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Facilitated subcutaneous immunoglobulin (fSCIG) 10% is an immunoglobulin replacement therapy that utilizes recombinant human hyaluronidase (rHuPH20) to enhance immunoglobulin dispersion and absorption, allowing for longer treatment intervals similar to intravenous immunoglobulin (up to once monthly). fSCIG 10% is indicated in the USA for treating adults and children aged ≥ 2 years with primary immunodeficiency diseases (PIDs). This prospective, non-interventional, open-label, multicenter, post-authorization safety study (NCT02593188) was conducted in the USA from November 2015 to October 2021 to assess the long-term safety of fSCIG 10% in routine clinical practice. Patients with PIDs aged ≥ 16 years who were prescribed and/or had started fSCIG 10% treatment were enrolled. In total, 253 patients were enrolled and included (full analysis set). Participants received fSCIG 10% treatment for a median (interquartile range) of 10.0 (3.5-11.8) months, with the majority of infusions administered every 4 weeks (54.4% [1197/2201 infusions]) and at home (62.6% [1395/2230 infusions]). Overall, 98.5% of infusions were administered without rate reduction, interruption, or discontinuation due to adverse events (AEs). Treatment-related, non-serious AEs were experienced by 52 patients (20.6%, 284 events). Two patients (0.8%) each experienced one treatment-related serious AE (aseptic meningitis and deep vein thrombosis). Development of antibodies against rHuPH20 was uncommon; 14/196 patients (7.1%) tested positive for binding antibodies (titer ≥ 1:160) with no neutralizing antibodies detected. There was no relationship between anti-rHuPH20 antibody positivity and the occurrence of treatment-related serious or non-serious AEs. Long-term, repeated self-administration of fSCIG 10% was well tolerated in US clinical practice by patients with PIDs.

INTRODUCTION: Recent studies have documented the negative impact of the COVID-19 pandemic on low-income families, rural and underserved areas, and racial and ethnic minority populations. However, less is known about immigrants healthcare access and utilization, including telehealth use. This study investigated disparities in healthcare access and utilization by immigration status among adults aged 18-64 years during the COVID-19 pandemic. METHODS: This cross-sectional study pooled data from the 2020 and 2021 National Health Interview Survey (NHIS). Multivariable logistic regression models were used to estimate the variation of healthcare access and utilization by citizenship and nativity status. Immigration status (U.S.-born citizen, naturalized U.S. citizen, and non-citizen) served as the key independent variable. Healthcare access measures were dichotomized indicators of whether individuals had delayed medical care either due to cost or due to COVID-19. Healthcare utilization measures included whether individuals visited a doctor, used the emergency room, or had a telehealth visit during COVID-19. RESULTS: Compared to U.S.-born citizens, non-citizen immigrants were more likely to delay medical care due to cost (adjusted OR = 1.375, [95%CI: 1.137, 1.662]), less likely to visit a doctor (adjusted OR = 0.71, [95%CI: 0.617, 0.817]), or visit an emergency room (adjusted OR = 0.756, [95%CI: 0.635, 0.901]). Non-citizen immigrants were less likely to have a telehealth visit (either video or phone visits) during COVID-19 (adjusted OR = 0.634, [95%CI: 0.557, 0.723]). DISCUSSION: Compared to U.S.-born citizens, lower healthcare and telehealth utilization persisted among non-citizen immigrants during the pandemic.

Aim: To assess the long-term safety of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% in European routine clinical practice.Materials & methods: This prospective, noninterventional, open-label, post-authorization safety study (EUPAS5812) sourced data on adverse events, immunogenicity, treatment regimens and product administration for 106 adult patients prescribed fSCIG 10% across 17 sites in six European countries from July 2014 to February 2020.Results: In total, 1171 treatment-emergent adverse events were reported in 94 patients (88.7%); 25.5% of these events were considered related to fSCIG 10%. Positive binding antibody titers developed in three patients; no neutralizing antibodies to recombinant human hyaluronidase were detected.Conclusion: This real-world study of fSCIG 10% is the longest to date and confirms its long-term safety and tolerability in adults with antibody deficiency diseases.

OBJECTIVE: To examine differences in the use of high- and low-value health care between immigrant and US-born adults. DATA SOURCE: The 2007-2019 Medical Expenditure Panel Survey. STUDY DESIGN: We split the sample into younger (ages 18-64 years) and older adults (ages 65 years and over). Our outcome measures included the use of high-value care (eight services) and low-value care (seven services). Our key independent variable was immigration status. For each outcome, we ran regressions with and without individual-level characteristics. DATA COLLECTION/EXTRACTION METHODS: N/A. PRINCIPAL FINDINGS: Before accounting for individual-level characteristics, the use of high- and low-value care was lower among immigrant adults than US-born adults. After accounting for individual-level characteristics, this difference decreased in both groups of younger and older adults. For high-value care, significant differences were observed in five services and the direction of the differences was mixed. The use of breast cancer screening was lower among immigrant than US-born younger and older adults (-5.7 [95% CI: -7.4 to -3.9] and -2.9 percentage points [95% CI: -5.6 to -0.2]) while the use of colorectal cancer screening was higher among immigrant than US-born younger and older adults (2.6 [95% CI: 0.5 to 4.8] and 3.6 [95% CI: 0.2 to 7.0] percentage points). For low-value care, we did not identify significant differences except for antibiotics for acute upper respiratory infection among younger adults and opioids for back pain among older adults (-3.5 [95% CI: -5.5 to -1.5] and -3.8[95% CI: -7.3 to -0.2] percentage points). Particularly, differences in socioeconomic status, health insurance, and care access between immigrant and US-born adults played a key role in accounting for differences in the use of high- and low-value health care. The use of high-value care among immigrant and US-born adults increased over time, but the use of low-value care did not decrease. CONCLUSION: Differential use of high- and low-value care between immigrant and US-born adults may be partly attributable to differences in individual-level characteristics, especially socioeconomic status, health insurance, and access to care.

This cross-sectional study examines changes in levels of health care coverage and cost-related delays in care for Latino individuals after elimination of the individual coverage mandate from the Affordable Care Act (ACA).

In acute ischemic stroke patients with large vessel occlusion, the characteristics of the occluding thrombus on neuroimaging may be associated with recanalization after endovascular thrombectomy (EVT); however, the relationship between magnetic susceptibility of thrombus and clinical outcome remains unclear. We utilized quantitative susceptibility mapping (QSM) MRI to assess the magnetic susceptibility of thrombus in acute ischemic stroke patients undergoing EVT, and to evaluate its relationship with recanalization and functional outcomes. Patients with documented intracranial artery occlusion were consecutively recruited from one research center of the RESCUE-RE study (a registration study for Critical Care of Acute Ischemic Stroke After Recanalization). All the recruited patients underwent a 3D multi-echo MRI scan on a 3.0 T scanner for both susceptibility-weighted imaging (SWI) and QSM quantification of the thrombus. Among 61 patients included in the analyses, 51 (75.0 %) patients achieved thrombolysis in cerebral infarction (TICI) 2b/3 and 22 (36.1 %) patients had favorable functional outcomes. Successful recanalization was significantly associated with a higher thrombus magnetic susceptibility mean value (0.27 ± 0.09 vs 0.20 ± 0.09 ppm, p = 0.020) and lower coefficient of variation (0.42 ± 0.12 vs 0.52 ± 0.19, p = 0.024). ROC curve analysis showed the optimal cutoff value for thrombus susceptibility for predicting good clinical outcomes was 0.25 ppm (sensitivity 86.4 %, specificity 69.2 %). In multivariable logistic regression analyses, increased thrombus magnetic susceptibility was independently and significantly associated with good functional outcomes (adjusted odds ratio 15.11 [95 % confidence interval 2.64-86.46], p = 0.002). This study demonstrated that the increased thrombus magnetic susceptibility is associated with successful recanalization and favorable functional outcomes for intracranial artery occluded stroke patients.

BackgroundUnder emergency coronavirus disease 2019 pandemic regulations, Medicare granted temporary payment parity with in-person visits for audio-only (telephone) telemedicine visits. This policy was designed to expand telemedicine to patients without camera-equipped devices and broadband internet. However, audio-only telemedicine use has been substantial.ObjectiveThe aim of this study was to explore whether the rate of audio-only telemedicine during the pandemic is related to patient access to technology or provider behavior.DesignCross-sectional analysis of the Summer and Fall 2020 Medicare Current Beneficiary Survey coronavirus disease 2019 supplements, using multivariable logistic models and accounting for complex survey design.SubjectsA total of 3375 participants in the summer survey and 2633 participants in the fall 2020 were offered a telemedicine visit to replace a scheduled in-person visit by their usual care provider.MeasuresWe compared beneficiaries who were exclusively offered audio-only telemedicine to beneficiaries who were offered video telemedicine or both audio and video.ResultsWe found that among Medicare beneficiaries who were offered telemedicine to replace a scheduled in-person appointment, ~35% were exclusively offered audio-only. 65.8% of beneficiaries exclusively offered audio-only reported having a smartphone/tablet and home internet. After controlling for personal access to technology, Hispanic [adjusted odds ratio (AOR)=2.09, P

Since the 1960s the immigrant population in the United States has increased fourfold, reaching 44.7 million, or 13.7 percent of the US population, in 2018. The shifting immigrant demography presents several challenges for US health policy makers. We examine recent trends in immigrant health and health care after the Great Recession and the nationwide implementation of the Affordable Care Act. Recent immigrants are more likely to have lower incidence of chronic health conditions than other groups in the US, although these differences vary along the citizenship and documentation status continuum. Health care inequities among immigrants and US-born residents increased after the Great Recession and later diminished after the Affordable Care Act took effect. Unremitting inequities remain, however, particularly among noncitizen immigrants. The number of aging immigrants is growing, which will present a challenge to the expansion of coverage to this population. Health care and immigration policy changes are needed to integrate immigrants successfully into the US health care system.

Unlike other epithelial cancer types, circulating tumor cells (CTCs) are less frequently detected in the peripheral blood of non-small cell lung cancer (NSCLC) patients using epithelial marker-based detection approaches despite the aggressive nature of NSCLC. Here, we demonstrate hexokinase-2 (HK2) as a metabolic function-associated marker for the detection of CTCs. In 59 NSCLC patients bearing cytokeratin-positive (CKpos) primary tumors, HK2 enables resolving cytokeratin-negative (HK2high/CKneg) CTCs as a prevalent population in about half of the peripheral blood samples with positive CTC counts. However, HK2high/CKneg tumor cells are a minority population in pleural effusions and cerebrospinal fluids. Single-cell analysis shows that HK2high/CKneg CTCs exhibit smaller sizes but consistent copy number variation profiles compared with CKpos counterparts. Single-cell transcriptome profiling reveals that CK expression levels of CTCs are independent of their epithelial-to-mesenchymal transition (EMT) status, challenging the long-standing association between CK expression and EMT. HK2high/CKneg CTCs display metastasis and EGFR inhibitor resistance-related molecular signatures and are selectively enriched in patients with EGFRL858R driver oncogene mutation as opposed to EGFR19Del , which is more frequently found in patients with prevalent CKpos CTCs in the blood. Consistently, treatment-naïve patients with a larger number or proportion of HK2high/CKneg CTCs in the blood exhibit poor therapy response and shorter progression-free survival. Collectively, our approach resolves a more complete spectrum of CTCs in NSCLC that can potentially be exploited to identify patient prognosis before therapy.

PALB2 has been identified as a breast and pancreatic cancer susceptibility gene. Utilizing a targeted sequencing approach, we discovered two novel germline missense PALB2 variants c.191C>T and c.311C>T, encoding p.Ser64Leu and p.Pro104Leu, respectively, in individuals in a pancreatic cancer registry. No missense PALB2 variants from familial pancreatic cancer patients, and few PALB2 variants overall, have been functionally characterized. Given the known role of PALB2, we tested the impact of p.Ser64Leu and p.Pro104Leu variants on DNA damage responses. Neither p.Ser64Leu nor p.Pro104Leu have clear effects on interactions with BRCA1 and KEAP1, which are mediated by adjacent motifs in PALB2. However, both variants are associated with defective recruitment of PALB2, and the RAD51 recombinase downstream, to DNA damage foci. Furthermore, p.Ser64Leu and p.Pro104Leu both largely compromise DNA double-strand break-initiated homologous recombination, and confer increased cellular sensitivity to ionizing radiation (IR) and the poly (ADP-ribose) polymerase (PARP) inhibitor Olaparib. Taken together, our results represent the first demonstration of functionally deleterious PALB2 missense variants associated with familial pancreatic cancer and of deleterious variants in the N-terminus outside of the coiled-coil domain. Furthermore, our results suggest the possibility of personalized treatments, using IR or PARP inhibitor, of pancreatic and other cancers that carry a deleterious PALB2 variant.

Pneumocystis jirovecii, the fungal agent of human Pneumocystis pneumonia, is closely related to macaque Pneumocystis. Little is known about other Pneumocystis species in distantly related mammals, none of which are capable of establishing infection in humans. The molecular basis of host specificity in Pneumocystis remains unknown as experiments are limited due to an inability to culture any species in vitro. To explore Pneumocystis evolutionary adaptations, we have sequenced the genomes of species infecting macaques, rabbits, dogs and rats and compared them to available genomes of species infecting humans, mice and rats. Complete whole genome sequence data enables analysis and robust phylogeny, identification of important genetic features of the host adaptation, and estimation of speciation timing relative to the rise of their mammalian hosts. Our data reveals insights into the evolution of P. jirovecii, the sole member of the genus able to infect humans.

Circulating rare cells in the blood are of great significance for both materials research and clinical applications. For example, circulating tumor cells (CTCs) have been demonstrated as useful biomarkers for "liquid biopsy" of the tumor. Circulating fetal nucleated cells (CFNCs) have shown potential in noninvasive prenatal diagnostics. However, it is technically challenging to detect and isolate circulating rare cells due to their extremely low abundance compared to hematologic cells. Nanostructured substrates offer a unique solution to address these challenges by providing local topographic interactions to strengthen cell adhesion and large surface areas for grafting capture agents, resulting in improved cell capture efficiency, purity, sensitivity, and reproducibility. In addition, rare-cell retrieval strategies, including stimulus-responsiveness and additive reagent-triggered release on different nanostructured substrates, allow for on-demand retrieval of the captured CTCs/CFNCs with high cell viability and molecular integrity. Several nanostructured substrate-enabled CTC/CFNC assays are observed maturing from enumeration and subclassification to molecular analyses. These can one day become powerful tools in disease diagnosis, prognostic prediction, and dynamic monitoring of therapeutic response-paving the way for personalized medical care.

Accurate prediction of chemo- or targeted therapy responses for patients with similar driver oncogenes through a simple and least-invasive assay represents an unmet need in the clinical diagnosis of non-small cell lung cancer. Using a single-cell on-chip metabolic cytometry and fluorescent metabolic probes, we show metabolic phenotyping on the rare disseminated tumor cells in pleural effusions across a panel of 32 lung adenocarcinoma patients. Our results reveal extensive metabolic heterogeneity of tumor cells that differentially engage in glycolysis and mitochondrial oxidation. The cell number ratio of the two metabolic phenotypes is found to be predictive for patient therapy response, physiological performance, and survival. Transcriptome analysis reveals that the glycolytic phenotype is associated with mesenchymal-like cell state with elevated expression of the resistant-leading receptor tyrosine kinase AXL and immune checkpoint ligands. Drug targeting AXL induces a significant cell killing in the glycolytic cells without affecting the cells with active mitochondrial oxidation.

We examine changes in health insurance coverage and access to and utilization of health care before and after the national implementation of the Patient Protection and Affordable Care Act (ACA) among the U.S. adult immigrant population. Data from the 2011-2016 National Health Interview Survey are used to compare adult respondents in 2011-2013 (before the ACA implementation) and 2014-2016 (after the ACA implementation). Multivariable logistic regression analyses are used to compare changes over time. This study shows that the ACA has closed the coverage gap that previously existed between U.S. citizens and non-citizen immigrants. We find that naturalized citizens, non-citizens with more than 5 years of U.S. residency, and non-citizens with 5 years or less of U.S. residency reduced their probability of being uninsured by 5.81, 9.13, and 8.23%, respectively, in the first 3 years of the ACA. Improvements in other measures of access and utilization were also observed.

Rationale: Our objective was to develop a circulating tumor cell (CTC)-RNA assay for characterizing clinically relevant RNA signatures for the assessment of androgen receptor signaling inhibitor (ARSI) sensitivity in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: We developed the NanoVelcro CTC-RNA assay by combining the Thermoresponsive (TR)-NanoVelcro CTC purification system with the NanoString nCounter platform for cellular purification and RNA analysis. Based on the well-validated, tissue-based Prostate Cancer Classification System (PCS), we focus on the most aggressive and ARSI-resistant PCS subtype, i.e., PCS1, for CTC analysis. We applied a rigorous bioinformatic process to develop the CTC-PCS1 panel that consists of prostate cancer (PCa) CTC-specific RNA signature with minimal expression in background white blood cells (WBCs). We validated the NanoVelcro CTC-RNA assay and the CTC-PCS1 panel with well-characterized PCa cell lines to demonstrate the sensitivity and dynamic range of the assay, as well as the specificity of the PCS1 Z score (the likelihood estimate of the PCS1 subtype) for identifying PCS1 subtype and ARSI resistance. We then selected 31 blood samples from 23 PCa patients receiving ARSIs to test in our assay. The PCS1 Z scores of each sample were computed and compared with ARSI treatment sensitivity. Results: The validation studies using PCa cell line samples showed that the NanoVelcro CTC-RNA assay can detect the RNA transcripts in the CTC-PCS1 panel with high sensitivity and linearity in the dynamic range of 5-100 cells. We also showed that the genes in CTC-PCS1 panel are highly expressed in PCa cell lines and lowly expressed in background WBCs. Using the artificial CTC samples simulating the blood sample conditions, we further demonstrated that the CTC-PCS1 panel is highly specific in identifying PCS1-like samples, and the high PCS1 Z score is associated with ARSI resistance samples. In patient bloods, ARSI-resistant samples (ARSI-R, n=14) had significantly higher PCS1 Z scores as compared with ARSI-sensitive samples (ARSI-S, n=17) (Rank-sum test, P=0.003). In the analysis of 8 patients who were initially sensitive to ARSI (ARSI-S) and later developed resistance (ARSI-R), we found that the PCS1 Z score increased from the time of ARSI-S to the time of ARSI-R (Pairwise T-test, P=0.016). Conclusions: Using our new methodology, we developed a first-in-class CTC-RNA assay and demonstrated the feasibility of transforming clinically-relevant tissue-based RNA profiling such as PCS into CTC tests. This approach allows for detecting RNA expression relevant to clinical drug resistance in a non-invasive fashion, which can facilitate patient-specific treatment selection and early detection of drug resistance, a goal in precision oncology.

We examined changes in health insurance coverage and access to and use of health care among adult (ages 18-64) Latinos in the US before (2007-13) and after (2014-16) implementation of the main provisions of the Affordable Care Act. Data from the California Health Interview Survey were used to compare respondents in the two periods. We used multivariable and decomposition regression analyses to investigate the role of documentation status in access disparities between Mexicans and other Latinos in California. Our findings show that after the implementation of these provisions in California, insurance coverage increased for US- and foreign-born Latinos, including undocumented Latinos. Our decomposition analyses show that after implementation, disparities between Mexicans and other Latinos declined with respect to having coverage and a usual source of care. Without the implementation of these provisions in 2014, these disparities would have been 5.76 percent and 0.31 percent larger, respectively. In contrast, legal documentation status was positively associated with disparities between Mexicans and other Latinos in having coverage and physician visits. If Mexican Latinos had had the same share of undocumented immigrants as other Latinos, disparities in health insurance coverage would have declined by 24.17 percent.

Cardiovascular, respiratory, and related disorders (CVRDs) are the leading causes of adult death worldwide, and substantial inequalities in care of patients with CVRDs exist between countries of high income and countries of low and middle income. Based on current trends, the UN Sustainable Development Goal to reduce premature mortality due to CVRDs by a third by 2030 will be challenging for many countries of low and middle income. We did systematic literature reviews of effectiveness and cost-effectiveness to identify priority interventions. We summarise the key findings and present a costed essential package of interventions to reduce risk of and manage CVRDs. On a population level, we recommend tobacco taxation, bans on trans fats, and compulsory reduction of salt in manufactured food products. We suggest primary health services be strengthened through the establishment of locally endorsed guidelines and ensured availability of essential medications. The policy interventions and health service delivery package we suggest could serve as the cornerstone for the management of CVRDs, and afford substantial financial risk protection for vulnerable households. We estimate that full implementation of the essential package would cost an additional US$21 per person in the average low-income country and $24 in the average lower-middle-income country. The essential package we describe could be a starting place for low-income and middle-income countries developing universal health coverage packages. Interventions could be rolled out as disease burden demands and budgets allow. Our outlined interventions provide a pathway for countries attempting to convert the UN Sustainable Development Goal commitments into tangible action.

Pro-carcinogenic bacteria have the potential to initiate and/or promote colon cancer, in part via immune mechanisms that are incompletely understood. Using ApcMin mice colonized with the human pathobiont enterotoxigenic Bacteroides fragilis (ETBF) as a model of microbe-induced colon tumorigenesis, we show that the Bacteroides fragilis toxin (BFT) triggers a pro-carcinogenic, multi-step inflammatory cascade requiring IL-17R, NF-κB, and Stat3 signaling in colonic epithelial cells (CECs). Although necessary, Stat3 activation in CECs is not sufficient to trigger ETBF colon tumorigenesis. Notably, IL-17-dependent NF-κB activation in CECs induces a proximal to distal mucosal gradient of C-X-C chemokines, including CXCL1, that mediates the recruitment of CXCR2-expressing polymorphonuclear immature myeloid cells with parallel onset of ETBF-mediated distal colon tumorigenesis. Thus, BFT induces a pro-carcinogenic signaling relay from the CEC to a mucosal Th17 response that results in selective NF-κB activation in distal colon CECs, which collectively triggers myeloid-cell-dependent distal colon tumorigenesis.

Circulating tumor cells (CTCs) are cancer cells shredded from either a primary tumor or a metastatic site and circulate in the blood as the potential cellular origin of metastasis. By detecting and analyzing CTCs, we will be able to noninvasively monitor disease progression in individual cancer patients and obtain insightful information for assessing disease status, thus realizing the concept of "tumor liquid biopsy". However, it is technically challenging to identify CTCs in patient blood samples because of the extremely low abundance of CTCs among a large number of hematologic cells. In order to address this challenge, our research team at UCLA pioneered a unique concept of "NanoVelcro" cell-affinity substrates, in which CTC capture agent-coated nanostructured substrates were utilized to immobilize CTCs with remarkable efficiency. Four generations of NanoVelcro CTC assays have been developed over the past decade for a variety of clinical utilities. The 1st-gen NanoVelcro Chips, composed of a silicon nanowire substrate (SiNS) and an overlaid microfluidic chaotic mixer, were created for CTC enumeration. The 2nd-gen NanoVelcro Chips (i.e., NanoVelcro-LMD), based on polymer nanosubstrates, were developed for single-CTC isolation in conjunction with the use of the laser microdissection (LMD) technique. By grafting thermoresponsive polymer brushes onto SiNS, the 3rd-gen Thermoresponsive NanoVelcro Chips have demonstrated the capture and release of CTCs at 37 and 4 °C respectively, thereby allowing for rapid CTC purification while maintaining cell viability and molecular integrity. Fabricated with boronic acid-grafted conducting polymer-based nanomaterial on chip surface, the 4th-gen NanoVelcro Chips (Sweet chip) were able to purify CTCs with well-preserved RNA transcripts, which could be used for downstream analysis of several cancer specific RNA biomarkers. In this review article, we will summarize the development of the four generations of NanoVelcro CTC assays, and the clinical applications of each generation of devices.

A glycan-stimulated and poly(3,4-ethylene-dioxythiophene)s (PEDOT)-based nanomaterial platform is fabricated to purify circulating tumor cells (CTCs) from blood samples of prostate cancer (PCa) patients. This new platform, phenylboronic acid (PBA)-grafted PEDOT NanoVelcro, combines the 3D PEDOT nanosubstrate, which greatly enhances CTC capturing efficiency, with a poly(EDOT-PBA-co-EDOT-EG3) interfacial layer, which not only provides high specificity for CTC capture upon antibody conjugation but also enables competitive binding of sorbitol to gently release the captured cells. CTCs purified by this PEDOT NanoVelcro chip provide well-preserved RNA transcripts for the analysis of the expression level of several PCa-specific RNA biomarkers, which may provide clinical insights into the disease.

ObjectiveTo estimate health care expenditure trends among young adults ages 19-25 before and after the 2010 implementation of the Affordable Care Act (ACA) provision that extended eligibility for dependent private health insurance coverage.Data sourcesNationally representative Medical Expenditure Panel Survey data from 2008 to 2012.Study designWe conducted repeated cross-sectional analyses and employed a difference-in-differences quantile regression model to estimate health care expenditure trends among young adults ages 19-25 (the treatment group) and ages 27-29 (the control group).Principal findingsOur results show that the treatment group had 14 percent lower overall health care expenditures and 21 percent lower out-of-pocket payments compared with the control group in 2011-2012. The overall reduction in health care expenditures among young adults ages 19-25 in years 2011-2012 was more significant at the higher end of the health care expenditure distribution. Young adults ages 19-25 had significantly higher emergency department costs at the 10th percentile in 2011-2012. Differences in the trends of costs of private health insurance and doctor visits are not statistically significant.ConclusionsIncreased health insurance enrollment as a consequence of the ACA provision for dependent coverage has successfully reduced spending and catastrophic expenditures, providing financial protections for young adults.

Circulating fetal nucleated cells (CFNCs) in maternal blood offer an ideal source of fetal genomic DNA for noninvasive prenatal diagnostics (NIPD). We developed a class of nanoVelcro microchips to effectively enrich a subcategory of CFNCs, i.e., circulating trophoblasts (cTBs) from maternal blood, which can then be isolated with single-cell resolution by a laser capture microdissection (LCM) technique for downstream genetic testing. We first established a nanoimprinting fabrication process to prepare the LCM-compatible nanoVelcro substrates. Using an optimized cTB-capture condition and an immunocytochemistry protocol, we were able to identify and isolate single cTBs (Hoechst+/CK7+/HLA-G+/CD45-, 20 μm > sizes > 12 μm) on the imprinted nanoVelcro microchips. Three cTBs were polled to ensure reproducible whole genome amplification on the cTB-derived DNA, paving the way for cTB-based array comparative genomic hybridization (aCGH) and short tandem repeats analysis. Using maternal blood samples collected from expectant mothers carrying a single fetus, the cTB-derived aCGH data were able to detect fetal genders and chromosomal aberrations, which had been confirmed by standard clinical practice. Our results support the use of nanoVelcro microchips for cTB-based noninvasive prenatal genetic testing, which holds potential for further development toward future NIPD solution.

Previous neuroimaging studies suggest a negative relationship between the apolipoprotein (ApoE) ε4 allele and brain integrity in human immunodeficiency virus (HIV)-infected (HIV+) individuals, although the presence of this relationship across adulthood remains unclear. The purpose of this study is to clarify the discrepancies using a large, diverse group of HIV+ individuals and multiple imaging modalities sensitive to HIV. The association of ApoE ε4 with structural neuroimaging and magnetic resonance spectroscopy (MRS) was examined in 237 HIV+ individuals in the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Cortical and subcortical gray matter, abnormal and total white matter, ventricles, sulcal cerebrospinal fluid (CSF), and cerebellar gray matter, white matter, and CSF volumes, and MRS concentrations of myo-inositol, creatine, N-acetyl-aspartate, and choline in the frontal white matter (FWM), frontal gray matter (FGM), and basal ganglia were examined. Secondary analyses explored this relationship separately in individuals ≥50 years old (n = 173) and

Amino acid availability activates signaling by the mammalian target of rapamycin (mTOR) complex 1, mTORC1, a master regulator of cell growth. The class III PI-3-kinase Vps34 mediates amino acid signaling to mTORC1 by regulating lysosomal translocation and activation of the phospholipase PLD1. Here, we identify leucyl-tRNA synthetase (LRS) as a leucine sensor for the activation of Vps34-PLD1 upstream of mTORC1. LRS is necessary for amino acid-induced Vps34 activation, cellular PI(3)P level increase, PLD1 activation, and PLD1 lysosomal translocation. Leucine binding, but not tRNA charging activity of LRS, is required for this regulation. Moreover, LRS physically interacts with Vps34 in amino acid-stimulatable non-autophagic complexes. Finally, purified LRS protein activates Vps34 kinase in vitro in a leucine-dependent manner. Collectively, our findings provide compelling evidence for a direct role of LRS in amino acid activation of Vps34 via a non-canonical mechanism and fill a gap in the amino acid-sensing mTORC1 signaling network.

Jealousy is not only a way of experiencing love but also a stabilizer of romantic relationships, although morbid romantic jealousy is maladaptive. Being engaged in a formal romantic relationship can tune one's romantic jealousy towards a specific target. Little is known about how the human brain processes romantic jealousy by now. Here, by combining scenario-based imagination and functional MRI, we investigated the behavioral and neural correlates of romantic jealousy and their development across stages (before vs. after being in a formal relationship). Romantic jealousy scenarios elicited activations primarily in the basal ganglia (BG) across stages, and were significantly higher after the relationship was established in both the behavioral rating and BG activation. The intensity of romantic jealousy was related to the intensity of romantic happiness, which mainly correlated with ventral medial prefrontal cortex activation. The increase in jealousy across stages was associated with the tendency for interpersonal aggression. These results bridge the gap between the theoretical conceptualization of romantic jealousy and its neural correlates and shed light on the dynamic changes in jealousy.

It is important to understand the source of health-care disparities between Latinos and other children in the United States. We examine parent-reported health-care access and utilization among Latino, White, and Black children (≤17 years old) in the United States in the 2006-2011 National Health Interview Survey. Using Blinder-Oaxaca decomposition, we portion health-care disparities into two parts (1) those attributable to differences in the levels of sociodemographic characteristics (e.g., income) and (2) those attributable to differences in group-specific regression coefficients that measure the health-care 'return' Latino, White, and Black children receive on these characteristics. In the United States, Latino children are less likely than Whites to have a usual source of care, receive at least one preventive care visit, and visit a doctor, and are more likely to have delayed care. The return on sociodemographic characteristics explains 20-30% of the disparity between Latino and White children in the usual source of care, delayed care, and doctor visits and 40-50% of the disparity between Latinos and Blacks in emergency department use and preventive care. Much of the health-care disadvantage experienced by Latino children would persist if Latinos had the sociodemographic characteristics as Whites and Blacks.

To evaluate the value of combining the detection of intratumoral macroscopic fat and hemorrhage in the differentiation of the benign from malignant solid renal masses.Conventional magnetic resonance imaging (MRI), chemical shift (CS)-MRI, and susceptibility-weighted imaging were performed in 152 patients with 152 solid renal masses, including 48 benign and 104 malignant masses all pathologically confirmed. The presence of macroscopic fat detected by CS-MRI and hemorrhage detected by susceptibility-weighted imaging were evaluated in all masses. The rates of macroscopic fat and hemorrhage observed between benign and malignant masses were compared by a χ test. All masses found to contain macroscopic fat with or without hemorrhage were considered to be benign. The remaining masses (without macroscopic fat) found not to contain hemorrhage were considered to be benign. Only those found to contain hemorrhage alone were considered to be malignant. The evaluation indexes for differentiating and forecasting the benign and malignant masses were calculated.Significant differences in the rate of macroscopic fat (observed in 85.42% of benign masses vs. 0% of malignant masses) and hemorrhage (observed in 4.17% of benign masses vs. 95.19% of malignant masses) were measured in the benign and malignant groups (P

Although depressive symptoms are common during adolescence, little research has examined gene-environment interaction on youth depression. This study chose the brain-derived neurotrophic factor (BDNF) gene, tested the interaction between a functional polymorphism resulting amino acid substitution of valine (Val) to methionine (Met) in the proBDNF protein at codon 66 (Val66Met), and maternal parenting on youth depressive symptoms in a sample of 780 community adolescents of Chinese Han ethnicity (aged 11-17, M = 13.6, 51.3 % females). Participants reported their depressive symptoms and perceived maternal parenting. Results indicated the BDNF Val66Met polymorphism significantly moderated the influence of maternal warmth-reasoning, but not harshness-hostility, on youth depressive symptoms. Confirmatory model evaluation indicated that the interaction effect involving warmth-reasoning conformed to the differential-susceptibility rather than diathesis-stress model of person-X-environment interaction. Thus, Val carriers experienced less depressive symptoms than Met homozygotes when mothering was more positive but more symptoms when mothering was less positive. The findings provided evidence in support of the differential susceptibility hypothesis of youth depressive symptoms and shed light on the importance of examining the gene-environment interaction from a developmental perspective.

ObjectiveTo examine racial and ethnic disparities in health care access and utilization after the Affordable Care Act (ACA) health insurance mandate was fully implemented in 2014.Research designUsing the 2011-2014 National Health Interview Survey, we examine changes in health care access and utilization for the nonelderly US adult population. Multivariate linear probability models are estimated to adjust for demographic and sociodemographic factors.ResultsThe implementation of the ACA (year indicator 2014) is associated with significant reductions in the probabilities of being uninsured (coef=-0.03, P

BackgroundThe employment of professional interviewers from academic survey centers to conduct surveys has been standard practice. Because one goal of community-engaged research is to provide professional skills to community residents, this paper considers whether employing locally trained lay interviewers from within the community may be as effective as employing interviewers from an academic survey center with regard to unit and item nonresponse rates and cost.MethodsTo study a nutrition-focused intervention, 1035 in-person household interviews were conducted in East Los Angeles and Boyle Heights, 503 of which were completed by lay community interviewers. A chi-square test was used to assess differences in unit nonresponse rates between professional and community interviewers and Welch's t tests were used to assess differences in item nonresponse rates. A cost comparison analysis between the two interviewer groups was also conducted.ResultsInterviewers from the academic survey center had lower unit nonresponse rates than the lay community interviewers (16.2% vs. 23.3%; p < 0.01). However, the item nonresponse rates were lower for the community interviewers than the professional interviewers (1.4% vs. 3.3%; p < 0.01). Community interviewers cost approximately $415.38 per survey whereas professional interviewers cost approximately $537.29 per survey.ConclusionsWith a lower cost per completed survey and lower item nonresponse rates, lay community interviewers are a viable alternative to professional interviewers for fieldwork in community-based research. Additional research is needed to assess other important aspects of data quality interviewer such as interviewer effects and response error.

Liquid biopsy of tumor through isolation of circulating tumor cells (CTCs) allows non-invasive, repetitive, and systemic sampling of disease. Although detecting and enumerating CTCs is of prognostic significance in metastatic cancer, it is conceivable that performing molecular and functional characterization on CTCs will reveal unprecedented insight into the pathogenic mechanisms driving lethal disease. Nanomaterial-embedded cancer diagnostic platforms, i.e., NanoVelcro CTC Assays represent a unique rare-cell sorting method that enables detection isolation, and characterization of CTCs in peripheral blood, providing an opportunity to noninvasively monitor disease progression in individual cancer patients. Over the past decade, a series of NanoVelcro CTC Assays has been demonstrated for exploring the full potential of CTCs as a clinical biomarker, including CTC enumeration, phenotyping, genotyping and expression profiling. In this review article, the authors will briefly introduce the development of three generations of NanoVelcro CTC Assays, and highlight the clinical applications of each generation for various types of solid cancers, including prostate cancer, pancreatic cancer, lung cancer, and melanoma.

Previous studies have demonstrated focal but limited molecular similarities between circulating tumor cells (CTCs) and biopsies using isolated genetic assays. We hypothesized that molecular similarity between CTCs and tissue exists at the single cell level when characterized by whole genome sequencing (WGS). By combining the NanoVelcro CTC Chip with laser capture microdissection (LCM), we developed a platform for single-CTC WGS. We performed this procedure on CTCs and tissue samples from a patient with advanced prostate cancer who had serial biopsies over the course of his clinical history. We achieved 30X depth and ≥ 95% coverage. Twenty-nine percent of the somatic single nucleotide variations (SSNVs) identified were founder mutations that were also identified in CTCs. In addition, 86% of the clonal mutations identified in CTCs could be traced back to either the primary or metastatic tumors. In this patient, we identified structural variations (SVs) including an intrachromosomal rearrangement in chr3 and an interchromosomal rearrangement between chr13 and chr15. These rearrangements were shared between tumor tissues and CTCs. At the same time, highly heterogeneous short structural variants were discovered in PTEN, RB1, and BRCA2 in all tumor and CTC samples. Using high-quality WGS on single-CTCs, we identified the shared genomic alterations between CTCs and tumor tissues. This approach yielded insight into the heterogeneity of the mutational landscape of SSNVs and SVs. It may be possible to use this approach to study heterogeneity and characterize the biological evolution of a cancer during the course of its natural history.

ObjectivesWe examined the association between the size and growth of Latino populations and hospitals' uncompensated care in California.MethodsOur sample consisted of general acute care hospitals in California operating during 2000 and 2010 (n = 251). We merged California hospital data with US Census data for each hospital service area. We used spatial analysis, multivariate regression, and fixed-effect models.ResultsWe found a significant association between the growth of California's Latino population and hospitals' uncompensated care in the unadjusted regression. This association was still significant after we controlled for hospital and community population characteristics. After we added market characteristics into the final model, this relationship became nonsignificant.ConclusionsOur findings suggest that systematic support is needed in areas with rapid Latino population growth to control hospitals' uncompensated care, especially if Latinos are excluded from or do not respond to the insurance options made available through the Affordable Care Act. Improving availability of resources for hospitals and providers in areas with high Latino population growth could help alleviate financial pressures.

Supramolecular nanosubstrate-mediated delivery (SNSMD) leverages the power of molecular self-assembly and a nanostructured substrate platform for the low toxicity, highly efficient co-delivery of biological factors encapsulated in a nanovector. Human fibroblasts are successfully reprogrammed into induced pluripotent stems and transdifferentiated into induced neuronal-like cells.

We previously found that p97 ATPase inhibitors 2-(2-amino-1H-benzo[d]imidazol-1-yl)-N-benzyl-8-methoxyquinazolin-4-amine (ML240) and 2-(2H-benzo[b][1,4]oxazin-4(3H)-yl)-N-benzyl-5,6,7,8-tetrahydroquinazolin-4-amine (ML241) specifically target the D2 domain of wild-type p97. In addition, one of the major p97 cofactors, p47, decreases their potencies by ∼50-fold. In contrast, N(2) ,N(4) -dibenzylquinazoline-2,4-diamine (DBeQ) targets both the D1 and D2 domains and shows only a four- to sixfold decrease in potency against the p97-p47 complex. To elucidate structure-activity relationships for the inhibitors, we screened 200 p97 inhibitor analogues for their ability to inhibit the ATPase activity of either or both of the D1 or D2 domains, as well for their effects on p47 potency. The selectivity of 29 of these compounds was further examined by eight-dose titrations. Four compounds showed modest selectivity for inhibiting the ATPase activity of D1. Eleven compounds inhibited D2 with greater potencies, and four showed similar potencies against D1 and D2. p47 decreased the potencies of the majority of the compounds and increased the potencies of five compounds. These results highlight the possibility of developing domain-selective and complex-specific p97 inhibitors in order to further elucidate the physiological roles of p97 and its cofactors.

ObjectiveWe study the association between the timing of the Great Recession (GR) and health spending among uninsured adults distinguishing by citizenship/nativity status and time of U.S. residence.Data sourceUninsured U.S. citizens and noncitizens from the 2005-2006 and 2008-2009 Medical Expenditure Panel Survey.Study designThe probability of reporting any health spending and the natural logarithm of health spending are our main dependent variables. We compare health spending across population categories before/during the GR. Subsequently, we implement two-part regression analyses of total and specific health-spending measures. We predict average health spending before/during the GR with a smearing estimation.Principal findingsThe probability of reporting any spending diminished for recent immigrants compared to citizens during the GR. For those with any spending, recent immigrants reported higher spending during the GR (27 percent). Average reductions in total spending were driven by the decline in the share of the population reporting any spending among citizens and noncitizens.ConclusionsOur study findings suggest that recent immigrants could be forgoing essential care, which later translates into higher spending. It portrays the vulnerability of a population that would remain exposed to income shocks, even after the Affordable Care Act (ACA) implementation.

Predictive modeling of human disease based on the microbiota holds great potential yet remains challenging. Here, 50 adults underwent controlled transitions from naturally occurring gingivitis, to healthy gingivae (baseline), and to experimental gingivitis (EG). In diseased plaque microbiota, 27 bacterial genera changed in relative abundance and functional genes including 33 flagellar biosynthesis-related groups were enriched. Plaque microbiota structure exhibited a continuous gradient along the first principal component, reflecting transition from healthy to diseased states, which correlated with Mazza Gingival Index. We identified two host types with distinct gingivitis sensitivity. Our proposed microbial indices of gingivitis classified host types with 74% reliability, and, when tested on another 41-member cohort, distinguished healthy from diseased individuals with 95% accuracy. Furthermore, the state of the microbiota in naturally occurring gingivitis predicted the microbiota state and severity of subsequent EG (but not the state of the microbiota during the healthy baseline period). Because the effect of disease is greater than interpersonal variation in plaque, in contrast to the gut, plaque microbiota may provide advantages in predictive modeling of oral diseases.

Anal human papillomavirus (HPV) infections are common, and the incidence of anal cancer is high in HIV-infected men who have sex with men (MSM). To evaluate the performance of HPV assays in anal samples, we compared the cobas HPV test (cobas) to the Roche Linear Array HPV genotyping assay (LA) and cytology in HIV-infected MSM. Cytology and cobas and LA HPV testing were conducted for 342 subjects. We calculated agreement between the HPV assays and the clinical performance of HPV testing and HPV genotyping alone and in combination with anal cytology. We observed high agreement between cobas and LA, with cobas more likely than LA to show positive results for HPV16, HPV18, and other carcinogenic types. Specimens testing positive in cobas but not in LA were more likely to be positive for other markers of HPV-related disease compared to those testing negative in both assays, suggesting that at least some of these were true positives for HPV. cobas and LA showed high sensitivities but low specificities for the detection of anal intraepithelial neoplasia grade 2/3 (AIN2/3) in this population (100% sensitivity and 26% specificity for cobas versus 98.4% sensitivity and 28.9% specificity for LA). A combination of anal cytology and HPV genotyping provided the highest accuracy for detecting anal precancer. A higher HPV load was associated with a higher risk of AIN2/3 with HPV16 (P(trend) < 0.001), HPV18 (P(trend) = 0.07), and other carcinogenic types (P(trend) < 0.001). We demonstrate that cobas can be used for HPV detection in anal cytology specimens. Additional tests are necessary to identify men at the highest risk of anal cancer among those infected with high-risk HPV.

ObjectiveWe study the association between the timing of the Great Recession (GR) and health spending among uninsured adults distinguishing by citizenship/nativity status and time of U.S. residence.Data sourceUninsured U.S. citizens and noncitizens from the 2005-2006 and 2008-2009 Medical Expenditure Panel Survey.Study designThe probability of reporting any health spending and the natural logarithm of health spending are our main dependent variables. We compare health spending across population categories before/during the GR. Subsequently, we implement two-part regression analyses of total and specific health-spending measures. We predict average health spending before/during the GR with a smearing estimation.Principal findingsThe probability of reporting any spending diminished for recent immigrants compared to citizens during the GR. For those with any spending, recent immigrants reported higher spending during the GR (27 percent). Average reductions in total spending were driven by the decline in the share of the population reporting any spending among citizens and noncitizens.ConclusionsOur study findings suggest that recent immigrants could be forgoing essential care, which later translates into higher spending. It portrays the vulnerability of a population that would remain exposed to income shocks, even after the Affordable Care Act (ACA) implementation.

ObjectiveTo examine the association between the Great Recession of 2007-2009 and health care expenditures along the health care spending distribution, with a focus on racial/ethnic disparities.Data sources/study settingSecondary data analyses of the Medical Expenditure Panel Survey (2005-2006 and 2008-2009).Study designQuantile multivariate regressions are employed to measure the different associations between the economic recession of 2007-2009 and health care spending. Race/ethnicity and interaction terms between race/ethnicity and a recession indicator are controlled to examine whether minorities encountered disproportionately lower health spending during the economic recession.Principal findingsThe Great Recession was significantly associated with reductions in health care expenditures at the 10th-50th percentiles of the distribution, but not at the 75th-90th percentiles. Racial and ethnic disparities were more substantial at the lower end of the health expenditure distribution; however, on average the reduction in expenditures was similar for all race/ethnic groups. The Great Recession was also positively associated with spending on emergency department visits.ConclusionThis study shows that the relationship between the Great Recession and health care spending varied along the health expenditure distribution. More variability was observed in the lower end of the health spending distribution compared to the higher end.

The rate of bacterial photoinactivation in plasma by methylene blue (MB), especially for Gram-negative bacteria, has been reported to be lower, by about an order of magnitude, than the rate of inactivation in PBS and water solutions. This low inactivation rate we attribute to the bleaching of the 660-nm absorption band of MB in plasma that results in low yields of MB triplet states and consequently low singlet oxygen generation. We have recorded the change of the MB 660-nm-band optical density in plasma, albumin, and cysteine solutions, as a function of time, after 661-nm excitation. The transient triplet spectra were recorded and the singlet oxygen generated in these solutions was determined by the rate of decrease in the intensity of the 399-nm absorption band of 9, 10-anthracene dipropionic acid. We attribute the bleaching of MB, low singlet oxygen yield, and consequently the low inactivation rate of bacteria in plasma to the attachment of a hydrogen atom, from the S-H group of cysteine, to the central nitrogen atom of MB and formation of cysteine dimer.

This study identifies differences in health insurance predictors and investigates the main reported reasons for lacking health insurance coverage between short-stayed (≤ 10 years) and long-stayed (>10 years) US immigrant adults to parse the possible consequences of the Affordable Care Act among immigrants by length of stay and documentation status. Foreign-born adults (18-64 years of age) from the 2009 California Health Interview Survey are the study population. Health insurance coverage predictors and the main reasons for being uninsured are compared across cohorts and by documentation status. A logistic-regression two-part multivariate model is used to adjust for confounding factors. The analyses determine that legal status is a strong health insurance predictor, particularly among long-stayed undocumented immigrants. Immigration status is the main reported reason for lacking health insurance. Although long-stayed documented immigrants are likely to benefit from the Affordable Care Act implementation, undocumented immigrants and short-stayed documented immigrants may encounter difficulties getting health insurance coverage.

BACKGROUND: Artificial selection played an important role in the origin of modern Glycine max cultivars from the wild soybean Glycine soja. To elucidate the consequences of artificial selection accompanying the domestication and modern improvement of soybean, 25 new and 30 published whole-genome re-sequencing accessions, which represent wild, domesticated landrace, and Chinese elite soybean populations were analyzed. RESULTS: A total of 5,102,244 single nucleotide polymorphisms (SNPs) and 707,969 insertion/deletions were identified. Among the SNPs detected, 25.5% were not described previously. We found that artificial selection during domestication led to more pronounced reduction in the genetic diversity of soybean than the switch from landraces to elite cultivars. Only a small proportion (2.99%) of the whole genomic regions appear to be affected by artificial selection for preferred agricultural traits. The selection regions were not distributed randomly or uniformly throughout the genome. Instead, clusters of selection hotspots in certain genomic regions were observed. Moreover, a set of candidate genes (4.38% of the total annotated genes) significantly affected by selection underlying soybean domestication and genetic improvement were identified. CONCLUSIONS: Given the uniqueness of the soybean germplasm sequenced, this study drew a clear picture of human-mediated evolution of the soybean genomes. The genomic resources and information provided by this study would also facilitate the discovery of genes/loci underlying agronomically important traits.

Using two nationally representative data sets, this study examined health care expenditure disparities between Caucasians and different Asian American subgroups. Multivariate analyses demonstrate that Asian Americans, as a group, have significantly lower total expenditures compared with Caucasians. Results also point to considerable heterogeneities in health care spending within Asian American subgroups. Findings suggest that language assistance programs would be effective in reducing disparities among Caucasians and Asian American subgroups with the exception of Indians and Filipinos, who tend to be more proficient in English. Results also indicate that citizenship and nativity were major factors associated with expenditure disparities. Socioeconomic status, however, could not explain expenditure disparities. Results also show that Asian Americans have lower physician and pharmaceutical costs but not emergency department or hospital expenditures. These findings suggest the need for culturally competent policies specific to Asian American subgroups and the necessity to encourage cost-effective treatments among Asian Americans.

ObjectivesWe examined the associations of local public health system organization and local health department resources with county-level sexually transmitted disease (STD) incidence rates in large US health jurisdictions.MethodsWe linked annual county STD incidence data (2005-2008) to local health department director responses (n = 211) to the 2006 wave of the National Longitudinal Study of Local Public Health Systems, the 2005 national Local Health Department Profile Survey, and the Area Resource File. We used nested mixed effects regression models to assess the relative contribution of local public health system organization, local health department financial and resource factors, and sociodemographic factors known to be associated with STD incidence to county-level (n = 307) STD incidence.ResultsJurisdictions with local governing boards had significantly lower county-level STD incidence. Local public health systems with comprehensive services where local health departments shoulder much of the effort had higher county-level STD rates than did conventional systems.ConclusionsMore integration of system partners in local public health system activities, through governance and interorganizational arrangements, may reduce the incidence and burden of STDs.

Immigration status is a likely deterrent of mental health care utilization in the United States. Using the Medical Expenditure Panel Survey and National Health Interview survey from 2002 to 2006, multivariable logistic regressions were used to estimate the effects of immigration status on mental health care utilization among patients with depression or anxiety disorders. Multivariate regressions showed that immigrants were significantly less likely to take any prescription drugs, but not significantly less likely to have any physician visits compared to US-born citizens. Results also showed that improving immigrants' health care access and health insurance coverage could potentially reduce disparities between US-born citizens and immigrants by 14-29% and 9-28% respectively. Policy makers should focus on expanding the availability of regular sources of health care and immigrant health coverage to reduce disparities on mental health care utilization. Targeted interventions should also focus on addressing immigrants' language barriers, and providing culturally appropriate services.

Proteins perform most cellular functions in macromolecular complexes. The same protein often participates in different complexes to exhibit diverse functionality. Current ensemble approaches of identifying cellular protein interactions cannot reveal physiological permutations of these interactions. Here we describe a single-molecule pull-down (SiMPull) assay that combines the principles of a conventional pull-down assay with single-molecule fluorescence microscopy and enables direct visualization of individual cellular protein complexes. SiMPull can reveal how many proteins and of which kinds are present in the in vivo complex, as we show using protein kinase A. We then demonstrate a wide applicability to various signalling proteins found in the cytosol, membrane and cellular organelles, and to endogenous protein complexes from animal tissue extracts. The pulled-down proteins are functional and are used, without further processing, for single-molecule biochemical studies. SiMPull should provide a rapid, sensitive and robust platform for analysing protein assemblies in biological pathways.

BackgroundPrevious studies have examined racial and ethnic disparities in the receipt of family-centered care among children with special health care needs and health plan enrollees, but the extent of disparities in the general pediatric population remains unclear.ObjectiveTo examine racial and ethnic disparities in the receipt of family-centered care among a general population of US children.MethodsLinked data from the Medical Expenditure Panel Survey and the National Health Interview Survey (2003-2006) were used to study 4 family-centered care items and an overall composite measure of family-centered care. Adjusted models examined the extent to which child characteristics, socioeconomic, and access to care factors explained racial and ethnic disparities in the provision of family-centered care.ResultsBlack children have similar experiences as white children on overall family-centered care and on each of the 4 components of family-centered care in models that adjust for child characteristics and socioeconomic factors. In contrast, differences in dimensions of and overall family-centered care between white children and Latino children, irrespective of interview language, persist after multivariate adjustment.ConclusionsFuture research should examine the extent to which Latino-white differences in the receipt of family-centered care can be narrowed with programs and policies geared at improving parental education, health literacy, the quality of provider communication, and quality improvement strategies for health care systems.