Myelodysplastic syndromes mortality in Spain: a comprehensive age-period-cohort and joinpoint analysis / Mortalidad por síndromes mielodisplásicos en España: análisis integral de cohortes por períodos de edad y de puntos de unión

Objective: The present study aims to assess the mortality trends in myelodysplastic syndromes (MDS) in Spain from 1980 to 2021. Methods: Deaths and mid-year population data were collected from the National Institute of Statistics. We estimated age-standardised mortality rates (ASMRs) per 100,000 person-years for all ages and ages 35–64. Joinpoint regression identified significant changes in mortality trends. The independent effects of age, period and birth cohort on MDS mortality were also examined. Results: MDS-related deaths gradually increased from 36 in 1980 to 1118 in 2021, with an overall increase of 6.6% in age-standardised mortality rates (ASMRs) for both men and women. Joinpoint analysis identified four periods for both men and women: 1980–1987 (stable rates), 1987–1990 (sharp increase), 1990–1999 (slower increase) and 1999–2021 (stable rates). ASMRs (35–64 years) increased by 2.5% over the study period, with a turning point identified in 1996 when rates decreased. Mortality from MDS increases with age and is higher in men. The cohort's relative risk increased until the mid-1950s and then stabilised, whilst the period relative risk increased between 1982 and 1996 and then stabilised. Conclusion: The results of this study indicate a progressive increase in MDS-related deaths in Spain between 1980 and 2021. Notably, this increase was more pronounced in men than in women. Analysis of birth cohort trends revealed shifts in MDS risk, characterised by an increase until the mid-twentieth century, followed by a stabilisation. Using joinpoint analysis, four distinct periods were identified, shedding light on the changing patterns of mortality over time. These findings help to shape future research directions and inform public health strategies. They also provide optimism for advances in MDS treatment and potential reductions in mortality.(AU)

A mechanistic review on growing multiple therapeutic applications of lutein and its global market research.

Lutein is a naturally occurring carotenoid synthesized by plants and algae that has a beneficial effect on several biological processes and associated ailments. Its immediate application is in ophthalmology, where it significantly lowers the incidences of age-related macular degeneration (AMD). It also has anti-inflammatory action, treatment of diabetic retinopathy, and cataracts, and enhancement of visual contrast. To critically assess lutein biosynthesis, therapeutic applicability, and market research literature. We have discussed its theoretical frameworks, experimental evidence, limitations, as well as clinical trial results, and future research prospects. The literature for this review article was mined and compiled by collecting and analyzing articles from several databases, including ScienceDirect, Google Scholar, PubMed, Wiley Online Library, Patentscope, and ClinicalTrials.gov published until March 30, 2022. Patent publications were identified using the search terms like IC:(C07C67/56) AND EN_AB:(lutein) OR EN_TI:(lutein) OR EN_AB:(extraction) OR EN_TI:(process). According to the literature, lutein is an essential nutrient given that it cannot be synthesized in the human body and acts as an antioxidant, affecting AMD, diabetic retinopathy, Rheumatic diseases, inflammation, and cancer. Due to inadequate production and laborious extraction, lutein is expensive despite its high demand and applicability. Market research predicts a 6.3% compound annual growth rate for lutein by 2032. Optimizing lutein extraction for high yield and purity is necessary. Lutein has proven applicability in various ailments as well as cosmetics that can be developed as a candidate drug for various diseases discussed in the review.

Efficacy and classification of Sesamum indicum linn seeds with Rosa damascena mill oil in uncomplicated pelvic inflammatory disease using machine learning.

Background and objectives: As microbes are developing resistance to antibiotics, natural, botanical drugs or traditional herbal medicine are presently being studied with an eye of great curiosity and hope. Hence, complementary and alternative treatments for uncomplicated pelvic inflammatory disease (uPID) are explored for their efficacy. Therefore, this study determined the therapeutic efficacy and safety of Sesamum indicum Linn seeds with Rosa damascena Mill Oil in uPID with standard control. Additionally, we analyzed the data with machine learning. Materials and methods: We included 60 participants in a double-blind, double-dummy, randomized standard-controlled study. Participants in the Sesame and Rose oil group (SR group) (n = 30) received 14 days course of black sesame powder (5 gm) mixed with rose oil (10 mL) per vaginum at bedtime once daily plus placebo capsules orally. The standard group (SC), received doxycycline 100 mg twice and metronidazole 400 mg thrice orally plus placebo per vaginum for the same duration. The primary outcome was a clinical cure at post-intervention for visual analogue scale (VAS) for lower abdominal pain (LAP), and McCormack pain scale (McPS) for abdominal-pelvic tenderness. The secondary outcome included white blood cells (WBC) cells in the vaginal wet mount test, safety profile, and health-related quality of life assessed by SF-12. In addition, we used AdaBoost (AB), Naïve Bayes (NB), and Decision Tree (DT) classifiers in this study to analyze the experimental data. Results: The clinical cure for LAP and McPS in the SR vs SC group was 82.85% vs 81.48% and 83.85% vs 81.60% on Day 15 respectively. On Day 15, pus cells less than 10 in the SR vs SC group were 86.6% vs 76.6% respectively. No adverse effects were reported in both groups. The improvement in total SF-12 score on Day 30 for the SR vs SC group was 82.79% vs 80.04% respectively. In addition, our Naive Bayes classifier based on the leave-one-out model achieved the maximum accuracy (68.30%) for the classification of both groups of uPID. Conclusion: We concluded that the SR group is cost-effective, safer, and efficacious for curing uPID. Proposed alternative treatment (test drug) could be a substitute of standard drug used for Female genital tract infections.

Placental Histopathological Lesions and Adverse Neonatal Outcomes in Patients with Inflammatory Bowel Diseases- A retrospective Cohort Study.

Inflammatory bowel diseases (IBD) are significantly associated with adverse pregnancy and neonatal outcomes, though the pathomechanism is yet unknown. To investigate the relationship between IBD and adverse pregnancy outcomes by comparing neonatal outcomes and placental histopathology in two matched groups of patients with and without IBD. In this retrospective study, data of all patients who gave birth between 2008-2021 and were diagnosed with IBD were reviewed and compared to a control group matching two control cases for every IBD case. Neonatal outcomes and placental pathology were compared between the groups. Compared to the control group (n=76), the placentas of patients with IBD (n=36) were characterized by significantly lower placental weight (p < 0.001), and higher rates of maternal vascular malperfusion lesions (MVM, p < 0.001) and maternal and fetal inflammatory response lesions (p < 0.001). Neonates of patients with IBD were more frequently small for gestational age (SGA) (p=0.01), with increased rates of need for phototherapy (p = 0.03), respiratory morbidity and NICU admission (p < 0.001 for both outcomes). Multivariate logistic regression analyses adjusting for possible confounders (including maternal age, gestational age, chronic hypertension, smoking, and thrombophilia) confirmed the independent association between IBD and composite MVM lesions (aOR 4.31, p < 0.001), maternal inflammatory responses (aOR 40.22, p < 0.001) and SGA infants (aOR 4.31, p = 0.013). IBD is associated with increased rates of placental histopathological lesions and adverse pregnancy outcomes, including SGA infants. These novel findings imply the role of placental malperfusion and inflammatory processes in pregnancy complications of IBD patients, which should be followed accordingly. Approval of local ethics committee # WOMC-0219-20.

Effect modification of polypharmacy on incident frailty by chronic kidney disease in older adults.

BACKGROUND: Frailty and polypharmacy are common conditions in older adults, especially in those with chronic kidney disease (CKD). Therefore, we analyzed the association of polypharmacy and incident frailty and the effect modification by CKD in very old adults. METHODS: In non-frail individuals within the Berlin Initiative (cohort) Study, polypharmacy (≥ 5 medications) was assessed according to multiple definitions based on the number of regular and on demand prescription and over the counter drugs, as well as vitamins and supplements. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73m2 and/or an albumin-creatinine ratio ≥ 30 mg/g. Incident frailty was assessed at follow-up using Fried criteria. Logistic regression was applied to assess (1) the association of different polypharmacy definitions with incident frailty and (2) effect modification by CKD. RESULTS: In this cohort study, out of 757 non-frail participants (mean age 82.9 years, 52% female, 74% CKD), 298 (39%) participants reported polypharmacy. Over the observation period of 2.1 years, 105 became frail. Individuals with polypharmacy had 1.96 adjusted odds (95% confidence interval (CI): 1.20-3.19) of becoming frail compared to participants without polypharmacy. The effect of polypharmacy on incident frailty was modified by CKD on the additive scale (relative excess risk due to interaction: 1.56; 95% CI 0.01-3.12). CONCLUSIONS: This study demonstrates an association of polypharmacy and incident frailty and suggests strong evidence for an effect modification of CKD on polypharmacy and incident frailty. Revision of prescriptions could be a target strategy to prevent frailty occurrence, especially in older adults with CKD.

[Mechanism of Kuntai Capsules in treatment of polycystic ovary syndrome rat models based on AGE-RAGE signal pathway].

This study aims to investigate the impact of Kuntai Capsules(KTC) on polycystic ovarian syndrome(PCOS) rat models and explore the underlying mechanism. Fifty female SD rats were randomly divided into five groups(10 rats in each group), including control group, model group, low-, medium-, and high-dose KTC group. Except for the control group, the other groups were injected with dehydroepiandrosterone(DHEA) combined with a high-fat diet(HFD) to induce the PCOS rat model for 28 days. 0.315, 0.63, and 1.26 g·kg~(-1)·d~(-1) KTC was dissolved in the same amount of normal saline and given to low-, medium-, and high-dose KTC groups by gavage. Both control group and model group were given the same amount of normal saline for 15 days. After administration, fasting blood glucose(FBG) was measured by a glucose meter. Fasting insulin(FINS), luteinizing hormone(LH), testosterone(T), and follicle-stimulating hormone(FSH) were detected by enzyme-linked immunosorbent assay(ELISA), and LH/FSH ratio and insulin resistance index(HOMA-IR) were calculated. The pathological morphology of ovarian tissue was observed by hematoxylin-eosin(HE) staining. The expression levels of collagen α type Ⅲ 1 chain(COL3A1), apoptotic factors Bax, and Bcl-2 were detected using Western blot and immunofluorescence. The mRNA expressions of COL3A1, Bax, and Bcl-2 in ovarian tissue were performed by real-time PCR(RT-PCR). The results show that compared with the control group, the body weight, serum levels of FBG, FINS, LH, T, LH/FSH, and HOMA-IR are higher in model group(P<0.05 or P<0.01), and the level of FSH is lower(P<0.05). In model group, a large number of white blood cells are found in the vaginal exfoliated cells, mainly in the interictal phase. There are more cystic prominences on the surface of the ovary. The thickness of the granular cell layer is reduced, and oocytes are absent. COL3A1 and Bax protein expression levels are increased(P<0.01), while Bcl-2 protein expression levels are decreased(P<0.05) in the ovarian tissue COL3A1 and Bax mRNA expression levels are increased in ovarian tissue(P<0.05). Compared with the model group, the body weight, FBG, FINS, LH, T, LH/FSH, and HOMA-IR in low-, medium-, and high-dose KTC groups are decreased(P<0.05 or P<0.01), while the levels of FSH in medium-, and high-dose KTC groups are increased(P<0.05 or P<0.01). Low-, medium-, and high-dose KTC groups gradually show a stable interictal phase. The surface of the ovary is smooth. Oocytes and mature follicles can be seen in ovarian tissue, and the thickness of the granular cell layer is increased. The expression level of COL3A1 protein decreases in low-and medium-dose KTC groups(P<0.05 or P<0.01), and that of Bax protein decreases in low-dose KTC group(P<0.05 or P<0.01), and the expression level of Bcl-2 protein increases in low-dose KTC group(P<0.01). The expression levels of COL3A1 and Bax mRNA decreased in the low-dose KTC group(P<0.05), while the expression levels of Bcl-2 mRNA increased(P<0.05). In summary, KTC can inhibit ovarian granulosa cell apoptosis and reduce follicular atresia by regulating the AGE-RAGE signaling pathway. It can promote insulin secretion, reduce blood sugar and body weight, restore serum hormone levels, improve symptoms of PCOS, alleviate morphological damage of the ovary, and restore ovarian function, which is of great value in the treatment of PCOS.

Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review.

Age-related Macular Degeneration (AMD) is a multifactorial ocular pathology that destroys the photoreceptors of the macula. Two forms are distinguished, dry and wet AMD, with different pathophysiological mechanisms. Although treatments were shown to be effective in wet AMD, they remain a heavy burden for patients and caregivers, resulting in a lack of patient compliance. For dry AMD, no real effective treatment is available in Europe. It is, therefore, essential to look for new approaches. Recently, the use of long-chain and very long-chain polyunsaturated fatty acids was identified as an interesting new therapeutic alternative. Indeed, the levels of these fatty acids, core components of photoreceptors, are significantly decreased in AMD patients. To better understand this pathology and to evaluate the efficacy of various molecules, in vitro and in vivo models reproducing the mechanisms of both types of AMD were developed. This article reviews the anatomy and the physiological aging of the retina and summarizes the clinical aspects, pathophysiological mechanisms of AMD and potential treatment strategies. In vitro and in vivo models of AMD are also presented. Finally, this manuscript focuses on the application of omega-3 fatty acids for the prevention and treatment of both types of AMD.

The multi-faceted nature of age-associated osteoporosis.

Age-associated osteoporosis (AAOP) poses a significant health burden, characterized by increased fracture risk due to declining bone mass and strength. Effective prevention and early treatment strategies are crucial to mitigate the disease burden and the associated healthcare costs. Current therapeutic approaches effectively target the individual contributing factors to AAOP. Nonetheless, the management of AAOP is complicated by the multitude of variables that affect its development. Main intrinsic and extrinsic factors contributing to AAOP risk are reviewed here, including mechanical unloading, nutrient deficiency, hormonal disbalance, disrupted metabolism, cognitive decline, inflammation and circadian disruption. Furthermore, it is discussed how these can be targeted for prevention and treatment. Although valuable as individual targets for intervention, the interconnectedness of these risk factors result in a unique etiology for every patient. Acknowledgement of the multifaceted nature of AAOP will enable the development of more effective and sustainable management strategies, based on a holistic, patient-centered approach.

Soil C:N:P stoichiometry in rhizosphere and non-rhizosphere of Pinus sylvestris var. mongolica forests.

The aim of this study was to reveal the stoichiometric characteristics of carbon, nitrogen and phosphorus in rhizosphere and non-rhizosphere soils of Pinus sylvestris var. mongolica in the Hulunbuir desert. We investigated the contents and stoichiometry of organic carbon, total nitrogen, and total phosphorus contents of rhizosphere and non-rhizosphere soils across different stand ages (28, 37 and 46 a) of P. sylvestris var. mongolica plantations, with P. sylvestris var. mongolica natural forest as the control. We analyzed the correlation between soils properties and soil stoichiometry. The results showed that rhizosphere effect significantly affected soil N:P, and stand age significantly affected soil organic carbon content in P. sylvestris var. mongolica plantation. Soil organic carbon content in plantation was significantly lower than that in natural forest. Soil organic carbon and total nitrogen contents of plantations in both rhizosphere and non-rhizosphere soils firstly decreased and then increased with increasing stand age, while total phosphorus firstly increased and then decreased in rhizosphere soils, and firstly decreased and then increased in non-rhizosphere soils. There was significant positive correlations between C:N and C:P in rhizosphere soils but not in non-rhizosphere soils, suggesting that higher synergistic rhizosphere soil N and P limitation. The mean N:P values of rhizosphere and non-rhizosphere soils were 4.98 and 8.40, respectively, indicating that the growth of P. sylvestris var. mongolica was restricted by soil N and the rhizosphere soils were more N-restricted. The C:N:P stoichiometry of rhizosphere and non-rhizosphere soils were significantly influenced by soil properties, with available phosphorus being the most important driver. The growth of P. sylvestris var. mongolica was limited by N in the Hulunbuir desert, and root system played an obvious role in enriching and maintaining soil nutrients. It was recommended that soil nitrogen should be supplemented appropriately during the growth stage of P. sylvestris var. mongolica plantation, and phosphorus should be supplemented appropriately according to the synergistic nature of nitrogen and phosphorus limitation.

Rising Trends of Childhood Attention-Deficit/Hyperactivity Disorder in a Large Integrated Healthcare Delivery System in Southern California, 2010-2021.

OBJECTIVE: To evaluate trends of attention-deficit/hyperactivity disorder (ADHD) diagnosis rates among children aged 5-17 years over the past decade (2010-2021) and to investigate whether there have been differences in temporal changes based on race and ethnicity, sex, or income. STUDY DESIGN: Childhood ADHD diagnosis was ascertained from electronic health records using International Classification of Diseases ninth revision (314.xx) and International Classification of Diseases tenth revision (F90.x) codes. Data were stratified by child's sex, race and ethnicity, and household income, and rates of ADHD were estimated before and after adjustment for potential confounders. RESULTS: The overall ADHD diagnosis rates increased from 3.5% in 2010 to 4.0% in 2021. ADHD diagnosis was most prevalent among White children (6.1%), then Black (4.6%), Other/multiple (3.7%), Hispanic (3.1%), and Asian/Pacific Islander (PI) (1.7%). ADHD was also highly prevalent among boys (73.3%) or family income≥$70,000 (50.0%). ADHD diagnosis increased among Black (4.2% to 5.1%), Hispanic (2.8% to 3.6%), and Asian/PI children (1.5% to 2.0%) but remained stable for White (6.2% to 6.1%) and Other/multiple race/ethnic children (3.7% to 3.7%). Increases in the prevalence among girls were also observed. CONCLUSION: The prevalence of ADHD in children has risen with the largest increases observed for Black, Hispanic, and Asian/PI children. Rates among less affluent families and girls have also been increasing, narrowing the gaps in diagnosis rates previously observed. These increases may reflect improvements in screening and provision of care among demographics where ADHD has been historically underdiagnosed.

Integrating Fall Prevention Strategies into EMS Services to Reduce Falls and Associated Healthcare Costs for Older Adults.

Purpose: The purpose of this study is to detail the implementation of fall prevention initiatives through emergency medical services (EMS) and associated outcomes. Methods: Paramedics with MedStar Mobile Healthcare utilized the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) fall prevention model to screen and direct intervention through 9-1-1 emergency response, High Utilization Group (HUG), and 30-day Hospital Readmission Avoidance (HRA) programs. Outcomes from 9-1-1 calls measured the number of older adults screened for falls and identified risk factors. The HUG and HRA programs measured change in quality of life with EuroQol-5D, referral service utilization, falls, emergent healthcare utilization, and hospital readmission data. Analysis included costs associated with reduced healthcare usage. Results: Emergency paramedics provided fall risk screening for 50.5% (n=45,090) of adults aged 65 and older and 59.3% were at risk of falls, with 48.1% taking medications known to increase the risk of falls. Services provided through the HUG and HRA programs, along with additional needed referral services, resulted in a 37.2% reduction in fall-related 9-1-1 calls and a 29.5% increase in overall health status related to quality of life. Analysis of the HUG program revealed potential savings of over $1 million with a per-patient enrolled savings of $19,053. The HRA program demonstrated a 16.4% hospital readmission rate, in comparison to a regional average of 30.2%, and a cost-savings of $4.95 million or $15,618 per enrolled patient. Conclusion: Implementation of the STEADI model into EMS services provides an effective and cost-saving model for addressing fall prevention for older adults, provides meaningful and impactful improvement for older adults, and could serve as a model for other EMS programs.

This study explored the feasibility and impact of implementing an evidence-based fall prevention model into emergency medical services for older adults. The outcomes resulted in an efficient and effective manner to screen older adults for falls during emergency response services and connect high-risk older adults with in-home follow-up care from community paramedics. In addition, fall prevention services were provided for vulnerable adults following a recent discharge from hospital care. These initiatives to address fall prevention resulted in a majority of older adults receiving preventive fall risk screening during emergency response calls, significant changes in quality of life measures for adults with multiple comorbidities and fall risk, and significant potential cost savings in reduced healthcare services.

Behavioural determinants of women of reproductive age in the indigenous Talang Mamak Ethnic group.

The Talang Mamak tribe is an indigenous tribe that lives in groups (the extended family) in rural locations. All decisions are made after much deliberation. Traditional birth attendants are still used for childbirth. The objective of the study is to analyze the factors that influence reproductive health-needing behavior among Talang Mamak women of reproductive age. With 160 respondents, data was analyzed using logistic regression. The study discovered that education p = 0.001 with PR=4,738, knowledge p = 0.001 with PR=13,800, attitude p= 0.001 with PR=3,133, and tradition p= 0.001 with PR=226.66 are variables that influence the behavior of women of reproductive age toward needing reproductive health services. Among the five variables influencing the outcome, one stands out: tradition, which has an Exp(ß) value of 192.422. The multivariate results show that three variables are included in the modeling: tradition p = 0.001, knowledge p = 0.001, and education p = 0.001. Good traditions, good knowledge, and higher education in the Talang Mamak tribe have a more behavioral probability of needing reproductive health services in women of reproductive age 99%, while another 1% probability by other variables is not examined in this study.

La tribu Talang Mamak est une tribu indigène qui vit en groupes (la famille élargie) dans les zones rurales. Toutes les décisions sont prises après de longues délibérations. Les accoucheuses traditionnelles sont encore utilisées pour l'accouchement. L'objectif de l'étude est d'analyser les facteurs qui influencent le comportement en matière de santé reproductive chez les femmes Talang Mamak en âge de procréer. Avec 160 répondants, les données ont été analysées par régression logistique. L'étude a découvert que l'éducation p = 0,001 avec PR = 4 738, la connaissance p = 0,001 avec PR = 13 800, l'attitude p = 0,001 avec PR = 3 133 et la tradition p = 0,001 avec PR = 226,66 sont des variables qui influencent le comportement des femmes en situation de procréation. âge pour avoir besoin de services de santé reproductive. Parmi les cinq variables influençant le résultat, une se démarque : la tradition, qui a une valeur Exp(ß) de 192,422. Les résultats multivariés montrent que trois variables sont incluses dans la modélisation : tradition p = 0,001, connaissances p = 0,001 et éducation p = 0,001. Les bonnes traditions, les bonnes connaissances et l'enseignement supérieur dans la tribu Talang Mamak ont une probabilité comportementale plus élevée d'avoir besoin de services de santé reproductive chez les femmes en âge de procréer (99 %), tandis qu'une autre probabilité de 1 % selon d'autres variables n'est pas examinée dans cette étude.

The effect of UNIMMAP multiple micronutrient supplements versus iron-folic acid and placebo in anemia reduction among women of reproductive age in Kebribeyah Woreda, Somali Regional State, Ethiopia: a study protocol for a community-based individual RCT.

BACKGROUND: Women of reproductive age (WRA) in developing countries are often at risk of micronutrient deficiencies due to inadequate intakes and excessive losses. OBJECTIVE: The purpose of this trial is to assess the effectiveness of United Nations International Multiple Micronutrient Antenatal Preparation-Multiple Micronutrient Supplements (UNIMMAP-MMS) versus iron-folic acid (IFA) among WRA in reducing anemia. METHODS: Three parallel groups of WRA will participate in a community-based, individually randomized, double-blinded, placebo-controlled superiority trial. After consent, the sample of 375 mildly or moderately anemic women based on hemoglobin by Hemocue will be randomly assigned across two interventions and one control arm. Trial participants in intervention arms will receive UNIMMAP-MMS or IFA while those in the control arm will receive placebos twice a week for 17 weeks. The primary outcome will be a change in mean hemoglobin (Hb) concentrations. Outcome assessors and study participants will be blinded to the type of supplements and study arm. DISCUSSION: The World Health Organization (WHO) added UNIMMAP-MMS to its essential medicine lists in 2021 but recommended rigorous study. Several factors in addition to inadequate intakes of iron and folic acid contribute to the high prevalence of anemia among WRA in the Somali region. The findings of this study will provide evidence on the effect of UNIMMAP-MMS and IFA on Hb concentrations and anemia prevalence among anemic WRA. TRIAL REGISTRATION: ClinicalTrials.gov NCT05682261. Registered on January 12, 2023.

Bioenergetic signatures of neurodevelopmental regression.

Background: Studies have linked autism spectrum disorder (ASD) to physiological abnormalities including mitochondrial dysfunction. Mitochondrial dysfunction may be linked to a subset of children with ASD who have neurodevelopmental regression (NDR). We have developed a cell model of ASD which demonstrates a unique mitochondrial profile with mitochondrial respiration higher than normal and sensitive to physiological stress. We have previously shown similar mitochondrial profiles in individuals with ASD and NDR. Methods: Twenty-six ASD individuals without a history of NDR (ASD-NoNDR) and 15 ASD individuals with a history of NDR (ASD-NDR) were recruited from 34 families. From these families, 30 mothers, 17 fathers and 5 typically developing (TD) siblings participated. Mitochondrial respiration was measured in peripheral blood mononuclear cells (PBMCs) with the Seahorse 96 XF Analyzer. PBMCs were exposed to various levels of physiological stress for 1 h prior to the assay using 2,3-dimethoxy-1,4-napthoquinone. Results: ASD-NDR children were found to have higher respiratory rates with mitochondria that were more sensitive to physiological stress as compared to ASD-NoNDR children, similar to our cellular model of NDR. Differences in mitochondrial respiration between ASD-NDR and TD siblings were similar to the differences between ASD-NDR and ASD-NoNDR children. Interesting, parents of children with ASD and NDR demonstrated patterns of mitochondrial respiration similar to their children such that parents of children with ASD and NDR demonstrated elevated respiratory rates with mitochondria that were more sensitive to physiological stress. In addition, sex differences were seen in ASD children and parents. Age effects in parents suggested that mitochondria of older parents were more sensitive to physiological stress. Conclusion: This study provides further evidence that children with ASD and NDR may have a unique type of mitochondrial physiology that may make them susceptible to physiological stressors. Identifying these children early in life before NDR occurs and providing treatment to protect mitochondrial physiology may protect children from experiencing NDR. The fact that parents also demonstrate mitochondrial respiration patterns similar to their children implies that this unique change in mitochondrial physiology may be a heritable factor (genetic or epigenetic), a result of shared environment, or both.

Clinical vitamin A deficiency among preschool aged children in southwest Ethiopia.

Background: The clinical manifestations of vitamin A deficiency (VAD) involve night blindness, bitot's spots, corneal xerosis, and corneal scars. It is the most important cause of preventable childhood blindness among children and causes morbidity and mortality. Even though Ethiopia implemented high-potency vitamin A supplements, the occurrence of VAD remains significant. This study was to identify determinants of clinical VAD among preschool-aged children (PSC) in southwest Ethiopia. Method: A community-based survey was conducted among 411 randomly selected PSCs. A pretested and structured questionnaire coupled with clinical observation for signs of vitamin A deficiency by a trained ophthalmologist was used to collect the data. An anthropometric measurement of height was taken and analyzed using WHO Anthro to calculate Z-scores for each index. The public health significance of VAD was declared after comparison with international references. A bi-variable and multi-variable logistic analysis was done. We reported the adjusted odds ratio (AOR), 95% confidence interval, and p-value. Result: A total of 411 children were screened for clinical VAD, and the overall prevalence was 2.2% (95% CI: 1.5-2.5). Of which, night blindness affects 1.2%, bitot's spots affects 0.7%, and corneal xerosis affects 0.2%, indicating a major public health problem compared to the international reference. The odds of clinical VAD were 81% lower among children who received vitamin A supplementation (VAS; AOR = 0.19, 95% CI: 0.04-0.92). On the other hand, PSC of mothers who had attended ANC visits were 89% less likely to develop clinical VAD (AOR = 0.11, 95% CI: 0.02-0.53). In addition, the study revealed that the odds of developing clinical VAD are 82% lower among PSC aged 36 to 47 months (AOR = 0.18; 95% CI: 0.03-0.97). Conclusion: The prevalence of clinical VAD among PSC is a public health problem and is associated with ANC visits, VAS status, and the age of the child, which could be used to target interventions to further reduce existing VAD. Further studies using reliable dietary intake and biomarker data could further depict the burden of subclinical VAD.

A thematic analysis of how men and women post 56 years, unwind from work during their free time.

BACKGROUND: Recent research indicates that as men age, their tendency to ruminate about work decreases, while ruminating remains high in women, which poses an increased risk for impaired health among older women. OBJECTIVE: This study explored gender differences/similarities in the process of unwinding from work in men and women aged between 56-65 years. METHODS: Semi-structured qualitative interviews were conducted online with eight men and eight women, recruited from a UK leading organization that provides health care solutions between May and June 2022. Participants were asked about their job role and responsibilities, their leisure time activities, how they unwind post work, and their experiences of thinking about work related thoughts outside of work. Transcripts were analyzed using an inductive analysis. RESULTS: Three superordinate themes were identified that underpinned their ability to unwind: 'Work style', 'Creating work-life balance' and 'Switching off from one's responsibilities'. Women reported a more perfectionist approach, they set high standards for themselves, were worried about making mistakes, and demonstrated, if in a supervisory role, a more nurturing and holistic approach to their colleagues/subordinates, while men, were more focused on task completion. Most women, but not men, also described difficulties in psychologically switching off from work, and stated they could only truly relax outside the home, when they are away from household activities. CONCLUSION: The study provides nuanced insights into the experiences of unwinding from work, and the findings suggest the need for person-centric approaches in developing interventions to help workers over 56 years to psychologically disengage from work.

A review of the dietary diversity and micronutrient adequacy among the women of reproductive age in low- and middle-income countries.

The dietary quality of women of reproductive age (WRA) is particularly important during preconception, conception, and pregnancy for themselves and their offspring. Poorly diversified diets resulting in inadequate micronutrient consumption may have adverse effects on their health. This narrative review summarizes the findings of studies reporting on dietary diversity and micronutrient intake by WRA in low- and middle-income countries (LMICs). Studies on WRA aged 15-49 years in LMICs, with a sample size of more than 150, report dietary diversity and multiple micronutrient intake based on 24-h dietary recall/food weighed record/food frequency questionnaire, and published between January 2011 and June 2021 were included. The results were compared to the Food and Agriculture Organization (FAO) recommended cut-off for dietary diversity and the Indian Council of Medical Research (ICMR) recommended age- and sex-specific estimated average requirements (EARs) for micronutrient intake. This review includes 35 articles, of which 21 focused on dietary diversity and 14 on micronutrient intake. The results showed that WRA in LMICs had inadequate dietary diversity, with mean food group consumption of only 3.0-4.84, and around 42.3%-90% of women consumed inadequately diversified diets (<5 food groups). Additionally, most studies found that WRA did not consume adequate amounts of essential micronutrients, particularly calcium, iron, zinc, vitamin A, thiamin, riboflavin, folate, and vitamin B12. However, the intake of vitamin C, niacin, and vitamin B6 was above the required levels. In conclusion, this review highlights the common inadequacy of dietary diversity and multiple micronutrient intake among WRA in most LMICs. Effective measures involving improving dietary diversity, food fortification with micronutrients, and supplementation programs could help improve the dietary quality and intake of optimal micronutrients by women in LMICs.

Genetics and Age-Related Macular Degeneration: A Practical Review for Clinicians.

Age-related macular degeneration (AMD) is a multifactorial genetic disease, with at least 52 identifiable associated gene variants at 34 loci, including variants in complement factor H (CFH) and age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase-1 (ARMS2/HTRA1). Genetic factors account for up to 70% of disease variability. However, population-based genetic risk scores are generally more helpful for clinical trial design and stratification of risk groups than for individual patient counseling. There is some evidence of pharmacogenetic influences on various treatment modalities used in AMD patients, including Age-Related Eye Disease Study (AREDS) supplements, photodynamic therapy (PDT), and anti-vascular endothelial growth factor (anti-VEGF) agents. However, there is currently no convincing evidence that genetic information plays a role in routine clinical care.

Assessing brain involvement in Fabry disease with deep learning and the brain-age paradigm.

While neurological manifestations are core features of Fabry disease (FD), quantitative neuroimaging biomarkers allowing to measure brain involvement are lacking. We used deep learning and the brain-age paradigm to assess whether FD patients' brains appear older than normal and to validate brain-predicted age difference (brain-PAD) as a possible disease severity biomarker. MRI scans of FD patients and healthy controls (HCs) from a single Institution were, retrospectively, studied. The Fabry stabilization index (FASTEX) was recorded as a measure of disease severity. Using minimally preprocessed 3D T1-weighted brain scans of healthy subjects from eight publicly available sources (N = 2160; mean age = 33 years [range 4-86]), we trained a model predicting chronological age based on a DenseNet architecture and used it to generate brain-age predictions in the internal cohort. Within a linear modeling framework, brain-PAD was tested for age/sex-adjusted associations with diagnostic group (FD vs. HC), FASTEX score, and both global and voxel-level neuroimaging measures. We studied 52 FD patients (40.6 ± 12.6 years; 28F) and 58 HC (38.4 ± 13.4 years; 28F). The brain-age model achieved accurate out-of-sample performance (mean absolute error = 4.01 years, R2 = .90). FD patients had significantly higher brain-PAD than HC (estimated marginal means: 3.1 vs. -0.1, p = .01). Brain-PAD was associated with FASTEX score (B = 0.10, p = .02), brain parenchymal fraction (B = -153.50, p = .001), white matter hyperintensities load (B = 0.85, p = .01), and tissue volume reduction throughout the brain. We demonstrated that FD patients' brains appear older than normal. Brain-PAD correlates with FD-related multi-organ damage and is influenced by both global brain volume and white matter hyperintensities, offering a comprehensive biomarker of (neurological) disease severity.

Dose-Responsive Effects of Iron Supplementation on the Gut Microbiota in Middle-Aged Women.

Oral iron supplementation is the first-line treatment for addressing iron deficiency, a concern particularly relevant to women who are susceptible to sub-optimal iron levels. Nevertheless, the impact of iron supplementation on the gut microbiota of middle-aged women remains unclear. To investigate the association between iron supplementation and the gut microbiota, healthy females aged 40-65 years (n = 56, BMI = 23 ± 2.6 kg/m2) were retrospectively analyzed from the Alberta's Tomorrow Project. Fecal samples along with various lifestyle, diet, and health questionnaires were obtained. The gut microbiota was assessed by 16S rRNA sequencing. Individuals were matched by age and BMI and classified as either taking no iron supplement, a low-dose iron supplement (6-10 mg iron/day), or high-dose iron (>100 mg/day). Compositional and functional analyses of microbiome data in relation to iron supplementation were investigated using various bioinformatics tools. Results revealed that iron supplementation had a dose-dependent effect on microbial communities. Elevated iron intake (>100 mg) was associated with an augmentation of Proteobacteria and a reduction in various taxa, including Akkermansia, Butyricicoccus, Verrucomicrobia, Ruminococcus, Alistipes, and Faecalibacterium. Metagenomic prediction further suggested the upregulation of iron acquisition and siderophore biosynthesis following high iron intake. In conclusion, adequate iron levels are essential for the overall health and wellbeing of women through their various life stages. Our findings offer insights into the complex relationships between iron supplementation and the gut microbiota in middle-aged women and underscore the significance of iron dosage in maintaining optimal gut health.