Strong Dose-response Relationship Research Articles

Risk factors for secondary bladder cancer following prostate cancer radiotherapy.

This review investigates the complex landscape of secondary bladder cancer (SBC) after radiotherapy for prostate cancer (PCa). External beam radiotherapy (EBRT) poses an increased risk for SBC, while brachytherapy seems to be associated with smaller increased risks for SBC due to its targeted radiation delivery, sparing the surrounding bladder tissue. Secondary cancers in the bladder are the most frequently diagnosed secondary cancers in the PCa patient population treated with radiotherapy. Patient-related factors are pivotal, with age emerging as a dual-edged factor. While advanced age is a recognized risk for bladder cancer, younger PCa patients exhibit higher susceptibility to radiation-induced cancers. Smoking, a well-established bladder cancer risk factor, increases this vulnerability. Studies highlight the synergistic effect of smoking and radiation exposure, amplifying the likelihood of genetic mutations and SBC. The latency period of SBC, which spans years to decades, remains a critical aspect. There is a strong dose-response relationship between radiation exposure and SBC risk, with higher doses consistently being associated with a higher SBC risk. While specific models for therapeutic radiation-induced SBC are lacking, insights from related studies, like the Atomic Bomb survivor research, emphasize the bladder's sensitivity to radiation-induced cancer. Chemotherapy in combination with radiotherapy, although infrequently used in PCa, emerges as a potential risk for bladder cancer. Bladder cancer's complex epidemiology, encompassing risk factors, treatment modalities, and cancer types, provides a comprehensive backdrop. As research refines understanding, we hope that this review contributes to guide clinicians, inform patient care, and shape preventive strategies on SBC.

Association between blood urea nitrogen to creatinine ratio and 3-month outcome in patients with acute ischaemic stroke: a retrospective cohort study from a large healthcare system

ObjectivesThe blood urea nitrogen to creatinine (BUN/Cr) ratio is associated with early neurological deterioration in acute ischaemic stroke (AIS). However, the predictive value of the BUN/Cr ratio for the AIS...

Associations between residential environments and late-onset schizophrenia in UK Biobank: Interaction with genetic risk factor

BackgroundEnvironment and genes both contribute to schizophrenia. However, the impact of different natural environments surrounding residential addresses on schizophrenia in urban settings remains unknown. This study aimed to investigate the association of urbanisation, measured by residential environments, with late-onset schizophrenia and explore whether genetic risk for schizophrenia modified the associations. MethodsWe examined the associations between residential environments and late-onset schizophrenia and its interaction with genetic risk factors in UK Biobank, followed from 2006 to 2010 (baseline) to Dec 2021. Residential environments, including greenspace, domestic garden, blue space, and total natural environment, were evaluated using land use coverage percentage. The polygenic risk score (PRS) of schizophrenia was derived using a Bayesian approach and adjusted it against ancestry. Cox proportional hazard regression model was used to assess the associations between per interquartile (IQR) increase of each type of residential environments and late-onset schizophrenia. Interactive effects of PRS and residential environments on late-onset schizophrenia were assessed on both additive and multiplicative scales. ResultsA total of 393,680 participants were included in the analysis, with 844 cases of late-onset schizophrenia being observed after 12.8 years of follow-up. Within 300 m buffer surrounding the residential addresses, per interquartile increase in greenspace (31.5 %) and total natural environment (34.4 %) were both associated with an 11 % (HR = 0.89, 95 % CI 0.80, 0.99) lower risk of late-onset schizophrenia. Domestic garden and blue space did not show significant protective effects on late-onset schizophrenia. A strong dose-response relationship between schizophrenia PRS and schizophrenia was found, while no additive or multiplicative interaction effects were present between residential environments and PRS on late-onset schizophrenia. ConclusionResidential greenspace and total natural environment may protect against late-onset schizophrenia in older people regardless of genetic risk. These findings shed light on the prevention of schizophrenia and urban planning to optimise ecosystem benefits linked to schizophrenia.

#2379 Acute kidney injury as a key predictor of major adverse cardiovascular events in chronic kidney disease patients

Abstract Background and Aims Chronic kidney disease (CKD) significantly raises cardiovascular event risks. The influence of acute-on-chronic kidney incidents is less understood. This study examines the link between acute kidney injury (AKI) episodes and subsequent Major Adverse Cardiovascular Events (MACE) in CKD patients. Method From 2013 to 2016, the CKD-REIN cohort enrolled 3033 adults with CKD stages 3-5 (average age 67; 66% male; mean eGFR 33 mL/min/1.73m²) from 40 French outpatient nephrology clinics, reflecting national geographic and legal diversity. During a 5-year follow-up, all AKI episodes, whether inpatient or outpatient, were identified, confirmed, and categorized per KDIGO-AKI standards by an expert panel. Cardiovascular events were evaluated using clinical trial Cardiovascular and Stroke Endpoint Definitions. MACE cumulative incidences (myocardial infarction, stroke, heart failure hospitalization, cardiovascular death) post-AKI were calculated using Aalen-Johansen methods, accounting for kidney failure and death risks. The impact of the first AKI episode on MACE risk was analyzed using a multivariable Cox model, treating AKI as a time-variable and stratifying by characteristics (in/outpatient status, AKI stage, pre-renal causes, renal recovery at discharge). Factors like demographics, cardiovascular risks, CKD severity, and treatments were considered. Interaction and sensitivity analyses were performed, excluding those with prior AKI or cardiovascular disease. Results During a median follow-up of 5.2 years, 530 patients experienced an incident AKI episode. The cumulative incidence of MACE at 1 year following this initial episode of AKI was 8.1% [95% confidence interval, 6.1; 10.8], with a median time to occurrence of 6.7 months after AKI. After adjustment for multiple confounders, we observed a substantial increased hazard of MACE associated with a first episode of AKI (HR = 5.99 [4.63; 7.76], p < 0.001), and this association remained significant for each MACE component (Fig. 1A). A dose-response relationship was observed, with higher risks in more severe AKI cases (KDIGO grades 2-3) and among hospitalized versus non-hospitalized patients (Fig. 1B). This association was also observed across all subgroups, without any interaction with age, sex, nor major comorbidities (diabetes, history of AKI, or cardiovascular events), as well as in various sensitivity analyses. Overall, we estimated an attributable risk fraction of 18.1% [13.6; 22.4] for MACE associated with AKI episodes within this population. Conclusion Our study highlights a strong dose-response relationship between incident AKI events and the risk of subsequent major cardiovascular events in CKD patients. These findings suggest that AKI may not only be a marker of increased cardiovascular risk but also a potential mediator of this risk. From a clinical perspective, these results underscore the importance of close monitoring and management of AKI in CKD patients to reduce the risk of MACE. This study improves our understanding of the interplay between renal and cardiovascular health, emphasizing the need for integrated care approaches in this high-risk population.

Preclinical Evaluation of JAB-2485, a Potent AURKA Inhibitor with High Selectivity and Favorable Pharmacokinetic Properties.

As a critical mitotic regulator, Aurora kinase A (AURKA) is aberrantly activated in a wide range of cancers. Therapeutic targeting of AUKRA is a promising strategy for the treatment of solid tumors. In this study, we evaluated the preclinical characteristics of JAB-2485, a small-molecule inhibitor of AURKA currently in Phase I/IIa clinical trial in the US (NCT05490472). Biochemical studies demonstrated that JAB-2485 is potent and highly selective on AURKA, with subnanomolar IC50 and around 1500-fold selectivity over AURKB or AURKC. In addition, JAB-2485 exhibited favorable pharmacokinetic properties featured by low clearance and good bioavailability, strong dose-response relationship, as well as low risk for hematotoxicity and off-target liability. As a single agent, JAB-2485 effectively induced G2/M cell cycle arrest and apoptosis and inhibited the proliferation of small cell lung cancer, triple-negative breast cancer, and neuroblastoma cells. Furthermore, JAB-2485 exhibited robust in vivo antitumor activity both as monotherapy and in combination with chemotherapies or the bromodomain inhibitor JAB-8263 in xenograft models of various cancer types. Together, these encouraging preclinical data provide a strong basis for safety and efficacy evaluations of JAB-2485 in the clinical setting.

Greater variability in HDL-C was associated with an increased risk of cognitive decline in the middle- and elderly Chinese: A cohort study

BackgroundPrevious studies into relationship between high-density lipoprotein cholesterol (HDL-C) and cognitive decline were constrained to a single measurement, leaving the association between HDL-C variability and risk of cognitive decline unclear. MethodsWe identified 5930 participants from the China Health and Retirement Longitudinal Study (CHARLS) who were devoid for stroke, dementia, and memory-related diseases at baseline and underwent a minimum of 2 sequential health examinations during 2011-2015. Variability in HDL-C was defined as (1) variability independent of the mean (VIM), (2) average real variability (ARV), and (3) standard deviation (SD) of HDL-C change from baseline and follow-up visits. Cognitive function was evaluated in 2018 by Mini-mental state examination (MMSE) in the Chinese version. Logistic regression was employed to explore the association between HDL-C variability and cognitive decline. Odd ratios (OR) and 95 % confidence intervals (CI) were reported. ResultsThe study included participants from CHARLS, mean age of 57.84±8.44 years and 44 % male. After adjustment for covariates, the highest quartile of VIM was associated with an increased risk of cognitive decline [OR:1.049, 95 %CI: 1.014-1.086] compared to the lowest quartile. For each SD increment of VIM, the OR was 1.015 (95 %CI:1.003-1.027). Strong dose-response relationships were identified (P for trend: 0.005). Consistent results were obtained for other measures of HDL-C variability (ARV and SD). Similar patterns were identified in different dimensions of cognition. ConclusionsElevated HDL-C variability was associated with increased cognitive decline risk. Strategies to reducing HDL-C variability may lower the risks of cognitive decline among the general population.

Objective sleep characteristics and hypertension: a community-based cohort study.

The link between sleep quality and hypertension risk is well-established. However, research on the specific dose-relationship between objective sleep characteristics and hypertension incidence remains limited. This study aims to explore the dose-relationship association between objective sleep characteristics and hypertension incidence. A community-based prospective cohort study design was employed using data from the Sleep Heart Health Study (SHHS). A total of 2,460 individuals were included in the study, of which 780 had hypertension. Baseline personal characteristics and medical history were collected. Objective sleep characteristics were obtained through polysomnography (PSG). Multivariate logistic regression models were utilized for analysis. Restricted cubic splines (RCS) were used to examine dose-relationship associations. After adjusting for covariates, the percentage of total sleep duration in stage 2 (N2%) was positively associated with hypertension incidence, while the N3% was negatively associated with hypertension incidence Odds ratio (OR) = 1.009, 95% confidence interval (CI) [1.001, 1.018], P = 0.037; OR = 0.987, 95% CI: [0.979, 0.995], P = 0.028, respectively. For every 10% increase in N2 sleep, the risk of developing hypertension increases by 9%, while a 3% decrease in N3 sleep corresponds to a 0.1% increase in the incidence of hypertension. In the subgroup of non-depression, a positive association between N2% and hypertension was significant statistically (OR = 1.012, 95%CI, 1.002, 1.021, P = 0.013, Pinteraction = 0.013). RCS demonstrated that the risk of developing hypertension was lower when N2% ranged from 38% to 58% and rapidly increased thereafter (P = 0.002, non-linear P = 0.040). The lowest risk for hypertension incidence risk of N3% occurring at 25%, and a significant increase below 15% or above 40% (P = 0.001, non-linear P = 0.008). There's a negative association between N3% and the incidence of hypertension, and a positive association between N2% and the incidence of hypertension, particularly among non-depression individuals. These associations exhibit strong non-linear dose-response relationships.

Cumulative blood pressure predicts risk of stroke in individuals with type 2 diabetes

AimsTo determine whether cumulative blood pressure (BP) could predict stroke in individuals with type 2 diabetes (T2D). MethodsBP levels at baseline and the initial three visits were obtained from individuals participating in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial who had not experienced a stroke. Cumulative elevations in BP were assessed by adding the weighted mean BP values at various time intervals. The association of cumulative BP with stroke was evaluated by a multivariate-adjusted Cox proportional hazard model analysis. ResultsOverall, 8282 participants were included (62.10% males and 37.90% females; mean age, 62.73 years). With a median follow-up period of 6.36 years, 324 (3.91%) and 305 (3.68%) patients had any and nonfatal stroke events, respectively. Only baseline systolic BP (SBP) independently predicted any stroke after adjustment for potential confounders, whereas cumulative SBP and pulse pressure independently predicted elevated stroke events. A strong dose–response relationship between cumulative BP and stroke was identified, and conventional risk factors combined with cumulative SBP improved prediction efficiency. ConclusionCumulative SBP independently predicts stroke in individuals with T2D and provides an incremental predictive value for stroke compared with baseline BP assessments. Trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00000620)

Impacts of Poverty and Lifestyles on Mortality: A Cohort Study in Predominantly Low-Income Americans

Low socioeconomic status has been linked to increased mortality. However, the impacts of poverty, alone or combined with health behaviors, on mortality and life expectancy have not been adequately investigated. Data from the Southern Community Cohort Study was used, including nearly 86,000 participants recruited during 2002-2009 across 12 US southeastern states. Analysis was conducted from February 2022 to January 2023. During a median follow-up of 12.1 years, 19,749 deaths were identified. A strong dose-response relationship was found between household incomes and mortality, with a 3.3-fold (95%CI=3.1-3.6) increased all-cause mortality observed for individuals in the lowest income group (<$15,000/year) compared with those in the highest group (≥$50,000/year). Within each income group, mortality monotonically increased with declining healthy lifestyle score. Risk was significantly lower among those in the lowest income but healthiest lifestyle group, compared to those with the highest income but unhealthiest lifestyle (HR=0.82, 95%CI=0.69-0.97). Poor White participants appeared to experience higher all-cause mortality than poor Black participants. Life expectancy was more than 10.0 years shorter for those in the lowest income group compared with those in the highest income group. Poverty is strongly associated with increased risk of death, but the risks could be modestly abated by a healthier lifestyle. These findings call for a comprehensive strategy for enhancing a healthy lifestyle and improving income equality to reduce death risks, particularly among those experiencing health disparities due to poverty.

Lifestyle risk factors of self-reported fibromyalgia in the Norwegian Women and Cancer (NOWAC) study

BackgroundWhile the aetiology of fibromyalgia syndrome (FM) remains unknown, lifestyle factors have been linked to the disorder. However, there are few studies on the association between lifestyle factors and FM, thus we examine the risk of self-reported fibromyalgia given selected lifestyle factors.MethodsWe used data from 75,485 participants in the Norwegian Women and Cancer study. Information on FM and the lifestyle factors body mass index (BMI), physical activity level, smoking status/intensity, and alcohol consumption were obtained from baseline and follow-up questionnaires. We used Cox proportional hazards model to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsAfter a median follow-up time of 10 years, we observed 2,248 cases of self-reported fibromyalgia. Overweight (BMI 25-29.9 kg/m2) and obese (BMI ≥ 30 kg/m2) women had a relative risk of 1.34 (95% CI 1.21–1.47) and 1.62 (95% CI 1.41–1.87), respectively, compared to women with normal weight (BMI 18.5–24.9 kg/m2). Very low physical activity level (1–2) was associated with a 31% higher risk of self-reported fibromyalgia (HR 1.31, 95% CI 1.09–1.57) when compared to moderate physical activity level (5–6). There was a strong dose-response relationship between smoking status/intensity and self-reported fibromyalgia (p for trend < 0.001). Compared with moderate alcohol consumption (4.0–10 g/day), the risk of self-reported FM was 72% (HR 1.72; 95% CI 1.45–2.03) higher among teetotallers, and 38% (HR 1.38, 95% CI 1.23–1.54) higher among those with low consumption (0.1–3.9 g/day).ConclusionsOverweight and obesity, very low physical activity level, smoking, and alcohol consumption were associated with an increased risk of self-reported FM.

Childhood social capital and drug use disorder in adulthood: A retrospective study on antecedent determinants of the type of drug use.

Based on a sample of Danish adults who were enroled in treatment for drug use disorders as a prerequisite for qualifying for receiving unemployment benefits, we analyse the relationship between low social capital in childhood (LSCC) and the type of drug use in adulthood. The type of drug use is measured by distinguishing between those who were treated for using hard drugs (e.g., heroin and cocaine) and those who were treated for using soft drugs (cannabis). Extracting data from the initial treatment registration report, social capital is operationalised into seven different LSCC categories, and the total number of LSCC (the LSCC score) is recorded. Based on logistic regressions, the LSCC score shows a strong graded dose-response relationship with hard drug use. With each additional LSCC, the probability of being treated for hard drug use increases with 9%. Parental child abuse is the most important single predictor of being treated for hard drug use. Having been parentally abused as a child raises the probability by 32%. The results hold after controlling for age, initiation age, and number of years of drug use, all of which show a significant reversed U-shaped relationship with hard drug use.

Abstract 3009: Measured and genetically-predicted leukocyte telomere length and lung cancer risk in the prospective UK Biobank

Abstract Telomere length is a biomarker reflective of aging and genomic instability. We previously found associations between longer measured leukocyte telomere length (LTL) and increased lung cancer risk in a pooled nested case-control study with 847 cases. Additionally, we reported that longer genetically-predicted telomere length (gTL) using a polygenic risk score (PRS) with 7 single nucleotide polymorphisms (SNPs) was associated with increased lung cancer risk among never-smoking Asian women. To investigate further, we conducted prospective cohort analyses of pre-diagnostic LTL and gTL in relation to risk of overall lung cancer and its subtypes in the UK Biobank. With over triple the number of cases, we had expanded statistical power to investigate lung cancer, adenocarcinoma (LUAD), and squamous cell carcinoma (SCC) among subgroups defined by smoking status and sex in this predominantly European study population. We analyzed 371,890 participants at baseline. Over the 12.36±1.64SD year follow-up, 2829 incident lung cancer cases were diagnosed, including 1078 LUAD and 487 SCC. LTL was measured using qPCR. Using European data, we calculated a weighted PRS for gTL. The PRS was derived from 130 linkage disequilibrium pruned SNPs (r2 &amp;gt; 0.01) associated with longer LTL in the UK Biobank. Multivariable Cox regression was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of lung cancer in relation to log-transformed continuous and quartiles (Q) of LTL and gTL separately. Associations were estimated in the overall analytic sample and among smoking-sex subgroups. We conducted Mendelian Randomization (MR) analyses using MR-PRESSO with 130 genetic instruments to assess causal associations between LTL and lung cancer among Europeans.We found a strong dose-response relationship between longer LTL and increased lung cancer risk (p-trend= 2.6E-05), with the highest quartile being statistically significant (HRQ4vs.Q1=1.27, 95%CI: 1.15-1.42). The association was apparent for LUAD (p-trend=6.6E-10; HRQ4vs.Q1=1.78, 95%CI: 1.50-2.12), but not SCC. The lung cancer associations were prominent among never-smoking women (p-trend=4.0E-05) and never-smoking men (p-trend=2.0E-03). We also found dose-response relationships between longer gTL and risk of lung cancer (p-trend=4.2E-06) and LUAD (p-trend=2.1E-08). Additionally, we found evidence for causal associations between longer LTL and risk of lung cancer (HRper 1 SD gTL=1.87, 95%CI: 1.49-2.36, p=4.0E-07) and LUAD (HRper 1 SD gTL=2.45, 95%CI: 1.69-3.57, p=6.5E-06). Longer leukocyte telomere length potentially reflects biological processes relevant to the pathogenesis of lung cancer, particularly LUAD. Citation Format: Jason Yat-Yang Wong, Batel Blechter, Aubrey K. Hubbard, Jianxin Shi, Wei Hu, Mohammad Rahman, Shahinaz Gadalla, Mitchell Machiela, Nathaniel Rothman, Qing Lan. Measured and genetically-predicted leukocyte telomere length and lung cancer risk in the prospective UK Biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3009.

The Association between Time Spent in Domestic Work and Mental Health among Women and Men.

Unpaid domestic work has been found to be negatively associated with mental health, especially among women, in previous studies but the measures of domestic work vary. The aim of this study was to elucidate the association between time spent in domestic work and mental health in the general population. The study is based on 14,184 women and men aged 30-69 years who responded to a survey questionnaire in Central Sweden in 2017 (overall response rate: 43%). Multivariate logistic regression models, adjusting for age group, educational level, family status, employment status, economic difficulties, and social support, were used to study the association between hours spent in domestic work and depressive symptoms and self-reported diagnosed depression, respectively. In total, 26.7% of the respondents reported depressive symptoms and 8.8% reported diagnosed depression. No independent associations between hours spent in domestic work and depressive symptoms were found. Among women, the lowest prevalence of depression was found among those who spend 11-30 h per week in domestic work. Among men, the prevalence of self-reported diagnosed depression was highest among those who spend 0-2 h per week in domestic work, but no other statistically significant associations between time spent in domestic work and depression were found. In addition, a strong dose-response relationship was found between experiencing domestic work as burdensome and both depressive symptoms and self-reported diagnosed depression among women and men. Investigating time spent in unpaid domestic work may not be sufficient to assess the association between exposure to domestic work and mental health. Conversely, strain in domestic work may be a more important factor contributing to the prevalence of poor mental health in the general population.

Unblinding and demand characteristics in the treatment of depression

Blinding of treatment allocation in clinical trials in psychiatry is regarded as an ideal. The potential impact of unblinding chimes with a general concern for psychological research: so-called demand characteristics can undermine confidence in findings from experimental and clinical studies. Scepticism can result in nihilism. The reliance on subjective report of symptoms in clinical trials of drug efficacy in depression provides an important example. It is regularly implied that if subjective effects, including specific adverse reactions, unblind participants to an active treatment then evidence for its efficacy is suspect. In fact, the strong association between dose and subjective effects does not translate into a strong relationship with efficacy in randomised controlled trials (RCTs) of conventional antidepressant drugs; this observation falsifies the proposition that unblinding is the principal mechanism driving RCT outcomes in studies of depression. Instead, changes in brain function, that occur soon after treatment starts, do predict treatment outcomes and align with our understanding of neurotransmitter effects from neuroscience. Psychedelic experience for the treatment of depression must be unblinding, but the effect results directly from serotonergic receptor activation and changes in brain connectivity. Where such effects are part of a novel mechanism of action, a strong dose response relationship would be expected, irrespective of unblinding. We highlight the importance of exploring blinding as a mechanism, confirming dose-related outcomes, and dissociating unblinding effects from efficacy. Unblinding does not necessarily invalidate the subjective experience of sustained recovery from depression.

War exposure, posttraumatic stress disorder, and complex posttraumatic stress disorder among parents living in Ukraine during the Russian war.

High rates of posttraumatic stress disorder (PTSD) have been documented in war-affected populations. The prevalence of Complex PTSD (CPTSD) has never been assessed in an active war zone. Here, we provide initial data on war-related experiences, and prevalence rates of ICD-11 PTSD and CPTSD in a large sample of adults in Ukraine during the Russian war. We also examined how war-related stressors, PTSD, and CPTSD were associated with age, sex, and living location in Ukraine. Self-report data were gathered from a nationwide sample of 2004 adult parents of children under 18 from the general population of Ukraine approximately 6 months after Russia's invasion. All participants were exposed to at least one war-related stressor, and the mean number of exposures was 9.07 (range=1-26). Additionally, 25.9% (95% CI=23.9%, 27.8%) met diagnostic requirements for PTSD and 14.6% (95% CI=12.9%, 16.0%) met requirements for CPTSD. There was evidence of a strong dose-response relationship between war-related stressors and meeting criteria for PTSD and CPTSD. Participants who had the highest exposure to war-related stressors were significantly more likely to meet the requirements for PTSD (OR=4.20; 95% CI=2.96-5.95) and CPTSD (OR=8.12; 95% CI=5.11-12.91) compared to the least exposed. Humanitarian responses to the mental health needs of the Ukrainian population will need to take account of posttraumatic stress reactions. Education in diagnosing and treating PTSD/CPTSD, especially in the situation of a significant lack of human resources and continuing displacement of the population, is necessary.

Dose-response relationship of photobiomodulation therapy and oxidative stress markers in healing dynamics of diabetic neuropathic ulcers in Wistar rats

Purpose:Diabetic foot ulcers are reported to be the most expensive complications of diabetes, with high morbidity and mortality rates. If the necessary care is not provided for the wound to heal, the individual may end up amputating the affected feet. Photobiomodulation therapy is a promising non-pharmacological treatment option for wound healing. The objective of the present study is to establish a dose-response relationship between photobiomodulation therapy and oxidative stress markers in the healing dynamics of diabetic neuropathic ulcers in Wistar rats.Methodology:Diabetic neuropathy was induced in 126 Albino Wistar rats. An excisional wound of an area of 2cm2 was made on the neuropathy-induced leg. Photobiomodulation therapy of dosages 4, 6, 8, 10, 12, and 15 J/cm2 of wavelengths 655 and 808 nm was irradiated. The control group animals were kept un-irradiated. The outcome measures were assessed during wound healing’s inflammatory, proliferative and remodelling phases.Results:In the experimental group, animals treated with photobiomodulation therapy at doses of 4, 6, and 8 J/cm2 showed better wound healing dynamics. Photobiomodulation therapy modulated the reactive oxygen species and antioxidant levels, thereby improving the oxidative status of the wound.Conclusion:Photobiomodulation therapy of dosages 4, 6, and 8 J/cm2 is effective and is a promising adjuvant modality in treating diabetic neuropathic ulcers. There was a strong dose-response relationship in the experimental groups treated with 4, 6 and 8 J/ cm2.

Association between the triglyceride-glucose (TyG) index and increased blood pressure in normotensive subjects: a population-based study

BackgroundInsulin resistance (IR) is an important contributor to the development of hypertension (HTN), and the triglyceride-glucose (TyG) index has been proposed as a simple, reliable marker of IR. This study investigated the association between the TyG index and blood pressure (BP) elevation in a large general population.MethodsThe study enrolled 15,721 adults with no history of cardiometabolic diseases from the 2016–2019 Korea National Health and Nutrition Examination Survey. Participants were classified into quartiles based on the TyG index and BP was categorized as normal BP, elevated BP, pre-HTN, and HTN. The associations of the TyG index with BP categories were assessed using multivariate multinomial logistic regression models with normal BP as the reference group.ResultsThe mean systolic/diastolic BP and prevalence of HTN increased with the TyG index (P for trend < 0.001). The continuous TyG index had a strong dose-response relationship with increased odds of elevated BP, pre-HTN, and HTN. Compared with the lowest TyG index quartile, the highest TyG index quartile was significantly associated with higher odds of having elevated BP (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.24–1.87; P for trend < 0.001), pre-HTN (OR, 2.22; 95% CI, 1.95–2.53; P for trend < 0.001), and HTN (OR, 4.24; 95% CI, 3.49–5.16; P for trend < 0.001).ConclusionWe found that a higher TyG index was positively associated with the risk of increased BP in normal healthy individuals. This study suggests that the TyG index might serve as a potential predictor of HTN. However, further studies with larger sample sizes and various target populations in longitudinal designs are needed.

Changes in HDL cholesterol, particles, and function associate with pediatric COVID-19 severity.

BackgroundMyriad roles for high-density lipoprotein (HDL) beyond atheroprotection include immunologic functions implicated in the severity of coronavirus disease-2019 (COVID-19) in adults. We explored whether there is an association between HDL and COVID-19 severity in youth.MethodsA pediatric cohort (N = 102), who tested positive for COVID-19 across a range of disease manifestations from mild or no symptoms, to acute severe symptoms, to the multisystem inflammatory syndrome of children (MIS-C) was identified. Clinical data were collected from the medical record and reserve plasma aliquots were assessed for lipoproteins by NMR spectroscopy and assayed for HDL functional cholesterol efflux capacity (CEC). Findings were compared by COVID-19 status and symptom severity. Lipoprotein, NMR spectroscopy and CEC data were compared with 30 outpatient COVID negative children.ResultsDecreasing HDL cholesterol (HDL-c), apolipoprotein AI (ApoA-I), total, large and small HDL particles and HDL CEC showed a strong and direct linear dose-response relationship with increasing severity of COVID-19 symptoms. Youth with mild or no symptoms closely resembled the uninfected. An atypical lipoprotein that arises in the presence of severe hepatic inflammation, lipoprotein Z (LP-Z), was absent in COVID-19 negative controls but identified more often in youth with the most severe infections and the lowest HDL parameters. The relationship between HDL CEC and symptom severity and ApoA-I remained significant in a multiply adjusted model that also incorporated age, race/ethnicity, the presence of LP-Z and of GlycA, a composite biomarker reflecting multiple acute phase proteins.ConclusionHDL parameters, especially HDL function, may help identify youth at risk of more severe consequences of COVID-19 and other novel infectious pathogens.

Associations of cumulative depressive symptoms with subsequent cognitive decline and adverse health events: Two prospective cohort studies

BackgroundThe course of depression is variable; however, few studies examined the relationship between long-term cumulative depressive symptoms and adverse health outcomes in the elderly. MethodsIn this cohort study, we used data from the Health and Retirement Study (HRS) over 24 years and the English Longitudinal Study of Ageing (ELSA) over 16 years. Cumulative depressive symptoms were estimated by calculating the areas under the curve based on the Center for Epidemiological Research Depression scale assessed at four examinations. Outcomes include cognitive decline, incident dementia, cardiovascular disease (CVD), cancer, and all-cause mortality. ResultsA total of 8284 American (mean age: 60.1 years; male: 35.4 %) and 4314 British (60.1 years; 42.4 %) were included in the analysis. The median follow-up was 16.1 years in the HRS and 9.9 years in the ELSA. Similar results were observed in two cohorts. Comparing with the first tertile of cumulative depressive symptoms, the third tertile experienced faster cognitive decline (p = 0.013 in the ELSA and p < 0.001 in the HRS), increased risk of dementia (both p < 0.001), CVD (both p < 0.001) and all-cause mortality (p = 0.002 in the HRS). Strong dose-response relationships were observed. We did not found clearly association between cumulative depressive symptoms and incident cancer. ConclusionsThis study suggests that long-term cumulative depressive symptoms were associated with subsequent faster cognitive decline and greater risks for dementia, CVD and all-cause mortality, but not cancer. These findings provide insights on potential effective strategy that may improve health in the elderly, future clinical trials are needed to determine causality.

Impact of cannabis legalization on healthcare utilization for psychosis and schizophrenia in Colorado.

Emergency department (ED) visits involving psychosis and schizophrenia have increased at a rate exceeding population growth in the United States over the past decade. Research shows a strong dose-response relationship between chronic use of high-potency cannabis and odds of developing symptoms of psychosis. The aim of this study was to evaluate the impact of cannabis legalization on psychosis and schizophrenia-related ED visits in Colorado. Using administrative data from Colorado Hospital Association (CHA) on county-level quarterly ED visits between January 1, 2013, and December 31, 2018, we applied a difference-in-difference analysis to examine how new exposure to recreational cannabis dispensaries after 2014 differentially influenced the rate of ED visits for psychosis and schizophrenia, comparing counties with no prior medical cannabis dispensary exposure to counties with low or high medical dispensary exposure. As recreational dispensaries per 10,000 residents increased, there was no significant association with the rate of schizophrenia ED visits per capita (incidence rate ratio or IRR: 0.95, 95% CI [0.69, 1.30]) while the rate of psychosis visits increased 24% (IRR: 1.24, 95% CI [1.02, 1.49]). Counties with no previous medical dispensaries experienced larger increases in schizophrenia ED visits than counties already exposed to a low level of medical dispensaries, but this effect was not significant. Counties with low baseline medical exposure had lower increases in rates of psychosis visits than counties with high baseline medical exposure (IRR 0.83, 95% CI [0.69, 0.99]). There was a positive association between the number of cannabis dispensaries and rates of psychosis ED visits across all counties in Colorado. Although it is unclear whether it is access to products, or the types of products that may be driving this association, our findings suggest there is a potential impact on the mental health of the local population that is observed after cannabis legalization.