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Pharmaceutics May 2024ApTOLL, a TLR4 modulator aptamer, has demonstrated cerebroprotective effects in a permanent ischemic stroke mouse model, as well as safety and efficacy in early phase...
ApTOLL, a TLR4 modulator aptamer, has demonstrated cerebroprotective effects in a permanent ischemic stroke mouse model, as well as safety and efficacy in early phase clinical trials. We carried out reverse translation research according to STAIR recommendations to further characterize the effects and mechanisms of ApTOLL after transient ischemic stroke in rats and to better inform the design of pivotal clinical trials. Adult male rats subjected to transient middle cerebral artery occlusion were treated either with ApTOLL or the vehicle intravenously at different doses and time-points. ApTOLL was compared with TAK-242 (a TLR4 inhibitor). Female rats were also studied. After neurofunctional evaluation, brains were removed for infarct/edema volume, hemorrhagic transformation, and histologic determinations. Peripheral leukocyte populations were assessed via flow cytometry. ApTOLL showed U-shaped dose-dependent cerebroprotective effects. The maximum effective dose (0.45 mg/kg) was cerebroprotective when given both before reperfusion and up to 12 h after reperfusion and reduced the hemorrhagic risk. Similar effects occurred in female rats. Both research and clinical ApTOLL batches induced slightly superior cerebroprotection when compared with TAK-242. Finally, ApTOLL modulated circulating leukocyte levels, reached the brain ischemic tissue to bind resident and infiltrated cell types, and reduced the neutrophil density. These results show the cerebroprotective effects of ApTOLL in ischemic stroke by reducing the infarct/edema volume, neurofunctional impairment, and hemorrhagic risk, as well as the peripheral and local immune response. They provide information about ApTOLL dose effects and its therapeutic time window and target population, as well as its mode of action, which should be considered in the design of pivotal clinical trials.
PubMed: 38931862
DOI: 10.3390/pharmaceutics16060741 -
Journal of Clinical Medicine Jun 2024Vertebral compression fractures (VCFs) are prevalent in the elderly population and might be the source of back pain if they are fresh and yet unhealed. In many cases,...
Vertebral compression fractures (VCFs) are prevalent in the elderly population and might be the source of back pain if they are fresh and yet unhealed. In many cases, it is a diagnostic challenge to differentiate fresh VCFs from healed united fractures, which retain similar radiographic characteristics but no longer generate pain. This information is crucial for appropriate management. The aim of this study was to evaluate the role of bone scintigraphy (BS) in identifying fresh VCFs appropriate for targeted treatment when compared to the findings of Computerized Tomography (CT). : We retrospectively reviewed 190 patients with back pain suspected to stem from a recent VCF that underwent both a CT and a BS and compared the imaging patterns per vertebra. : The studies were concordant in the majority of cases (95.5%), diagnosing 84.4% normal vertebrae, 6.4% acute VCFs, and 4.7% chronic VCFs. However, in 37 patients, 45 occult acute VCFs were only detected on BS and not on CT. Multivariate logistic regression analysis revealed that these patients were older and had lower bone density compared to the rest of the study population. Additionally, 40 patients had acute VCFs visible on CT, but with no increased or low intensity uptake on BS. These cases were associated with a shorter time period between trauma and BS, a higher prevalence of male patients, and a higher bone density. Acute VCFs with no increased uptake or low levels of uptake were found only within the first six days of the trauma. : BS detects radiologically occult fractures and can differentiate if a radiographically evident VCF is indeed clinically active, guiding possible treatment options. To avoid missing acute VCFs, BS should be performed six days or more after the injury.
PubMed: 38930156
DOI: 10.3390/jcm13123627 -
Medicina (Kaunas, Lithuania) May 2024This study aimed to identify the incidence of sarcopenia and disease risk factors in Korean adults and to provide data for sarcopenia prevention. Based on the Korea...
This study aimed to identify the incidence of sarcopenia and disease risk factors in Korean adults and to provide data for sarcopenia prevention. Based on the Korea National Health and Nutrition Survey, 2008-2011, we selected 14,185 adults over the age of 20 who participated in sarcopenia diagnostic tests and health surveys. We analyzed sarcopenia risk factors using complex sample multi-logistic regression analysis. The prevalence of sarcopenia in Korea was 31.3%, with 20.2% in men and 40.4% in women. In men, there was a higher risk of sarcopenia in those of older age, without a spouse, with a low body mass index (BMI), who never engage in resistance exercise, or who do mid-level intensity resistance exercises. In women, sarcopenia risk was higher in those in their 20s compared to those in their 60s, and risk factors included a low BMI, high-density lipoprotein cholesterol and waist circumference measurements, alcohol consumption, aerobic exercise, and resistance exercise. Interventions and lifestyle improvements will help prevent the onset of sarcopenia in elderly men and young women with risk factors such as a low BMI.
Topics: Humans; Sarcopenia; Republic of Korea; Female; Male; Cross-Sectional Studies; Risk Factors; Middle Aged; Prevalence; Adult; Aged; Body Mass Index; Sex Factors; Epidemiologic Studies; Exercise; Logistic Models
PubMed: 38929514
DOI: 10.3390/medicina60060899 -
International Journal of Environmental... May 2024Osteoporosis is considered a serious public health problem that particularly affects the postmenopausal period. In 2018, in the Republic of Kazakhstan, the prevalence of...
Osteoporosis is considered a serious public health problem that particularly affects the postmenopausal period. In 2018, in the Republic of Kazakhstan, the prevalence of osteoporosis was 10.0, and the incidence was 3.7 new cases, per 100,000 adults, respectively. The objective of this study was to assess the prevalence of osteoporosis and indicate the main factors affecting low bone mineral density by screening the adult population of the Abay region, Kazakhstan. The target group comprised 641 respondents aged between 18 and 65 years old, from a Kazakh population, who had been living in the Abay region since birth. All participants filled out a questionnaire and were subjected to a bone mineral density measurement by means of dual-energy X-ray absorptiometry (DXA) between 15 July 2023 and 29 February 2024. Logistic regression analysis was conducted to assess the association between low bone mineral density and key demographic characteristics, such as lifestyle factors and nutritional habits. We identified the prevalence of low bone mass (osteopenia) and osteoporosis to be 34.1%, with the highest prevalence of 48.3% being found in the older population group (50+ years). The regression analysis revealed a number of indicators associated with the likelihood of bone sparing. However, only four of these showed significance in the final multivariate model (R = 22.4%). These were age (adjusted odds ratio (AOR) 1.05) and fracture history (AOR 1.64) directly associated with the likelihood of low bone density. Meanwhile, the body mass index (AOR 0.92) and the consumption of nuts and dried fruits (AOR 0.48) reduced the chance of bone tissue demineralization. Additional studies examining the prevalence and any emerging risk factors for osteoporosis are needed to advance clinical epidemiological knowledge and implement public health programs.
Topics: Humans; Kazakhstan; Middle Aged; Adult; Female; Risk Factors; Prevalence; Bone Density; Osteoporosis; Male; Young Adult; Adolescent; Aged; Absorptiometry, Photon; Bone Diseases, Metabolic
PubMed: 38928928
DOI: 10.3390/ijerph21060681 -
Diagnostics (Basel, Switzerland) Jun 2024Low-density lipoprotein cholesterol (LDL-C), which makes up about 70% of the cholesterol in the blood, is critical in the formation of arteriosclerotic plaques,...
Low-density lipoprotein cholesterol (LDL-C), which makes up about 70% of the cholesterol in the blood, is critical in the formation of arteriosclerotic plaques, increasing the risk of heart disease. LDL-C levels are estimated using Friedewald, Martin and Sampson equations, though they have limitations with high triglycerides. Our aim is to compare the effectiveness of these equations versus the ultracentrifugation technique in individuals with and without dyslipidemia and identify precision. There were 113 participants, 59 healthy controls and 54 dyslipidemic patients. Samples were collected after fasting. LDL-C was estimated using the Friedewald, Martin and Sampson equations. The purified LDL-C, ultracentrifugated and dialysized control group without dyslipidemia vs. patients with coronary artery disease (CAD) showed differences in age, HDL-C, triglycerides and glucose non-HDL-C ( = 0.001 in all). There were correlations in CGWD between ultracentrifugation and Sampson R-squared (R) = 0.791. In the dyslipidemia control group, ultracentrifugation and Friedewald R = 0.911. In patients with CAD, correlation between ultracentrifugation and Sampson R = 0.892; Bland-Altman confirmed agreement in controls without dyslipidemia. The Martin and Sampson equations are interchangeable with ultracentrifugation. Conclusion: The role of LDL analysis using precise techniques is necessary to obtain better control of disease outcomes after the use of precise therapies and suggests verifying its importance through clinical trials.
PubMed: 38928656
DOI: 10.3390/diagnostics14121241 -
Genes Jun 2024Crucian carp ( is widely distributed in the world and has become an economically freshwater fish. The population in Lake Dali Nur can tolerate the extreme alkaline...
Crucian carp ( is widely distributed in the world and has become an economically freshwater fish. The population in Lake Dali Nur can tolerate the extreme alkaline environment with alkalinity over 50 mmol/L (pH 9.6), thus providing a special model for exploring alkali-tolerant molecular markers in an extremely alkaline environment. In this study, we constructed a high-density and high-resolution linkage map with 16,224 SNP markers based on genotyping-by-sequencing (GBS) consisting of 152 progenies and conducted QTL studies for alkali-tolerant traits. The total length of the linkage map was 3918.893 cM, with an average distance of 0.241 cM. Two QTLs for the ammonia-N-tolerant trait were detected on LG27 and LG45. A QTL for the urea-N-tolerant trait was detected on LG27. Interestingly, mapping the two QTLs on LG27 revealed that the mapped genes were both located in the intron of CDC42. GO functional annotation and KEGG enrichment analysis results indicated that the biological functions might be involved in the cell cycle, cellular senescence, MAPK, and Ras signaling pathways. These findings suggest that CDC42 may play an important role in the process of dealing with extremely alkaline environments.
Topics: Animals; Quantitative Trait Loci; Polymorphism, Single Nucleotide; Chromosome Mapping; Goldfish; Carps; Alkalies
PubMed: 38927687
DOI: 10.3390/genes15060751 -
Genes Jun 2024Worldwide molecular research of economically important (Poaceae) is mainly focused on the invasions of this species from Europe to North America. Until the present...
Worldwide molecular research of economically important (Poaceae) is mainly focused on the invasions of this species from Europe to North America. Until the present study, the genetic diversity of the had not been studied across the Baltic countries. The objective of this research is to evaluate the diversity of Lithuanian populations of at simple sequence repeat (SSR) loci comparatively among populations of the Baltic countries, Luxembourg, and the Russian Far East (Eurasian), evaluating differentiation between Lithuanian populations and ornamental accessions, and relating these with environmental features. For six selected Lithuanian river basin populations, GBS low density SNPs were used to determine genetic diversity. Bayesian analysis showed that Eurasian populations of consist of two gene clusters. Statistically significant genetic differentiation among European and Eurasian populations was documented. Lithuanian genotypes growing naturally along rivers are genetically distinct from cultivated ornamentals. GBS-SNPs divided the six selected Nemunas river basins into three distinct groups with one, two, or three rivers in separate groupings for genetic diversity. Genetic diversity is primarily within, rather than among, Lithuanian, eastern European, and Eurasian populations of across the continent. Thus, restoration efforts would benefit from local population seed origination.
Topics: Microsatellite Repeats; Phalaris; Polymorphism, Single Nucleotide; Genetic Variation; Europe, Eastern
PubMed: 38927670
DOI: 10.3390/genes15060734 -
Biomedicines Jun 2024Lipoprotein(a) is a low-density-lipoprotein-like particle that consists of apolipoprotein(a) bound to apolipoprotein(b). It has emerged as an established causal risk... (Review)
Review
Lipoprotein(a) is a low-density-lipoprotein-like particle that consists of apolipoprotein(a) bound to apolipoprotein(b). It has emerged as an established causal risk factor for atherosclerotic cardiovascular disease, stroke, and aortic valve stenosis through multifactorial pathogenic mechanisms that include inflammation, atherogenesis, and thrombosis. Despite an estimated 20% of the global population having elevated lipoprotein(a) levels, testing remains underutilized due to poor awareness and a historical lack of effective and safe therapies. Although lipoprotein(a) has a strong association with coronary artery disease and cerebrovascular disease, its relationship with peripheral artery disease is less well established. In this article, we review the epidemiology, biology, and pathogenesis of lipoprotein(a) as it relates to peripheral artery disease. We also discuss emerging treatment options to help mitigate major adverse cardiac and limb events in this population.
PubMed: 38927436
DOI: 10.3390/biomedicines12061229 -
International Journal of Health... Jun 2024The escalating trend of obesity in Malaysia is surmounting, and the lack of evidence on the environmental influence on obesity is untenable. Obesogenic environmental...
BACKGROUND
The escalating trend of obesity in Malaysia is surmounting, and the lack of evidence on the environmental influence on obesity is untenable. Obesogenic environmental factors often emerge as a result of shared environmental, demographic, or cultural effects among neighbouring regions that impact lifestyle. Employing spatial clustering can effectively elucidate the geographical distribution of obesity and pinpoint regions with potential obesogenic environments, thereby informing public health interventions and further exploration on the local environments. This study aimed to determine the spatial clustering of body mass index (BMI) among adults in Malaysia.
METHOD
This study utilized information of respondents aged 18 to 59 years old from the National Health and Morbidity Survey (NHMS) 2014 and 2015 at Peninsular Malaysia and East Malaysia. Fast food restaurant proximity, district population density, and district median household income were determined from other sources. The analysis was conducted for total respondents and stratified by sex. Multilevel regression was used to produce the BMI estimates on a set of variables, adjusted for data clustering at enumeration blocks. Global Moran's I and Local Indicator of Spatial Association statistics were applied to assess the general clustering and location of spatial clusters of BMI, respectively using point locations of respondents and spatial weights of 8 km Euclidean radius or 5 nearest neighbours.
RESULTS
Spatial clustering of BMI independent of individual sociodemographic was significant (p < 0.001) in Peninsular and East Malaysia with Global Moran's index of 0.12 and 0.15, respectively. High-BMI clusters (hotspots) were in suburban districts, whilst the urban districts were low-BMI clusters (cold spots). Spatial clustering was greater among males with hotspots located closer to urban areas, whereas hotspots for females were in less urbanized areas.
CONCLUSION
Obesogenic environment was identified in suburban districts, where spatial clusters differ between males and females in certain districts. Future studies and interventions on creating a healthier environment should be geographically targeted and consider gender differences.
Topics: Humans; Male; Adult; Body Mass Index; Female; Malaysia; Obesity; Middle Aged; Young Adult; Adolescent; Cluster Analysis; Spatial Analysis; Environment; Health Surveys
PubMed: 38926856
DOI: 10.1186/s12942-024-00376-5 -
Alzheimer's Research & Therapy Jun 2024Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive...
BACKGROUND
Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype.
METHODS
Participants from a large, prospective, population-based, Swedish study were included (n = 3,229). Linear regression models were used to examine baseline hypertension, body mass index (BMI), long-term glucose levels (HbA), different lipid levels, physical activity, alcohol consumption, smoking, education, APOE genotype, age and sex. All models were adjusted for follow-up time and basic demographics, and, in a second step, all significant predictors were included to examine independent effects. Follow-up outcomes were memory and attention/executive functions.
RESULTS
The mean age at baseline was 56.1 (SD 5.7) years and 59.7% were women. The mean follow-up time was 17.4 (range 14.3-20.8) years. When examining independent effects, APOE ε4 genotype(p < 0.01), and higher HbA(p < 0.001), were associated with future low memory function. Higher BMI (p < 0.05), and HbA(p < 0.05), lower high-density lipoprotein cholesterol (HDL-C)(p < 0.05)and stroke(p < 0.001) were associated with future low attention/executive function. The strongest factors associated with both better memory and attention/executive functions were higher education and alcohol consumption. Further, significant interaction effects between predictors and APOE genotype were found. For memory function, the protective effects of education were greater among ɛ4-carriers(p < 0.05). For attention/executive function, the protective effects of alcohol were greater among ɛ2 or ɛ4-carriers(p < 0.05). Also, attention/executive function was lower among ɛ4-carriers with higher BMI(p < 0.05) and ɛ2-carriers with higher HbA1c-levels(p < 0.05).
CONCLUSIONS
Targeting cardiovascular risk factors in mid-life could have greater effect on future attention/executive functions rather than memory, whereas targeting diabetes could be beneficial for multiple cognitive domains. In addition, effects of different risk factors may vary depending on the APOE genotype. The varied cognitive profiles suggest that different mechanisms and brain regions are affected by the individual risk factors. Having detailed knowledge about the specific cognitive effects of different risk factors might be beneficial in preventive health counseling.
Topics: Humans; Female; Male; Middle Aged; Risk Factors; Follow-Up Studies; Prospective Studies; Sweden; Executive Function; Cognition; Attention; Body Mass Index; Memory; Glycated Hemoglobin; Aged; Alcohol Drinking; Genotype; Apolipoprotein E4; Neuropsychological Tests; Cognitive Dysfunction
PubMed: 38926747
DOI: 10.1186/s13195-024-01497-6