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Background and objectives: Polycystic ovary syndrome (PCOS) displays a phenotype-dependent cardio-metabolic risk. By performing a systematic search of the literature, we aimed to summarize metabolomic signatures associated with obesity in PCOS women.

BACKGROUND: Low back pain (LBP) is a significant public health problem that can result in physical disability and financial burden for the individual and society. Physical therapy is effective for managing LBP and includes evaluation of posture and movement, interventions directed at modifying posture and movement, and prescription of exercises. However, physical therapists have limited tools for objective evaluation of low back posture and movement and monitoring of exercises, and this evaluation is limited to the time frame of a clinical encounter. There is a need for a valid tool that can be used to evaluate low back posture and movement and monitor exercises outside the clinic. To address this need, a fabric-based, wearable sensor, Motion Tape (MT), was developed and adapted for a low back use case. MT is a low-profile, disposable, self-adhesive, skin-strain sensor developed by spray coating piezoresistive graphene nanocomposites directly onto commercial kinesiology tape. OBJECTIVE: The objectives of this study were to (1) validate MT for measuring low back posture and movement and (2) assess the acceptability of MT for users. METHODS: A total of 10 participants without LBP were tested. A 3D optical motion capture system was used as a reference standard to measure low back kinematics. Retroreflective markers and a matrix of MTs were placed on the low back to measure kinematics (motion capture) and strain (MT) simultaneously during low back movements in the sagittal, frontal, and axial planes. Cross-correlation coefficients were calculated to evaluate the concurrent validity of MT strain in reference motion capture kinematics during each movement. The acceptability of MT was assessed using semistructured interviews conducted with each participant after laboratory testing. Interview data were analyzed using rapid qualitative analysis to identify themes and subthemes of user acceptability. RESULTS: Visual inspection of concurrent MT strain and kinematics of the low back indicated that MT can distinguish between different movement directions. Cross-correlation coefficients between MT strain and motion capture kinematics ranged from -0.915 to 0.983, and the strength of the correlations varied across MT placements and low back movement directions. Regarding user acceptability, participants expressed enthusiasm toward MT and believed that it would be helpful for remote interventions for LBP but provided suggestions for improvement. CONCLUSIONS: MT was able to distinguish between different low back movements, and most MTs demonstrated moderate to high correlation with motion capture kinematics. This preliminary laboratory validation of MT provides a basis for future device improvements, which will also involve testing in a free-living environment. Overall, users found MT acceptable for use in physical therapy for managing LBP.

The strategic management is a relatively new discipline in its own right, whose foundations were laid since antiquity. Many concepts borrowed from various areas had an outstanding contribution in the formation and evolution of strategic management until nowadays. The dual pendulum metaphor reflects the existing tensions over time between internal and external factors of the organization and the relationships that exist between the two types of factors, the strategic management being outlined also by the simultaneous movement of the two pendulums.

Type 2 diabetes disproportionately impacts ethnic minorities and individuals from low socioeconomic status. Diabetes self-management education and support has been shown to improve clinical outcomes in these populations, and mobile health (mHealth) interventions can reduce barriers to access. Dulce Digital-Me (DD-Me) was developed to integrate adaptive mHealth technologies to enhance self-management and reduce disparities in the high-risk, underserved Hispanic population. The objective of the present study was to evaluate reach, adoption, and implementation of an mHealth diabetes self-management education and support intervention in this underrepresented population. The present analysis is a multimethod process evaluation using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. The study was effective in reaching a sample that was representative of the intended population; only modest but significant differences were observed in sex and age. The DD-Me health coach (HC) cited several important facilitators of intervention adoption, including outreach frequency and personalization, and the automated HC report. Implementation fidelity was high, with participants receiving >90% of intended interventions. Participants who received DD-Me with support from a HC were most engaged, suggesting utility and acceptability of integrating HCs with mHealth interventions. Perceptions of implementation among study participants were positive and consistent across study arms. This evaluation revealed the target population was successfully reached and engaged in the digital health interventions, which was implemented with high fidelity. Further studies should evaluate the efficacy and maintenance of the study following the RE-AIM model to determine whether this intervention warrants expansion to additional settings and populations.

Multiple myeloma, the disease characterized by the malignant proliferation of plasma cells that invades the bone marrow, produces osteolytic lesions and secretes monoclonal proteins. Several biomarkers have been shown to represent important tools in the pathogenesis of myeloma and offer insights into bone degradation and formation. The objectives of this current study were to assess the associations of modern biomarkers (TNF-α: tumor necrosis factor; IFN: Interferon; FreeRANKL: Free Receptor Activator for Nuclear Factor kappa B Ligand; RANKL: Receptor Activator for Nuclear Factor kappa B Ligand, Beta crosslaps, IL-6: Interleukin 6) with osteolytic lesions status after first-line treatment and to evaluate the correlations between modern and classical biomarkers (LDH: Lactate Dehydrogenase; VSH: Erythrocyte Sedimentation Rate; Hgb: Hemoglobin, Calcium, Albumin, B2microglobulin) stratified by osteolytic lesions status. A total of 35 patients diagnosed with multiple myeloma divided into two groups according to the osteolytic bone lesions, were studied: (1) unchanged status of osteolytic lesions and (2) changed status of osteolytic lesions. After fist-line treatment, we found a significant difference in Albumin (p = 0.0029) and Calcium levels (p = 0.0304), patients with a changed status in osteolytic lesions having higher values of Albumin and Calcium compared to those without changes in status of osteolytic lesions. After first-line treatment, decreased IL-6 values were significantly correlated with elevated values of Albumin (ρ = −0.96, p = 0.0005) in the patients with changed status of osteolytic lesions. Post-treatment values of IFN showed a significant positive correlation with Hemoglobin (ρ = 0.47, p = 0.0124), IL-6 (ρ = 0.55, p = 0.0026) and TNF-alpha values (ρ = 0.54, p = 0.0029). The results obtained from patients with unmodified lytic lesions identified a significant correlation between the biomarkers IL-6, Free RANKL, and IFN-beta with the classical marker LDH. This association highlights the involvement of these markers in promoting bone destruction and the development of osteolytic lesions.

While standalone Voice Assistants (VAs) are promising to support older adults daily routine and wellbeing management, onboarding and setting up these devices can be challenging. Although some older adults choose to seek assistance from technicians and adult children, easy set up processes that facilitate independent use are still critical, especially for those who do not have access to external resources. We aim to understand the older adults experience while setting up commercially available voice-only and voice-first screen-based VAs. Rooted in participants observations and semi-structured interviews, we designed a within-subject study with 10 older adults using Amazon Echo Dot and Echo Show. We identified the values of the built-in touchscreen and the instruction documents, as well as the impact of form factors, and outline important directions to support older adult independence with VAs.

IntroductionThe current study aimed to investigate the rates of anxiety, clinical depression, and suicidality and their changes in health professionals during the COVID-19 outbreak.Materials and methodsThe data came from the larger COMET-G study. The study sample includes 12,792 health professionals from 40 countries (62.40% women aged 39.76 ± 11.70; 36.81% men aged 35.91 ± 11.00 and 0.78% non-binary gender aged 35.15 ± 13.03). Distress and clinical depression were identified with the use of a previously developed cut-off and algorithm, respectively.Statistical analysisDescriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses, and Factorial Analysis of Variance (ANOVA) tested relations among variables.ResultsClinical depression was detected in 13.16% with male doctors and 'non-binary genders' having the lowest rates (7.89 and 5.88% respectively) and 'non-binary gender' nurses and administrative staff had the highest (37.50%); distress was present in 15.19%. A significant percentage reported a deterioration in mental state, family dynamics, and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (24.64% vs. 9.62%; p

Abstract Most lung cancer patients with metastatic cancer eventually relapse with drug-resistant disease following treatment and EGFR mutant lung cancer is no exception. Genome-wide CRISPR screens, to either knock out or overexpress all protein-coding genes in cancer cell lines, revealed the landscape of pathways that cause resistance to the EGFR inhibitors osimertinib or gefitinib in EGFR mutant lung cancer. Among the most recurrent resistance genes were those that regulate the Hippo pathway. Following osimertinib treatment a subpopulation of cancer cells are able to survive and over time develop stable resistance. These ‘persister’ cells can exploit non-genetic (transcriptional) programs that enable cancer cells to survive drug treatment. Using genetic and pharmacologic tools we identified Hippo signalling as an important non-genetic mechanism of cell survival following osimertinib treatment. Further, we show that combinatorial targeting of the Hippo pathway and EGFR is highly effective in EGFR mutant lung cancer cells and patient-derived organoids, suggesting a new therapeutic strategy for EGFR mutant lung cancer patients.

UNLABELLED: The Geriatrics 5Ms: Medications, Mind, Mobility, what Matters most and Multicomplexity is a framework to address the complex needs of older adults. Intelligent Voice Assistants (IVAs) are increasingly popular and have potential to support health-related needs of older adults. We utilized previously collected qualitative data on older adults views of how an IVA may address their health-related needs and ascertained their fit into the Geriatrics 5Ms framework. The codes describing health challenges and potential IVA solutions fit the framework: (1) Medications: difficulty remembering medications. SOLUTION: reminders. (2) Mind: isolation, anxiety, memory loss. SOLUTION: companionship, memory aids. (3) Mobility: barriers to exercise. SOLUTION: incentives, exercise ideas. (4) Matters most: eating healthy foods. SOLUTION: suggest and order nutritious foods, (5) Multicomplexity; managing multimorbidity. SOLUTION: symptom tracking and communicating with health care professionals. Incorporating the 5Ms framework into IVA design can aid in addressing health care priorities of older adults.

BackgroundBy 2034, the number of US individuals with diabetes is predicted to increase from 23.7 to 44.1 million, and annual diabetes-related spending is expected to grow from $113 to $336 billion. Up to 55% of US Hispanics born in the year 2000 are expected to develop diabetes during their lifetime. Poor healthcare access and cultural barriers prevent optimal care, adherence, and clinical benefit, placing Hispanics at disproportionate risk for costly diabetes complications. Mobile technology is increasingly prevalent in all populations and can circumvent such barriers. Our group developed Dulce Digital, an educational text messaging program that improved glycemic control relative to usual care. Dulce Digital-Me (DD-Me) has been tailored to a participant's individual needs with a greater focus on health behavior change.MethodsThis is a three-arm, parallel group, randomized trial with equal allocation ratio enrolling Hispanic adults with low income and poorly managed type 2 diabetes (N = 414) from a San Diego County Federally Qualified Health Center. Participants are randomized to receive Dulce Digital, Dulce Digital-Me-Automated, or Dulce Digital-Me-Telephonic. The DD-Me groups include Dulce Digital components plus personalized goal-setting and feedback delivered via algorithm-driven automated text messaging (DD-Me-Automated) or by the care team health coach (DD-Me-Telephonic) over a 12-month follow-up period. The study will examine the comparative effectiveness of the three groups in improving diabetes clinical control [HbA1c, primary outcome; low-density lipoprotein cholesterol (LDL-C), and systolic blood pressure (SBP)] and patient-provider communication and patient adherence (i.e., medication, self-management tasks) over 12 months and will examine cost-effectiveness of the three interventions.DiscussionOur comparative evaluation of three mHealth approaches will elucidate how technology can be integrated most effectively and efficiently within primary care-based chronic care model approaches to reduce diabetes disparities in Hispanics and will assess two modes of personalized messaging delivery (i.e., automated messaging vs. telephonic by health coach) to inform cost and acceptability.Trial registrationNCT03130699-All items from the WHO Trial Registration data set are available in https://clinicaltrials.gov/ct2/show/study/NCT03130699 .

BackgroundLow back pain (LBP) is a significant public health problem that can result in physical disability and financial burden for the individual and society. Physical therapy is effective for managing LBP and includes evaluation of posture and movement, interventions directed at modifying posture and movement, and prescription of exercises. However, physical therapists have limited tools for objective evaluation of low back posture and movement and monitoring of exercises, and this evaluation is limited to the time frame of a clinical encounter. There is a need for a valid tool that can be used to evaluate low back posture and movement and monitor exercises outside the clinic. To address this need, a fabric-based, wearable sensor, Motion Tape (MT), was developed and adapted for a low back use case. MT is a low-profile, disposable, self-adhesive, skin-strain sensor developed by spray coating piezoresistive graphene nanocomposites directly onto commercial kinesiology tape. ObjectiveThe objectives of this study were to (1) validate MT for measuring low back posture and movement and (2) assess the acceptability of MT for users. MethodsA total of 10 participants without LBP were tested. A 3D optical motion capture system was used as a reference standard to measure low back kinematics. Retroreflective markers and a matrix of MTs were placed on the low back to measure kinematics (motion capture) and strain (MT) simultaneously during low back movements in the sagittal, frontal, and axial planes. Cross-correlation coefficients were calculated to evaluate the concurrent validity of MT strain in reference motion capture kinematics during each movement. The acceptability of MT was assessed using semistructured interviews conducted with each participant after laboratory testing. Interview data were analyzed using rapid qualitative analysis to identify themes and subthemes of user acceptability. ResultsVisual inspection of concurrent MT strain and kinematics of the low back indicated that MT can distinguish between different movement directions. Cross-correlation coefficients between MT strain and motion capture kinematics ranged from –0.915 to 0.983, and the strength of the correlations varied across MT placements and low back movement directions. Regarding user acceptability, participants expressed enthusiasm toward MT and believed that it would be helpful for remote interventions for LBP but provided suggestions for improvement. ConclusionsMT was able to distinguish between different low back movements, and most MTs demonstrated moderate to high correlation with motion capture kinematics. This preliminary laboratory validation of MT provides a basis for future device improvements, which will also involve testing in a free-living environment. Overall, users found MT acceptable for use in physical therapy for managing LBP.

Summary: Chronic pain is associated with alterations in fundamental cellular processes. Here, we investigate whether Beclin 1, a protein essential for initiating the cellular process of autophagy, is involved in pain processing and is targetable for pain relief. We find that monoallelic deletion of Becn1 increases inflammation-induced mechanical hypersensitivity in male mice. However, in females, loss of Becn1 does not affect inflammation-induced mechanical hypersensitivity. In males, intrathecal delivery of a Beclin 1 activator, tat-beclin 1, reverses inflammation- and nerve injury-induced mechanical hypersensitivity and prevents mechanical hypersensitivity induced by brain-derived neurotrophic factor (BDNF), a mediator of inflammatory and neuropathic pain. Pain signaling pathways converge on the enhancement of N-methyl-D-aspartate receptors (NMDARs) in spinal dorsal horn neurons. The loss of Becn1 upregulates synaptic NMDAR-mediated currents in dorsal horn neurons from males but not females. We conclude that inhibition of Beclin 1 in the dorsal horn is critical in mediating inflammatory and neuropathic pain signaling pathways in males.

IntroductionDuring the COVID-19 pandemic various degrees of lockdown were applied by countries around the world. It is considered that such measures have an adverse effect on mental health but the relationship of measure intensity with the mental health effect has not been thoroughly studied. Here we report data from the larger COMET-G study pertaining to this question.Material and methodsDuring the COVID-19 pandemic, data were gathered with an online questionnaire from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Anxiety was measured with the STAI, depression with the CES-D and suicidality with the RASS. Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively.Statistical analysisIt included the calculation of Relative Risk (RR), Factorial ANOVA and Multiple backwards stepwise linear regression analysis RESULTS: Approximately two-thirds were currently living under significant restrictions due to lockdown. For both males and females the risk to develop clinical depression correlated significantly with each and every level of increasing lockdown degree (RR 1.72 and 1.90 respectively). The combined lockdown and psychiatric history increased RR to 6.88 The overall relationship of lockdown with severity of depression, though significant was small.ConclusionsThe current study is the first which reports an almost linear relationship between lockdown degree and effect in mental health. Our findings, support previous suggestions concerning the need for a proactive targeted intervention to protect mental health more specifically in vulnerable groups.

Background: Heart transplantation (HT) remains the ultimate treatment for end-stage heart failure. An endomyocardial biopsy (EMB) is “the gold standard” diagnostic procedure used in HT rejection surveillance. The aim of this study is to provide a detailed analysis of the histopathological characteristics of the EMB and to investigate if there is a correlation between some histopathological changes, such as fibrosis, vasculitis, Quilty effect (Q.E.), myocytes damage, and the presence of episodes of acute rejection. Methods: In this retrospective study, 200 EMBs were included, coming from 65 patients transplanted in the Emergency Institute for Cardiovascular Diseases and Transplantation (ICvDT) Targu Mures between 2012 and 2024. Fibrosis, vasculitis, Q.E., myocyte damage, etc., were microscopically evaluated to see if these parameters correlate with rejection episodes. Results: The mean age was 38.18 years (SD 15.67), 25% of biopsies being recorded in the 41–50 age group. 77.14% of total acute cellular rejection (ACR) was of mild rejection, with most registered in the 11–20 age group; the cases of severe rejection being recorded in the 41–50 age group. Antibody-mediated rejection (AMR) was recorded more frequently in women with a representation of 23.4%, compared to 8.5% of men. 86.7% (39 cases) of the total number of EMBs with fibrosis score 3 and 71.4% (15 cases) of the total EMBs with fibrosis score 2 were recorded in men, compared to the 28.6% (6 cases) of fibrosis score 2 recorded in women (p = 0.013). 50.0% of all the EMB recorded in the 61–70 age group showed fibrosis score 3, compared to 34.8% of those from the 21–30 age group. The Q.E. was identified in 13% of the biopsies and, in some patients, it was observed across 3–4 successive biopsies. Mild vasculitis was associated in 34.9% of cases with ISHLT ≥ 1R and moderate vasculitis was associated in 87.5% of cases with ISHLT ≥ 1R. Conclusions: Fibrosis was detected much more frequently in men and in the 61–70 age group. In addition to the histopathological changes specific to acute rejection, there are other pathological changes, such as the Q.E., and vasculitis and myocytes damage and disarray, that seem to suggest a close connection with rejection, but extensive studies are needed to confirm this.

Background and Objectives: Hypertensive disorders, particularly pre-eclampsia, pose significant risks during pregnancy, affecting both maternal and neonatal health. The study aims to analyze short- and long-term health implications for mothers and their children, comparing those with pre-eclampsia to those without, to improve understanding of risk factors, diagnostic markers, and outcomes. Materials and Methods: This retrospective observational study involved 235 patients, 98 with pre-eclampsia and 137 without, monitored from 2015 to 2018 at the Obstetrics and Gynecology Department of the “Pius Brînzeu” Emergency County Clinical Hospital in Timișoara, Romania. Results: Women with pre-eclampsia were older, had higher BMIs, and more frequently had a family history of pre-eclampsia, hypertension, and diabetes. They also had lower educational and socioeconomic levels and fewer prenatal visits. Biochemical markers such as higher proteinuria, elevated sFlt-1, and lower PlGF were significant in diagnosing pre-eclampsia. Short-term maternal complications like eclampsia, HELLP syndrome, and acute kidney injury were more prevalent in the pre-eclampsia group. Neonatal outcomes included higher rates of preterm birth, low birth weight, and NICU admissions. Long-term mothers with a history of pre-eclampsia had higher incidences of chronic hypertension, cardiovascular disease, kidney problems, diabetes, and mental health disorders. Their children faced increased risks of neuropsychological delays, chronic respiratory issues, behavioral disorders, learning difficulties, and frequent infections. Conclusions: The study highlights the significant short- and long-term health impacts of pre-eclampsia on both mothers and their children. Early monitoring, intervention, and comprehensive management are crucial in mitigating these risks. These findings underscore the need for personalized care strategies to improve health outcomes for affected individuals.

Background: Conventional vaccines rarely cause severe allergic reactions. However, the rapid development and approval of COVID-19 vaccines left limited initial data on their adverse reactions, particularly in individuals with a history of allergy. The aim of this study was to assess and compare the safety profile of different doses and brands of COVID-19 vaccines in subjects with a history of allergy vs. those without a history of allergy. Methods: From February 2021 to February 2023, a web-based prospective study gathered vaccinee-reported outcomes using electronic questionnaires across eleven European countries. Baseline and up to six follow-up questionnaires captured data on vaccinee demographics, as well as both solicited and unsolicited adverse reactions. Results: Overall, 3476 vaccinees with a history of allergy were matched with 13,872 vaccinees from the general population at the first vaccination cycle and were included in the analysis. A total of 825 vaccinees with a history of allergy who had received a booster dose, matched to 3297 vaccinees from the general population, were included in the analysis. Higher rates of ADRs occurred after the first vaccination cycle compared to after the booster dose (64–91% vs. 56–79%). However, most reported ADRs were solicited and not serious, and no case of anaphylaxis was reported. Women and vaccinees with a history of allergy reported ADRs more frequently than men and the matched controls, respectively. Compared to other COVID-19 vaccines, a higher proportion of vaccinees experiencing at least one ADR following their first vaccination cycle was observed with Comirnaty and Vaxzevria. Statistically significant differences were observed among the study cohorts for median TTO after the second dose, and for median TTR following the first vaccination cycle and booster dose (p < 0.001). Conclusions: Typically, any drug or vaccine use carries a risk of severe allergic reactions, yet the benefits of vaccination generally outweigh these potential risks, as shown with the COVID-19 vaccines.

Rosa canina L., commonly known as rosehip, is of notable scientific interest for its applications in nutrition, cosmetics, and pharmaceuticals. This review article highlights its health-promoting properties, including antioxidant, anti-inflammatory, hepatoprotective, and anticarcinogenic effects, attributed to its rich content of phenolic acids, carotenoids, tocopherols, and vitamins. With growing interest in sustainable practices, rosehip by-products are increasingly valorized. For instance, cold-pressed rosehip seed oil is a valuable source of polyunsaturated fatty acids, while incorporating rosehip pomace into snacks enhances their nutritional profile, positioning them as potential functional foods and dietary supplements. This article aims to provide a comprehensive overview of advancements in utilizing rosehip and its by-products, emphasizing their role in enriching food and pharmaceutical products with nutritional and functional bioactivities.

IntroductionThere are few published empirical data on the effects of COVID-19 on mental health, and until now, there is no large international study.Material and methodsDuring the COVID-19 pandemic, an online questionnaire gathered data from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively.Statistical analysisDescriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses and Factorial Analysis of Variance (ANOVA) tested relations among variables.ResultsProbable depression was detected in 17.80% and distress in 16.71%. A significant percentage reported a deterioration in mental state, family dynamics and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (31.82% vs. 13.07%). At least half of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop depression was associated with history of Bipolar disorder and self-harm/attempts (RR = 5.88). Suicidality was not increased in persons without a history of any mental disorder. Based on these results a model was developed.ConclusionsThe final model revealed multiple vulnerabilities and an interplay leading from simple anxiety to probable depression and suicidality through distress. This could be of practical utility since many of these factors are modifiable. Future research and interventions should specifically focus on them.