Chronic Low Level Research Articles

A Rare Case of Subclinical Hypophosphatasia In An Adult Patient

Background: Hypophosphatasia (HPP) is a rare genetic condition caused by a mutation in the ALPL gene. It is often misdiagnosed due to its wide range of clinical presentations and late onset of symptoms. Case Presentation: We present a case of a 48-year-old male with seemingly subclinical hypophosphatasia who initially presented with slight tooth pain. Upon further examination, chronic low alkaline phosphatase levels were identified, leading to genetic testing that confirmed HPP. The patient's elevated vitamin B6 levels and the identification of a heterozygous exon 2 deletion mutation in the ALPL gene were key diagnostic findings. Conclusion: This case highlights the spectrum of symptoms that patients with HPP can present and emphasizes the importance of considering HPP as a differential diagnosis for patients with low alkaline phosphatase levels. Recognizing this condition is crucial, as standard treatments for hypocalcemia, such as bisphosphonates, are contraindicated in HPP patients. Continued research and publication of mild and subclinical forms of HPP are vital to improve the understanding and management of this disease.

Effects of using wearable devices to monitoring physical activity in pulmonary rehabilitation programs for chronic respiratory diseases: A systematic review protocol.

Pulmonary rehabilitation (PR) is an intervention aimed at the comprehensive care of individuals with chronic respiratory diseases. Patients with chronic obstructive pulmonary disease (COPD) and asthma present low levels of physical fitness because they avoid physical exercises due to the fear of triggering recurrent symptoms. Wearable devices have been integrated into behavioral modification interventions for physical activity in PR protocols. Therefore, this review aims to identify how wearable devices are being utilized for monitoring chronic respiratory diseases in pulmonary rehabilitation programs. Searches will be conducted on Medline, Cochrane Central Register of Controlled Trials, Embase (CENTRAL), CINAHL and PEDro electronic databases, as well as a search in the grey literature. We will include baseline data from randomized clinical trials reporting the use of wearable devices for monitoring physical activity in protocols for pulmonary rehabilitation programs for chronic respiratory diseases. Studies that discuss only the development of algorithms or applications for the assessment of diseases or unavailable full texts will be excluded. The main reviewer will conduct the initial search and exclusion of duplicates, while two independent reviewers will select studies, extract data, and assess the methodological quality using the PEDro tool. CRD42024504137.

In Vitro Effects of Fentanyl on Aortic Viscoelasticity in a Rat Model of Melatonin Deficiency.

Melatonin influences arterial biomechanics, and its absence could cause remodeling of the arterial wall, leading to increased stiffness. Direct effects of fentanyl on the aortic wall have also been observed previously. This study aimed to evaluate in vitro the effects of fentanyl on aortic viscoelasticity in a rat model of melatonin deficiency and to test the hypothesis that melatonin deficiency leads to increased arterial wall stiffness. The viscoelasticity was estimated in strip preparations from pinealectomized (pin, melatonin deficiency) and sham-operated (sham, normal melatonin) adult rats using the forced oscillations method. In the untreated aortic wall pin, the viscoelasticity was not significantly altered. However, combined with 10-9 M fentanyl, the pin increased the natural frequency (f0) and modulus of elasticity (E') compared to the sham-operated. Independently, fentanyl treatment decreased f0 and E' compared separately to untreated sham and pin preparations. The effects of fentanyl were neither dose-dependent nor affected by naloxone, suggesting a non-opioid mechanism. Furthermore, an independent effect of naloxone was also detected in the normal rat aortic wall, resulting in reduced E'. Additional studies are needed that may improve the clinical decisions for pain management and anesthesia for certain patients with co-occurring chronic low levels of blood plasma melatonin and some diseases.

Sex hormone supplementation improves breathing and restores respiratory neuroplasticity following C2 hemisection in rats.

In addition to loss of sensory and motor function below the level of the lesion, traumatic spinal cord injury (SCI) may reduce circulating steroid hormones that are necessary for maintaining normal physiological function for extended time periods. For men, who comprise nearly 80% of new SCI cases each year, testosterone is the most abundant circulating sex steroid. SCI often results in significantly reduced testosterone production and may result in chronic low testosterone levels. Testosterone plays a role in respiratory function and the expression of respiratory neuroplasticity. When testosterone levels are low, young adult male rats are unable to express phrenic long-term facilitation (pLTF), an inducible form of respiratory neuroplasticity invoked by acute, intermittent hypoxia (AIH). However, testosterone replacement can restore this respiratory neuroplasticity. Complicating the interpretation of this finding is that testosterone may exert its influence in three possible ways: 1) directly through androgen receptor (AR) activation, 2) through conversion to dihydrotestosterone (DHT) by way of the enzyme 5α-reductase, or 3) through conversion to 17β-estradiol (E2) by way of the enzyme aromatase. DHT signals via AR activation similar to testosterone, but with higher affinity, while E2 activates local estrogen receptors. Evidence to date supports the idea that exogenous testosterone supplementation exerts its influence through estrogen receptor signaling under conditions of low circulating testosterone. Here we explored both recovery of breathing function (measured with whole body barometric plethysmography) and the expression of AIH-induced pLTF in male rats following C2-hemisection SCI. One week post injury, rats were supplemented with either E2 or DHT for 7days. We hypothesized that E2 would enhance ventilation and reveal pLTF following AIH in SCI rats. To our surprise, though E2 did beneficially impact overall breathing recovery following C2-hemisection, both E2 supplementation and DHT restored the expression of AIH-induced pLTF 2weeks post-SCI.

Anemia and Fatigue in Patients with Chronic Kidney Failure

Chronic renal failure results in impaired kidney function, effectively eliminating metabolic waste and regulating fluid and electrolyte balance. The accumulation of waste metabolites is thought to impact the occurrence of anemia and fatigue. However, no research has shown a correlation between the incidence of anemia and fatigue in sufferers of chronic kidney failure. This study aimed to evaluate the relationship between hemoglobin levels and the degree of fatigue experienced by individuals diagnosed with chronic kidney disease. This research uses a cross-sectional study approach. The study population consisted of patients with chronic kidney failure at one of the hospitals in Lumajang Regency who were identified by the indicator of high BUN values. The sample size for this research was 50 people selected through purposive sampling. The data type used is primary data, with the independent variable being the Hb value, while the dependent variable is the level of fatigue in chronic kidney failure patients. The results of the Pearson correlation test in this study showed that there was a significant relationship between the percentage of hemoglobin levels in the blood and the level of fatigue in chronic kidney failure patients (p-value = <0,000; α = 0.05), with a strength of relationship 0,6092 which means the level Hemoglobin in the blood and the level of fatigue have a perfect degree of correlation. In patients with chronic renal failure and low hemoglobin levels, their fatigue levels will become more severe. Insufficient hemoglobin levels lead to a reduced count of red blood cells, causing a decline in the body's capacity to transport oxygen. This inadequate oxygen supply hampers the oxidation process and energy production in the form of ATP within the body's cells. Consequently, patients with chronic renal failure may undergo a substantial decrease in energy levels and experience significant tiredness.

Financial Health Literacy and Community-Dwelling Older Adults: A Concept Analysis

Aim. To examine and clarify the concept financial health literacy (FHL) within the context of aging and healthcare. Background. Older adults have a high chronic disease burden and low financial and health literacy levels which often leads to high healthcare costs and poor self-management. Clarification of the concept FHL is necessary to better support nursing care and successful self-management. Design. Concept analysis using literary synthesis. Data Sources. Electronic databases were used to find scientific literature (i.e., PubMed, CINAHL, and Business Source Complete), and online dictionaries were used to find basic definitions. Review Methods. Walker and Avant’s eight-step method was used as a guide to construct a concept analysis of FHL. Clinical, aging, financial, and economic studies were reviewed to determine defining attributes, antecedents, and consequences of FHL on the older adult’s health. Results. FHL is defined as the knowledge, skills, and ability to make decisions that allow an individual to manage finances to optimally meet healthcare-related and household expenses, including resources to self-manage health, and plan for short-term, long-term, and end-of-life healthcare. Personal context, opportunity, and access are antecedents to FHL. There are 3 defining attributes: knowledge about health and financial-related concepts, skills in health and financial planning, and healthcare and financial-related decision-making behaviors. The 4 consequences of FHL include effective healthcare utilization, effective cost management, effective self-management, and positive health outcomes. Conclusions. FHL is a complex, multidimensional concept. A better understanding of this concept has significant nursing implications for research, clinical, practice, education, and policy development. Older adults have unique health and financial needs due to the complexity of retirement, living on a fixed income, and self-management of chronic diseases. Development of a FHL assessment tool and intervention is needed and may be supported based on the results of this concept analysis.

Immunological and genetic profile of the pediatric population in the nitrate geochemical province

BACKGROUND: Contamination of groundwater with nitrates may result in substantial adverse effects on the health of various population groups.
 AIM: To study the immune status and genetic profile of children residing in the nitrate geochemical province in the Perm Region.
 MATERIAL AND METHODS: We conducted a study on a total of 78 preschool children residing in areas with varying levels of nitrate in the underground drinking water sources. The children were divided into two groups for comparison purposes. The first group consisted of 43 children who consumed drinking water that met the acceptable standards for nitrate content. The second group comprised 35 children who consumed drinking water with elevated levels of nitrates. To assess the impact of nitrate content on the children’s health, several measurements were taken. Firstly, the level of nitrates in the household drinking water was analyzed. Additionally, the concentration of N-nitrosamines and nitrate ions in the children’s urine, was determined. To evaluate the immunoregulation parameters, the technology of flow cytometry and enzyme immunoassay were employed, along with PCR to examine genetic polymorphisms.
 RESULTS: A statistically significant difference (p 0.001) was observed in the nitrate content of drinking water between the observation area and the comparison area, with the former showing levels 2.8 times higher. Furthermore, children in the observation group exhibited a significant increase (p 0.05) of 2.3 times in N-nitrosodiethylamine content and 1.6 times in nitrate ion concentration in their urine compared to children in the comparison group. In addition, the observation group displayed a significant decrease (p 0.05) in the number of NKT cells and an increase in the levels of CD3+CD25+-, CD3+CD95+-cells, bax, IL-17, Annexin V-FITC+PI–-, and Annexin V-FITC+PI+-lymphocytes, when compared to the results obtained from the comparison group. Moreover, the presence of polymorphisms in candidate genes associated with tumor formation (CYP1A1 (rs1048943), MMP9 (rs17576), PPARD (rs2016520), BRCA1 G/A (rs3950989)) was also identified.
 CONCLUSION: Our results suggest that children who are exposed to chronic low-levels of nitrates (at a concentration of 1.2 MPC) through drinking water from underground sources exhibit an excessive presence of N-nitrosodiethylamine and nitrate ions in their urine. These findings, in conjunction with the genetic profile of genes responsible for tumor formation, influences the characteristics of the immune response.

Obesity and the Development of Arthritis Among Adults in the United States Using NHANES Data.

The alarming increase in the prevalence of obesity and arthritis in America in recent times is concerning both in terms of the deleterious health effects on the individuals and economic cost. The wear and tear on the musculoskeletal and the inflammatory effects of obesity may be the reasons for the rise in arthritis among individuals with obesity. To investigate the association between obesity and the development of arthritis among adults in the United States. A total of 17 016 participants were included from the 2012 to 2018 National Health and Nutrition Examination Survey (NHANES). Most of the participants were aged 30 years and above (79.7%). The racial distribution included 64.0% Non-Hispanic whites, 15.3% Hispanics, 11.4% Non-Hispanics blacks, and 9.4% from all other races. Obesity was defined as a body mass index (BMI) > 30 kg/m², and the outcome variable of interest, arthritis status, was self-reported. Survey weighted logistic regression was performed to calculate the odds ratio (OR) and 95% confidence interval controlling for potential confounding factors. Nearly 40% of all participants were individuals with obesity, and 27.5% reported having some form of arthritis. The risk of developing arthritis was higher in individuals with obesity (OR: 1.55, 95% CI: 1.35-1.80), women (OR: 1.94, 95%CI: 1.66-2.28), and individuals 30 years or older (OR: 10.81, 95% CI: 6.36-18.37) with non-Hispanic whites being the most affected race. The C-reactive protein (CRP) and white blood cell count (WBC) levels were higher in all individuals with obesity even though there was no statistical difference between individuals with obesity with and without arthritis. Obesity substantially heightens the risk of developing arthritis due to the mechanical stress on weight-bearing joints and subsequent chronic-low level inflammation contributing to disease progression.

Impairments of Spatial Memory and N-methyl-d-aspartate Receptors and Their Postsynaptic Signaling Molecules in the Hippocampus of Developing Rats Induced by As, Pb, and Mn Mixture Exposure.

Exposure to metal mixtures is recognized as a real-life scenario, needing novel studies that can assess their complex effects on brain development. There is still a significant public health concern associated with chronic low levels of metal exposure. In contrast to other metals, these three metals (As, Pb, and Mn) are commonly found in various environmental and industrial contexts. In addition to additive or synergistic interactions, concurrent exposure to this metal mixture may also have neurotoxic effects that differ from those caused by exposure to single components. The NMDA receptor and several important signaling proteins are involved in learning, memory, and synaptic plasticity in the hippocampus, including CaMKII, postsynaptic density protein-95 (PSD-95), synaptic Ras GTPase activating protein (SynGAP), a negative regulator of Ras-MAPK activity, and CREB. We hypothesized that alterations in the above molecular players may contribute to metal mixture developmental neurotoxicity. Thus, the aim of this study was to investigate the effect of these metals and their mixture at low doses (As 4 mg, Pb 4 mg, and Mn 10 mg/kg bw/p.o) on NMDA receptors and their postsynaptic signaling proteins during developing periods (GD6 to PD59) of the rat brain. Rats exposed to As, Pb, and Mn individually or at the same doses in a triple-metal mixture (MM) showed impairments in learning and memory functions in comparison to the control group rats. Declined protein expressions of NR2A, PSD-95, p- CaMKII, and pCREB were observed in the metal mix-exposed rats, while the expression of SynGAP was found to be enhanced in the hippocampus as compared to the controls on PD60. Thereby, our data suggest that alterations in the NMDA receptor complex and postsynaptic signaling proteins could explain the cognitive dysfunctions caused by metal-mixture-induced developmental neurotoxicity in rats. These outcomes indicate that incessant metal mixture exposure may have detrimental consequences on brain development.

Physical activity in leisure time and motivation among citizens with chronic disease in in Denmark

Abstract Background Physical activity (PA) has a preventive effect on chronic disease, but PA also promotes health among citizens with chronic disease. However, the presence of chronic disease may be a barrier for PA engagement. The aim of this study was to examine the difference between citizens with various chronic diseases and all citizens in The Capital Region of Denmark in terms of the proportion who reports low PA levels in their leisure time, wants to be more physically active, and has been advised to exercise by their doctor. Methods Information from national registers on hospital diagnoses and medical treatment was used to identify citizens with chronic diseases. Data from “The Danish Capital Region Health Survey” among citizens (≥16 years) in The Capital Region in 2021 (N = 56,245, response rate=54.9%) were used to obtain information about citizens’ movement behaviour in leisure time, their motivation to become more physically active and whether they have been advised by their doctor to exercise. Results for several diseases will be presented but heart disease is used as example in this abstract. Results Preliminary results show that the proportion in 2021 who has reported low PA levels in their leisure time is almost twice as high among citizens with heart disease (35%) compared with all citizens in The Capital Region (18%). Less citizens with heart disease (62%) are motivated to become more physically active compared with all citizens in The Capital Region (73%). The proportion who has been advised to exercise by their doctor is not significantly different among citizens with heart disease (31%) and all citizens in The Capital Region (28%). Conclusions Among citizens with heart disease low PA levels in leisure time are more prevalent, they are less motivated to become more physically active and, despite their chronic illness, they receive advice from their doctor to the same extent. For citizens with chronic disease, it is important to engage in PA. Key messages • Among citizens with chronic diseases low PA levels in leisure time are more prevalent and they are less motivated to become physically active compared with all citizens in The Capital region in DK. • Despite their illness, they receive advice from their doctor about exercising to the same extent as all citizens in The Capital Region of Denmark.

OR06-01 Pre-conceptional And Gestational Exposure To A Real-life Environmental Chemical Mixture Increases Maternal Oxidative Stress And Disrupts The Cytokine Milieu In Sheep

Abstract Disclosure: S. Thangaraj: None. M. Bellingham: None. S. Pennathur: None. R. Lea: None. K. Sinclair: None. N. Evans: None. V. Padmanabhan: None. Due to potential effects on health, exposure to environmental chemicals (ECs) is of global concern, especially to pregnant women. As the maternal endocrine milieu can have critical effects on pregnancy outcomes and the programming of later onset diseases in offspring, it is important to study the impact of real-life EC exposure, i.e., chronic low levels of mixtures of ECs, in pregnant women. Biosolids, derived from human wastewater treatment, exemplify the array and concentrations of chemicals humans are exposed to and provides a novel model to probe the effects of real-life EC mixture exposure. Offspring of sheep grazed on biosolids-treated pasture are characterized by reproductive and metabolic disruptions. We hypothesized that biosolids exposure will disrupt the maternal cytokine and oxidative stress milieu, which are important in programming offspring health outcomes. EasyCare ewes (Ovis aries) were maintained from 1 month before mating and during gestation on pastures fertilized with either biosolids (BTP), or inorganic fertilizer supplying equivalent levels of nitrogen (Control). The levels of 14 cytokines (IFN-γ, ILs 1α, 1β, 4, 6, 10, 17A, 36RA, MIPs 1α, 1β, IP-10, TNF-α and VEGF-A) were quantified in maternal plasma (15 ewes/group) collected on day 90 of the 144-day gestation period, using Milliplex xMAP assay. Total antioxidant status, reactive oxygen metabolites (Rel Assay Diagnostics) and the lipid peroxidation product - malondialdehyde (Cayman Chemical) were assayed using kits. Chlorotyrosine, nitrotyrosine and dityrosine were quantified by tandem mass spectrometry. Statistical significance between control and BTP groups was assessed by t-test after replacing values below limit of detection (LOD) to LOD/sqrt(2). ANOVA was used to test for difference between groups based on fetal sex. P values < 0.05 were considered significant. Fetal sex-specific effects were not seen. Overall, reactive oxygen metabolites were 1.48-fold higher in the BTP group (P = 0.006). Total antioxidant status, malondialdehyde and all 3 tyrosine moieties did not differ between control and BTP groups. In contrast, there was a decrease in the proinflammatory cytokines IL-1β (1.6-fold) and IL-17A (1.9-fold) and anti-inflammatory IL-36RA (1.5-fold) in the BTP group compared to the controls. The increase in reactive oxygen metabolites in the face of decreased inflammatory markers suggests compensatory mechanisms may be operant. Contrary to the control group, a positive correlation was observed between chlorotyrosine and IL-1α and TNFα in the BTP group, suggestive of additional independent effects of biosolids exposure on the maternal cytokine milieu. These results suggest that exposure to ECs in biosolids disrupts the maternal cytokine and oxidative stress milieu likely contributing to the aberrant reproductive and metabolic effects in the offspring. Presentation: Thursday, June 15, 2023

Developmental programming: Impact of preconceptional and gestational exposure to a real-life environmental chemical mixture on maternal steroid, cytokine and oxidative stress milieus in sheep

BackgroundGestational exposure to environmental chemicals (ECs) is associated with adverse, sex-specific offspring health effects of global concern. As the maternal steroid, cytokine and oxidative stress milieus can have critical effects on pregnancy outcomes and the programming of diseases in offspring, it is important to study the impact of real-life EC exposure, i.e., chronic low levels of mixtures of ECs on these milieus. Sheep exposed to biosolids, derived from human waste, is an impactful model representing the ECs humans are exposed to in real-life. Offspring of sheep grazed on biosolids-treated pasture are characterized by reproductive and metabolic disruptions. ObjectiveTo determine if biosolids exposure disrupts the maternal steroid, cytokine and oxidative stress milieus, in a fetal sex-specific manner. MethodsEwes were maintained before mating and through gestation on pastures fertilized with biosolids (BTP), or inorganic fertilizer (Control). From maternal plasma collected mid-gestation, 19 steroids, 14 cytokines, 6 oxidative stress markers were quantified. Unpaired t-test and ANOVA were used to test for differences between control and BTP groups (n = 15/group) and between groups based on fetal sex, respectively. Correlation between the different markers was assessed by Spearman correlation. ResultsConcentrations of the mineralocorticoids - deoxycorticosterone, corticosterone, the glucocorticoids - deoxycortisol, cortisol, cortisone, the sex steroids - androstenedione, dehydroepiandrosterone, 16-OH-progesterone and reactive oxygen metabolites were higher in the BTP ewes compared to Controls, while the proinflammatory cytokines IL-1β and IL-17A and anti-inflammatory IL-36RA were decreased in the BTP group. BTP ewes with a female fetus had lower levels of IP-10. DiscussionThese findings suggest that pre-conceptional and gestational exposure to ECs in biosolids increases steroids, reactive oxygen metabolites and disrupts cytokines in maternal circulation, likely contributors to the aberrant phenotypic outcomes seen in offspring of BTP sheep - a translationally relevant precocial model.

Postponed healthcare in The Netherlands during the COVID-19 pandemic and its impact on self-reported health.

Healthcare services have been seriously disrupted during the COVID-19 pandemic. The aim of this study was to examine the extent to which Dutch citizens have experienced postponed healthcare and how this affected their self-reported health. In addition, individual characteristics that were associated with experiencing postponed healthcare and with self-reported negative health effects were investigated. An online survey about postponed healthcare and its consequences was developed, and sent out to participants of the Dutch LISS (Longitudinal Internet Studies for the Social Sciences) panel (n = 2.043). Data were collected in August 2022. Multivariable logistic regression analyses were carried out to explore characteristics associated with postponed care and self-reported negative health outcomes. Of the total population surveyed, 31% of the panel experienced postponed healthcare, either initiated by the healthcare provider (14%), on their own initiative (12%) or as a combination of both (5%). Postponed healthcare was associated with being female (OR = 1.61; 95% CI = 1.32; 1.96), presence of chronic diseases (OR = 1.55, 95% CI = 1.24; 1.95), high income (OR = 0.62, 95% CI = 0.48; 0.80) and worse self-reported health (poor vs. excellent OR = 2.88, 95% CI = 1.17; 7.11). Overall, 40% experienced temporary or permanent self-reported negative health effects due to postponed care. Negative health effects as a result of postponed care were associated with presence of chronic conditions and low income levels (p < 0.05). More respondents with worse self-reported health and foregone healthcare reported permanent health effects as compared to those with temporary health effects (p < 0.05). People with an impaired health status are most likely to experiencing postponed healthcare and negative health consequences as a result. Furthermore, those with negative health consequences decided to forego health by themselves more often. As part of long-term plans to maintain the accessibility of healthcare services, specific attention should be paid to reaching out to people with an impaired health status.

#6857 MATHEMATICAL MODEL FOR ADVERSE CARDIOVASCULAR EVENTS RISK ASSESSMENT IN KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Kidney transplantation is the most cardioprotective method of renal replacement therapy. Nevertheless, cardiovascular diseases are one of the main reason of mortality of with functioning kidney graft. The aim is creation of a mathematical model for adverse cardiovascular events risk assessment in kidney transplant recipients (KTR). Method The study included 237 kidney transplant recipients whose age was 47.1±10.8 years. For three years of observation 79 (33.3%) patients had adverse cardiovascular events (CVE) (acute coronary syndrome, life-threatening rhythm disturbance, complicated hypertensive crisis). The comparison group was 158 (66.7%) recipients without cardiovascular events. The study groups were comparable by gender, age and traditional cardiovascular risk factors. Results The proportion of patients with obesity and the graft glomerular filtration rate less than 30 ml/min/1.73 m2 were higher in KTR with CVE than in KTR without CVE –– 27.8% (n = 22) versus 12.7% (n = 20) and 12.7% (n = 10) versus 3.2% (n = 5), p&amp;lt;0.01. p&amp;lt;0.01. The erythrocytosis and an increased NT-proBNP blood level was more common in KTR with CVE than in KTR without CVE – 29.1% (n = 23) versus 16.5% (n = 26), p&amp;lt;0.05 and 27.8% (n = 22) versus 11.4% (n = 18), p&amp;lt;0.01. KTR with CVE had a longer duration of chronic kidney disease than KTR without CVE – 21.1±12.2 years versus 16.6±9.6 years, p&amp;lt;0.01. Triglycerides and low density lipoproteins blood levels of KTR with CVE were higher than those of KTR without CVE – 1.70 (1.30-2.50) mmol/L versus 1.45 (1.08-1.80) and 2.97±0.88 mmol/L versus 2.61±0.69 mmol/L, p&amp;lt;0.01, respectively. was more common in KTR with CVE than in KTR without CVE. The above factors were included in the mathematical model. $Y\; = \;\frac{1}{{\;1 + {e^{( {4,156 - 1,033X1 - 0,037X2 - 1,003X3 - 0,384X4 - 0,470X5 - 1,712X6 - 1,119X7} )}}}},$ X1 - body mass index &amp;gt; 30 kg/m2 (0 - no, 1 - yes), X2 - duration of chronic kidney disease (years); X3 - erythrocytosis (0 - no, 1 - yes), X4 - triglycerides blood level (mmol/l); X5 - low density lipoproteins blood level (mmol/l); X6 - glomerular filtration less than 30 ml/min/1.73 m2 (0 - no, 1 - yes), X7 - increased NT-proBNP blood level (0 - no, 1 - yes) The formula predicts low risk of CVE in kidney transplant recipients with an estimated value of Y&amp;lt;0.35, with Y≥0.35 - high risk. Conclusion Obesity, graft dysfunction erythrocytosis, an elevated NT-proBNP blood level, longer duration of chronic kidney disease, higher triglycerides and low density lipoproteins blood levels can be used to assess cardiovascular risk in kidney transplant recipients.

Primary and pharmaceutical care usage concurrent associations with a severe smoke episode and low ambient air pollution in early life

BACKGROUND: Due to climate change, landscape fires account for an increasing proportion of air pollution emissions, and their impacts on primary and pharmaceutical care are little understood.OBJECTIVES: To evaluate associations between exposure in two early life periods to severe levels of PM2.5 from a mine fire, background PM2.5, and primary and pharmaceutical care.METHODS: We linked records of births, general practitioner (GP) presentations and prescription dispensing for children born in the Latrobe Valley, Australia, 2012–2014, where a severe mine fire occurred in February–March 2014 in an area with otherwise low levels of ambient PM2.5. We assigned modelled exposure estimates for fire-related (cumulative over the fire and peak 24-hour average) and annual ambient PM2.5 to residential address. Associations with GP presentations and dispensing of prescribed medications in the first two years of life (exposure in utero) and in the two years post-fire (exposure in infancy) were estimated using two-pollutant quasi-Poisson regression models.RESULTS: Exposure in utero to fire-related PM2.5 was associated with an increase in systemic steroid dispensing (Cumulative: IRR = 1.11, 95%CI = 1.00–1.24 per 240 μg/m3; Peak: IRR = 1.15, 95%CI = 1.00–1.32 per 45 μg/m3), while exposure in infancy was associated with antibiotic dispensing (Cumulative: IRR = 1.05, 95%CI = 1.00–1.09; Peak: IRR = 1.06, 95%CI = 1.00–1.12). Exposure in infancy to ambient PM2.5, despite relatively low levels from a global perspective (Median = 6.1 μg/m3), was associated with an increase in antibiotics (IRR = 1.10, 95%CI = 1.01–1.19 per 1.4 μg/m3) and in GP presentations (IRR = 1.05, 95%CI = 1.00–1.11), independently from exposure to the fire. We also observed differences in associations between sexes with GP presentations (stronger in girls) and steroid skin cream dispensing (stronger in boys).DISCUSSION: Severe medium-term concentrations of PM2.5 were linked with increased pharmaceutical treatment for infections, while chronic low levels were associated with increased prescriptions dispensed for infections and primary care usage. Our findings also indicated differences between sexes.

Salivary cortisol awakening levels are reduced in human subjects with intermittent explosive disorder compared with controls

BackgroundThe role of the hypothalamic-pituitary-adrenal (HPA) axis in human aggressive behavior is poorly characterized, though some studies report that, unlike depression, circulating or salivary levels of cortisol are low compared with controls. MethodsIn this study, we collected three salivary cortisol levels (two in the morning and one in the evening) on three separate days in 78 adult study participants with (n = 28) and without (n = 52) prominent histories of impulsive aggressive behavior. Plasma C-Reactive Protein (CRP) and Interleukin-6 (IL-6) were also collected in most study participants. Aggressive study participants meet DSM-5 criteria for Intermittent Explosive Disorder (IED) while non-aggressive participants either had a history of a psychiatric disorder or no such history (Controls). ResultsMorning, but not evening, salivary cortisol levels were significantly lower in IED (p < 0.05), compared with control, study participants. In addition, salivary cortisol levels correlated with measures of trait anger (partial r = −0.26, p < 0.05) and aggression (partial r = −0.25, p < 0.05) but not with measures of impulsivity, psychopathy, depression, history of childhood maltreatment, or other tested variables that often differ in individuals with IED. Finally, plasma CRP levels correlated inversely with morning salivary cortisol levels (partial r = −0.28, p < 0.05); plasma IL-6 levels showed a similar, though not statistically significant (rp = −0.20, p = 0.12) relationship with morning salivary cortisol levels. ConclusionThe cortisol awakening response appears to be lower in individuals with IED compared with controls. In all study participants, morning salivary cortisol levels correlated inversely with trait anger, trait aggression, and plasma CRP, a marker of systemic inflammation. This suggests the present of a complex interaction between chronic-low level inflammation, the HPA axis, and IED that warrants further investigation.

Peptoids as potential therapeutics to reduce S100B-induced RAGE-associatedneuroinflammation in Alzheimer's disease.

Receptor for advanced glycation end-products (RAGE)-associated chronic neuroinflammation has been linked with Alzheimer's disease (AD) pathology. RAGE ligand S100B, which is elevated in AD brain, can induce release of inflammatory cytokines and upregulate RAGE. Consequently, targeting RAGE to reduce chronic inflammation represents a novel therapeutic strategy for AD. Peptoids are ideal potential AD therapeutics as they resist proteolytic degradation by repositioning side-chains from the α-carbon to the amide nitrogen and exhibit facile blood-brain barrier permeability. Peptoids designed to mimic RAGE ligands demonstrated strong binding affinity to RAGE in our previous studies. We hypothesize that these peptoids can attenuate S100B-induced activation of RAGE, thus reducing pro-inflammatory cytokine release associated with chronic neuroinflammation. Differentiated THP-1 macrophages were exposed to chronic low-levels of S100B to confirm upregulation of cytokine release. Macrophages were then treated with 0-50-μM peptoids (JPT1 or JPT1a) in the presence of S100B. To observe peptoid modulation of S100B-induced inflammation, cytokine analysis via immunoassay was performed using cell culture supernatants. Additionally, RAGE was incubated in the presence of 0-500-nM peptoid to achieve equilibrium. Unbound RAGE was quantified via modified ELISA to determine the binding affinity. S100B-treated THP-1 macrophages elicited anticipated inflammatory response evidenced by dose-dependent upregulation of cytokines. When THP-1 macrophages were incubated with peptoids and S100B, peptoids attenuated these S100B-induced inflammatory responses. Moreover, the peptoids demonstrated nanomolar binding affinity for RAGE. Peptoids modulate inflammatory responses induced by RAGE ligand S100B, including inflammatory cytokine release. These results implicate peptoids as a potential therapeutic agent for not only AD but also other inflammation-related illnesses. Because these peptoids have additionally exhibited the ability to modulate Aβ aggregation and transform the morphology of the aggregates formed, they may function as dual-target therapeutics for AD.

The Effectiveness of an After-school Sport Sampling Intervention on Urban Middle School Youth in the Midwest: Posttest-Only Study

Effective and scalable interventions are needed to combat chronic low levels of youth physical activity. After-school sport sampling programs may be vital interventions for teaching sports and increasing physical literacy and physical activity, which result in healthy lifelong habits that are maintained into adulthood. The purpose of this study was to test the effectiveness of an after-school sport sampling intervention among underserved youth in the Midwest. Youth (n=81) in 3 middle schools within a large Midwest city participated in an 8-month, after-school physical activity intervention that aimed to increase moderate- and vigorous-intensity physical activity, improve physical literacy, and decrease BMI. Difference scores for this 2-group, posttest-only design were calculated. A series of 2-tailed t tests were conducted to assess between-group differences. The intervention group had significantly better physical literacy (t115=7.57; P=.004) and engaged in more moderate- and vigorous-intensity physical activity minutes per week (t115=4.28; P=.04) and steps per day (t115=4.29; P=.03). An after-school sport sampling program may be an effective solution for combating youth physical inactivity. Future research should assess the scalability of this intervention with larger populations and in different areas. RR2-10.2196/37126.

Biocrust diazotrophs and bacteria rather than fungi are sensitive to chronic low N deposition.

Anthropogenic long-term nitrogen (N) deposition may dramatically impact biocrusts due to the overarching N limitation of soil biota in deserts. Even low levels of N may reach a critical loading threshold altering biocrust constituents and function. To identify the impact of chronic and continuous low levels of N deposition on biocrusts, we created a realistic gradient mirroring anthropogenic N addition rate (2:1 NH4 + : NO3 - rates: 0.3, 0.5, 1.0, 1.5, 3g N m-2 yr-1 ) and measured the response of bacteria and fungi within cyanobacterial-dominated biocrusts over 8 years in a temperate desert, the Gurbantunggut Desert, China. We found that once N deposition reached 1.5g N m-2 yr-1 biocrust bacterial communities, including diazotrophs, were altered while no such tipping point existed for fungi. Above the threshold, bacterial richness was enhanced, the relative abundance of Chloroflexi, FBP and Gemmatimonadetes was elevated, and diazotrophs shifted from being dominated by Nostocaceae and Scytonemataceae (Cyanobacteria) to free-living Bradyrhizobiaceae (Alphaproteobacteria). Alternatively, the relative recovery of a few fungal species within the Lecanorales, Pleosporales and Verrucariales became either enriched or diminished due to N deposition. The chronic addition of N resulted in a dense and interconnected bacterial co-occurrence network that accentuated a functional shift from networks dominated by phototrophic species within the Nostocaceae, Xenococcaceae, Phormidiaceae and Scytonemataceae (Cyanobacteria) to ammonia-oxidizing species within the Nitrosomonadaceae (Betaproteobacteria) and nitrifying bacteria [i.e. Nitrospiraceae (Nitrospirae)]. Based on structural equation models, the effects of N additions on biocrust constituents were imposed through indirect effects on pH, soil electrical conductivity and ammonium concentrations. In summary, biocrust constituents are generally insensitive to chronic low levels of N depositions until rates reach above 1.5g N m-2 yr-1 with diazotrophs being the most sensitive biocrust constituents followed by bacteria and finally fungi. Ultimately once the threshold is reached N deposition favours biocrust constituents utilizing inorganic N and other C sources over relying on phototrophic and/or N-fixing cyanobacteria for C and N.

Condition of membranes of erythrocytes of peripheral blood of elderly people with chronic tiredness and low level of tolerance to physical load

Purpose: The aim of the work is to study the osmotic stability and morpho-functional features of peripheral blood erythrocytes of patients with chronic fatigue syndrome depending on the level of exercise tolerance and associated risk factors. groups of factors that may be the cause, so the development of measures to eliminate them is an urgent problem today, which requires the development of effective ways to correct chronic fatigue syndrome. It is known that the peripheral part of erythron actively responds to changes that occur in the whole body after the action of various factors, including those factors that lead to chronic fatigue syndrome.&#x0D; Material and methods of research. The examination was performed on the basis of the Department of Vascular Neurology of the Central Clinical Hospital of Ivano-Frankivsk. The study involved 30 patients aged 55-65 years (mean age 60.6 + 1.2 years), who were divided into 3 groups: 1 gr. included 10 patients with chronic fatigue syndrome and a high level of exercise tolerance. The 2nd group included 10 patients with chronic fatigue syndrome and the average level of exercise tolerance, the composition of 3 gr. included 10 patients with chronic fatigue syndrome associated cardiovascular pathology (angina pectoris, hypertension) and low exercise tolerance (3 gr.).&#x0D; Results. It is established that chronic fatigue syndrome proceeds in 3 phases and has natural stages of development which are characterized by three groups of etiological factors and the corresponding levels of teletransitivity to physical activity, each of which corresponds to a certain erythrocyte profile and level of osmotic stability of erythrocytes which are offered to use as prognostic and diagnostic characteristics. chronic fatigue syndrome.&#x0D; Conclusions. The study of the quantitative composition of peripheral blood erythrocytes and hemoglobin, as well as their ratio (color index) in patients with chronic fatigue syndrome on the background of low levels of exercise tolerance revealed a decrease in erythrocytes and hemoglobin by 42% and 25%, respectively, indicating the presence of anemic hypoxia. 2. In conditions of chronic fatigue there is a decrease in osmotic resistance of erythrocytes, as evidenced by a decrease in the number of osmotically stable erythrocytes with a gradual decrease in the concentration of NaCl solution (3.0%; 0.5%; 0.46%; 0.3%). 3. In chronic fatigue there is a deterioration of membranes in peripheral blood erythrocytes, as evidenced by a decrease in their osmotic stability and an increase in the number of irreversibly altered forms of РВЕ, as well as a decrease in peripheral blood erythrocytes, which is closely correlated with decreased tolerance to exercise.