Mutations in Disordered Regions Can Cause Disease by Creating Dileucine Motifs.

Many disease-causing missense mutations affect intrinsically disordered regions (IDRs) of proteins, but the molecular mechanism of their pathogenicity is enigmatic. Here, we employ a peptide-based proteomic screen to investigate the impact of mutations in IDRs on protein-protein interactions. We find that mutations in disordered cytosolic regions of three transmembrane proteins (GLUT1, ITPR1, and CACNA1H) lead to an increased clathrin binding. All three mutations create dileucine motifs known to mediate clathrin-dependent trafficking. Follow-up experiments on GLUT1 (SLC2A1), the glucose transporter causative of GLUT1 deficiency syndrome, revealed that the mutated protein mislocalizes to intracellular compartments. Mutant GLUT1 interacts with adaptor proteins (APs) in vitro, and knocking down AP-2 reverts the cellular mislocalization and restores glucose transport. A systematic analysis of other known disease-causing variants revealed a significant and specific overrepresentation of gained dileucine motifs in structurally disordered cytosolic domains of transmembrane proteins. Thus, several mutations in disordered regions appear to cause "dileucineopathies."

Context-specific regulation of cell survival by a miRNA-controlled BIM rheostat.

Knockout of the ubiquitously expressed miRNA-17∼92 cluster in mice produces a lethal developmental lung defect, skeletal abnormalities, and blocked B lymphopoiesis. A shared target of miR-17∼92 miRNAs is the pro-apoptotic protein BIM, central to life-death decisions in mammalian cells. To clarify the contribution of miR-17∼92:Bim interactions to the complex miR-17∼92 knockout phenotype, we used a system of conditional mutagenesis of the nine Bim 3' UTR miR-17∼92 seed matches. Blocking miR-17∼92:Bim interactions early in development phenocopied the lethal lung phenotype of miR-17∼92 ablation and generated a skeletal kinky tail. In the hematopoietic system, instead of causing the predicted B cell developmental block, it produced a selective inability of B cells to resist cellular stress; and prevented B and T cell hyperplasia caused by Bim haploinsufficiency. Thus, the interaction of miR-17∼92 with a single target is essential for life, and BIM regulation by miRNAs serves as a rheostat controlling cell survival in specific physiological contexts.

Spatio-temporal trends of mercury levels in alluvial gold mining spoils areas monitored between rainy and dry seasons in the Peruvian Amazon.

Artisanal and small-scale gold mining (ASGM) in the Amazon has degraded tropical forests and escalated mercury (Hg) pollution, affecting biodiversity, ecological processes and rural livelihoods. In the Peruvian Amazon, ASGM annually releases some 181 tons of Hg into the environment. Despite some recent advances in understanding the spatial distribution of Hg within gold mine spoils and the surrounding landscape, temporal dynamics in Hg movement are not well understood. We aimed to reveal spatio-temporal trends of soil Hg in areas degraded by ASGM.,. We analyzed soil and sediment samples during the dry and rainy seasons across 14 ha of potentially contaminated sites and natural forests, in the vicinities of the Native community of San Jacinto in Madre de Dios, Peru. Soil Hg levels of areas impacted by ASGM (0.02 ± 0.02 mg kg-1) were generally below soil environmental quality standards (6.60 mg kg-1). However, they showed high variability, mainly explained by the type of natural cover vegetation, soil organic matter (SOM), clay and sand particles. Temporal trends in Hg levels in soils between seasons differed between landscape units distinguished in the mine spoils. During the rainy season, Hg levels decreased up to 45.5% in uncovered soils, while in artificial pond sediments Hg increased by up to 961%. During the dry season, uncovered degraded soils were more prone to lose Hg than sites covered by vegetation, mainly due to higher soil temperatures and concomitantly increasing volatilization. Soils from natural forests and degraded soil covered by regenerating vegetation showed a high capacity to retain Hg mainly due to the higher plant biomass, higher SOM, and increasing concentrations of clay particles. Disturbingly, our findings suggest high Hg mobility from gold mine spoil to close by sedimentary materials, mainly in artificial ponds through alluvial deposition and pluvial lixiviation. Thus, further research is needed on monitoring, and remediation of sediments in artificial to design sustainable land use strategies.

Analyzing Alternative Behavioral Crisis Response Models in the U.S.

In the U.S., communities often rely on the criminal justice system to respond to, house, and treat individuals with mental health and substance use problems. This has resulted in a crisis response system that relies on police officers to respond to mental and behavioral health crisis due to a lack of options. Unfortunately, these encounters can be dangerous for individuals in need of help. Additionally, this has led to a disproportionate number of individuals with mental illness and substance use disorders being housed in prisons. Alternatives to our current crisis response system already exist in the form of community-based mobile crisis response teams that rely on mental health workers instead of law enforcement. This review examines such programs that have been enacted in multiple cities across the country. Analysis of these alternative crisis response models shows that community-based programs are more effective, efficient, and safer than the current standard that relies on law enforcement. This analysis highlights the need for the establishment of community-based crisis response teams as the national standard.

Design of Wearable Textile Electrodes for the Monitorization of Patients with Heart Failure.

Heart failure is a severe medical condition with an important worldwide incidence that occurs when the heart is unable to efficiently pump the patient's blood throughout the body. The monitoring of edema in the lower limbs is one of the most efficient ways to control the evolution of the condition. Impedance spectroscopy has been proposed as an efficient technique to monitor body volume in patients with heart failure. It is necessary to research new wearable devices for remote patient monitoring, which can be easily worn by patients in a continuous way. In this work, we design and implement new wearable textile electrodes for the monitoring of edema evolution in patients with heart failure. Impedance spectroscopy measurements were carried out in 5 healthy controls and 2 patients with heart failure using our wearable electrodes for 3 days. The results show the appropriateness of impedance spectroscopy and our wearable electrodes to monitor body volume evolution. Impedance spectroscopy is shown to be an efficient marker of the presence of edema in heart failure patients. Initial patient positive feedback was obtained for the use of the wearable device.

CRISPRi-induced transcriptional regulation of IAH1 gene and its influence on volatile compounds profile in Kluyveromyces marxianus DU3.

Mezcal is a traditional Mexican distilled beverage, known for its marked organoleptic profile, which is influenced by several factors, such as the fermentation process, where a wide variety of microorganisms are present. Kluyveromyces marxianus is one of the main yeasts isolated from mezcal fermentations and has been associated with ester synthesis, contributing to the flavors and aromas of the beverage. In this study, we employed CRISPR interference (CRISPRi) technology, using dCas9 fused to the Mxi1 repressor factor domain, to down-regulate the expression of the IAH1 gene, encoding for an isoamyl acetate-hydrolyzing esterase, in K. marxianus strain DU3. The constructed CRISPRi plasmid successfully targeted the IAH1 gene, allowing for specific gene expression modulation. Through gene expression analysis, we assessed the impact of IAH1 down-regulation on the metabolic profile of volatile compounds. We also measured the expression of other genes involved in volatile compound biosynthesis, including ATF1, EAT1, ADH1, and ZWF1 by RT-qPCR. Results demonstrated successful down-regulation of IAH1 expression in K. marxianus strain DU3 using the CRISPRi system. The modulation of IAH1 gene expression resulted in alterations in the production of volatile compounds, specifically ethyl acetate, which are important contributors to the beverage's aroma. Changes in the expression levels of other genes involved in ester biosynthesis, suggesting that the knockdown of IAH1 may generate intracellular alterations in the balance of these metabolites, triggering a regulatory response. The application of CRISPRi technology in K. marxianus opens the possibility of targeted modulation of gene expression, metabolic engineering strategies, and synthetic biology in this yeast strain.

Effect of Processing Methods of Human Saliva on the Proteomic Profile and Protein-Mediated Biological Processes.

The use of saliva as a protein source prior to microbiological and biological assays requires previous processing. However, the effect of these processing methods on the proteomic profile of saliva has not been tested. Stimulated human saliva was collected from eight healthy volunteers. Non-processed saliva was compared with 0.22 µm filtered, 0.45 µm filtered, and pasteurized saliva, by liquid chromatography-mass spectrometry. Data are available via ProteomeXchange with identifier PXD039248. The effect of processed saliva on microbial adhesion was tested using bacterial and fungus species and in biological cell behavior using HaCaT immortalized human keratinocytes. Two hundred and seventy-eight proteins were identified in non-processed saliva, of which 54 proteins (≈19%) were exclusive. Saliva processing reduced identified proteins to 222 (≈80%) for the 0.22 µm group, 219 (≈79%) for the 0.45 µm group, and 201 (≈72%) for the pasteurized saliva, compared to non-processed saliva. The proteomic profile showed similar molecular functions and biological processes. The different saliva processing methods did not alter microbial adhesion (ANOVA, p > 0.05). Interestingly, pasteurized saliva reduced keratinocyte cell viability. Saliva processing methods tested reduced the proteomic profile diversity of saliva but maintained similar molecular functions and biological processes, not interfering with microbial adhesion and cell viability, except for pasteurization, which reduced cell viability.

PTRH2 is Necessary for Purkinje Cell Differentiation and Survival and its Loss Recapitulates Progressive Cerebellar Atrophy and Ataxia Seen in IMNEPD Patients.

Hom ozygous variants in the peptidyl-tRNA hydrolase 2 gene (PTRH2) cause infantile-onset multisystem neurologic, endocrine, and pancreatic disease. The objective is to delineate the mechanisms underlying the core cerebellar phenotype in this disease. For this, we generated constitutive (Ptrh2LoxPxhCMVCre, Ptrh2-/- mice) and Purkinje cell (PC) specific (Ptrh2LoxPxPcp2Cre, Ptrh2ΔPCmice) Ptrh2 mutant mouse models and investigated the effect of the loss of Ptrh2 on cerebellar development. We show that Ptrh2-/- knockout mice had severe postnatal runting and lethality by postnatal day 14. Ptrh2ΔPC PC specific knockout mice survived until adult age; however, they showed progressive cerebellar atrophy and functional cerebellar deficits with abnormal gait and ataxia. PCs of Ptrh2ΔPC mice had reduced cell size and density, stunted dendrites, and lower levels of ribosomal protein S6, a readout of the mammalian target of rapamycin pathway. By adulthood, there was a marked loss of PCs. Thus, we identify a cell autonomous requirement for PTRH2 in PC maturation and survival. Loss of PTRH2 in PCs leads to downregulation of the mTOR pathway and PC atrophy. This suggests a molecular mechanism underlying the ataxia and cerebellar atrophy seen in patients with PTRH2 mutations leading to infantile-onset multisystem neurologic, endocrine, and pancreatic disease.

Endoscopic sleeve gastroplasty: early results of a minimally invasive procedure in patients with obesity.

OBJECTIVES: We aimed to analyze the efficacy and safety of endoscopic sleeve gastroplasty at 3 months as well as to determine factors influencing post-procedural weight loss. METHODS: Seventy-three patients with obesity classes I, II and III (BMI 31.1-46.6 kg/m2) underwent ESG between September 2021 and April 2022 at a tertiary care hospital using Overstitch (Apollo Endosurgery, Austin, TX). ESG's efficacy and safety was evaluated at 1 and 3 months post-procedure with regard to excess weight loss (EWL) and total weight loss (TWL). Categorical variables were expressed as percentages and compared with chi-square test while continuous variables were expressed as mean ± standard deviation and compared with paired t test and analysis of variance (ANOVA) as applicable. Pearson's correlation was used to determine association between factors at baseline and weight loss. RESULTS: Mean age was 49.2 ± 9.7 years with 61 (83.6%) patients being female. Mean initial weight was 105.7 ± 15.7 kg, and mean BMI was 38.6 ± 3.5 kg/m2. Median hospitalization was 2.0 ± 1.8 days with 62 (84.9%) patients discharged after 24 h. One patient had accidental suturing of the stomach to the abdominal wall and diaphragm which was managed laparoscopically. Mean %EWL was 25.4 ± 7.1 and 36.3 ± 11.4, and %TBWL was 11.2 ± 2.6 and 15.8 ± 4.2 at 1 and 3 months, respectively. Significant excess weight loss at 3 months was only observed in patients with BMI < 40 kg/m2 (p = 0.001). CONCLUSIONS: ESG is safe and effective to manage obesity. Significant weight loss at 3 months was only observed in patients with obesity class I and class II.

Optimization of a Validated Protocol That Determines Bioavailable Fluoride in Toothpastes.

A validated protocol used to determine how much of total fluoride is bioavailable in toothpaste formulations was evaluated if it could be simplified regarding the following parameters: (1) concentration of the slurry (0.25-4%), (2) centrifugation speed (1,000-12,000 g) and time (1-10 min), and (3) incubation time for FPO32- ion hydrolysis and insoluble-F dissolution (15-60 min). Fresh and aged Na2FPO3/CaCO3 and fresh NaF/SiO2-based toothpastes were analyzed (n = 9). The improvements were the centrifugation at 1,000 g for 5 min is enough to separate insoluble-F and the time for FPO32- ion hydrolysis and insoluble-F dissolution can be shortened to 30 min.

Clinical performance of and patient satisfaction with conventional complete dentures with different occlusal schemes: A systematic review of systematic reviews.

STATEMENT OF PROBLEM: The complete denture occlusal scheme may influence clinical performance and patient satisfaction. However, a consensus on which occlusal scheme should be used for complete denture users is lacking. As a result, many dentists choose the scheme based on their preferences and clinical experience. PURPOSE: The purpose of this review was to assess the methodological quality and summarize the scientific evidence from secondary studies about the influence of occlusal schemes on the clinical performance of and patient satisfaction with complete dentures. MATERIAL AND METHODS: Ten sources were surveyed according to the patient, intervention, comparison, outcome (PICO) strategy. Systematic reviews that evaluated the clinical performance and patient satisfaction (O) of rehabilitated edentulous patients with conventional complete dentures (P) under different occlusal schemes (I/C) were included. Methodological quality was assessed by using A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 tool by 2 authors independently. The effect of each occlusal scheme in comparison with others was summarized and classified as positive, neutral, negative, or inconclusive based on the conclusions of the systematic review concerning clinical performance and patient satisfaction outcomes. RESULTS: The search led to the inclusion of 10 systematic reviews. Seven were classified as of critically low, 2 as low, and 1 as moderate methodological quality. The following occlusal designs were included and analyzed: bilateral balanced occlusion, lingualized occlusion, canine guidance, group function, and monoplane occlusion. Bilateral balanced occlusion and canine guidance obtained satisfactory results for both outcomes. Lingualized occlusion showed a trend toward better results than other occlusal schemes for normal and resorbed ridges. Group function presented mainly inconclusive results, and monoplane occlusion did not deliver satisfactory outcomes. CONCLUSIONS: The present overview concluded that occlusal schemes might interfere with the clinical performance of and patient satisfaction with complete dentures. Lingualized, bilateral balanced, and canine guidance are preferred compared with monoplane occlusion, but lingualized occlusion tends to show better results in some reviews. However, the results should be carefully considered because of the low quality of the systematic reviews included.

Targeted Therapies and Utility of the Lung-molGPA in Non-Small-Cell Lung Cancer Patients with Brain Metastases.

INTRODUCTION: Therapeutic advances have increased the survival of non-small-cell lung cancer (NSCLC) patients as well as the lifetime risk of being diagnosed with brain metastases (BM). Although BM have historically been associated with poor prognosis, it is unclear whether they remain a strong predictor of reduced survival. This study aimed to evaluate the prognostic value of BM and the utility of the Lung-molGPA. METHODS: This single-center retrospective database analysis included 1,393 NSCLC patients with newly diagnosed BM who registered at the Instituto Nacional de Cancerología of Mexico (INCan) from 2010 to 2020. The Kaplan-Meier method and log-rank test were used for the survival analysis. Survival times were calculated from the date of NSCLC diagnosis (OS), or BM diagnosis, to the date of death or last follow-up. Cox proportional-hazards models were used to calculate the hazard ratio (HR) for death and the significance of the parameters evaluated. RESULTS: Out of 1,058 patients who underwent genetic testing for epidermal growth factor receptor (EGFR) mutations and/or anaplastic lymphoma kinase (ALK) rearrangements, 650 had a positive tumor mutational/rearrangement status (543 had EGFR mutations, 104 had ALK rearrangements, and 3 had both EGFR and ALK alterations). Median OS did not differ between patients with BM and without BM (17.7 months [95% CI, 15.4-19.0] vs. 16.6 months [95% CI, 14.3-19.0]; p = 0.362). In contrast, the presence of BM was associated with worse OS in patients with a negative tumor mutational status (HR: 1.225 [95% CI, 1.041-1.443]; p = 0.015), who did not receive TKI therapy (HR: 1.269 [95% CI, 1.082-1.488]; p = 0.003), or with non-adenocarcinoma histology (HR: 1.582 [95% CI, 1.118-2.238]; p = 0.01). The median survival after BM diagnosis was 4.27, 6.96, 14.68, and 18.89 months for adenocarcinoma patients with Lung-molGPA scores 0-1, 1.5-2, 2.5-3, and 3.5-4, respectively (p < 0.0001). For non-adenocarcinoma patients with Lung-molGPA scores 0-1, 1.5-2, and 2.5-3, the corresponding estimates were 0.95, 2.89, and 9.39 months, respectively (p < 0.0001). CONCLUSIONS: These results show that the prognosis of NSCLC patients with BM is no longer uniformly poor and should be individually assessed. Furthermore, the validity of the Lung-molGPA was confirmed in an independent population from a different geographical region.

Identification of genes related to hydrolysis and assimilation of Agave fructans in Candida apicola NRRL Y-50540 and Torulaspora delbrueckii NRRL Y-50541 by denovo transcriptome analysis.

Fructans are the main sugar in agave pine used by yeasts during mezcal fermentation processes, from which Candida apicola NRRL Y-50540 and Torulaspora delbrueckii NRRL Y-50541 were isolated. De novo transcriptome analysis was carried out to identify genes involved in the hydrolysis and assimilation of Agave fructans (AF). We identified a transcript annotated as SUC2, which is related to ß-fructofuranosidase activity, and several differential expressed genes involved in the transcriptional regulation of SUC2 such as: MIG1, MTH1, SNF1, SNF5, REG1, SSN6, SIP1, SIP2, SIP5, GPR1, RAS2, and PKA. Some of these genes were specifically expressed in some of the yeasts according to their fructans assimilation metabolism. Different hexose transporters that could be related to the assimilation of fructose and glucose were found in both the transcriptomes. Our findings provide a better understanding of AF assimilation in these yeasts and provide resources for further metabolic engineering and biotechnology applications.

Expanding the structure-activity relationship of cytotoxic diphenyl macrocycles.

Twenty-four biaryl tetrapeptide macrocycles were synthesized as an extension of our previous work. Two groups of compounds were constructed for establishing a structure-activity relationship: one having an aromatic substituent at α-position of one exo-peptide and the other group with a variation in the size of the lipophilic chain. Compound 13t had the best cytotoxicity from all the compounds tested (in a panel of six human cancer cell lines) and low toxicity on one healthy cell line. The study identified the lipophilic chain as the main structural moiety for improving the biological activity, being the seven-carbon chain the optimal length. On the other hand, the aromatic rings at α-position did not enhance the cytotoxicity.

Synthesis of nuevamine and a cyano-chilenine analog via divergent C(sp3)-H bond functionalization of isoindolinone derivatives.

Divergent C(sp3)-H bond functionalizations of isoindolinone derivatives were developed to synthesize nuevamine, a cyano-chilenine derivative, and two related analogs. A copper-catalyzed C-H cross-dehydrogenative coupling (via cation formation) allowed the formation of a new C-C bond leading to the direct assembly of the isoindolo[1,2-a]isoquinolinone tetracyclic system of the nuevamine. The syntheses of the cyano-chilenine derivatives were carried out by installing two nitrile groups under basic conditions (via anion formation). Then, the isoindolobenzazepinic system of the chilenine skeleton was constructed by a Houben-Hoesch cyclization process. The present methodology has the advantage of not requiring the use of pre-functionalized substrates.

Clinical Impact of the COVID-19 Pandemic in Mexican Patients with Thoracic Malignancies.

BACKGROUND: Accumulated evidence indicates that patients with lung cancer are a vulnerable population throughout the pandemic. Limited information is available in Latin America regarding the impact of the pandemic on medical care. The goal of this study was to describe the clinical and social effect of COVID-19 on patients with thoracic cancer and to ascertain outcomes in those with a confirmed diagnosis. MATERIALS AND METHODS: This cohort study included patients with thoracic neoplasms within a single institution between March 1, 2020, and February 28, 2021. All variables of interest were extracted from electronic medical records. During this period, the Depression Anxiety and Stress Scale 21 (DASS-2) was applied to evaluate and identify more common psychological disorders. RESULTS: The mean age for the total cohort (n = 548) was 61.5 ± 12.9 years; non-small cell lung cancer was the most frequent neoplasm (86.9%), advanced stages predominated (80%), and most patients were under active therapy (82.8%). Any change in treatment was reported in 23.9% of patients, of which 78.6% were due to the COVID-19 pandemic. Treatment delays (≥7 days) were the most frequent modifications in 41.9% of cases, followed by treatment suspension at 37.4%. Patients without treatment changes had a more prolonged progression-free survival and overall survival (hazard ratio [HR] 0.21, p < .001 and HR 0.28, p < .001, respectively). The mean DASS-21 score was 10.45 in 144 evaluated patients, with women being more affected than men (11.41 vs. 9.08, p < .001). Anxiety was reported in 30.5% of cases, followed by depression and distress in equal proportions (18%). Depressed and stressed patients had higher odds of experiencing delays in treatment than patients without depression (odds ratio [OR] 4.5, 95% confidence interval [CI] 1.53-13.23, p = .006 and OR 3.18, 95% CI 1.2-10.06, p = .006, respectively). CONCLUSION: Treatment adjustments in patients with thoracic malignancies often occurred to avoid COVID-19 contagion with detrimental effects on survival. Psychological disorders could have a role in adherence to the original treatment regimen. IMPLICATIONS FOR PRACTICE: The pandemic has placed an enormous strain on health care systems globally. Patients with thoracic cancers represent a vulnerable population, with increased morbidity and mortality rates. In Mexico, treatment modifications were common during the pandemic, and those who experienced delays had worse survival outcomes. Most treatment modifications were related to a patient decision rather than a lockdown of health care facilities in which mental health impairment plays an essential role. Moreover, the high case fatality rate highlights the importance of improving medical care access. Likewise, to develop strategies facing future threats that may compromise health care systems in non-developed countries.

Multicomponent synthesis and preliminary anti-inflammatory activity of lipophilic diphenylamines.

Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are some of the most prescribed medications for pain but the incidence of adverse effects -especially during chronic treatment- points out the requirement of new analgesics. In this study, we showed an efficient two-steps synthesis of diphenylamine-containing dipeptides consisting of a multicomponent process followed by a Buchwald-Hartwig cross-coupling reaction. We prepared 16 diphenylamine derivatives and evaluated their in vivo anti-inflammatory activity through an ear edema model using 12-O-tetradecanoylpholbol-13-acetate. Furthermore, the toxicity of the more potent compounds in the Artemia salina model and their cell viability using murine RAW 264.7 cells is reported. The fluorinated compound 10k becomes a reliable candidate since it reduced the TPA-induced edema to 92%, lacked cytotoxicity against murine macrophages, and had minimal toxicity in Artemia salina.

Multicomponent synthesis and anti-proliferative screening of biaryl triazole-containing cyclophanes.

We report a practical two-step approach involving a Ugi 4-CR/ azide-alkyne cycloaddition for the synthesis of biaryl-containing cyclophanes. The series represents an extension of our previously reported macrocycles as an effort to enhance the anti-proliferative activity of this scaffold. In this variant, we incorporate a biphenyl moiety in the framework, thus enhancing the macrocycle size, lipophilicity, and structural diversity. Macrocycles were tested against different cell lines, being more cytotoxic against prostate (PC-3 and DU-145) and breast (MCF-7) tumor cells. Gratifyingly, the most active compound showed a significative enhancement of PC-3 growth inhibition with respect to our previous series, reaffirming the potential anti-proliferative activity of this kind of cyclophanes.

Pairing multicomponent stators with aromatic rotators for new emissive molecular rotors.

We demonstrate here that the Ugi-Sonogashira protocol can be successfully used to obtain five new molecular rotors 10a-e with strong emission. They have been synthesized by combining multicomponent Ugi stators and several aromatic rotary components: phenylene, p-xylene, naphthalene and anthracene. The synthesized conjugated rotors are highly fluorescent (Φf = 0.39 to Φf = 0.10), and changes in their emission were observed upon variations of the surrounding media. Particularly, we found that they are sensitive to aggregation (THF/water) or high viscosity (methanol/glycerol) conditions. This work paves the way to develop new emissive rotors with exciting photophysical properties.

Asthma and Physical Activity in Urban Children.

OBJECTIVES: Asthma and obesity disproportionately affect urban minority children. Avoidance of physical activity contributes to obesity, and urban children with asthma are at risk for lower levels of physical activity. We examined associations between lung function and moderate to vigorous physical activity (MVPA) and moderators of this association in a diverse sample of children with asthma. METHODS: Urban children (N = 142) ages 7-9 with persistent asthma and their caregivers completed a study of asthma and physical activity. Longitudinal mixed effects models examining daily-level asthma and physical activity evaluated the association between asthma and MVPA, and the moderating effect of weight, and cultural/contextual factors on this association. RESULTS: Average daily MVPA was below recommended guidelines. Differences in MVPA were found by racial/ethnic group (p = .04) and weight (p = .001). Poorer asthma status was associated with lower MVPA in Latino and Black participants (p's < .05), and in normal weight youth (p = .01). Body mass index (BMI) moderated the association between asthma and MVPA. Those with lower BMI had more optimal asthma status and higher MVPA levels, whereas associations attenuated for participants with higher BMI (p = .04). Caregivers' perceptions of neighborhood safety and fear of asthma were marginally associated with children's symptoms and MVPA: as perceptions of safety decreased and fear increased, associations between asthma and MVPA weakened (p's = .09 and .07, respectively). CONCLUSIONS: Suboptimal asthma status is associated with less MVPA in urban children. Weight status and cultural/contextual factors play a role in the association and are worthy targets for future research and intervention.