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PurposeSickle cell disease (SCD) imparts an increased risk for obstructive sleep apnea (OSA) in childhood. Studies of pediatric SCD have identified an increased risk for pain and neurologic complications with comorbid OSA. We determined the rate of a broad range of SCD-related medical complications to better characterize the spectrum of SCD complications related to OSA.MethodsRetrospective chart review at a single hematology clinic identified 641 youth with SCD who received consistent screenings for OSA as part of routine hematological health maintenance visits over an 11-year period. Medical complication rates in the 136 children with OSA determined by polysomnography exams were compared to 136 matched controls at lower risk for OSA due to negative OSA screenings or exams.ResultsChildren with SCD and OSA had higher overall rates of SCD complications than low OSA-risk controls; lung morbidity showed the largest effect size. Infection, cardiovascular, and neurologic complications occurred at higher rates in children with OSA. Children with comorbid OSA had higher rates of SCD complications both before and after OSA diagnosis.ConclusionsOSA in children with SCD is associated with higher rates of a broad range of SCD complications, including pneumonia and acute chest syndrome. Routine screenings, diagnosis, and increased therapeutic intervention for children with comorbid OSA could decrease SCD morbidity.

Discovery and validation of genetic variants that influence disease severity in children with sickle cell anemia (SCA) could lead to early identification of high-risk patients, better screening strategies, and intervention with targeted and preventive therapy. We hypothesized that newly identified genetic risk factors for the general African American population could also impact laboratory biomarkers known to contribute to the clinical disease expression of SCA, including variants influencing the white blood cell count and the development of albuminuria and abnormal glomerular filtration rate. We first investigated candidate genetic polymorphisms in well-characterized SCA pediatric cohorts from three prospective NHLBI-supported clinical trials: HUSTLE, SWiTCH, and TWiTCH. We also performed whole exome sequencing to identify novel genetic variants, using both a discovery and a validation cohort. Among candidate genes, DARC rs2814778 polymorphism regulating Duffy antigen expression had a clear influence with significantly increased WBC and neutrophil counts, but did not affect the maximum tolerated dose of hydroxyurea therapy. The APOL1 G1 polymorphism, an identified risk factor for non-diabetic renal disease, was associated with albuminuria. Whole exome sequencing discovered several novel variants that maintained significance in the validation cohorts, including ZFHX4 polymorphisms affecting both the leukocyte and neutrophil counts, as well as AGGF1, CYP4B1, CUBN, TOR2A, PKD1L2, and CD163 variants affecting the glomerular filtration rate. The identification of robust, reliable, and reproducible genetic markers for disease severity in SCA remains elusive, but new genetic variants provide avenues for further validation and investigation.

Brown adipose tissue (BAT) burns, rather than stores, energy and has thus been explored as a way to combat obesity. Aaron Cypess and his colleagues isolate neck fat from adult humans and show that BAT exists in this region, define its anatomical localization in the neck relative to white adipose tissue and demonstrate that it is functional. The imbalance between energy intake and expenditure is the underlying cause of the current obesity and diabetes pandemics. Central to these pathologies is the fat depot: white adipose tissue (WAT) stores excess calories, and brown adipose tissue (BAT) consumes fuel for thermogenesis using tissue-specific uncoupling protein 1 (UCP1) 1 , 2 . BAT was once thought to have a functional role in rodents and human infants only, but it has been recently shown that in response to mild cold exposure, adult human BAT consumes more glucose per gram than any other tissue 3 . In addition to this nonshivering thermogenesis, human BAT may also combat weight gain by becoming more active in the setting of increased whole-body energy intake 4 , 5 , 6 , 7 . This phenomenon of BAT-mediated diet-induced thermogenesis has been observed in rodents 8 and suggests that activation of human BAT could be used as a safe treatment for obesity and metabolic dysregulation 9 . In this study, we isolated anatomically defined neck fat from adult human volunteers and compared its gene expression, differentiation capacity and basal oxygen consumption to different mouse adipose depots. Although the properties of human neck fat vary substantially between individuals, some human samples share many similarities with classical, also called constitutive, rodent BAT.

The foundation's philanthropy has grown to significance primarily through good stewardship of its investments. Since inception, the Fremont Area Community Foundation has granted millions of dollars each year to local organizations and programs. According to the U.S. Bureau of Labor Statistics, by 2009 unemployment peaked at 15.1 percent. [...]it is our responsibility to report back to the community: Key Points * In 2011, the Fremont Area Community Foundation launched a community investment strategy, focused on education, poverty, and economic development, that shaped corresponding aspirational goals aimed at improving the quality of life for residents of rural Newaygo County, Mich. * While there had been significant community involvement and input into foundation planning for a number of years, the announcement of these strategic goals and their implementation created some apprehension among the local nonprofits. The new funding paradigms were a big change, and it took several years for many of the grantees, with assistance in the form of backbone services and tools to monitor impact, to make the transition to new ways of thinking about their work. * As the foundation moves ahead with its second five-year strategic plan, it is being guided through a continued process of change by research and learning, community feedback, results from key grantee surveys, and evidence of where the work has contributed to positive outcomes for the population it serves. Since inception, the Fremont Area Community Foundation has granted millions of dollars each year to local organizations and programs.

We investigated the association of increased cerebral blood flow velocity with specific language abilities in children with sickle cell disease (SCD). Thirty-nine children ages 5 to 8 years old with high-risk genotypes of SCD underwent cognitive testing, which included tests of language skills, visual motor skills, and attention/working memory as part of a routine hematology health-maintenance visit. Transcranial Doppler (TCD) velocities were obtained from review of medical records, with the velocities that were in closest temporal proximity to the cognitive assessment used in the analysis. TCD velocities predicted scores on tests of syntactical skills, even when controlling for anemia severity. Semantic and phonological ability and other cognitive skills were not strongly related to TCD velocities. Elevated blood flow velocities in children with high-risk SCD may contribute to a specific language impairment or to a broader dysfunction of short-term and/or working memory. This study underscores the need for clinicians to monitor language skills of children with SCD who have elevated TCD velocities, as these cognitive abilities might be particularly sensitive to cerebrovascular disruption related to their disease. (JINS, 2010, 16, 326–334.)

The physical effects of sickle cell disease (SCD) begin in infancy or early childhood, yet most behavioral studies have focused on school-age children. We evaluated the impact of higher versus lower neurologic risk on language, motor abilities, executive functions, and temperament in toddlers and early preschoolers with SCD. Thirty-nine children with higher risk SCD were compared to 22 children with lower risk SCD. Language and motor abilities were lower in older compared with younger children but were unrelated to sickle cell subgroups. Executive functions, particularly working memory, were poorer in children with higher risk SCD regardless of age. Parent-reported activity level was also lower in children with higher risk. Specific behavioral influences of SCD are evident early in childhood and include working memory decrements. Executive function deficits in SCD can emerge early in life and may be an important context for other areas of cognitive and behavioral development. (JINS, 2007, 13, 933–943.)

Introduction This real-world, cross-sectional study compared sociodemographic, clinical and treatment characteristics, and patient-reported outcomes (PROs) among racial/ethnic groups in patients with atopic dermatitis (AD) who are candidates for systemic therapy. Methods This study included adults with dermatologist- or dermatology practitioner-diagnosed AD enrolled in the CorEvitas AD Registry (July 2020–July 2021). All patients initiated systemic therapy within 12 months prior to or at enrollment or had moderate-to-severe AD (vIGA-AD ®  ≥ 3 and Eczema Area and Severity Index [EASI] ≥ 12) at enrollment. Patients were categorized into five mutually exclusive racial/ethnic groups: non-Hispanic White, Black, Asian, Other/Multiracial, and Hispanic (any race). Patient, clinical, and treatment characteristics were captured at enrollment. Differences in means or proportions of characteristics among racial/ethnic groups were descriptively summarized using effect sizes. Adjusted prevalence ratios and mean differences were estimated (White race/ethnicity group as the reference category) with 95% confidence intervals (CI). Results Among 1288 patients, 64% ( n  = 822) were White, 13% ( n  = 167) Black, 10% ( n  = 129) Asian, 8% ( n  = 97) Hispanic, and 6% ( n  = 73) Other/Multiracial. In adjusted analyses, statistically more severe EASI lichenification was noted among Black compared with White patients at the head and neck (mean difference, 0.21, [95% CI 0.06, 0.36]; p  = 0.01), trunk (0.32, [0.17, 0.47]; p  < 0.001), upper extremities (0.27, [0.09, 0.44]; p  = 0.008), and lower extremities (0.39, [0.21, 0.57]; p  < 0.001). Statistically more severe EASI lichenification was observed among Asian vs White patients in certain areas (mean difference, head and neck, 0.22 [0.04, 0.39], p  = 0.01; trunk, 0.25 [0.07, 0.43], p  < 0.001; lower extremities, 0.22 [0.01, 0.43], p  < 0.001) and SCORing for AD lichenification (mean difference: 0.34 [0.15, 0.52]; p  < 0.001). Significantly higher mean pruritus over the past 7 days for Black (mean difference: 0.63 [0.01, 1.26] and Hispanic patients (0.60 [0.11, 1.09]; p  = 0.03) vs White patients was observed. Among AD clinical features, the prevalence of facial erythema was significantly lower among Black compared with White patients (prevalence ratio = 0.38, [0.22, 0.67]; p  = 0.007). Conclusion Racial/ethnic differences exist in sociodemographic, clinical and treatment characteristics, disease severity, and PROs among real-world AD patients who are candidates for systemic therapy. Recognizing these variations may be of critical importance for dermatologists for the design and delivery of targeted/personalized medicine approaches.

Introduction This observational study evaluated response in patients with rheumatoid arthritis (RA) who switched from an interleukin-6 receptor inhibitor (IL-6Ri) to a Janus kinase inhibitor (JAKi) and vice versa. Methods Adult patients with RA, who initiated IL-6Ri or JAKi (following discontinuation of JAKi or IL-6Ri, respectively) during/after December 2012 and had a 6-month follow-up visit were enrolled. Clinical outcomes were evaluated at baseline and the follow-up visit. Continuous outcomes included Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire (HAQ), pain, fatigue, tender joint count, swollen joint count, Physician Global Assessment (MDGA), Patient Global Assessment (PtGA), and morning stiffness duration. Categorical outcomes included the proportion of patients achieving CDAI low disease activity (LDA), remission, and minimal clinically important differences (MCIDs) for HAQ, pain, fatigue, MDGA, and PtGA. Continuous outcomes were summarized as mean changes from baseline, and categorical outcomes as response rates. Differences in the outcome measures between groups were evaluated using linear and logistic regression models. Results Between IL-6Ri ( n  = 100) and JAKi initiators ( n  = 129), no significant differences were noted for continuous outcomes. Within both groups, a significant proportion of patients achieved LDA, remission, and MCIDs for other measures, although the odds of achieving LDA were higher among IL-6Ri (vs. JAKi) initiators with moderate-to-severe disease (adjusted odds ratio: 3.30 [1.01, 10.78]). Conclusions Patients with RA can achieve improvement in response when switching between IL-6Ri and JAKi. Although both therapies affect the IL-6 pathway, there are distinct mechanisms of action, which likely contribute to their clinical improvement, when reciprocally switched as follow-on treatments.

This department publishes brief news articles, announcements, and guest editorials on current mathematics education issues that stimulate the interest of TCM readers and cause them to think about an issue or consider a specific viewpoint about some aspect of mathematics education.

This real-world study investigated the impact of patient-reported disease burden and health-related quality of life (HRQoL) on switching from systemic nonbiologic to biologic therapy in patients with plaque psoriasis. Biologic therapy-naive (biologic-naive) patients aged ≥18 years who were using systemic nonbiologic treatment and who enrolled in the CorEvitas Psoriasis Registry between April 2015 and August 2022 were included. Measures of patient-reported disease burden and HRQoL were collected at Registry enrollment. The primary outcome of interest was initiation of biologic therapy within 45 days of enrollment. Multivariable logistic regression models were fitted separately for each patient-reported measure, adjusting for patient, disease, and treatment characteristics, including physician-rated disease severity. Adjusted odds ratios of switching to biologic therapy were estimated for greater versus lesser burden for each measure. Of 848 included patients, 323 (38.1%) switched to biologic treatment. Greater patient-reported burden was independently associated with switching, with significantly higher adjusted odds ratios (95% confidence interval) for greater versus lesser burden as measured by the Dermatology Life Quality Index (1.55 [1.08-2.23], =0.017), visual analog scale (VAS) for itch (2.14 [1.49-3.08], <0.001), VAS for skin pain (2.18 [1.45-3.29], <0.001), VAS for fatigue (1.66 [1.15-2.40], =0.007), Patient Global Assessment-VAS (3.09 [1.94-4.91], <0.001), and with activities impairment on the Work Productivity and Activity Impairment questionnaire (2.51 [1.72-3.65], <0.001). In addition to clinically assessed disease severity, patient-reported disease burden and quality of life may drive the switch to biologic treatment in real-world patients with plaque psoriasis.