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Effective control of mosquito requires adequate knowledge of not just the breeding sites but also the habitats and all other environmental factors relating to the Anopheline vector’s life. This is not just to avoid the nuisance they cause but most importantly to curtail the spread of the diseases they transmit. This paper identified environmental factors being chiefly responsible for the proliferation of the vector with Geographic Information System (GIS) and Remote Sensing (RS) as viable tools in the control of the diseases they transmit. Effective application and utilization of the spatial technologies also forms a major aspect in the Malaria Early Warning System (MEWS). GIS and RS technology explore all minute details related to the environment, thus it remains a vibrant tool in the epidemiological studies of vector borne diseases.

Ideal partner preferences (i.e., ratings of the desirability of attributes like attractiveness or intelligence) are the source of numerous foundational findings in the interdisciplinary literature on human mating. Recently, research on the predictive validity of ideal partner preference matching (i.e., Do people positively evaluate partners who match vs. mismatch their ideals?) has become mired in several problems. First, articles exhibit discrepant analytic and reporting practices. Second, different findings emerge across laboratories worldwide, perhaps because they sample different relationship contexts and/or populations. This registered report-partnered with the Psychological Science Accelerator-uses a highly powered design ( N = 10,358) across 43 countries and 22 languages to estimate preference-matching effect sizes. The most rigorous tests revealed significant preference-matching effects in the whole sample and for partnered and single participants separately. The "corrected pattern metric" that collapses across 35 traits revealed a zero-order effect of β = .19 and an effect of β = .11 when included alongside a normative preference-matching metric. Specific traits in the "level metric" (interaction) tests revealed very small (average β = .04) effects. Effect sizes were similar for partnered participants who reported ideals before entering a relationship, and there was no consistent evidence that individual differences moderated any effects. Comparisons between stated and revealed preferences shed light on gender differences and similarities: For attractiveness, men's and (especially) women's stated preferences underestimated revealed preferences (i.e., they thought attractiveness was less important than it actually was). For earning potential, men's stated preferences underestimated-and women's stated preferences overestimated-revealed preferences. Implications for the literature on human mating are discussed. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Background Sickle cell anemia (SCA) is a common condition of public health concern in Nigeria. Different therapeutic approaches have been developed to manage SCA, including blood transfusion. In a bid to develop a sustainable solution to the blood supply pool, the SmileBuilders Initiative organizes a blood donation drive (Donate-A-Pint Project) quarterly in Ibadan, Nigeria. This study aimed to assess the awareness, knowledge, and attitudes of blood donors in Ibadan, Nigeria, towards SCA. Methods A descriptive cross-sectional study was conducted at the University College Hospital Blood Bank in Ibadan over a period of three months. A validated questionnaire, based on similar studies in Nigeria, was used to collect data from blood donors. The SPSS version 23 was used for data analysis, and the chi-square test of independence assessed associations between variables, with a significance level of 0.05. Results Among 205 donors, 68.8% were male, and 42.4% were in the age category of ≥25 years. Most donors (60.0%) were university students. While 12.3% had never heard of SCA, 79.5% were aware of their genotype. Regarding the intrauterine diagnosis of hemoglobin SS (HbSS), 20.0% would allow pregnancy, 31.7% would abort, and 48.3% were undecided. Most respondents (73.2%) had good knowledge of SCA (mean score = 7.0/10.0). If partners were found to have SCA after marriage, 42.9% were undecided. Knowledge of SCA was significantly associated with sex (p = 0.017) and education level (p = 0.001). Conclusion Blood donors in Ibadan have good knowledge, awareness, and attitudes toward SCA. However, more health education would benefit the population., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The University of Ibadan and University College Hospital Research Ethics Committee (UI/UCH REC) issued approval UI/EC/22/0368. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Amusat et al.)

Introduction: An estimated one billion people globally are currently suffering from hypertension. Prevention and management of hypertension are suboptimal especially in low- and middle-income countries leading to increased complications and deaths. With increased mobile phone coverage globally, this study aims to review mobile health technologies used for the prevention and management of hypertension., Methods: We conducted a literature search on electronic databases using identified keywords involving "hypertension", "mobile health technology" and their synonyms. Snowballing technique was also used. Papers were screened at two levels by independent reviewers. The targets were studies published in peer-reviewed journals reporting mobile health interventions for hypertension prevention and management. Only primary research studies published in English from January 2017 to April 2024 were included. Google Forms were used to extract the data along with other characteristics, and selected articles were categorised into: mobile application, web-based solutions, and Short Message Service (SMS) and other offline solutions., Result: The search yielded 184 articles, and 44 studies were included in the review. Most (n = 26) were randomised control trials. Twenty-two studies (22) focused only on mobile applications solutions, 12 on SMS and other offline mHealth, 5 web-based solutions, and 5 combined more than one type of mobile health technology. The United States of America had the majority of studies (n = 17), with 6 studies from other American countries, 11 from Asia and nine from Europe, while only one from Africa. A total of 36 studies reported that mobile health technology significantly improved hypertension care through reduced blood pressure, improved adherence to follow-up visits and medications, and lifestyle changes. SMS and offline mHealth strategies have also demonstrated effectiveness in promoting self-management and reducing racial disparities in hypertension care., Conclusion: Mobile health technology has the potential to play a significant role in the prevention and management of hypertension. However, there is a need for mobile health solutions for hypertension prevention and management in African countries and other developing countries. Integrating mHealth into primary healthcare delivery would also go a long way in strengthening patient care and reducing the burden on healthcare systems., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

This research offers a comprehensive exploration of the microbial communities associated with vector mosquitoes from South Korea. Aedes albopictus, Anopheles sinensis, and Culex molestus are vectors of pathogens, and understanding the intricacies of their microbiome profile is paramount for unraveling their roles in disease transmission dynamics. In this study, we characterized the microbiome of the midguts of adult female vector mosquitoes collected from different locations in South Korea. After DNA extraction from dissected mosquito midguts, we used the Illumina MiSeq next-generation sequencing to obtain sequences spanning the V4 hypervariable region of the bacteria 16S rRNA. Morphological and molecular characterization using 506-bp mitochondrial 16S rRNA was used to identify the mosquito species before amplicon sequencing. Across the three vector mosquitoes surveyed, 21 bacteria genera belonging to 20 families and 5 phyla were discovered. Proteobacteria and Bacteriodota were the major phyla of bacteria associated with the three mosquito species. There were significant differences in the gut microbiome genera composition between the species and little variation in the gut microbiome between individuals of the same mosquito species. Wolbachia is the most dominant genus in Aedes while Aeromonas, Acinetobacter, and unassigned taxa are the most common in An. sinensis. In addition to that, Chromobacterium, Chryseobacterium, and Aeromonas are dominant in Cx. molestus. This study sheds light on the complex interactions between mosquitoes and their microbiome, revealing potential implications for vector competence, disease transmission, and vector control strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Bioinformatics, the interdisciplinary field that combines biology, computer science, and data analysis, plays a pivotal role in advancing our understanding of life sciences. In the African context, where the diversity of biological resources and healthcare challenges is substantial, fostering bioinformatics literacy and proficiency among students is important. This perspective provides an overview of the state of bioinformatics literacy among African students, highlighting the significance, challenges, and potential solutions in addressing this critical educational gap. It proposes various strategies to enhance bioinformatics literacy among African students. These include expanding educational resources, fostering collaboration between institutions, and engaging students in research projects. By addressing the current challenges and implementing comprehensive strategies, African students can harness the power of bioinformatics to contribute to innovative solutions in healthcare, agriculture, and biodiversity conservation, ultimately advancing the continent's scientific capabilities and improving the quality of life for her people. In conclusion, promoting bioinformatics literacy among African students is imperative for the continent's scientific development and advancing frontiers of biological research., Competing Interests: Authors AsA, AbA, MH, AuA, SA, LS, EE, AM, and KR are members of NOBLEKINMAT Ltd. Bioinformatics Research Group. Authors MH was employed by Green Climate Fund. Author AuA was employed by ProCogia. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Akintola, Aborode, Hamza, Amakiri, Moore, Abdulai, Iyiola, Sulaimon, Effiong, Ogunyemi, Dosunmu, Maigoro, Lawal, Raheem and Hwang.)

We performed a systematic review and meta-analysis on prospective studies that provided risk estimates for the impact of 3 different MRI markers of small vessel disease (SVD), namely white matter hyperintensities (WMH), cerebral microbleeds (CMB) and lacunes, on cognitive decline in relatively healthy older adults without cognitive deficits at baseline. A total of 23 prospective studies comprising 11,486 participants were included for analysis. Extracted data was pooled, reviewed and meta-analysed separately for global cognition, executive function, memory and attention. The pooled effect size for the association between cerebral SVD and cognitive decline was for global cognition -0.10 [-0.14; -0.05], for executive functioning -0.18 [-0.24; - 0.11], for memory -0.12 [-0.17; -0.07], and for attention -0.17 [-0.23; -0.11]. Results for the association of individual MRI markers of cerebral SVD were statistically significant for WMH and global cognition -0.15 [-0.24; -0.06], WMH and executive function -0.23 [-0.33; -0.13], WMH and memory -0.19 [-0.29; -0.09], WMH and attention -0.24 [-0.39; -0.08], CMB and executive function -0.07 [-0.13; -0.02], CMB and memory -0.11 [-0.21; -0.02] and CMB and attention -0.13 [-0.25; -0.02]. In conclusion, presence of MRI markers of cerebral SVD were found to predict an increased risk of cognitive decline in relatively healthy older adults. While WMH were found to significantly affect all cognitive domains, CMB influenced decline in executive functioning over time as well as (in some studies) decline in memory and attention., Competing Interests: Declaration of conflicting interestsAlexander Jansma: reports no disclosuresJeroen de Bresser:The research of Jeroen de Bresser is supported by Alzheimer Nederland under grant WE.03-2019-08.Diana van Heemst: reports no disclosuresAbimbola A. Akintola: reports no disclosuresJan W. Schoones: reports no disclosures

Objectives: Urinary tract infection (UTI) is common among older women. However, diagnosis is challenging because of frequent chronic lower urinary tract symptoms, cognitive impairment, and a high prevalence of asymptomatic bacteriuria (ASB). Current urine diagnostics lack specificity, leading to unnecessary treatment and antimicrobial resistance. This study aimed to evaluate the diagnostic accuracy of 12 urine biomarkers for diagnosing UTI in older women., Methods: In this case-control study, cases were women ≥65 years with ≥2 new-onset lower urinary tract symptoms, pyuria, and one uropathogen ≥10 4  CFU/mL. Controls were asymptomatic and classified as ASB (one uropathogen ≥10 5  CFU/mL), negative culture, or mixed flora. Urine biomarker concentrations were measured through liquid chromatography-mass spectrometry and ELISA. Diagnostic accuracy parameters of individual biomarkers and a biomarker model were derived from receiver operating characteristic curves., Results: We included 162 community-dwelling and institutionalized older women. Five urine inflammatory biomarkers demonstrated high discriminative ability (area under the curve ≥0.80): interleukin 6, azurocidin, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinases 2, and C-X-C motif chemokine 9. Azurocidin exhibited the highest diagnostic accuracy (sensitivity 86% [95% CI 75%-93%] and specificity 89% [95% CI 82%-94%] at 16.7 ng/mmol creatinine). A combined biomarker and pyuria model showed improved diagnostic accuracy in patients with UTI and ASB, compared with pyuria alone., Discussion: We identified several urine biomarkers that accurately differentiated older women with UTI from asymptomatic women, including ASB. These findings represent a potential advancement towards improved diagnostics for UTI in older women and warrant validation in a diverse population., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Aging is associated with changes in heart rate (HR), heart rate variability (HRV), and 24-h rhythms in HR. Longevity has been linked to lower resting HR, while a higher resting HR and a decreased HRV were linked to cardiovascular events and increased mortality risk. HR and HRV are often investigated during a short electrocardiogram (ECG) measurement at a hospital. In this study, we aim to investigate the relationship between HR parameters with familial longevity and chronological age derived from continuous ambulatory ECG measurements collected over a period of 24 to 90 hours. We included 73 middle-aged participants (mean (SD) age: 67.0 (6.16) years), comprising 37 offspring of long-lived families, 36 of their partners, and 35 young participants (22.8 (3.96) years). We found no association with familial longevity, but middle-aged participants had lower 24-h HR (average and maximum HR, not minimum HR), lower amplitudes, and earlier trough and peak times than young participants. Associations in HR with chronological age could be caused by the aging process or by differences in environmental factors. Interestingly, middle-aged participants had a less optimal HRV during long-term recordings in both the sleep and awake periods, which might indicate that their heart is less adaptable than that of young participants. This could be a first indication of deteriorated cardiovascular health in middle-aged individuals.

Background: Conduct Disorder (CD) is a repetitive disruptive behaviour that violates the rights of others, manifests in rules violation, aggression, hostility, and deceitfulness and has assumed prominence in its association with juvenile offending and criminality in adulthood. Despite this knowledge, little research attention is given to ascertaining effective psychobehavioural interventions to manage this problem, especially amongst Nigerian adolescents., Aim: This study examined the efficacy of two psychobehavioural strategies to manage CD amongst in-school adolescents in Ibadan, Nigeria., Setting: Ibadan, Southwestern Nigeria., Method: A randomised controlled trial (RCT) of adolescents with CD was performed. Sixteen participants (aged 12-17 years) who reported high CD from an assessment of 1006 in-school adolescents of selected secondary schools in Ibadan were randomly grouped to receive either cognitive behavioural therapy (CBT), social skills training (SST) or combined CBT and SST. The Frequency of Delinquent Behaviour Scaling Instrument (FDBSI) was used for assessments., Results: Significant reduction in CD was observed among participants exposed to CBT ( t [6] = 8.510), p < 0.05) at 8 weeks, SST ( t [6] = 12.728), p < 0.05) at 8 weeks, and combined CBT and SST ( t [8] = 12.728, p < 0.05) at the 6 week mark of interventions respectively., Conclusion: From the study, CBT and SST are effective in managing CD. However, the combined psychobehavioural intervention of CBT and SST was more effective in managing CD, based on a faster therapeutic effect than the independent psychobehavioural intervention of CBT and SST., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2022. The Authors.)

Malaria is one of the deadliest infectious diseases in Africa. Many measures have been taken over the past few years to reduce the burden of malaria on public health following the recommendation of WHO, still, malaria has continued to rake devastation in Africa. Combating malaria in Africa has grown into an international concern. The eradication of malaia is a long-standing goal of public health initiatives globally. The development of vaccines will go a long way to provide the required immunity needed for the people living with malaria or vulnerable to malaria. It is imperative that a vaccine should be produced and rolled out for use, especially during the time of the COVID-19 pandemic when attention is given to mitigating the impact of the pandemic on public health. The malaria vaccine will reduce the number of hospital admission for malaria illness among children and other age groups. Africa will need to build strong innovations to overcome country-specific challenges in vaccination drive, human resources, and supply chain management. Accelerating education, sensitization, diagnosis, and eradication through joint efforts of the government, healthcare professionals and general population will help to prevent the dual synchronous epidemic of COVID-19 and Malaria in Africa., Competing Interests: NA., (© 2022 The Authors.)

NIMA-related kinase7 (NEK7) plays a multifunctional role in cell division and NLRP3 inflammasone activation. A typical expression or any mutation in the genetic makeup of NEK7 leads to the development of cancer malignancies and fatal inflammatory disease, i.e., breast cancer, non-small cell lung cancer, gout, rheumatoid arthritis, and liver cirrhosis. Therefore, NEK7 is a promising target for drug development against various cancer malignancies. The combination of drug repurposing and structure-based virtual screening of large libraries of compounds has dramatically improved the development of anticancer drugs. The current study focused on the virtual screening of 1200 benzene sulphonamide derivatives retrieved from the PubChem database by selecting and docking validation of the crystal structure of NEK7 protein (PDB ID: 2WQN). The compounds library was subjected to virtual screening using Auto Dock Vina. The binding energies of screened compounds were compared to standard Dabrafenib. In particular, compound 762 exhibited excellent binding energy of -42.67 kJ/mol, better than Dabrafenib (-33.89 kJ/mol). Selected drug candidates showed a reactive profile that was comparable to standard Dabrafenib. To characterize the stability of protein-ligand complexes, molecular dynamic simulations were performed, providing insight into the molecular interactions. The NEK7-Dabrafenib complex showed stability throughout the simulated trajectory. In addition, binding affinities, pIC50, and ADMET profiles of drug candidates were predicted using deep learning models. Deep learning models predicted the binding affinity of compound 762 best among all derivatives, which supports the findings of virtual screening. These findings suggest that top hits can serve as potential inhibitors of NEK7. Moreover, it is recommended to explore the inhibitory potential of identified hits compounds through in-vitro and in-vivo approaches.

We present the complete mitochondrial genome of a Malaria vector Mosquito Anopheles sinensis Wiedemann, 1828 from South Korea. The mitochondrial genome is about 15,421 bp long and contains 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and an A-T rich region. The present data were compared with those from China with respect to PCG sequence differences, tRNA structure, gene order, and control region (CR) structure. An. sinensis mitochondrial genomes from northeast Asia share identical gene composition and gene order. In contrast, they have distinct differences in the CR within the range 8.75% (51/583 bp) to 9.95% (58/583 bp). The phylogenetic analysis showed that An. sinensis from South Korea was clustered together with those from China, but there existed distinct genetic distance between the two. Likewise, mitochondrial genome sequences from other Anopheles species were employed to infer phylogenetic relationships among the members of the genus Anopheles . This study further promotes the enrichment of An. sinensis mitochondrial genome data, providing useful information for their mitochondrial genetic differences along with geographical distances in northeast Asia., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Methyl benzoate (MBe) is a volatile organic molecule found in various plants; it is used as an insect semiochemical. MBe also has a biorational insecticidal effect against various agricultural and urban arthropod pests. The present study was the first to assess the larvicidal potential of MBe against fourth-instar larvae of the mosquitoes Aedes albopictus (Skuse) and Culex pipiens (L.). A positive association was observed between MBe concentrations and larval mortality in both the species. The highest mortality recorded was 100% for Ae. albopictus and 56% for Cx. pipiens after 24 h of exposure to 200 ppm MBe. The lethal median concentration (LC50) values of MBe against fourth-instar larvae of Ae. albopictus and Cx. pipiens were 61 ppm and 185 ppm, respectively. These results suggest that MBe has great potential for use as an environmentally friendly larvicidal agent for mosquito control., (© The Author(s) 2022. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The fall armyworm, Spodoptera frugiperda , is an important agricultural pest native to tropical and subtropical regions of the Western Hemisphere, and has invaded Africa and further spread into most countries of Asia within two years. Here, we analyzed the genetic variation of invaded populations by comparing the nucleotide sequences of two genes: the nuclear Z-chromosome linked gene triose phosphate isomerase ( Tpi ) and the mitochondrial gene cytochrome oxidase subunit I ( COI ) of 27 specimens collected in Africa (DR Congo, Tanzania, Uganda, and Zimbabwe) and Asia (Bangladesh, Korea, Nepal, and Vietnam). The results revealed that 25 specimens were from a heterogeneous hybrid ( Tpi -corn strain and COI -rice strain; Tpi -C/ COI -R) of the corn strain male and rice strain female, but two specimens were from a homogenous corn strain ( Tpi -corn strain and COI -corn strain; Tpi -C/ COI -C). The further analysis of the fourth exon and the fourth intron sequences of the Tpi gene identified at least four subgroups of the corn strain. These four genetic subgroups were identified in Africa and Asia, suggesting no significant genetic change due to the rapid migration within two years. Our study provides essential information for understanding the genetic diversity of fall armyworm in new habitats.

Context: Hormones of the hypothalamic-pituitary-target gland axes are mostly investigated separately, whereas the interplay between hormones might be as important as each separate hormonal axis., Objective: Our aim is to determine the interrelationships between GH, TSH, ACTH, and cortisol in healthy older individuals., Design: We made use of 24-hour hormone serum concentrations assessed with intervals of 10 minutes from 38 healthy older individuals with a mean age (SD) of 65.1 (5.1) years from the Leiden Longevity Study. Cross-correlation analyses were performed to assess the relative strength between 2 24-hour hormone serum concentration series for all possible time shifts. Cross-approximate entropy was used to assess pattern synchronicity between 2 24-hour hormone serum concentration series., Results: Within an interlinked hormonal axis, ACTH and cortisol were positively correlated with a mean (95% confidence interval) correlation coefficient of 0.78 (0.74-0.81) with cortisol following ACTH concentrations with a delay of 10 minutes. Between different hormonal axes, we observed a negative correlation coefficient between cortisol and TSH of -0.30 (-0.36 to -0.25) with TSH following cortisol concentrations with a delay of 170 minutes. Furthermore, a positive mean (95% confidence interval) correlation coefficient of 0.29 (0.22-0.37) was found between TSH and GH concentrations without any delay. Moreover, cross-approximate entropy analyses showed that GH and cortisol exhibit synchronous serum concentration patterns., Conclusions: This study demonstrates that interrelations between hormones from interlinked as well as different hypothalamic-pituitary-target gland axes are observed in healthy older individuals. More research is needed to determine the biological meaning and clinical consequences of these observations., (© Endocrine Society 2019.)

Introduction: Evidence concerning the effectiveness of non-pharmacological interventions that are applied to people with dementia living in long-term care facilities is inconsistent. The purpose of this protocol is to describe the methodological considerations that will guide the completion of a scoping review that will inventorise and assess the effectiveness of the various non-pharmacological interventions that are documented in literature for improving quality of life of people with dementia living in long-term care., Methods and Analysis: This scoping review will combine the methodology outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews and Guidance for conducting systematic scoping reviews by Peters et al . PubMed; MEDLINE; CINAHL; Embase; Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials; Emcare; Sociological Abstracts and PsycINFO databases will be searched. Grey literature databases will also be explored. A two-stage screening process consisting of a title and abstract scan and a full-text review will be used to determine the eligibility of studies. Studies, irrespective of design, will be included that quantitatively assess quality of life of long-term care residents who receive non-pharmacological interventions for dementia. A pair of reviewers will independently assess all articles for eligibility, and all eligible articles will be abstracted and charted using a standardised form. The extracted data will undergo a 'narrative review' or a descriptive analysis of the contextual or process-oriented data and quantitative analysis reflecting the objectives of this scoping review., Ethics and Dissemination: Research ethics approval is not required for this scoping review. This review started off in October 2018, anticipated end date is June 2020. We plan to disseminate this research through publications, presentations at relevant national and international conferences and meetings with relevant stakeholders. This scoping review protocol has been registered at Open Science Framework (https://osf.io/tupbv)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: It is well known that adiposity is a risk factor for insulin resistance and type 2 diabetes mellitus. In the present study, we aimed to investigate the associations of measures of adiposity with indices of glycemia and of glycemic variability over a 72-h period in non-diabetic older adults., Methods: This cross-sectional study was conducted in non-diabetic individuals from the Active and Healthy Aging Study ( N  = 228), Switchbox ( N  = 116), and the Growing Old Together Study ( N  = 94). Body mass index (BMI) and waist circumference were measured, and indices of glycemia and glycemic variability were derived from continuous glucose monitoring (CGM) using the Mini-Med ® CGM system. Associations between adiposity and CGM were studied separately for the three cohorts, and derived estimates were subsequently meta-analyzed., Results: After meta-analyzing the results from the separate cohorts, individuals with a higher BMI had higher levels of glycemia. Individuals with BMI between 30 and 35 kg/m 2 had 0.28 mmol/L [95% confidence interval (CI): 0.12-0.44] higher 72 h-mean glucose concentration, 0.26 mmol/L (0.10-0.42) higher diurnal glucose (6:00 a.m. to 0:00 a.m.), and 0.39 mmol/L (0.19; 0.59) higher nocturnal glucose (3:00 a.m. to 6:00 a.m.) than participants with a normal weight (BMI 18.5-25 kg/m 2 ). However, no associations were observed between higher BMI and glycemic variability. Results for glycemia and glycemic variability were similarly observed for a high waist circumference., Conclusion: High adiposity associates with constant higher mean glucose levels over the day in non-diabetic older adults.

The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease. In this study, we assessed whether intranasal insulin can be used to enhance neuronal hypothalamic responses to glucose ingestion. In a randomized, double-blinded, placebo-controlled 4-double cross-over experiment, hypothalamic activation was measured in young non- diabetic subjects by determining blood-oxygen-level dependent MRI signals over 30 minutes before and after ingestion of 75 g glucose dissolved in 300 ml water, under intranasal insulin or placebo condition. Glucose ingestion under placebo condition lead to an average 1.4% hypothalamic BOLD decrease, under insulin condition the average response to glucose was a 2.2% decrease. Administration of water did not affect the hypothalamic BOLD responses. Intranasal insulin did not change circulating glucose and insulin levels. Still, circulating glucose levels showed a significant dampening effect on the BOLD response and insulin levels a significant strengthening effect. Our data provide proof of concept for future experiments testing the potential of intranasal application of insulin to ameliorate defective homeostatic control in patients with type 2 diabetes.

Background: Elevated concentrations of liver enzymes have been associated with an increased risk of developing type 2 diabetes mellitus. However, it remains unclear to which specific aspects of diurnal glucose metabolism these associate most. We aimed to investigate the associations between liver enzyme concentrations and 24 h-glucose trajectories in individuals without diabetes mellitus from three independent cohorts., Methods: This cross-sectional study included 436 participants without diabetes mellitus from the Active and Healthy Aging Study, the Switchbox Study, and the Growing Old Together Study. Fasting blood samples were drawn to measure gamma-glutamyltransferase (GGT), alanine transaminase, and aspartate transaminase. Measures of glycemia (e.g., nocturnal and diurnal mean glucose levels) and glycemic variability (e.g., mean amplitude of glucose excursions) were derived from continuous glucose monitoring. Analyses were performed separately for the three cohorts; derived estimates were additionally meta-analyzed., Results: After meta-analyses of the three cohorts, elevated liver enzyme concentrations, and specifically elevated GGT concentrations, were associated with higher glycemia. More specific, participants in the highest GGT tertile (GGT ≥37.9 U/L) had a 0.39 mmol/L (95% confidence interval: 0.23, 0.56) higher mean nocturnal glucose (3:00 to 6:00 a.m.) and a 0.23 mmol/L (0.10, 0.36) higher diurnal glucose (6:00 to 0:00 a.m.) than participants in the lowest GGT tertile (GGT <21.23 U/L). However, elevated liver enzyme concentrations were not associated with a higher glycemic variability., Conclusion: Though elevated liver enzyme concentrations did not associate with higher glycemic variability in participants without diabetes mellitus, specifically, elevated GGT concentrations associated with higher glycemia.

The biological clock, whose function deteriorates with increasing age, determines bodily circadian (i.e. 24h) rhythms, including that of cholesterol metabolism. Dampening of circadian rhythms has been associated with aging and disease. Therefore, we hypothesized that individuals with a familial predisposition for longevity have a higher amplitude circadian serum cholesterol concentration rhythm. The aim of this study was to investigate circadian rhythmicity of serum cholesterol concentrations in offspring of nonagenarian siblings and their partners. Offspring from nonagenarian siblings (n = 19), and their partners as controls (n = 18), were recruited from the Leiden Longevity Study. Participants (mean age 65 years) were studied in a controlled in-hospital setting over a 24-h period, receiving three isocaloric meals at 9:00 h, 12:00 h and 18:00 h. Lights were off between 23:00 h and 8:00 h. Serum total cholesterol (TC), HDL cholesterol (HDL-C), non-HDL-C and triglycerides (TG) were determined every 30 min over a 24-h period. Serum TC concentrations were higher during day than during night in offspring (5.2 vs. 4.7 mm, P < 0.001) and in controls (5.3 vs. 5.0 mm, P < 0.001). The difference in TC concentrations between day and night tended to be greater in offspring than in controls (0.5 vs. 0.3 mm, P = 0.109), reaching statistical significance in females (P = 0.045). Notably, the day-night serum differences in non-HDL-C were twofold greater in offspring than in controls (0.43 vs. 0.21 mm, P = 0.044) and most explicit in females (0.53 vs. 0.22, P = 0.078). We conclude that familial longevity is characterized by a high circadian rhythmicity of non-HDL-C in healthy elderly offspring from nonagenarian siblings., (© 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Insulin, a vasoactive modulator regulating peripheral and cerebral blood flow, has been consistently linked to aging and longevity. In this proof of principle study, using a randomized, double-blinded, placebo-controlled crossover design, we explored the effects of intranasally administered insulin (40IU) on cerebral blood flow (CBF) and perfusion in older (60-69 years, n=11) and younger (20-26 years, n=8) adults. Changes in CBF through the major cerebropetal arteries were assessed via phase contrast MR-angiography, and regional cortical tissue perfusion via pseudo-continuous arterial spin labelling. Total flow through the major cerebropetal arteries was unchanged in both young and old. In the older participants, intranasal insulin compared to placebo increased perfusion through the occipital gray matter (65.2±11.0 mL/100g/min vs 61.2±10.1 mL/100g/min, P=0.001), and in the thalamus (68.28±6.75 mL/100g/min versus 63.31±6.84 mL/100g/min, P=0.003). Thus, intranasal insulin improved tissue perfusion of the occipital cortical brain region and the thalamus in older adults.

Reduced growth hormone (GH) signaling has been consistently associated with increased health and lifespan in various mouse models. Here, we assessed GH secretion and its control in relation with human familial longevity. We frequently sampled blood over 24 h in 19 middle-aged offspring of long-living families from the Leiden Longevity Study together with 18 of their partners as controls. Circulating GH concentrations were measured every 10 min and insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3) every 4 h. Using deconvolution analysis, we found that 24-h total GH secretion was 28% lower (P = 0.04) in offspring [172 (128-216) mU L -1 ] compared with controls [238 (193-284) mU L -1 ]. We used approximate entropy (ApEn) to quantify the strength of feedback/feedforward control of GH secretion. ApEn was lower (P = 0.001) in offspring [0.45 (0.39-0.53)] compared with controls [0.66 (0.56-0.77)], indicating tighter control of GH secretion. No significant differences were observed in circulating levels of IGF-1 and IGFBP3 between offspring and controls. In conclusion, GH secretion in human familial longevity is characterized by diminished secretion rate and more tight control. These data imply that the highly conserved GH signaling pathway, which has been linked to longevity in animal models, is also associated with human longevity., (© 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Context: A trade-off between fertility and longevity possibly exists. The association of the male hypothalamic-pituitary-gonadal (HPG) axis with familial longevity has not yet been investigated., Objective: To study 24-h hormone concentration profiles of the HPG axis in men enriched for familial longevity and controls., Design: We frequently sampled blood over 24 h in 10 healthy middle-aged male offspring of nonagenarian participants from the Leiden Longevity Study together with 10 male age-matched controls. Individual 24-h luteinizing hormone (LH) and testosterone concentration profiles were analyzed by deconvolution analyses to estimate secretion parameters. Furthermore, the temporal relationship between LH and testosterone was assessed by cross-correlation analysis. We used (cross-)approximate entropy to quantify the strength of feedback and/or feedforward control of LH and testosterone secretion., Results: Mean [95% confidence interval (CI)] total LH secretion of the offspring was 212 (156-268) U/L/24 h, which did not differ significantly ( p  = 0.51) from the total LH secretion of controls [186 (130-242) U/L/24 h]. Likewise, mean (95% CI) total testosterone secretion of the offspring [806 (671-941) nmol/L/24 h] and controls [811 (676-947) nmol/L/24 h] were similar ( p  = 0.95). Other parameters of LH and testosterone secretion were also not significantly different between offspring and controls. The temporal relationship between LH and testosterone and the strength of feedforward/feedback regulation within the HPG axis were similar between offspring of long-lived families and controls., Conclusion: This relatively small study suggests that in healthy male middle-aged participants, familial longevity is not associated with major differences in the HPG axis. Selection on both fertility and health may in part explain the results.

Background: The Equivital (EQ02) is a multi-parameter telemetric device offering both real-time and/or retrospective, synchronized monitoring of ECG, HR, and HRV, respiration, activity, and temperature. Unlike the Holter, which is the gold standard for continuous ECG measurement, EQO2 continuously monitors ECG via electrodes interwoven in the textile of a wearable belt. Objective: To compare EQ02 with the Holter for continuous home measurement of ECG, heart rate (HR), and heart rate variability (HRV). Methods: Eighteen healthy participants wore, simultaneously for 24 h, the Holter and EQ02 monitors. Per participant, averaged HR, and HRV per 5 min from the two devices were compared using Pearson correlation, paired T -test, and Bland-Altman analyses. Accuracy and precision metrics included mean absolute relative difference (MARD). Results: Artifact content of EQ02 data varied widely between (range 1.93-56.45%) and within (range 0.75-9.61%) participants. Comparing the EQ02 to the Holter, the Pearson correlations were respectively 0.724, 0.955, and 0.997 for datasets containing all data and data with < 50 or < 20% artifacts respectively. For datasets containing respectively all data, data with < 50, or < 20% artifacts, bias estimated by Bland-Altman analysis was -2.8, -1.0, and -0.8 beats per minute and 24 h MARD was 7.08, 3.01, and 1.5. After selecting a 3-h stretch of data containing 1.15% artifacts, Pearson correlation was 0.786 for HRV measured as standard deviation of NN intervals (SDNN). Conclusions: Although the EQ02 can accurately measure ECG and HRV, its accuracy and precision is highly dependent on artifact content. This is a limitation for clinical use in individual patients. However, the advantages of the EQ02 (ability to simultaneously monitor several physiologic parameters) may outweigh its disadvantages (higher artifact load) for research purposes and/ or for home monitoring in larger groups of study participants. Further studies can be aimed at minimizing the artifacts.

Background: The rs7903146-T allele in the transcription factor 7-like 2 (TCF7L2) gene has been associated with impaired pancreatic insulin secretion, enhanced liver glucose production, and an increased risk of type 2 diabetes. Nevertheless, the impact of rs7903146 on daily glucose trajectories remains unclear. Continuous glucose monitoring (CGM) can estimate glycemia and glycemic variability based on consecutive glucose measurements collected over several days. The purpose of the present study was to investigate the associations of rs7903146 with glycemia and glycemic variability in middle-aged participants without diabetes., Methods: Complete data from 235 participants without diabetes from the Leiden Longevity Study were available. Participants were divided into two groups based on rs7903146 genotype; rs7903146-CC genotype carriers (N = 123) and rs7903146-CT/TT genotype carriers (N = 112). Validated parameters of glycemia (e.g., mean 24h glucose level) and glycemic variability (e.g., 24h standard deviation) were derived from data collected with a CGM system for a 72-hour period., Results: The study population was on average 64.7 years old (standard deviation = 5.9) and composed of 49.8% of women. Compared with rs7903146-CC carriers, rs7903146-CT/TT carriers exhibited a trend towards a higher mean 24-hour glucose level (5.21 versus 5.32 mmol/L; p-value = 0.15) and a significantly higher mean nocturnal glucose (3:00am- 6:00am; 4.48 versus 4.67 mmol/L; p-value = 0.03) that was explained for 34.6% by body weight and percentage body fat. No differences in measures of glycemic variability between the genotype groups were observed., Conclusion: Despite limited sample size, our study indicates that the rs7903146-T allele in TCF7L2 was associated with a higher mean nocturnal glucose dependent on body composition, which might suggest that rs7902146 affects liver-specific aspects of glucose metabolism.

Background: The validity of continuous glucose monitoring (CGM) is well established in diabetic patients. CGM is also increasingly used for research purposes in normo-glycemic individuals, but the CGM validity in such individuals is unknown. We studied the accuracy of CGM measurements in normo-glycemic individuals by comparing CGM-derived versus venous blood-derived glucose levels and measures of glycemia and glycemic variability., Methods: In 34 healthy participants (mean age 65.7 years), glucose was simultaneously measured every 10 minutes, via both an Enlite® CGM sensor, and in venous blood sampled over a 24-hour period. Validity of CGM-derived individual glucose measurements, calculated measures of glycemia over daytime (09:00h-23:00h) and nighttime (23:00h-09:00h), and calculated measures of glycemic variability (e.g. 24h standard deviation [SD]) were assessed by Pearson correlation coefficients, mean absolute relative difference (MARD) and paired t-tests., Results: The median correlation coefficient between CGM and venous glucose measurements per participant was 0.68 (interquartile range: 0.40-0.78), and the MARD was 17.6% (SD = 17%). Compared with venous sampling, the calculated measure of glycemia during daytime was 0.22 mmol/L higher when derived from CGM, but no difference was observed during nighttime. Most measures of glycemic variability were lower with CGM than with venous blood sampling (e.g., 24h SD: 1.07 with CGM and 1.26 with venous blood; p-value = 0.004)., Conclusion: In normo-glycemic individuals, CGM-derived glucose measurements had good agreement with venous glucose levels. However, the measure of glycemia was higher during the day and most measures of glycemic variability were lower when derived from CGM.

Context: Longevity is associated with changes in circulating levels of thyroid hormone (TH) and/or TSH in animals and humans, but underlying mechanisms remain elusive., Objective: We explored in 38 offspring of nonagenarian participants from the Leiden Longevity Study, who are enriched for longevity and in their partners, ultradian and circadian rhythmicity of TSH, temporal relationship, and feedback and forward interplay between TSH and TH., Methods: We collected blood samples every 10 minutes for 24 hours for TSH and TH profiles. We used a deconvolution analysis to estimate basal (nonpulsatile), pulsatile, and other secretion parameters to characterize ultradian rhythmicity and locally weighted polynomial regression of TSH to assess circadian rhythmicity. A cross-correlation analysis was used to investigate the temporal relationship between TSH and TH and cross-approximate entropy to assess feedback and forward interplay between TSH and TH., Results: Compared with partners, offspring displayed higher mean (95% confidence interval [CI]) basal TSH secretion (34.3 [95% CI 27.2-43.1] mU/L per 24 hours vs 18.5 [95% CI 14.4-23.7] mU/L per 24 hours, P = .001) but no differences in ultradian or circadian properties of TSH. The temporal relationship between TSH and free T3 at zero delay was higher in offspring (0.48 ± 0.2) compared with partners (0.26 ± 0.4) (P = .05), but the feedback and forward interplay between TSH and TH did not differ., Conclusions: Familial longevity is associated with increased basal TSH secretion and a strong temporal relationship between TSH and free T3 but not with differences in ultradian or circadian TSH rhythmicity or feedback and forward interplay between TSH and TH.

Subclinical hypothyroidism (SCH), defined as elevated thyroid stimulating hormone (TSH) and normal thyroid hormone levels, and cognitive impairment are both common in older people. While the relation between overt hypothyroidism and cognitive impairment is well established, data on the association between SCH and cognitive impairment are conflicting. This systematic review and meta-analysis was performed to assess available evidence on the association of SCH with cognition in community dwelling, relatively healthy older adults. PubMed, EMBASE, Web of Science, COCHRANE, CINAHL, PsycINFO, and Academic Search Premier (January 1966 to April 1, 2015) were searched without language restrictions, as were references of key articles, for studies on the association between SCH and cognition in older adults (>60 years). These studies were reviewed by two independent reviewers according to predefined criteria for eligibility and methodological quality, and data were extracted using standardized forms. Of the 844 reports initially identified, 270 remained after exclusion of duplicates. Of the 270, 15 studies comprising 19,944 subjects, of whom 1,199 had subclinical hypothyroidism were included. Data from the 15 studies was pooled, and meta-analyzed cross-sectionally for global cognition [assessed by Mini-Mental State Examination (MMSE)], executive function, and memory, using random effects models. Pooled effect size (ES) for MMSE was -0.01 (95% CI -0.09, 0.08), with heterogeneity (I (2)) of 55.1%. Pooled ES was < 0.001 (95% CI -0.10, 0.09) for executive function (I (2) = 13.5%), and 0.01 (95% CI -0.12, 0.14) for memory (I (2) = 46.9%). In addition, prospective analysis including four studies showed pooled ES of 0.033 (95% CI -0.001 - 0.067) for MMSE (I (2) < 0.001%), indicating that subclinical hypothyroidism was not significantly associated with accelerated cognitive decline. This systematic review and meta-analysis provides no evidence that supports an association between SCH and cognitive impairment in relatively healthy older adults.

Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain MRI was used to detect macro-structural damage (atrophy, white matter hyper-intensities, infarcts and/or micro-bleeds) and magnetization transfer imaging (MTI) to detect loss of micro-structural homogeneity that remains otherwise invisible on conventional MRI. Macro-structurally, higher fasted glucose was significantly associated with white matter atrophy (P = 0.028). Micro-structurally, decreased magnetization transfer ratio (MTR) peak height in gray matter was associated with higher fasted insulin (P = 0.010), AUCinsulin (P = 0.001), insulinogenic index (P = 0.008) and lower HOMA-IS index (P < 0.001). Similar significant associations were found for white matter. Thus, while higher glucose was associated with macro-structural damage, impaired insulin action was associated more strongly with reduced micro-structural brain parenchymal homogeneity. These findings offer some insight into the association between different parameters of glucose metabolism (impairment of which is characteristic of diabetes mellitus) and brain aging.

Objective: The hypothalamic-pituitary-adrenal (HPA)-axis is the most important neuro-endocrine stress response system of our body which is of critical importance for survival. Disturbances in HPA-axis activity have been associated with adverse metabolic and cognitive changes. Humans enriched for longevity have less metabolic and cognitive disturbances and therefore diminished activity of the HPA axis may be a potential candidate mechanism underlying healthy familial longevity. Here, we compared 24-h plasma ACTH and serum cortisol concentration profiles and different aspects of the regulation of the HPA-axis in offspring from long-lived siblings, who are enriched for familial longevity and age-matched controls., Design: Case-control study within the Leiden Longevity study cohort consisting of 20 middle-aged offspring of nonagenarian siblings (offspring) together with 18 partners (controls)., Methods: During 24 h, venous blood was sampled every 10 minutes for determination of circulatory ACTH and cortisol concentrations. Deconvolution analysis, cross approximate entropy analysis and ACTH-cortisol-dose response modeling were used to assess, respectively, ACTH and cortisol secretion parameters, feedforward and feedback synchrony and adrenal gland ACTH responsivity., Results: Mean (95% Confidence Interval) basal ACTH secretion was higher in male offspring compared to male controls (645 (324-1286) ngl/L/24 h versus 240 (120-477) ng/L/24 h, P = 0.05). Other ACTH and cortisol secretion parameters did not differ between offspring and controls. In addition, no significant differences in feedforward and feedback synchrony and adrenal gland ACTH responsivity were observed between groups., Conclusions: These results suggest that familial longevity is not associated with major differences in HPA-axis activity under resting conditions, although modest, sex-specific differences may exist between groups that might be clinically relevant.

Few studies have included subjects with the propensity to reach old age in good health, with the aim to disentangle mechanisms contributing to staying healthier for longer. The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating levels of thyroid stimulating hormone (TSH) and thyroid hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis may favour longevity without altering energy metabolism.

Impaired glucose metabolism and type 2 diabetes have been associated with cognitive decline, dementia, and with structural and functional brain features. However, it is unclear whether these associations differ in individuals that differ in familial longevity or age. Here, we investigated the association between parameters of glucose metabolism and microstructural brain integrity in offspring of long-lived families ("offspring") and controls; and age categories thereof. From the Leiden Longevity Study (LLS), 132 participants underwent an oral glucose tolerance test (OGTT) to assess glycemia [fasted glucose and glucose area-under-the-curve (AUC)], insulin resistance [fasted insulin, AUCinsulin, and homeostatic model assessment of insulin resistance (HOMA-IR)], and pancreatic Beta cell secretory capacity (insulinogenic index). 3 Tesla MRI and Magnetization Transfer (MT) imaging MT-ratio (MTR) peak-height was used to quantify differences in microstructural brain parenchymal tissue homogeneity that remain invisible on conventional MRI. Analyses were performed in offspring and age-matched controls, with and without stratification for age. In the full offspring group only, reduced MTR peak-height in gray and white matter was inversely associated with AUCinsulin, fasted insulin, HOMA-IR and insulinogenic-index (all p < 0.01). When dichotomized for age (≤65 years and >65 years): in younger controls, significantly stronger inverse associations were observed between MTR peak-height and fasted glucose, AUCglucose, fasted insulin, AUCinsulin and HOMA-IR in gray matter; and for AUCglucose, fasted insulin and HOMA-IR in white matter (all P-interaction < 0.05). Although the strength of the associations tended to attenuate with age in the offspring group, the difference between age groups was not statistically significant. Thus, associations between impaired insulin action and reduced microstructural brain parenchymal tissue homogeneity were stronger in offspring compared to controls, and seemed to diminish with age.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.nepr.2015.03.009. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

There is now an impressive body of literature implicating insulin and insulin signaling in successful aging and longevity. New information from in vivo and in vitro studies concerning insulin and insulin receptors has extended our understanding of the physiological role of insulin in the brain. However, the relevance of these to aging and longevity remains to be elucidated. Here, we review advances in our understanding of the physiological role of insulin in the brain, how insulin gets into the brain, and its relevance to aging and longevity. Furthermore, we examine possible future therapeutic applications and implications of insulin in the context of available models of delayed and accelerated aging.

Repeated 24 h blood sampling, which is required for time series analyses of metabolites and/or hormones that show strong fluctuations in blood concentration over time, has a higher failure rate in older adults. We tailored existing venipuncture protocols toward use for 24 h blood sampling (sampling frequency of 10 min) in older adults. The following modifications were made: •Pre-sampling: evidence based risk assessment of older adults.•During sampling:•Ultrasound-guided identification and characterisation of veins.•Use of 20-gauge arterial catheter with guide wire for venous access.•Measures to prevent and/or reduce unidirectional blood flow (fluid flow into but not out of the vein) included:•Use of hot water bottles to dilate veins.•Use of small gauge syringes, shortening of the extension line, and slowing of the blood withdrawal rate to reduce pressure on veins.•Stimulation of movement of the arm or retraction of the IV cannula to relieve mechanical flow obstruction.•Post-sampling: prevention of bruising and prolonged bleeding.

The aim of this study was to investigate the effect of crankcase oil on the cellular and functional integrity of rat skin. Thirty (30) rats were randomly grouped into six viz groups A-F. Group A (base-line control) received 2 ml of distilled water. 2.5 %, 5.0 %, 7.5 %, and 10.0 % v/v of the crankcase oil were prepared using unused oil as solvent and 2 ml of the concentrations were topically administered to groups C-F respectively for seven consecutive days. Group B served as positive control and received 2 ml of the unused oil. The rats were sacrificed 24 hours after the last administration, and blood and part of the skin were collected. Alkaline phosphatase (ALP), acid phosphatase (ACP), superoxide dismutase (SOD) and malondialdehyde level in the blood and skin samples collected were evaluated. Elemental analysis of the crankcase oil was also carried out. The result revealed high lead, iron and chromium levels. Blood lead concentration of rats was significantly (P<0.05) high after seven days of administration. ALP level in skin and serum increased significantly (P<0.05) with the concentration of crankcase oil. There was a significant decrease (P<0.05) in skin ACP activity while it increased significantly (P<0.05) in the serum. Similar results were observed in the SOD levels of the serum and the skin. The level increased significantly (P<0.05) in groups D-F when compared with controls. The MDA concentration of both serum and skin were significantly (P<0.05) elevated. This suggests toxic potential of used lubricating oil and its potential predisposition to cancer.

Background: Reported findings are inconsistent whether hypothalamic-pituitary-adrenal (HPA) signaling becomes hyperactive with increasing age, resulting in increasing levels of cortisol. Our previous research strongly suggests that offspring from long-lived families are biologically younger. In this study we assessed whether these offspring have a lower HPA axis activity, as measured by lower levels of cortisol and higher cortisol feedback sensitivity., Methods: Salivary cortisol levels were measured at four time points within the first hour upon awakening and at two time points in the evening in a cohort comprising 149 offspring and 154 partners from the Leiden Longevity Study. A dexamethasone suppression test was performed as a measure of cortisol feedback sensitivity. Age, gender and body mass index, smoking and disease history (type 2 diabetes and hypertension) were considered as possible confounding factors., Results: Salivary cortisol secretion was lower in offspring compared to partners in the morning (Area Under the Curve = 15.6 versus 17.1 nmol/L, respectively; p = 0.048) and in the evening (Area Under the Curve = 3.32 versus 3.82 nmol/L, respectively; p = 0.024). Salivary cortisol levels were not different after dexamethasone (0.5 mg) suppression between offspring and partners (4.82 versus 5.26 nmol/L, respectively; p = 0.28)., Conclusion: Offspring of nonagenarian siblings are marked by a lower HPA axis activity (reflected by lower diurnal salivary cortisol levels), but not by a difference in cortisol feedback sensitivity. Further in-depth studies aimed at characterizing the HPA axis in offspring and partners are needed.