Meta Analysis of the Correlation between Periodontal Health and Cognitive Impairment in the Older Population.

OBJECTIVE: To explore the correlation between periodontal health and cognitive impairment in the older population to provide the evidence for preventing cognitive impairment from the perspective of oral health care in older adults. METHODS: A comprehensive search was conducted in PubMed, Embase, the Cochrane Library, the Web of Science, the China National Knowledge Infrastructure, Wanfang Data, the China Science and Technology Journal Database, and the China Biomedical Literature Database, to include both cross-sectional and longitudinal cohort studies on the association between periodontal health and cognitive impairment in older adults. The search was completed in April 2023. Following quality assessment and data organization of the included studies, meta-analysis was performed using Review Manager 5.4. RESULTS: Twenty-two studies involving a total of 4,246,608 patients were included to comprehensively assess periodontal health from four dimensions (periodontitis, tooth loss, occlusal support, and masticatory ability), with the outcome variable of cognitive impairment (including mild cognitive impairment, Alzheimer's disease and all-cause dementia). Meta-analysis showed that, compared to those of periodontally healthy older adults, the risk of cognitive impairment in older adults with poor periodontal health, after adjusting for confounders, was significantly greater for those with periodontitis (OR=1.45, 95% CI: 1.20-1.76, P<0.001), tooth loss (OR=1.80, 95% CI: 1.50-2.15, P<0.001), compromised occlusal support (OR=1.87, 95% CI: 1.29-2.70, P=0.001), and reduced masticatory ability (OR=1.39, 95% CI: 1.11-1.75, P=0.005). The risk of cognitive impairment was higher in older adults with low-dentition than in those with high-dentition. Subgroup analysis revealed older individuals with fewer remaining teeth were at a higher risk of developing cognitive impairment compared to those with more remaining teeth, as shown by the comparison of number of teeth lost (7-17 teeth compared to 0-6 teeth) (OR=1.64, 95% CI: 1.13-2.39, P=0.01), (9-28 teeth compared to 0-8 teeth) (OR=1.13, 95% CI: 1.06-1.20, P<0.001), (19-28 teeth compared to 0-18 teeth) (OR=2.52, 95% CI: 1.32-4.80, P=0.005), and (28 teeth compared to 0-27 teeth) (OR=2.07, 95% CI: 1.54-2.77, P<0.001). In addition, tooth loss in older adults led to a significantly increased risk of mild cognitive impairment (OR=1.66, 95% CI: 1.43-1.91, P<0.001) and all-cause dementia (OR=1.35, 95% CI: 1.11-1.65, P=0.003), although the correlation between tooth loss and the risk of Alzheimer's disease was not significant (OR=3.89, 95% CI: 0.68-22.31, P=0.13). CONCLUSION: Poor periodontal health, assessed across four dimensions (periodontitis, tooth loss, occlusal support, and masticatory ability), represents a significant risk factor for cognitive impairment in older adults. The more missing teeth in older adults, the higher risk of developing cognitive impairment, with edentulous individuals particularly susceptible to cognitive impairment. While a certain degree of increased risk of Alzheimer's disease was observed, no significant association was found between tooth loss and the risk of developing Alzheimer's disease. Enhancing periodontal health management and delivering high-quality oral health care services to older adults can help prevent cognitive impairment.

[Disseminated tuberculosis with osteomyelitis of the right little finger as the first manifestation: a case report].

The clinical data of a child with disseminated tuberculosis with osteomyelitis of the right little finger as the first manifestation who was admitted to Tianjin Children's Hospital on April 8, 2023 were retrospectively analyzed. The child, a 14-year-old female, presented with osteomyelitis of the right little finger as the first manifestation. She still had recurrent fever after focal incision and drainage. She was referred to our hospital. The samples from multiple sites were positive for molecular biology detection of Mycobacterium tuberculosis. She was considered as disseminated tuberculosis and was given anti-tuberculosis treatment. The child has recovered well. Pediatric disseminated tuberculosis has variable clinical manifestations and lacks specificity. It is often misdiagnosed and has a high mortality rate. Clinicians should improve their understanding of the disease and ensure early diagnosis and treatment.

[Association of serum 25(OH)D3 with cardiovascular risk-related indicators: cross-sectional analysis of NHANES].

This study investigated the association between serum 25(OH)D3 levels and cardiovascular risk-related indicators. 4 727 participants aged 20 and above from the National Health and Nutrition Examination Survey 2015-2018 database were enrolled. Body mass index, hypersensitive C-reactive protein, high density lipoprotein cholesterol, systolic blood pressure, waist-height ratio, and total cholesterol were selected as the research indicators. Weighted multiple linear regression models, subgroup analyses, smooth curve fitting, and saturation threshold effect analyses were employed to explore the relationship between serum 25(OH)D3 and these indicators. The results showed that after full adjustment for covariates, every 1 nmol/L increase in serum 25(OH)D3, the changes in ß (95%CI) values for body mass index(BMI), hypersensitive C-reactive protein(hs-CRP), systolic blood pressure(SBP), waist-height ratio(WHtR), high density lipoprotein cholesterol(HDL-C), and total cholesterol(TC) were -0.05 (-0.06, -0.04) kg/m2, -0.01 (-0.02, -0.01) mg/L, -0.02 (-0.04, -0.01) mmHg, -0.000 7 (-0.000 8, -0.000 6), 0.10 (0.08, 0.11) mg/dl, and 0.08 (0.04, 0.12) mg/dl, respectively. Female participants were more sensitive to changes in serum 25(OH)D3, while participants aged 60 and above were relatively less sensitive. The relationship between serum 25(OH)D3 and these indicators partially exhibited nonlinear patterns across different gender and age subgroups. The saturation threshold effect analysis revealed 8 meaningful inflection points. In summary, vitamin D has a close association with cardiovascular risk-related indicators.

Impact of pandemics on primary care: changes in general practitioner antidepressant prescriptions and mental health referrals during lockdowns in England, UK.

OBJECTIVES: In recent times, the world has witnessed unprecedented challenges, with the COVID-19 pandemic being a major disruptor to various aspects of daily life. This article delves into the profound impact of pandemics on primary care, specifically focussing on changes in antidepressant prescriptions and mental health referrals before, during, and after lockdowns in England, UK. METHODS: In this retrospective study, we used anonymised individual-level electronic health record data from general practitioner (GP) practices in the North of England, UK. We applied a negative binomial-logit hurdle model and a multinominal logit regression model to assess the impact on antidepressant prescriptions and GP referral types, respectively. RESULTS: The initiation of antidepressant prescriptions showed a notable decrease during and post lockdowns, with a minor uptick in ongoing antidepressant prescriptions during the lockdown periods. Over the course of lockdowns and beyond, there was a growing trend of patients being referred to social prescribing interventions. Notably, individuals from ethnic minorities were more inclined to receive fewer medical treatments and more social prescribing interventions. CONCLUSION: The increase in antidepressant prescriptions during the pandemic-related lockdowns was expected due to these challenging circumstances. Reduced referrals to secondary mental health services occurred as online counselling services were deemed inappropriate by some doctors, and patients were hesitant to seek face-to-face help. Notably, there was a rise in social prescribing referrals, emerging as a valuable resource for psychological support amid heightened mental health strain. Additionally, ethnic minority patients were less likely to receive medical treatments but more likely to be referred to social prescribing services. Despite the inevitable negative impacts of the COVID-19 pandemic, these findings highlight the active role of non-clinical support in a social model of health, addressing unmet needs and reducing barriers to mental health care for certain groups.

[Effects of polyphyllin â ¦ on proliferation, apoptosis and cell cycle of diffuse large B-cell lymphoma cells].

The aim of this study was to investigate the effects of polyphyllin Ⅶ (PP Ⅶ) on proliferation, apoptosis, and cell cycle of diffuse large B-cell lymphoma (PLBCL) cell lines U2932 and SUDHL-4. The DLBCL cell lines were divided into a control group and a PPⅦ group, and experiments were conducted using MTT assay, flow cytometry, and Western blotting.Results showed that compared with the control group, PPⅦ significantly inhibited the proliferation of U2932 and SUDHL-4 cells (P<0.05). Apoptosis assays demonstrated that treatment with 0.50 and 1.00 µmol/L PP Ⅶ significantly increased the apoptosis rates of both cell lines (P<0.05), upregulated apoptosis-related proteins, and downregulated Bcl-2 protein level (P<0.05). Cell cycle analysis revealed that PPⅦ treatment led to an increase in G0/G1-phase cells (P<0.05) and a decrease in G2/M-phase cells (P<0.05), significantly downregulated cyclin D1, CDK4, CDK6, and survivin protein expression (P<0.05). In conclusion, PPⅦ exerted anti-lymphoma effects by inhibiting proliferation, promoting apoptosis, and inducing G0/G1 phase arrest in DLBCL cells.

[A single-center retrospective study of salvage allogeneic hematopoietic stem cell transplantation pretreated with MeCBA regimen for refractory/relapsed acute myeloid leukemia].

Thirty refractory relapsed acute myeloid leukemia (R/R AML) patients who received salvage allo-HSCT with MeCBA conditioning regimen from January 2018 to June 2022 at Henan Cancer Hospital were included, and their clinical data were reviewed. There were 16 males and 14 females among the 30 patients with a median age of 37 (16-53) years. There were 3 sibling allograft donor transplants, 1 unrelated donor transplant, and 26 haplotype transplants. The median course of pre-transplant chemotherapy was 4 (3-22). The time of neutrophil engraftment was 14 (9-22) days and 18 (10-40) days for platelet. The 30-day cumulative incidence of neutrophil engraftment was 100% and the 100-day cumulative incidence of platelet engraftment was 96.7% (95% CI 85.4% -97.5% ). 22 (73.3% ) patients experienced grade 1-2 gastrointestinal reactions, and there was no grade 3-4 organ toxicity. With a median follow-up of 37.1 months, the overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR), and non-recurrence mortality (NRM) rate at 3 years after transplantation were 70.0% (95% CI 50.3% -83.1% ), 65.3% (95% CI 44.8% -79.8% ), 21.2% (95% CI 9.2% -44.4% ) and 16.7% (95% CI 7.3% -35.5% ), respectively.

[Clinicopathological characteristics of gangliogliomas with anaplastic morphology].

Objective: To investigate the clinical, radiological, and pathological features of anaplastic gangliogliomas (AGGs) and to determine whether these tumors represent a distinct entity. Methods: Consecutive 667 cases of ganglioglioma (GG) diagnosed at the Xuanwu Hospital, Capital Medical University, Beijing, China between January 2015 and July 2023 were screened. Among these cases, 9 pathologically confirmed AGG cases were identified. Their clinical, radiological, treatment, and outcome data were analyzed retrospectively. Most of the tumor samples were subject to next-generation sequencing, while a subset of them were subject to DNA methylation profiling. Results: Among the 9 patients, there were five males and four females, with a median age of 8 years. Epileptic seizures (5/9) were the most frequently presented symptom. Radiological examinations showed three types of radiological manifestations: four cases showed abnormal MRI signals with no significant mass effects and mild enhancement; two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema, which showed significant heterogeneous enhancement and obvious mass effects, and one case displayed cystic cavity formation with nodules on MRI, which showed evident enhancements. All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway, including seven with BRAF p.V600E mutation and two with NF1 mutation. Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations, including three with CDKN2A homozygous deletion, one with a TERT promoter mutation, one with a H3F3A mutation, and one with a PTEN mutation. Conclusions: AGG exhibits a distinct spectrum of pathology, genetic mutations and clinical behaviors, differing from GG. Given these characteristics suggest that AGG may be a distinct tumor type, further expansion of the case series is needed. Therefore, a comprehensive integration of clinical, histological, and molecular analyses is required to correctly diagnose AGG. It will also help guide treatments and prognostication.

Control of proton transport and hydrogenation in double-gated graphene.

The basal plane of graphene can function as a selective barrier that is permeable to protons1,2 but impermeable to all ions3,4 and gases5,6, stimulating its use in applications such as membranes1,2,7,8, catalysis9,10 and isotope separation11,12. Protons can chemically adsorb on graphene and hydrogenate it13,14, inducing a conductor-insulator transition that has been explored intensively in graphene electronic devices13-17. However, both processes face energy barriers1,12,18 and various strategies have been proposed to accelerate proton transport, for example by introducing vacancies4,7,8, incorporating catalytic metals1,19 or chemically functionalizing the lattice18,20. But these techniques can compromise other properties, such as ion selectivity21,22 or mechanical stability23. Here we show that independent control of the electric field, E, at around 1 V nm-1, and charge-carrier density, n, at around 1 × 1014 cm-2, in double-gated graphene allows the decoupling of proton transport from lattice hydrogenation and can thereby accelerate proton transport such that it approaches the limiting electrolyte current for our devices. Proton transport and hydrogenation can be driven selectively with precision and robustness, enabling proton-based logic and memory graphene devices that have on-off ratios spanning orders of magnitude. Our results show that field effects can accelerate and decouple electrochemical processes in double-gated 2D crystals and demonstrate the possibility of mapping such processes as a function of E and n, which is a new technique for the study of 2D electrode-electrolyte interfaces.

Exploring the structure and hydrogen storage capacity of CeHn0/+ clusters.

The unique 4f orbitals and abundant electronic energy levels of rare earth elements enable effective doping and modification to enhance hydrogen storage performance, making it an increasingly prominent focus of research. The structures of neutral and cationic CeHn0/+ (n = 2-20) clusters have been determined using the Crystal Structure AnaLYsis by Particle Swarm Optimization (CALYPSO) method in conjunction with density functional theory (DFT). Interestingly, the CeH13 and CeH14+ exhibit remarkable stability in the doublet state with Cs and C2v symmetry, respectively. The adsorption energy of CeHn0/+ (n = 2-20) suggests a preference for H atoms to chemically adsorb on Ce atoms. The analysis of molecular orbital composition reveals that the stability of both CeH13 and CeH14+ is attributed to the significant hybridization between the H 1s and Ce 4f orbitals. Both CeH13 and CeH14+ demonstrate significant hydrogen storage capacities, with values reaching 8.5 wt% and 9.1 wt%, respectively.

Netrin-1 Promotes M2 Type Activation and Inhibits Pyroptosis of Microglial Cells by Depressing RAC1/Nf-?B Pathway to Alleviate Inflammatory Pain.

Netrin-1 (NTN-1) plays a vital role in the progress of nervous system development and inflammatory diseases. However, the role and underlying mechanism of NTN-1 in inflammatory pain (IP) are unclear. BV2 microglia were treated with LPS to mimic the cell status under IP. Adeno-associated virus carrying the NTN-1 gene (AAV-NTN-1) was used to overexpress NTN-1. Complete Freund's Adjuvant (CFA)-induced mouse was recruited as an in vivo model. MTT and commercial kits were utilized to evaluate cell viability and cell death of BV2 cells. The mRNA expressions and secretions of cytokines were measured using the ELISA method. Also, the pyroptosis and activation of BV2 cells were investigated based on western blotting. To verify the role of Rac1/NF-kappaB signaling, isochamaejasmin (ISO) and AAV-Rac1 were presented. The results showed that NTN-1 expression was decreased in LPS-treated BV2 microglia and spinal cord tissues of CFA-injected mice. Overexpressing NTN-1 dramatically reversed cell viability and decreased cell death rate of BV2 microglia under lipopolysaccharide (LPS) stimulation, while the level of pyroptosis was inhibited. Besides, AAV-NTN-1 rescued the activation of microglia and inflammatory injury induced by LPS, decreasing IBA-1 expression, as well as iNOS, IL-1beta and IL-6 secretions. Meanwhile AAV-NTN-1 promoted the anti-inflammation response, including increases in Arg-1, IL-4 and IL-10 levels. In addition, the LPS-induced activation of Rac1/NF-kappaB signaling was depressed by NTN-1 overexpression. The same results were verified in a CFA-induced mouse model. In conclusion, NTN-1 alleviated IP by suppressing pyroptosis and promoting M2 type activation of microglia via inhibiting Rac1/NF-?B signaling, suggesting the protective role of NTN-1 in IP. Keywords: Netrin-1, Inflammatory pain, Pyroptosis, Microglia M2 activation, Rac1/NF-kappaB.

[Advances of pathological research and classification in malformations of cortical development associated with refractory epilepsy].

With rapid development of genetic testing techniques, neuroimaging and neuroelectrophysiological technologies, our understanding of malformations of cortical development continues to be deepened and updated. In particular, mutations in genes related to the mammalian target of rapamycin (mTOR) signaling pathway have been successively discovered in focal cortical dysplasia (FCD). At the same time, the classification consensus on FCD issued by the International League Against Epilepsy (ILAE) in 2011 has encountered problems and challenges in diagnostic practice. Therefore, in 2022, ILAE proposed an updated version of the FCD classification based on the progress in molecular genetics over the past decade. The main addition to the classification system is "white matter lesions, " and it is also suggested to integrate histopathological, neuroimaging, and molecular testing results for multi-level integrated diagnosis to achieve reliable, clinically relevant, and therapeutic targeted final diagnosis.

[Acidophil stem cell pituitary neuroendocrine tumors/adenoma: a clinicopathological analysis of five cases].

Objective: To investigate the clinicopathological characteristics of acidophil stem cell pituitary neuroendocrine tumors (PitNET)/adenoma. Methods: Five cases of acidophil stem cell PitNET/adenoma were diagnosed between May 2022 and July 2023 at the Second Hospital of Hebei Medical University, Shijiazhuang, China. The clinicopathological features of the tumor were analyzed by using histology, immunohistochemistry, and electron microscopy. The relevant literature was reviewed. Results: There were 1 male and 4 females, aged from 23 to 69 years. Patient 3 was 55 years old at the time of diagnosis and first surgery, and relapsed 5 years later. The patients' median age was 32 years. Patients 1 and 5 showed elevated blood prolactin, with various degrees of hormonal symptoms except Patient 3, who showed only tumor compression symptoms. Imaging studies showed that all cases involved the sellar floor. The tumors of Patients 1, 2 and 5 were closely related to the cavernous sinus segment of the internal carotid artery. The tumors exhibited a diffuse growth pattern with chromophobic to slightly acidophilic cytoplasm. A few of tumor cells showed chromophobic cytoplasm. The nucleoli were conspicuous. Intranuclear inclusion bodies and variably-sized clear vacuoles were observed occasionally. Under electron microscope, marked mitochondrial abnormalities were observed, including increased mitochondria number, expanded hypertrophy, and absence of mitochondrial ridge fracture. Some mitochondrial matrices were dense, while some were vacuolated. Conclusions: Acidophil stem cell PitNET/adenoma is a rare type of pituitary adenomas/PitNETs. It often has a more clinically aggressive manner with immature cells, diffuse expression of PIT1, prolactin, and varying degrees of growth hormone expression. Because of the obvious diversity of their clinical hormone status and hormone immune expression, the diagnosis of this type tumor is still a challenge.

Synthesis and preclinical evaluation of novel 18F-vancomycin-based tracers for the detection of bacterial infections using positron emission tomography.

INTRODUCTION: Bacterial infections are a major problem in medicine, and the rapid and accurate detection of such infections is essential for optimal patient outcome. Bacterial infections can be diagnosed by nuclear imaging, but most currently available modalities are unable to discriminate infection from sterile inflammation. Bacteria-targeted positron emission tomography (PET) tracers have the potential to overcome this hurdle. In the present study, we compared three 18F-labelled PET tracers based on the clinically applied antibiotic vancomycin for targeted imaging of Gram-positive bacteria. METHODS: [18F]FB-NHS and [18F]BODIPY-FL-NHS were conjugated to vancomycin. The resulting conjugates, together with our previously developed [18F]PQ-VE1-vancomycin, were tested for stability, lipophilicity, selective binding to Gram-positive bacteria, antimicrobial activity and biodistribution. For the first time, the pharmacokinetic properties of all three tracers were compared in healthy animals to identify potential binding sites. RESULTS: [18F]FB-vancomycin, [18F]BODIPY-FL-vancomycin, and [18F]PQ-VE1-vancomycin were successfully synthesized with radiochemical yields of 11.7%, 2.6%, and 0.8%, respectively. [18F]FB-vancomycin exhibited poor in vitro and in vivo stability and, accordingly, no bacterial binding. In contrast, [18F]BODIPY-FL-vancomycin and [18F]PQ-VE1-vancomycin showed strong and specific binding to Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), which was outcompeted by unlabeled vancomycin only at concentrations exceeding clinically relevant vancomycin blood levels. Biodistribution showed renal clearance of [18F]PQ-VE1-vancomycin and [18F]BODIPY-FL-vancomycin with low non-specific accumulation in muscles, fat and bones. CONCLUSION: Here we present the synthesis and first evaluation of the vancomycin-based PET tracers [18F]BODIPY-FL-vancomycin and [18F]PQ-VE1-vancomycin for image-guided detection of Gram-positive bacteria. Our study paves the way towards real-time bacteria-targeted diagnosis of soft tissue and implant-associated infections that are oftentimes caused by Gram-positive bacteria, even after prophylactic treatment with vancomycin.

[Mediating effects of body mass index and lipid levels on the association between alcohol consumption and hypertension in occupational population].

Objective: To investigate the association between alcohol consumption and hypertension and SBP, DBP and the mediating effects of body mass index (BMI) and lipid level in occupational population, and provide reference for the intervention and prevention of hypertension. Methods: Based on the data of Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd., the information about the demographic characteristics, behavior and lifestyle, blood pressure and lipids level of the participants were collected through questionnaire survey, physical examination and blood biochemical test. Logistic/linear regression was used to analyze the association between alcohol consumption and hypertension, SBP and DBP. The individual and joint mediating effects of BMI, HDL-C, LDL-C, TG, and TC were explored through causal mediating analysis. A network analysis was used to explore the correlation between alcohol consumption, BMI and lipid levels, and hypertension. Results: A total of 22 887 participants were included, in whom 1 825 had newly detected hypertension. Logistic regression analysis found that current/former drinkers had a 33% increase of risk for hypertension compared with never-drinkers (OR=1.33, 95%CI:1.19-1.48). Similarly, alcohol consumption could increase SBP (ß=1.05, 95%CI:0.69-1.40) and DBP (ß=1.10, 95%CI:0.83-1.38). Overall, BMI and lipid levels could mediate the associations between alcohol consumption and hypertension, SBP and DBP by 21.91%, 28.40% and 22.64%, respectively. BMI and TG were the main mediators, and they were also the two nodes with the highest edge weight and bridge strength centrality in the network of alcohol consumption, BMI, lipid levels and hypertension. Conclusions: Alcohol consumption was associated with increased risk for hypertension, and BMI and TG were important mediators and key nodes in the network. It is suggested that paying attention to the alcohol consumption, BMI and TG might help prevent hypertension in occupational population.

[Association between work environment noise perception and cardiovascular diseases, depressive symptoms, and their comorbidity in occupational population].

Objective: To explore the association between occupational noise perception and cardiovascular disease (CVD), depression symptoms, as well as their comorbidity in occupational population and provide evidence for the prevention and control of physical and mental illnesses. Methods: A cross-sectional survey design was adopted, based on baseline data in population in 28 prefectures in Sichuan Province and Guizhou Province, and 33 districts (counties) in Chongqing municipality from Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd. during October to December 2021. A questionnaire survey was conducted to collect information about noise perception, depressive symptoms, and the history of CVD. Latent profile analysis model was used to determine identify noise perception type, and multinomial logistic regression analysis was conducted to explore the relationship between different occupational noise perception types and CVD, depression symptoms and their comorbidity. Results: A total of 30 509 participants were included, the mean age was (36.6±10.5) years, and men accounted for 82.0%. The direct perception of occupational noise, psychological effects and hearing/sleep impact of occupational noise increased the risk for CVD, depressive symptoms, and their comorbidity. By using latent profile analysis, occupational noise perception was classified into four levels: low, medium, high, and very high. As the level of noise perception increased, the association with CVD, depressive symptoms, and their comorbidity increased. In fact, very high level occupational noise perception were found to increase the risk for CVD, depressive symptoms, and their comorbidity by 2.14 (95%CI: 1.73-2.65) times, 8.80 (95%CI: 7.91-9.78) times, and 17.02 (95%CI: 12.78-22.66) times respectively compared with low-level occupational noise perception. Conclusions: Different types of occupational noise perception are associated with CVD and depression symptom, especially in the form of CVD complicated with depression symptom. Furthermore, the intensity of occupational noise in the work environment should be reduced to lower the risk for physical and mental health.