onset of the mental health conditions (77%, n = 167). Earlier age of starting to use marijuana was correlated with higher number of years of anxiety or tension in lifetime (r = −0.11, P = 0.05, n = 301). Perceived effects of marijuana use on mental health were variable. Most participants stated that marijuana improved their mental health (62%; n = 163), and some reported that marijuana did not improve their mental health (37%; n = 98). Conclusions Many ED patients have used marijuana, either currently or in the past. Mental health conditions are also common, including anxiety, depression, and suicidal thoughts. Most participants reported marijuana use starting at an age under 18. Marijuana use preceded the onset of mental health conditions in the majority of participants.

Abstract Background Risk factors for prolonged recovery after concussion have been well researched, but specific objective clinical examination findings have not. This study examined whether clinical examination results could predict delayed recovery (DR) in individuals with concussion diagnosis. A secondary aim explored the influence of early examination on individual prognosis. Methods The study was a retrospective, observational cohort design that included 163 individuals seen at a concussion clinic who were followed longitudinally until cleared for sports activity. Cognitive, visual, balance, vestibular, and cervical clinical testing and symptom assessment were performed at initial evaluation. DR was calculated by taking the median value associated with time to clearance for activity. Bivariate logistic regression analysis was calculated to determine odds ratios (and 95% confidence intervals) for the odds of DR with presence or absence of each clinical finding. Multivariate analyses were used to define the best predictors of DR. Results 80 of 163 individuals were considered delayed in their clearance to activity. Cognitive impairments (OR = 2.72; 95%CI = 1.40, 5.28), visual exam findings (OR = 2.98; 95%CI = 1.31, 6.80), and vestibular exam findings (OR = 4.28; 95%CI = 2.18, 8.43) all increased the odds of a DR. Multivariate modeling retained cognitive symptoms and clinical examination-vestibular testing as predictors of delayed recovery. Time to examination after injury was a mediator for DR. Conclusions The clinical examination provides value in identifying individuals who are likely to exhibit a delayed clearance. In particular, vestibular impairments identified clinically at initial evaluation and cognitive symptoms were associated with increased odds of a DR to return to activity. Our data support that early implementation of a standardized clinical examination can help to identify individuals who may be more at risk of prolonged recovery from concussion.

Abstract An anthropomorphic phantom is a radiologically accurate, tissue realistic model of the human body that can be used for research into innovative imaging and interventional techniques, education simulation and calibration of medical imaging equipment. Currently available CT phantoms are appropriate tools for calibration of medical imaging equipment but have major disadvantages for research and educational simulation. They are expensive, lacking the realistic appearance and characteristics of anatomical organs when visualized during X-ray based image scanning. In addition, CT phantoms are not modular hence users are not able to remove specific organs from inside the phantom for research or training purposes. 3D printing technology has evolved and can be used to print anatomically accurate abdominal organs for a modular anthropomorphic mannequin to address limitations of existing phantoms. In this study, CT images from a clinical patient were used to 3D print the following organ shells: liver, kidneys, spleen, and large and small intestines. In addition, fatty tissue was made using modelling beeswax and musculature was modeled using liquid urethane rubber to match the radiological density of real tissue in CT Hounsfield Units at 120kVp. Similarly, all 3D printed organ shells were filled with an agar-based solution to mimic the radiological density of real tissue in CT Hounsfield Units at 120kVp. The mannequin has scope for applications in various aspects of medical imaging and education, allowing us to address key areas of clinical importance without the need for scanning patients.