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Annals of Clinical and Translational... Jul 2024Impulse control disorders and their consequences display variability among individuals, indicating potential involvement of environmental and genetic factors. In this...
Impulse control disorders and their consequences display variability among individuals, indicating potential involvement of environmental and genetic factors. In this retrospective study, we analyzed a cohort of Parkinson's disease patients treated with dopamine agonists and investigated the influence of the dopamine D4 receptor gene polymorphism, DRD4 7R+, which is linked to psychiatric disorders, impulsive traits, and addictive behaviors. We found that DRD4 7R+ is a significant genetic risk factor associated with the severity of ICD.
PubMed: 38952083
DOI: 10.1002/acn3.52111 -
Parasites & Vectors Jul 2024Application of numerous malaria control interventions has led to reduction in clinical malaria cases and deaths but also the realisation that asymptomatic parasite...
BACKGROUND
Application of numerous malaria control interventions has led to reduction in clinical malaria cases and deaths but also the realisation that asymptomatic parasite carriers play a key role in sustaining transmission. This study assessed the effectiveness of using the Ultra-sensitive NxTek eliminate RDT (uRDT) and conventional SD Bioline HRP2 RDT (cRDT) in diagnosing asymptomatic parasitaemia while measuring the impact of mass testing, treatment and tracking (MTTT) on the prevalence of asymptomatic malaria over a 1-year period in Ghana.
METHODS
A total of 4000 targeted participants from two towns, Obom and Kofi Kwei, with their surrounding villages, were tested for asymptomatic malaria four times over the study period using uRDT (intervention) and the cRDT (control) respectively. Participants carrying malaria parasites were followed by home visit and phone calls for compliance to treatment, and filter paper blood blots collected from participants were used to determine true parasite carriage by PET-PCR. A mathematical model of the study site was developed and used to test the impact of test sensitivity and mass migration on the effect of MTTT.
RESULTS
The start and end point sensitivities of the cRDT were 48.8% and 41.7% and those for the uRDT were 52.9% and 59.9% respectively. After a year of MTTTs, asymptomatic parasite prevalence, as determined by PCR, did not differ statistically in the control site (40.6% to 40.1%, P = 0.730) but decreased at the intervention site (55.9% to 46.4%, P < 0.0001). Parasite prevalence by RDT, however, indicated statistical reduction in the control site (25.3% to 22.3%, P = 0.017) and no change in the intervention site (35.1% to 36.0%, P = 0.614). The model predicted a mild effect of both diagnostic sensitivity and human movement in diminishing the impact of MTTT in the study sites.
CONCLUSIONS
Asymptomatic parasite prevalence at the molecular level reduced significantly in the site where the uRDT was used but not where the cRDT was used. Overall, the uRDT exhibited higher sensitivity relative to the cRDT. Highly sensitive molecular techniques such as PET-PCR should be included in parasite prevalence estimation during MTTT exercises.
Topics: Ghana; Humans; Female; Male; Sensitivity and Specificity; Adult; Adolescent; Child, Preschool; Young Adult; Child; Diagnostic Tests, Routine; Parasitemia; Malaria, Falciparum; Middle Aged; Malaria; Plasmodium falciparum; Prevalence; Mass Screening; Infant
PubMed: 38951912
DOI: 10.1186/s13071-024-06354-x -
Cardiovascular Diabetology Jul 2024The available evidence on the impact of specific non-pharmacological interventions on glycaemic control is currently limited. Consequently, there is a need to determine... (Meta-Analysis)
Meta-Analysis Review
The available evidence on the impact of specific non-pharmacological interventions on glycaemic control is currently limited. Consequently, there is a need to determine which interventions could provide the most significant benefits for the metabolic health of young individuals with type 1 diabetes mellitus. The aim of this study was to identify optimal nonpharmacological interventions on glycaemic control, measured by glycated haemoglobin (HbA1c), in children and adolescents with type 1 diabetes. Systematic searches were conducted in PubMed, Web of Science, Scopus, and SPORTDiscus from inception to July 1, 2023. Randomised clinical trials (RCT) investigating nonpharmacological interventions (e.g., physical activity, nutrition, and behavioural therapies) were included. Primary outcome was change in HbA1c levels. Secondary outcome was change in daily insulin dose requirement. Seventy-four RCT with 6,815 participants (49.43% girls) involving 20 interventions were analysed using a network meta-analysis. Most interventions showed greater efficacy than standard care. However, multicomponent exercise, which includes aerobic and strength training (n = 214, standardised mean difference [SMD] =- 0.63, 95% credible interval [95% CrI] - 1.09 to - 0.16) and nutritional supplements (n = 146, SMD =- 0.49, - 0 .92 to - 0.07) demonstrated the greatest HbA1c reductions. These interventions also led to the larger decreases in daily insulin needs (n = 119, SMD =- 0.79, 95% CrI - 1.19 to - 0.34) and (n = 57, SMD =- 0.62, 95% CrI - 1.18 to - 0.12, respectively). The current study underscores non-pharmacological options such as multicomponent exercise and nutritional supplements, showcasing their potential to significantly improve HbA1c in youth with type 1 diabetes. Although additional research to confirm their efficacy is required, these approaches could be considered as potential adjuvant therapeutic options in the management of type 1 diabetes among children and adolescents.
Topics: Humans; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Adolescent; Child; Network Meta-Analysis; Female; Male; Treatment Outcome; Blood Glucose; Randomized Controlled Trials as Topic; Biomarkers; Bayes Theorem; Hypoglycemic Agents; Glycemic Control; Age Factors; Insulin; Dietary Supplements; Exercise Therapy; Exercise; Child, Preschool
PubMed: 38951907
DOI: 10.1186/s12933-024-02301-3 -
BMC Zoology Jul 2024The wild boar (Sus scrofa) was extinct in Sweden when a few animals established in the 1970s. Over the past 35 years, the species has made a substantial comeback. In...
BACKGROUND
The wild boar (Sus scrofa) was extinct in Sweden when a few animals established in the 1970s. Over the past 35 years, the species has made a substantial comeback. In this paper, we analyse wild boar population growth using three indices of population size. We also map the legislative decisions and research prompted by the expanding population. We discuss to what extent, in the eyes of the state, the view of wild boar and the management focus has shifted over time, from a perceived pest (eradication) to scarce (conservation), overabundant (reduction/control) or somewhere in between (sustainable management).
RESULTS
Wild boar harvest started in the early 1990s with a few hundred animals annually and peaked at 161,000 in 2020/2021. The distribution now comprises most of southern Sweden. Analyses of harvest and traffic accidents involving wild boar showed that the population grew exponentially until 2010/2011, after which the increase levelled off. Thus, logistic growth models showed the best fit for the full study period. We recorded 38 legislative decisions or commissions to government agencies regarding wild boar. The first decision in 1981 was to eradicate the free-ranging population. In 1987 however, the parliament decided that wild boar is native to Sweden and should be allowed in restricted extent. Later decisions mainly concerned hunting regulations and hunting methods as direct means to increase harvest and regulate the population. Another topic, increasing in importance over time, was to facilitate the use of wild boar meat to indirectly stimulate harvest. A local outbreak of African swine fever in 2023 necessitated a stamping out strategy in the affected area. We found 44 scientific papers regarding the present free-ranging population. Topics include movements and feeding patterns, hunting, reproduction, and population development.
CONCLUSIONS
The state historically regarded wild boar as a pest to be eradicated. This changed with the decision that wild boar should be allowed in restricted extent, suggesting a conservation approach. In response to population growth, the focus shifted to means facilitating sustainable management and, lately, reducing growth. The story of wild boar in Sweden illustrates attempts to mitigate conflicts and balance interests in wildlife management.
PubMed: 38951881
DOI: 10.1186/s40850-024-00202-2 -
Journal of Translational Medicine Jul 2024Uveal melanoma (UM), the most common adult intraocular tumor, is characterized by high malignancy and poor prognosis in advanced stages. Angiogenesis is critical for UM...
BACKGROUND
Uveal melanoma (UM), the most common adult intraocular tumor, is characterized by high malignancy and poor prognosis in advanced stages. Angiogenesis is critical for UM development, however, not only the role of vascular endothelial dysfunction in UM remains unknown, but also their analysis at the single-cell level has been lacking. A comprehensive analysis is essential to clarify the role of the endothelium in the development of UM.
METHODS
By using single-cell RNA transcriptomics data of 11 cases of primary and liver metastasis UM, we analyzed the endothelial cell status. In addition, we analyzed and validated ECs in the in vitro model and collected clinical specimens. Subsequently, we explored the impact of endothelial dysfunction on UM cell migration and explored the mechanisms responsible for the endothelial cell abnormalities and the reasons for their peripheral effects.
RESULTS
UM metastasis has a significantly higher percentage of vascular endothelial cells compared to in situ tumors, and endothelial cells in metastasis show significant senescence. Senescent endothelial cells in metastatic tumors showed significant Krüppel-like factor 4 (KLF4) upregulation, overexpression of KLF4 in normal endothelial cells induced senescence, and knockdown of KLF4 in senescent endothelium inhibited senescence, suggesting that KLF4 is a driver gene for endothelial senescence. KLF4-induced endothelial senescence drove tumor cell migration through a senescence-associated secretory phenotype (SASP), of which the most important component of the effector was CXCL12 (C-X-C motif chemokine ligand 12), and participated in the composition of the immunosuppressive microenvironment.
CONCLUSION
This study provides an undesirable insight of senescent endothelial cells in promoting UM metastasis.
Topics: Humans; Uveal Neoplasms; Melanoma; Liver Neoplasms; Endothelial Cells; Single-Cell Analysis; Kruppel-Like Factor 4; Cell Movement; Cellular Senescence; Kruppel-Like Transcription Factors; Cell Line, Tumor; Chemokine CXCL12; Gene Expression Regulation, Neoplastic; Female; Male
PubMed: 38951874
DOI: 10.1186/s12967-024-05430-1 -
BMC Endocrine Disorders Jul 2024The weight-adjusted waist index (WWI) is a recently developed obesity metric, and the aim of this study was to investigate the relationship between physical activity...
BACKGROUND
The weight-adjusted waist index (WWI) is a recently developed obesity metric, and the aim of this study was to investigate the relationship between physical activity (PA) and WWI and the homeostasis model assessment of insulin resistance (HOMA-IR) in adolescents, as well as the joint association of HOMA-IR.
METHODS
This study was based on the National Health and Nutrition Survey conducted between 2013 and 2016 and included 1024 adolescents whose median age was 15.4. Multivariate linear regression was used to examine the associations between HOMA-IR and PA and WWI. Using generalized additive models, a potential nonlinear link between WWI and HOMA-IR was evaluated. Subgroup analysis was also carried out.
RESULTS
The fully adjusted model revealed a positive association (β: 0.48, 95% CI: 0.43, 0.53) between the WWI and HOMA-IR. The HOMA-IR was lower in physically active (β: -0.16, 95% CI: -0.26, -0.05) participants versus inactive participants. Participants who had higher WWI and were not physically active (β: 0.69; 95% CI: 0.56, 0.82) had the highest levels of HOMA-IR compared to participants who had lower WWI and were physically active. Subgroup analysis revealed that these correlations were similar in males and females.
CONCLUSION
Our results demonstrated that higher WWI and PA were associated with a lower HOMA-IR and that WWI and PA had a combined association with HOMA-IR. The findings of this study are informative for the preventing insulin resistance in adolescents.
Topics: Humans; Insulin Resistance; Male; Female; Adolescent; Cross-Sectional Studies; Exercise; Waist Circumference; Body Weight; Body Mass Index; Nutrition Surveys
PubMed: 38951821
DOI: 10.1186/s12902-024-01633-1 -
BMC Public Health Jul 2024At the time of the emergence of COVID-19, denialist and anti-vaccine groups have also emerged and are shaking public confidence in vaccination.
BACKGROUND
At the time of the emergence of COVID-19, denialist and anti-vaccine groups have also emerged and are shaking public confidence in vaccination.
METHODS
A qualitative study was conducted using online focus groups. Participants had not received any doses of vaccination against the disease. A total of five focus group sessions were conducted with 28 participants. They were recruited by snowball sampling and by convenience sampling.
RESULTS
The two major topics mentioned by the participants were adverse effects and information. The adverse effects described were severe and included sudden death. In the case of information, participants reported: (1) consultation of websites on which scientists posted anti-vaccination content; and (2) distrust.
CONCLUSIONS
At a time when anti-vaccine groups pose a major challenge to public health in general, and to COVID-19 vaccination campaigns in particular, this study is a first step towards gaining deeper insight into the factors that lead to COVID-19 vaccine refusal.
Topics: Humans; Spain; COVID-19; Female; Male; Adult; COVID-19 Vaccines; Vaccination Hesitancy; Vaccination Refusal; Middle Aged; Focus Groups; Qualitative Research; Anti-Vaccination Movement; Aged; Young Adult; SARS-CoV-2
PubMed: 38951819
DOI: 10.1186/s12889-024-18864-5 -
BMC Cancer Jul 2024Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying...
INTRODUCTION
Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism. This study will compare the effects of the two main exercise modes, aerobic and resistance, on (1) circulatory myokine levels, (2) skeletal muscle-induced extracellular vesicle abundance and cargo contents, and (3) uptake of extracellular vesicles (EVs) in PCa cells in patients with localised or advanced PCa.
METHODS
A single-group cross-over design will be used for patients at opposite ends of the disease spectrum. A total of 32 patients (localised PCa, n = 16; metastatic castrate-resistant PCa, n = 16) will be recruited while capitalising on two ongoing studies. Ethics amendment has been approved for two ongoing trials to share data, implement the acute exercise sessions, and collect additional blood samples from patients. The patients will undertake two exercise sessions (aerobic only and resistance only) in random order one week apart. Blood will be collected before, after, and 30 min post-exercise. Circulating/EV-contained myokine levels (irisin, IL-6, IL-15, FGF-21, and SPARC) and plasma skeletal muscle-induced EVs will be measured using ELISA and flow cytometry. PCa cell line growth with or without collected plasma will be examined using PCa cell lines (LNCaP, DU-145, and PC-3), while evaluating cellular uptake of EVs. Ethics amendments have been approved for two capitalising studies to share data, implement acute exercise sessions and collect additional samples from the patients.
DISCUSSION
If findings show a differential impact of exercise mode on the establishment of an anti-cancer systemic environment, this will provide fundamental knowledge for developing targeted exercise prescriptions for patients with PCa across different disease stages. Findings will be reported in peer-reviewed publications and scientific conferences, in addition to working with national support groups to translate findings for the broader community.
TRIAL REGISTRATION
The registration for the two capitalising studies are NCT02730338 and ACTRN12618000225213.
Topics: Humans; Male; Extracellular Vesicles; Cross-Over Studies; Prostatic Neoplasms; Exercise; Muscle, Skeletal; Exercise Therapy; Cytokines; Aged; Middle Aged; Myokines
PubMed: 38951803
DOI: 10.1186/s12885-024-12530-0 -
Scientific Reports Jul 2024Life's Essential 8 (LE8) is a score that includes modifiable risk factors for cardiovascular disease. Four health behaviors (diet, physical activity, nicotine exposure...
Life's Essential 8 (LE8) is a score that includes modifiable risk factors for cardiovascular disease. Four health behaviors (diet, physical activity, nicotine exposure and sleep health) and four health factors (non-HDL cholesterol, blood glucose, blood pressure and body mass index) are included. These modifiable risk factors promote inflammation, and inflammation is one of the biological mechanisms of cardiovascular disease development. Thus, we examined the relationship between cardiovascular health measured by LE8 and low-grade inflammation measured by high-sensitivity C-reactive protein (hs-CRP) in the cross-sectional population-based Swedish CArdioPulmonary bioImage Study (SCAPIS). The study consisted of 28,010 participants between 50 and 64 years (51.5% women, mean age 57.5 years). All individual LE8 components were assigned a score between 0 (unhealthy) and 100 (healthy) points, and a global score was calculated. The association between LE8 scores and high-risk hs-CRP (defined as > 3.0 mg/L) was analyzed using adjusted logistic regression with spline analyses. There was a strong, dose response and inverse association between LE8 scores and levels of hs-CRP. Thus, those with a low LE8 score (= 50.0 points) had 5.8 higher (95% confidence interval [CI] 5.2-6.4) odds ratio (OR) of having high hs-CRP as compared to those with a high LE8 score (= 80.0 points). In conclusion, our findings show strong inverse associations between LE8 scores and levels of hs-CRP.
Topics: Humans; C-Reactive Protein; Female; Middle Aged; Male; Cardiovascular Diseases; Cross-Sectional Studies; Risk Factors; Sweden; Inflammation; Body Mass Index; Exercise; Health Behavior; Blood Pressure; Blood Glucose
PubMed: 38951604
DOI: 10.1038/s41598-024-65977-3 -
Scientific Reports Jul 2024Proline 4-hydroxylase 2 (P4HA2) is known for its hydroxylase activity, primarily involved in hydroxylating collagen precursors and promoting collagen cross-linking under...
Proline 4-hydroxylase 2 (P4HA2) is known for its hydroxylase activity, primarily involved in hydroxylating collagen precursors and promoting collagen cross-linking under physiological conditions. Although its overexpression influences a wide variety of malignant tumors' occurrence and development, its specific effects and mechanisms in oral squamous cell carcinoma (OSCC) remain unclear. This study focused on investigating the expression patterns, carcinogenic functions, and underlying mechanisms of P4HA2 in OSCC cells. Various databases, including TCGA, TIMER, UALCAN, GEPIA, and K-M plotter, along with paraffin-embedded samples, were used to ascertain P4HA2 expression in cancer and its correlation with clinicopathological features. P4HA2 knockdown and overexpression cell models were developed to assess its oncogenic roles and mechanisms. The results indicated that P4HA2 was overexpressed in OSCC and inversely correlated with patient survival. Knockdown of P4HA2 suppressed invasion, migration, and proliferation of OSCC cells both in vitro and in vivo, whereas overexpression of P4HA2 had the opposite effects. Mechanistically, the phosphorylation levels of the PI3K/AKT pathway were reduced following P4HA2 silencing. The study reveals that P4HA2 acts as a promising biomarker for predicting prognosis in OSCC and significantly affects metastasis, invasion, and proliferation of OSCC cells through the regulation of the PI3K/AKT signaling pathway.
Topics: Humans; Proto-Oncogene Proteins c-akt; Mouth Neoplasms; Cell Proliferation; Phosphatidylinositol 3-Kinases; Signal Transduction; Cell Line, Tumor; Neoplasm Invasiveness; Cell Movement; Procollagen-Proline Dioxygenase; Carcinoma, Squamous Cell; Gene Expression Regulation, Neoplastic; Animals; Mice; Female; Male; Neoplasm Metastasis; Middle Aged; Mice, Nude
PubMed: 38951593
DOI: 10.1038/s41598-024-64264-5