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Abstract Background Primary health care professionals are held accountable for various quality measures in the treatment of patients with chronic diseases such as diabetes. Uncontrolled type 2 diabetes (T2D) remains a considerable health problem; thus, further studying patients with this condition is important for delivering effective interventions. Social determinants of health (SDoH) have been shown to affect various aspects of diabetes care in different subpopulations. We studied the association of SDoH with uncontrolled T2D in a population of adult primary care patients. Methods We retrospectively searched our electronic health record for adult patients (≥18 years) with a diagnosis of T2D and a hemoglobin A1c (HbA1c) level of 8% or higher. Patients were empaneled to 2 primary care clinic sites between January 1, 2021, and January 31, 2022. Patients were grouped by HbA1c level to stratify patients according to the extent of uncontrolled T2D. Patient characteristics were compared among groups. Unadjusted and adjusted multinomial logistic regression analysis was used to estimate the odds of various SDoH factors among patient groups with different levels of uncontrolled T2D. Results The study cohort included 1,596 patients. Most patients were White (79%), and the median age was 58.8 years. The median HbA1c level was 8.9%, and approximately 68% of patients were obese (body mass index [BMI] ≥30). When the study population was grouped by HbA1c level (8% to

Background: Cotesting with the Papanicolaou (Pap) and human papillomavirus tests detects most precancerous and cancerous lesions and increases the sensitivity for detecting high-grade precancerous and invasive cervical cancers compared with human papillomavirus testing alone. Objective: To compare the use of the Papette brush (hereafter Papette) to the traditional spatula with endocervical brush (cytobrush) for cervical cancer screening. Design: Pragmatic observational study. Methods: Adult women aged 21–64 years who were eligible for a Papanicolaou test at a Midwest Community Internal Medicine practice underwent cervical cancer screening using the Papette or spatula with cytobrush from 18 August 2021 through 1 February 2022. Cluster sampling was used across the practice. Pathology reports were then analyzed to compare the number of satisfactory versus unsatisfactory results between the two collection techniques. Results: We collected results for 756 Pap tests. The test results were satisfactory with the Papette 93.8% of the time compared with 93.0% for the spatula with cytobrush. Conclusion: The Papette is not inferior to a spatula with cytobrush as a collection method for Pap tests.

Sirtuins are NAD+-dependent protein lysine deacylases implicated in metabolic regulation and aging-related dysfunctions. The nuclear isoform Sirt1 deacetylates histones and transcription factors and contributes, e.g., to brain and immune cell functions. Upon infection by human immunodeficiency virus 1 (HIV1), Sirt1 deacetylates the viral transactivator of transcription (Tat) protein to promote the expression of the viral genome. Tat, in turn, inhibits Sirt1, leading to the T cell hyperactivation associated with HIV infection. Here, we describe the molecular mechanism of Tat-dependent sirtuin inhibition. Using Tat-derived peptides and recombinant Tat protein, we mapped the inhibitory activity to Tat residues 34–59, comprising Tat core and basic regions and including the Sirt1 deacetylation site Lys50. Tat binds to the sirtuin catalytic core and inhibits Sirt1, Sirt2, and Sirt3 with comparable potencies. Biochemical data and crystal structures of sirtuin complexes with Tat peptides reveal that Tat exploits its intrinsically extended basic region for binding to the sirtuin substrate binding cleft through substrate-like β-strand interactions, supported by charge complementarity. Tat Lys50 is positioned in the sirtuin substrate lysine pocket, although binding and inhibition do not require prior acetylation and rely on subtle differences to the binding of regular substrates. Our results provide mechanistic insights into sirtuin regulation by Tat, improving our understanding of physiological sirtuin regulation and the role of this interaction during HIV1 infection.

Objective: This study determined the incidence rates for obesity among adult patients ages 20 and older empaneled in primary care practice in Midwest United States to potentially identify an optimum timeframe for initiating intervention. Background: Primary care practice patients are likely to reflect underlying community trends in overweight and obesity; however, data on overweight and obesity in primary care patients is limited. While childhood incidence rates of obesity have been well reported, there is still a paucity of data on the incidence of obesity among adult population; literature has mainly focused on its prevalence. Methods: Medical record review of identified cohort with BMI data was conducted. Population was stratified by age and sex and overweight category was subdivided into tertiles. Results: Majority of 40 390 individuals who comprised the final population and had follow-up data, consisted of adults ages 40 to 69 years (47.5%), female (59.8%) of non-Hispanic ethnicity (95.9%) with 21 379 (52.8%) falling in weight category of overweight. Incidence of obesity was 7% at 1 year and 16% at 3 years follow-up. Highest percentages of individuals who became obese at 1 and 3 years were in age category of 40 to 69 years among men and 20 to 39 years among women. In Cox regression analysis, there was statistically significant association to developing obesity among all tertile groups in the overweight category. Age and particularly gender appeared to be modifying factors to likelihood of developing obesity. Conclusion: Study results suggest that while obesity incidence is higher among certain age groups in both genders, middle-aged women, and men in all tertiles of overweight category are at highest risk and may be the optimum population to target for weight loss interventions. Findings support the initiation of population-based interventions before onset of obesity.

Purpose The purpose of the present study was to investigate body mass index, multi-morbidity, and COVID-19 Risk Score as predictors of severe COVID-19 outcomes. Patients Patients from this study are from a well-characterized patient cohort collected at Mayo Clinic between January 1, 2020 and May 23, 2020; with confirmed COVID-19 diagnosis defined as a positive result on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays from nasopharyngeal swab specimens. Measures Demographic and clinical data were extracted from the electronic medical record. The data included: date of birth, gender, ethnicity, race, marital status, medications (active COVID-19 agents), weight and height (from which the Body Mass Index (BMI) was calculated, history of smoking, and comorbid conditions to calculate the Charlson Comorbidity Index (CCI) and the U.S Department of Health and Human Services (DHHS) multi-morbidity score. An additional COVID-19 Risk Score was also included. Outcomes included hospital admission, ICU admission, and death. Results Cox proportional hazards models were used to determine the impact on mortality or hospital admission. Age, sex, and race (white/Latino, white/non-Latino, other, did not disclose) were adjusted for in the model. Patients with higher COVID-19 Risk Scores had a significantly higher likelihood of being at least admitted to the hospital (HR = 1.80; 95% CI = 1.30, 2.50; P

Objective To describe the process and outcome of creating a patient cohort in the early stages of the COVID-19 pandemic in order to better understand the process of and predict the outcomes of COVID-19. Patients and Methods A total of 1169 adults aged 18 years of age or older who tested positive in Mayo Clinic Rochester or the Mayo Clinic Midwest Health System between January 1 and May 23 of 2020. Results Patients were on average 43.9 years of age and 50.7% were female. Most patients were white (69.0%), and Blacks (23.4%) and Asians (5.8%) were also represented in larger numbers. Hispanics represented 16.3% of the sample. Just under half of patients were married (48.4%). Common comorbid conditions included: cardiovascular diseases (25.1%), dyslipidemia (16.0%), diabetes mellitus (11.2%), chronic obstructive pulmonary disease (6.6%), asthma (7.5%), and cancer (5.1%). All other comorbid conditions were less the 5% in prevalence. Data on 3 comorbidity indices are also available including the: DHHS multi-morbidity score, Charlson Comorbidity Index, and Mayo Clinic COVID-19 Risk Factor Score. Conclusion In addition to managing the ever raging pandemic and growing death rates, it is equally important that we develop adequate resources for the investigation and understanding of COVID-19-related predictors and outcomes.

This single arm prospective study assessed the impact of individualized wellness coaching intervention for primary care patients with prediabetes on self-reported changes in physical activity level and food choices. Five hundred sixty adult patients 18 years and older with prediabetes, seen in primary care clinic, were invited to participate in 12 weeks wellness coaching sessions delivered by certified coaches. Responses from questionnaires at baseline, 6 and 12 weeks were analyzed. Of 168 consented patients, 99 completed at least one coaching session; majority was elderly, female, overweight or obese. At baseline, 50% had

The aim of this in vitro study was to investigate the degree of C=C double bond conversion of high-viscosity dimethacrylate- or ormocer-based bulk-fill composites as a function of measurement depth. Four bulk-fill composites (Tetric EvoCeram Bulk Fill, x-tra fil, SonicFill, and Bulk Ormocer) and the conventional nanohybrid composite Tetric EvoCeram were applied in standardized Class II cavities (n = 6 per group) and photoactivated for 20 s at 1350 mW/cm2. The degree of conversion of the composites was assessed using Fourier-transform infrared spectroscopy at seven measurement depths (0.15, 1, 2, 3, 4, 5, 6 mm). Data were analyzed using repeated measures ANOVA and one-way ANOVA with Bonferroni post-hoc tests (α = 0.05). The investigated bulk-fill composites showed at least 80% of their maximum degree of conversion (80% DCmax) up to a measuring depth of at least 4 mm. Tetric EvoCeram Bulk Fill and Bulk Ormocer achieved more than 80% DCmax up to a measuring depth of 5 mm, x-tra fil up to 6 mm. The conventional nanohybrid composite Tetric EvoCeram achieved more than 80% DCmax up to 3 mm. In contrast to the conventional composite, the investigated ormocer- and dimethacrylate-based bulk-fill composites can be photo-polymerized in thick layers of up to at least 4 mm with regard to their degree of C=C double bond conversion.

Objective: Much has been written about the patients’ perspective concerning weight management in health care. The purpose of this survey study was to assess perspectives of primary care providers (PCPs) and nurses toward patient weight management and identify possible areas of growth. Patients and Methods: We emailed a weight management–focused survey to 674 eligible participants (437 [64.8%] nurses and 237 [35.2%] PCPs) located in 5 outpatient primary care clinics. The survey focused on opportunities, practices, knowledge, confidence, attitudes, and beliefs. A total of 219 surveys were returned (137 [62.6%] from nurses and 82 [34.4%] from PCPs). Results: Among 219 responders, 85.8% were female and 93.6% were white non-Hispanic. In this study, PCPs and nurses believed obesity to be a major health problem. While PCPs felt more equipped than nurses to address weight management ( P < .001) and reported receiving more training than nurses (50.0% vs 17.6%, respectively), both felt the need for more training on obesity (73.8% and 79.4%, respectively). Although, PCPs also spent more patient contact time providing weight management services versus nurses ( P < .001), the opportunity/practices score was lower for PCPs than nurses (−0.35 ± 0.44 vs −0.17 ± 0.41, P < .001) with PCPs more likely to say they lacked the time to discuss weight and they worried it would cause a poor patient-PCP relationship. The knowledge/confidence score also differed significantly between the groups, with nurses feeling less equipped to deal with weight management issues than PCPs (−0.42 ± 0.43 vs −0.03 ± 0.55, P < .001). Neither group seemed very confident, with those in the PCP group only answering with an average score of neutral. Conclusion: By asking nurses and PCP general questions about experiences, attitudes, knowledge, and opinions concerning weight management in clinical care, this survey has identified areas for growth in obesity management. Both PCPs and nurses would benefit from additional educational training on weight management.

Background: Health and Wellness Coaching has been shown to enhance treatment outcomes in the primary care setting. However, little is known about the experience and perceptions of patients who worked with a wellness coach as an integrated member of their primary health-care team. Objective: This project assessed patients’ experience and obtained their perceptions on barriers and facilitators to participation in a primary care–based wellness coaching program. Method: A survey was mailed to 99 primary care patients with prediabetes who participated in a 12-week wellness coaching program. Results: Sixty-two (63%) completed the survey; responders felt that participation in the wellness coaching program helped move them toward healthier lifestyle behavior and created a personal vision of wellness. Major themes associated with participation were supportive coaching relationship, increased self-accountability, increased goal-setting, and healthy behavior strategies. No significant barrier to participation was reported. Conclusion: Participants reported highly positive experience with the program; how to best integrate health and wellness coaching into the primary care setting needs to be explored.

This article presents an overview of the advancements that have been made in the use of photoplethysmography (PPG) for unobtrusive sleep studies. PPG is included in the quickly evolving and very popular landscape of wearables but has specific interesting properties, particularly the ability to capture the modulation of the autonomic nervous system during sleep. Recent advances have been made in PPG signal acquisition and processing, including coupling it with accelerometry in order to construct hypnograms in normal and pathologic sleep and also to detect sleep-disordered breathing (SDB). The limitations of PPG (e.g., oxymetry signal failure, motion artefacts, signal processing) are reviewed as well as technical solutions to overcome these issues. The potential medical applications of PPG are numerous, including home-based detection of SDB (for triage purposes), and long-term monitoring of insomnia, circadian rhythm sleep disorders (to assess treatment effects), and treated SDB (to ensure disease control). New contact sensor combinations to improve future wearables seem promising, particularly tools that allow for the assessment of brain activity. In this way, in-ear EEG combined with PPG and actigraphy could be an interesting focus for future research.

Ramona S DeJesus1, Kristin S Vickers2, Robert J Stroebel1, Stephen S Cha31Division of Primary Care Internal Medicine, Mayo Clinic, Rochester, MN, USA; 2Department of Psychiatry and Psychology, Mayo Clinic, MN, USA; 3Department of Biostatistics, Mayo Clinic, Rochester, MN, USAPurpose: The collaborative care model, using care managers, has been shown to be effective in achieving sustained treatment outcomes in chronic disease management. Little effort has been made to find out patient preferences for chronic disease care, hence, we conducted a study aimed at identifying these.Methods: A 20-item questionnaire, asking for patients’ and providers’ preferences and perceptions, was mailed out to 1000 randomly selected patients in Olmsted County, Minnesota, identified through a diabetes registry to have type 2 diabetes mellitus, a prototypical prevalent chronic disease. Surveys were also sent to 42 primary care providers.Results: There were 254 (25.4%) patient responders and 28 (66%) provider responders. The majority of patients (>70%) and providers (89%) expressed willingness to have various aspects of diabetes care managed by a care manager. Although 75% of providers would be comfortable expanding the care manager role to other chronic diseases, only 39.5% of patient responders would be willing to see a care manager for other chronic problems. Longer length of time from initial diagnosis of diabetes was associated with decreased patient likelihood to work with a care manager.Conclusion: Despite study limitations, such as the lack of validated measures to assess perceptions related to care management, our results suggest that patients and providers are willing to collaborate with a care manager and that both groups have similar role expectations of a care manager.Keywords: care manager, collaborative care, patient preference, diabetes care

Ramona S DeJesus1, Rajeev Chaudhry1, Dorinda J Leutink2, Melanie A Hinton1, Stephen S Cha3, Robert J Stroebel11Division of Primary Care Internal Medicine, 2Quality Management Services, 3Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USAAbstract: There continues to be a need for improved medical management of diabetes patients with hypertension in primary care. While several care models have shown effectiveness in achieving various outcomes among these patients, it remains unclear what care model is most effective in improving blood pressure control in primary care. In this prospective study, 54 patients with type 2 diabetes mellitus and blood pressure of >140/90 identified through the registry, were randomized into three groups. Group A attended a nurse educator-conducted class on diabetes and hypertension, group B attended the same class and was asked to monitor their home blood pressure using provided device, and group C served as control (usual care). Of the 24 subjects who completed the study, only 20% achieved the target blood pressure of 0.05). Efforts to intensify management of hypertension among type 2 diabetes patients did not result in better blood pressure control compared to usual care. Studies looking into factors which limit patients’ participation in group classes and determining patients’ preferences in disease management would be helpful in ensuring success of any chronic disease management program.Keywords: management, hypertension, diabetes mellitus type 2

Obesity and depression are often comorbid conditions. There appears to be a bidirectional relationship between these. Obesity at baseline has been shown to increase the risk of onset of depression and depression at baseline increased the odds for developing obesity. Less is understood about the impact of obesity on depression treatment outcomes. The authors’ hypothesis was that obesity (body mass index [BMI] ≥30 kg/m 2 ) and morbid obesity (BMI ≥ 40 kg/m 2 ) would each have negative effects on depression remission rates after 6 months of enrollment into collaborative care management for depression. In a retrospective analysis of 1111 depressed patients with a PHQ-9 (Patient Health Questionnaire) score of 10 or greater, multivariate analysis for the odds ratio of achieving remission at 6 months demonstrated that the patient’s BMI at baseline was not an independent risk factor for depression outcome at 6 months. Collaborative care management for depression has been shown to be effective for improving depression outcomes, yet minimal prior research has focused on other clinical comorbidities that might affect outcomes. Although obesity was common in the study population, it was reassuring, based on this study that 6-month depression treatment outcomes do not appear to be significantly affected by the patient’s baseline BMI.

In 2008, the Institute for Clinical Systems Improvement (ICSI) in Minnesota implemented a model of collaborative care management (CCM) for treatment of depression in primary care. This resulted in significant improvements on both clinical response and remission over usual care, although an increase in utilization metrics has been observed. Mental health comorbidities have previously been significantly associated with an increased likelihood of not responding to initial treatment. This retrospective study hypothesized that patients with mental health comorbidities are more likely to be associated with patients who were readmitted into CCM with recurrent depression. A total of 145 patients who had completed CCM were studied; of these, 32 were diagnosed with recurrent depression and were readmitted to CCM, and 113 were in remission for at least 4 months. There were no statistically significant demographic differences between the 2 groups. The initial screening GAD-7 score for anxiety was significantly increased in the readmission group (12.81 vs 9.20, P = .001) as was the average length of treatment from initial diagnosis to remission (168.09 vs 120.99 days, P = .002). All other initial screening tests were not different between the groups. When controlling for the independent variables by multiple logistic regression, the odds ratio for GAD-7 was 1.1156 (CI = 1.0.192 to 1.2212, P = .0177) and for days of treatment in CCM was 1.0123 (CI = 1.0041 to 1.0206, P = .0033). Patients who are readmitted to CCM for recurrent depression have a statistically increased risk of associated anxiety and a longer treatment course than those who have remained in remission for at least 4 months.

The collaborative care management (CCM) model has been demonstrated to be significantly more effective compared to usual care (UC) in depression management although an initial increase in cost measures was seen. In this paper, cost measures as well as clinical response were analyzed on patients with available follow-up data at six months. Records of 219 patients with follow-up data in CCM group and 119 in UC group were reviewed. At six months, there was a statistically significant clinical response rate among patients in CCM compared to UC group ( P < 0.0001). Likewise, 65% in CCM group was “symptom-free” at 6 months vs. 31.9% in UC group ( P < 0.0001). Among the responders in both groups, there was no statistical difference in cost measures. However, cost measures were significantly higher among non-responders compared to responders within CCM. Between the two models, the non-responders in UC had lower cost measures than the non-responders under CCM.

The high prevalence of no-shows in residents’ primary care clinic acts as a barrier to continuity of care, results in loss of outpatient learning opportunities, and may result in more emergency department (ED) visits. The authors seek to identify if high rates of no-shows correlate with more ED visits. In a selected primary care internal medicine (PCIM) continuity clinic, 650 patients were randomly selected, with 325 patients each from the faculty and resident practices. The number of ED visits between January 1, 2006, and December 30, 2008, was recorded. Demographic characteristics of the population were obtained, and comparisons between the faculty and resident groups were performed using Student t test. Linear multiple regression analysis was performed to compare frequency of ED visits between the faculty and the resident groups, controlling for age, interpreter requirement, number of ED visits, proportion of no-shows, and insurance type. A P value

Obesity is associated with the development of liver disease and its progression to hepatocellular carcinoma. This link may be attributed to adipocytokines such as visfatin and resistin which have been shown to promote liver cancer incidence and progression. Studies have yet to determine the role of visfatin and resistin in liver cancer, specifically in the context of obesity. The objective of this study was to investigate the effect of neutralizing visfatin and resistin in obese (OB) or normal weight (NW) sera to determine the contribution of these proteins in obesity-induced invasive liver cancer. Sera from OB or NW males was used to determine the efficacy of neutralizing visfatin and resistin to reduce the obesity-induced liver cancer phenotype. HepG2 and SNU-449 cells were exposed to OB and NW sera [+ or -] antibodies for visfatin or resistin. The neutralizing antibodies differentially suppressed invasion, reactive oxygen species production, and matrix metalloproteinase-9 secretion. These changes corresponded with a decrease in phosphorylated extracellular signal-regulated kinases and protein kinase B in HepG2 cells, but differences were not observed in CAP1 or p-catenin. In conclusion, visfatin and resistin have differential roles in obesity-associated liver cancer and may be potential targets to reverse the impact of obesity on liver cancer progression. Key words: obesity, hepatocellular carcinoma, matrix metalloproteinases, in vitro cell culture, invasion. L'obesite est associee avec l'apparition de la maladie hepatique et son evolution vers le carcinome hepatocellulaire. Ce lien pourrait etre attribue a des adipocytokines comme la visfatine et la resistine que l'on a montre pouvoir favoriser l'apparition et l'evolution du cancer du foie. Reste a montrer a l'aide d'etudes le role de la visfatine et de la resistine dans le cancer du foie, specifiquement dans un contexte d'obesite. Cette etude portait sur l'effet neutralisant de la visfatine et de la resistine dans le serum de sujets obeses (OB) ou de poids normal (PN) en vue d'etablir la contribution de ces proteines dans le cancer du foie invasif engendre par l'obesite. A l'aide de serum d'hommes OB ou de PN, nous avons tente d'etablir l'efficacite de la neutralisation de la visfatine et de la resistine en vue d'entrainer une attenuation du phenotype du cancer du foie engendre par l'obesite. Nous avons expose des cellules HepG2 SNU-449 a du serum de sujets OB ou de PN avec ou sans anticorps contre la visfatine ou la resistine. Les anticorps neutralisants ont entraine une inhibition differentielle complete du caractere invasif, de la production de derives reactifs de l'oxygene et de la secretion de metalloproteinases matricielles 9. Ces variations correspondaient a un abaissement d'ERK et d'Akt phosphoryles dans les cellules HepG2, mais nous n'observions pas ces differences en matiere de CAP1 ou de p-catenine. En conclusion, la visfatine et la resistine jouent des roles differentiels dans le cancer du foie associe avec l'obesite et pourraient constituer des cibles eventuelles en vue d'inverser l'incidence de l'obesite sur l'evolution du cancer du foie. [Traduit par la Redaction] Mots-cles : obesite, carcinome hepatocellulaire, metalloproteinases matricielles, cellules en culture in vitro, invasion., Introduction Liver cancer is the sixth most common cancer and the leading cause of cancer deaths worldwide (The American Cancer Society 2020; WCRF International 2020). In 2020, The American Cancer [...]

Background: Qualitative analysis can be a daunting and time-consuming task for those who are attempting to code qualitative data for the first time. Method: This article presents select secondary data analysis from a previously published study to demonstrate the applicability and usefulness of implementing a logic model approach to provide a framework for qualitative analysis. Results: The use of the logic model provided systematic organization during the analysis process, efficiency for analytical tasks, and enhanced trustworthiness by documenting each analysis step. The model allowed for easier visualization of data that facilitated a richer and more focused analysis. Conclusion: With qualitative data that are focused on processes or outcomes, implementing a logic model framework to categorize and organize data can be useful and efficient, particularly for a novice analyst whether analyzing qualitative text for quality improvement, evidence-based practice, program evaluation, or formal research. [J Contin Educ Nurs. 2024;55(6):297–301.] [ABSTRACT FROM AUTHOR]

Abstract The generation of tailored supercontinua is essential for studying ultrafast light-matter interactions and for a variety of practical applications requiring broadband light. Liquid-core fibers (LCFs) have emerged as an innovative nonlinear photonic platform, demonstrating high efficiency in nonlinear frequency conversion. In this study, we showcase that LCFs provide a stable platform for ultrafast supercontinuum generation in a selected higher-order vector mode at $$1.55\;\upmu \hbox {m}$$ 1.55 μ m . Specifically, we demonstrate soliton fission and double-dispersive wave generation using a radially polarized mode in a $$\hbox {CS}_{2}$$ CS 2 -silica liquid-core fiber. The experiments were performed in a temperature-controlled laboratory, showing excellent stability with no evidence of fiber degradation, material degradation, or drift-induced changes in mode excitation over extended periods under standard environmental conditions. Our results confirm that liquid-core fibers are a reliable platform for nonlinear photonics, suitable for applications such as computationally tailored supercontinuum generation, single pulse spxectroscopy, and tailored light sources, all of which rely on consistent and stable nonlinear frequency conversion.

Background: Advanced chronic liver disease (ACLD) patients are usually malnourished, and both conditions in combination increase the likelihood of unfavourable clinical outcomes. Handgrip strength (HGS) has been suggested as a relevant parameter for nutritional assessment and predictor of adverse clinical outcomes in ACLD. However, the HGS cut‐off values for ACLD patients have not yet been reliably established. The aims of this study were to preliminarily identify HGS reference values in a sample population of ACLD male patients and to assess their association with survival over a 12‐month follow‐up period. Methods: This was a prospective observational study with preliminary analysis of outpatients and inpatients. A total of 185 male patients with a medical diagnosis of ACLD met the inclusion criteria and were invited to participate in the study. The physiological variation in muscle strength related to the age of the individuals included in the study was considered to obtain cut‐off values. Results: After categorising HGS by age group (adults: 18–60 years; elderly: ≥60 years), the reference values obtained were 32.5 kg for the adults and 16.5 kg for the elderly. During the 12‐month follow‐up, 20.5% of the patients died, and 76.3% of those had been identified with reduced HGS. Conclusions: Patients with adequate HGS showed significantly higher 12‐month survival than those with reduced HGS within the same period. Our findings show that HGS is an important predictive parameter for clinical and nutritional follow‐up in ACLD male patients. Key points: Strength measurement is an indicator of nutritional status that is not compromised by the presence of oedema and ascites and, therefore, has an advantage over methods traditionally used in clinical practice for advanced chronic liver disease (ACLD) patients.However, to date, very few studies have presented cut‐off values for ACLD patients. Furthermore, studies that have accounted for variables that directly influence muscle strength, including age group and various levels of severity of liver disease, are scarce.As dynamometry is a low‐cost method and easily reproducible in clinical practice, handgrip strength (HGS) can be effectively applied for inpatient and outpatient nutritional care. HGS cut‐off values may be used to plan a more tailored nutritional therapy and, most importantly, for the early detection of individuals at greater risk of negative outcomes in ACLD.The results of this study show that reduced HGS was associated with increased mortality and reduced survival in ACLD male patients.A multicentre study which presents HGS cut‐off accurate enough to predict mortality in larger populations of ACLD adult and elderly patients of both sexes will bring certainty as to the applicability of our results to larger settings. [ABSTRACT FROM AUTHOR]

This paper explores the multifaceted nature of digital entrepreneurship, tracing its evolution alongside the digital transformation of the broader economy. Entrepreneurship research has expanded to encompass a wide range of theoretical perspectives. It outlines the evolution of theoretical perspectives in entrepreneurship studies, shifting from a focus on individual characteristics to a broader emphasis on environmental, social, and institutional factors. The paper highlights the diversity of methodological approaches utilized in entrepreneurship research, ranging quantitative, qualitative, and computational techniques. The advent of the internet opened the door for e-commerce in the 1990s, followed by the rise of Web 2.0 social platforms in the 2000s, further empowering entrepreneurs through user-generated content and the power of networks. The current phase of digital entrepreneurship is characterized by data-driven platforms, sophisticated algorithms, and the blurring of physical and digital boundaries. Theoretical frameworks, including innovation theory, resource-based views, lean startup methodologies, and institutional perspectives, aid in understanding the opportunities and challenges within this dynamic field. Digital entrepreneurship is presented as a dynamic force reshaping the modern economy. The paper traces the evolution of digital entrepreneurship through three key phases: the emergence of e-commerce in the 1990s, the rise of Web 2.0 social platforms in the 2000s, and the current dominance of data-driven platforms. The ongoing digital revolution has profoundly altered the entrepreneurial landscape, demanding new skills, strategies, and models for success. The COVID-19 pandemic further accelerated digital adoption across businesses and society. The paper underscores the significance of digital entrepreneurship within the context of technological advancement, institutional shifts, and evolving market dynamics.

Background: This study describes the characteristics of men attending a primary health care screening initiative, determines the proportion of men who have elevated International Prostate Symptom Score (IPSS) scores and prostate-specific antigen (PSA) levels, and determines any correlation between these scores as indicators for benign prostatic hyperplasia (BPH) or prostate cancer. Methods: Data were collected from all patient records during men’s health screening initiatives that occurred in December 2018, January 2019, and March 2019 in Trinidad and Tobago. A total of 350 medical records were analyzed to record patient demographics, PSA levels, and IPSS scores. Analysis of the data was performed with the use of Statistical Package for the Social Sciences software (version 27). Results: Most men who attended the screening initiative belonged to the 61–65 age group (20.57%), with more than half of the men being married (57.71%) and employed (52.57%) and of patients with comorbidities (17%), the most prevalent included hypertension (6%) and diabetes mellitus (3.7%). A mean PSA level of 2.94 ng/ml and a mean IPSS of 7.62 were recorded. Moreover, 11.5% of the males had elevated PSA levels (>4 ng/ml) and 32.9% had elevated IPSS levels (>8). There were correlations between PSA and IPSS values (r = 0.161 and P = 0.006). Age was a predictor of both IPSS and PSA values (r = 0.214, P = 0.000 and r = 0.192, P = 0.000, respectively). Among diabetic participants, a small but significant correlation between IPSS and diabetes was shown (r = 0.223, P = 0.028). As a predictor of elevated IPSS, diabetes had an odds ratio of 1.132 (95% confidence interval (CI): 1.021–1.255). Conclusion: Our findings are similar to those described in previous studies; however, further investigations are required to fully describe the relationship between PSA and IPSS. This may assist in advancing screening measures and improving health outcomes for men with BPH and prostate cancer. Primary care physicians should recognize the possible association between BPH and diabetes mellitus and offer appropriate screening where indicated.

Abstract Background Technology-based assessments using 2D virtual reality (VR) environments and goal-directed instrumented tasks can deliver digital health metrics describing upper limb sensorimotor function that are expected to provide sensitive endpoints for clinical studies. Open questions remain about the influence of the VR environment and task complexity on such metrics and their clinimetric properties. Methods We aim to investigate the influence of VR and task complexity on the clinimetric properties of digital health metrics describing upper limb function. We relied on the Virtual Peg Insertion Test (VPIT), a haptic VR-based assessment with a virtual manipulation task. To evaluate the influence of VR and task complexity, we designed two novel tasks derived from the VPIT, the VPIT-2H (VR environment with reduced task complexity) and the PPIT (physical task with reduced task complexity). These were administered in an observational longitudinal study with 27 able-bodied participants and 31 participants with multiple sclerosis (pwMS, VPIT and PPIT only) and the value of kinematic and kinetic metrics, their clinimetric properties, and the usability of the assessment tasks were compared. Results Intra-participant variability strongly increased with increasing task complexity (coefficient of variation + 56%) and was higher in the VR compared to the physical environment (+ 27%). Surprisingly, this did not translate into significant differences in the metrics’ measurement error and test–retest reliability across task conditions (p > 0.05). Responsiveness to longitudinal changes in pwMS was even significantly higher (effect size + 0.35, p

Abstract The concept of an innovative human–machine interface and interaction modes based on virtual and augmented reality technologies for airport control towers has been developed with the aim of increasing the human performances and situational awareness of air traffic control operators. By presenting digital information through see-through head-mounted displays superimposed over the out-of-the-tower view, the proposed interface should stimulate controllers to operate in a head-up position and, therefore, reduce the number of switches between a head-up and a head-down position even in low visibility conditions. This paper introduces the developed interface and describes the exercises conducted to validate the technical solutions developed, focusing on the simulation platform and exploited technologies, to demonstrate how virtual and augmented reality, along with additional features such as adaptive human–machine interface, multimodal interaction and attention guidance, enable a more natural and effective interaction in the control tower. The results of the human-in-the-loop real-time validation exercises show that the prototype concept is feasible from both an operational and technical perspective, the solution proves to support the air traffic controllers in working in a head-up position more than head-down even with low-visibility operational scenarios, and to lower the time to react in critical or alerting situations with a positive impact on the human performances of the user. While showcasing promising results, this study also identifies certain limitations and opportunities for refinement, aimed at further optimising the efficacy and usability of the proposed interface.

Background: Cotesting with the Papanicolaou (Pap) and human papillomavirus tests detects most precancerous and cancerous lesions and increases the sensitivity for detecting high-grade precancerous and invasive cervical cancers compared with human papillomavirus testing alone. Objective: To compare the use of the Papette brush (hereafter Papette) to the traditional spatula with endocervical brush (cytobrush) for cervical cancer screening. Design: Pragmatic observational study. Methods: Adult women aged 21–64 years who were eligible for a Papanicolaou test at a Midwest Community Internal Medicine practice underwent cervical cancer screening using the Papette or spatula with cytobrush from 18 August 2021 through 1 February 2022. Cluster sampling was used across the practice. Pathology reports were then analyzed to compare the number of satisfactory versus unsatisfactory results between the two collection techniques. Results: We collected results for 756 Pap tests. The test results were satisfactory with the Papette 93.8% of the time compared with 93.0% for the spatula with cytobrush. Conclusion: The Papette is not inferior to a spatula with cytobrush as a collection method for Pap tests. [ABSTRACT FROM AUTHOR]

Sirtuins are NAD+-dependent protein lysine deacylases implicated in metabolic regulation and aging-related dysfunctions. The nuclear isoform Sirt1 deacetylates histones and transcription factors and contributes, e.g., to brain and immune cell functions. Upon infection by human immunodeficiency virus 1 (HIV1), Sirt1 deacetylates the viral transactivator of transcription (Tat) protein to promote the expression of the viral genome. Tat, in turn, inhibits Sirt1, leading to the T cell hyperactivation associated with HIV infection. Here, we describe the molecular mechanism of Tat-dependent sirtuin inhibition. Using Tat-derived peptides and recombinant Tat protein, we mapped the inhibitory activity to Tat residues 34–59, comprising Tat core and basic regions and including the Sirt1 deacetylation site Lys50. Tat binds to the sirtuin catalytic core and inhibits Sirt1, Sirt2, and Sirt3 with comparable potencies. Biochemical data and crystal structures of sirtuin complexes with Tat peptides reveal that Tat exploits its intrinsically extended basic region for binding to the sirtuin substrate binding cleft through substrate-like β-strand interactions, supported by charge complementarity. Tat Lys50 is positioned in the sirtuin substrate lysine pocket, although binding and inhibition do not require prior acetylation and rely on subtle differences to the binding of regular substrates. Our results provide mechanistic insights into sirtuin regulation by Tat, improving our understanding of physiological sirtuin regulation and the role of this interaction during HIV1 infection. [ABSTRACT FROM AUTHOR]

Obesity increases the risk of advanced prostate cancer (PCa). The calcium sensing receptor (CaSR) has been shown to be responsive to obesity-mediated cytokines and is upregulated in metastatic PCa. This study used a novel in vitro approach, involving the exposure of PCa cells to sera, from obese or normal weight males, and to CaSR inhibitor NPS-2143. Cell viability was determined using MTT assay. MMP-9 activity and invasion were assessed using zymography and invasion chambers, respectively. Microscopy was used to visualize EMT proteins. qRT-PCR and immunoblot analysis were used to quantify changes in genes and proteins important for tumorigenesis. Exposure to obese sera increased the proliferation, and the invasive capacity of PCa cells and de-localized epithelial-mesenchymal transition markers, which were attenuated with CaSR inhibition. Exposure to obese sera upregulated mRNA expression of PTHrP and protein expression of COX-2, IL-6, and CaSR. Inhibition of CaSR downregulated the mRNA expression of PTHrP and RANK, and protein expression of pERK and TNF-α. Obesity was shown to increase invasion and upregulate the expression of genes and proteins involved in PCa tumorigenesis. CaSR inhibition downregulated the expression of several of these factors. Thus, CaSR is a potentially important protein to target in obesity-mediated PCa progression. [ABSTRACT FROM AUTHOR]

IntroductionOn 24 February 2022, Russia launched a large-scale offensive in Ukraine, resulting in significant casualties to civilians, including children. As part of a seven-stream trauma education initiative, a novel pediatric trauma fundamentals course (PTF) was developed to provide standalone pediatric trauma education by our academic/NGO partnership. The objective of the program was to develop, implement, and evaluate a novel PTF educational course in the active armed conflict zone of Ukraine.MethodsA novel two-day PTF course was internally developed, translated into Ukrainian, and implemented across eight Oblasts (regions) in Ukraine from November 2022 to December 2023. Participants completed pre-and post-assessments in knowledge and self-confidence, and critical skills were assessed against objective skill checklists. Change in knowledge and self-confidence were analyzed, respectively, with the nonparametric Wilcoxon matched-pairs signed-rank test and McNemar’s test for paired data. Anonymous course evaluations were solicited after each course. Six to eight-week follow-up surveys were conducted to assess skill utilization and stewardship.ResultsFour hundred and forty-six Ukrainian health care providers were trained during 30 courses across 8 Oblasts in Ukraine during the intervention period. Aggregated knowledge and self-confidence significantly improved across all measures. Ukrainian instructors of courses received higher raw scores across all evaluation points on instructor feedback surveys as compared to international instructors. Six to eight-week follow-up surveys demonstrated participants had positive views of the training, have used the training on patients, and have taught the material to other health care providers.DiscussionOur novel PTF intervention demonstrates a successful partnership-based model for implementing pediatric trauma education in an active conflict zone in Ukraine. Challenges to implementing such programs can be mitigated through strategic partnership-based models between academic institutions and organizations with local knowledge and expertise. Ukrainian instructors provide course experiences similar or superior to international instructors, likely due to multiple factors related to language, culture, and context.

Non-communicable diseases are the leading cause of global deaths. The risk of their development and progression is increased by modifiable behavioral risk factors. Yet, despite the known benefits of primary and secondary prevention, people often do not follow recommendations for a healthier lifestyle. To this end, mobile health (mHealth) applications offer features for behavioral interventions. Yet, reported user engagement is often low. The objective of the work presented in this article is thus to evaluate the suitability of Design Thinking (DT) as a means to inform the development of an mHealth application that helps increase long-term engagement, and consequently supports individuals in sustainably changing their lifestyle. Applying the DT approach, key user needs and challenges were investigated and used to design a first low-fidelity mHealth application prototype. Think-Aloud analysis, task completion, and post-test interviews were then used to evaluate the prototype and generate early-stage insights. Subsequently, a structured, retrospective analysis of this process, evaluating the insight-generation potential of each step in the DT process cycle, was used to reflect on its suitability to inform mHealth application development. The respective results highlight (1) the distinct value of the DT method, particularly in the early stages of a development project; (2) the strong need for interdisciplinary collaboration in such projects, so as to capture realistic end-user requirements and improve the overall effectiveness of the application design; and (3) the significance of integrating behavioral change theories into the design of mHealth applications, in order to promote long-term engagement.

The protein lysine deacylases of the NAD+-dependent Sirtuin family contribute to metabolic regulation, stress responses, and aging processes, and the human Sirtuin isoforms, Sirt1-7, are considered drug targets for aging-related diseases. The nuclear isoform Sirt1 deacetylates histones and transcription factors to regulate, e.g., metabolic adaptations and circadian mechanisms, and it is used as a therapeutic target for Huntington's disease and psoriasis. Sirt1 is regulated through a multitude of mechanisms, including the interaction with regulatory proteins such as the inhibitors Tat and Dbc1 or the activator AROS. Here, we describe a molecular characterization of AROS and how it regulates Sirt1. We find that AROS is a partly intrinsically disordered protein (IDP) that inhibits rather than activates Sirt1. A biochemical characterization of the interaction including binding and stability assays, NMR spectroscopy, mass spectrometry, and a crystal structure of Sirtuin/AROS peptide complex reveal that AROS acts as a competitive inhibitor, through binding to the Sirt1 substrate peptide site. Our results provide molecular insights in the physiological regulation of Sirt1 by a regulator protein and suggest the peptide site as an opportunity for Sirt1-targeted drug development. [ABSTRACT FROM AUTHOR]

BackgroundExtracellular particles (EPs), particularly extracellular vesicles, play a crucial role in regulating various pathological mechanisms, including immune dysregulations post-trauma. Their distinctive expression of cell-specific markers and regulatory cargo such as cytokines or micro-ribonucleic acid suggests their potential as early biomarkers for organ-specific damage and for identifying patients at risk for complications and mortality. Given the critical need for reliable and easily assessable makers to identify at-risk patients and guide therapeutic decisions, we evaluated the early diagnostic value of circulating EPs regarding outcomes in severely injured multiple-trauma patients.MethodsPlasma samples were collected from 133 severely injured trauma patients (Injury Severity Score (ISS) ≥16) immediately upon arrival at the emergency department (ED). Patients were categorized into survivors and non-survivors. Injury characteristics and outcomes related to sepsis, pneumonia, or early (

IntroductionAutism spectrum disorder (ASD) is characterised by difficulty with social communication and restricted, repetitive patterns of behaviour. This study aimed to improve understanding of the ASD patient experience with the treatment (bumetanide) regarding the changes in core symptoms and to assess changes considered as meaningful. To achieve this, qualitative interviews were conducted with caregivers of patients in two phase 3 clinical trials (NCT03715153; NCT03715166) of a novel ASD treatment.MethodsCaregivers were invited to participate in one interview after completion of the pivotal phase 3 study; for those of them who continued treatment after study completion, a second interview was held 3 months after trial completion. The interviews were conducted by qualitative researchers and followed a semi-structured interview guide. The interviews focused on patients’ ASD symptoms and their impact on their daily life before enrolment, and on any symptom changes patients experienced during the trial.ResultsOut of the 13 eligible patients’ caregivers, 11 were interviewed up to two times at clinical sites in the UK, Spain, and Italy. The caregivers reported impairments in a wide range of skills: deficits in communication and social interaction; restricted, repetitive patterns of behaviour, interests, or activities; and cognitive, emotional, and motor impairments. Compared to before the trial initiation, caregivers also reported improvements in the following domains: communication, interaction with others, cognition, aggression, emotions, repetitive movements, eating, and sleeping.ConclusionThe exit interviews provided a rich source of qualitative data, allowing a deeper understanding of caregivers’ and patients’ experience of the disease and allowing us to understand what constitutes a meaningful change. These data also helped identify important experiences that may inform the patient-reported outcome measurement strategy for future trials in ASD.

Abstract The Russian invasion of Ukraine on February 24, 2022, has had devastating effects on the Ukrainian population and the global economy, environment, and political order. However, little is known about the psychological states surrounding the outbreak of war, particularly the mental well-being of individuals outside Ukraine. Here, we present a longitudinal experience-sampling study of a convenience sample from 17 European countries (total participants = 1,341, total assessments = 44,894, countries with >100 participants = 5) that allows us to track well-being levels across countries during the weeks surrounding the outbreak of war. Our data show a significant decline in well-being on the day of the Russian invasion. Recovery over the following weeks was associated with an individual’s personality but was not statistically significantly associated with their age, gender, subjective social status, and political orientation. In general, well-being was lower on days when the war was more salient on social media. Our results demonstrate the need to consider the psychological implications of the Russo-Ukrainian war next to its humanitarian, economic, and ecological consequences.