Health related social needs and whole person health: Relationship between unmet social needs, health outcomes, and healthcare spending among commercially insured adults.

Commercially-insured adults comprise a majority of health plan members but are least likely to be surveyed about their social needs. Little is known, consequently, about health-related social needs (HRSNs) in this population. The primary aim of this study was to assess the prevalence of HRSNs and health among commercially-insured adults and estimate their relationship with health outcomes and spending. This cross-sectional study used survey data from a representative sample of Elevance Health commercially insured members residing in Georgia and Indiana (U.S.) Adult members reported on HSRNs across nine different domains. Survey data were linked to medical claims data, and regression models were used to estimate the relationship between HRSNs and self-reported health, emergency department visits, three major health outcomes, and healthcare spending (medical and pharmaceutical). Of 1,160 commercially insured adults, 76 % indicated ≥ 1 HRSN, and 29 % reported > 3 HRSNs, (i.e., "high" HRSN). Each HRSN was associated with 2.2 (95 % CI, 1.84-2.55) additional unhealthy days per month, 3.0 percent (95 % CI 1.36 - 4.57) higher prevalence of anxiety/depression, 2.2 percent (95 % CI 0.88 - 3.50) higher prevalence of hypertension, 3.9 more ED visits per 1,000 member-months (95 % CI, 0.29-7.42), and $1,418 higher total healthcare spending (95 % CI, $614.67-$2,220.39) over a 12-month period. The widespread prevalence of HRSNs among commercially insured adults demonstrates the importance of screening all health plan members for HRSNs-not just Medicare and Medicaid members. Commercially insured members who experience high HRSN are at significantly higher risk for worse health, even after controlling for income and demographic characteristics.

Cell cycle exits and U-turns: Quiescence as multiple reversible forms of arrest.

Cell proliferation control is essential during development and for maintaining adult tissues. Loss of that control promotes not only oncogenesis when cells proliferate inappropriately but also developmental abnormalities or degeneration when cells fail to proliferate when and where needed. To ensure that cells are produced at the right place and time, an intricate balance of pro-proliferative and anti-proliferative signals impacts the probability that cells undergo cell cycle exit to quiescence, or G0 phase. This brief review describes recent advances in our understanding of how and when quiescence is initiated and maintained in mammalian cells. We highlight the growing appreciation for quiescence as a collection of context-dependent distinct states.

Toxic Effects of Silver Ions on Early Developing Zebrafish Embryos Distinguished from Silver Nanoparticles.

Currently, effects of nanomaterials and their ions, such as silver nanoparticles (Ag NPs) and silver ions (Ag+), on living organisms are not yet fully understood. One of the vital questions is whether nanomaterials have distinctive effects on living organisms from any other conventional chemicals (e.g., their ions), owing to their unique physicochemical properties. Due to various experimental protocols, studies of this crucial question have been inconclusive, which hinders rational design of effective regulatory guidelines for safely handling NPs. In this study, we chronically exposed early developing zebrafish embryos (cleavage-stage, 2 hours post-fertilization, hpf) to a dilution series of Ag+ (0-1.2 µM) in egg water (1 mM NaCl, solubility of Ag+ = 0.18 µM) until 120 hpf. We systematically investigated effects of Ag+ on developing embryos and compared them with our previous studies of effects of purified Ag NPs on developing embryos. We found the concentration- and time-dependent effects of Ag+ on embryonic development, and only half of the embryos developed normally after being exposed to 0.25 µM (27 µg/L) Ag+ until 120 hpf. As the Ag+ concentration increases, the number of embryos that developed normally decreases, while the number of embryos that became dead increases. The number of abnormally developing embryos increases as the Ag+ concentration increases from 0 to 0.3 µM and then decreases as the concentration increases from 0.3 to 1.2 µM because the number of embryos that became dead increases. The concentration-dependent phenotypes were observed, showing fin fold abnormality, tail and spinal cord flexure, and yolk sac edema at low Ag+ concentrations (≤0.2 µM) and head and eye abnormalities along with fin fold abnormality, tail and spinal cord flexure, and yolk sac edema at high concentrations (≥0.3 µM). Severities of phenotypes and the number of abnormally developing embryos were far less than those observed in Ag NPs. The results also show concentration-dependent effects on heart rates and hatching rates of developing embryos, attributing to the dose-dependent abnormally developing embryos. In summary, the results show that Ag+ and Ag NPs have distinctive toxic effects on early developing embryos, and toxic effects of Ag+ are far less severe than those of Ag NPs, which further demonstrates that the toxicity of Ag NPs toward embryonic development is attributed to the NPs themselves and their unique physicochemical properties but not the release of Ag+ from the Ag NPs.

The molecular architecture of cell cycle arrest.

The cellular decision governing the transition between proliferative and arrested states is crucial to the development and function of every tissue. While the molecular mechanisms that regulate the proliferative cell cycle are well established, we know comparatively little about what happens to cells as they diverge into cell cycle arrest. We performed hyperplexed imaging of 47 cell cycle effectors to obtain a map of the molecular architecture that governs cell cycle exit and progression into reversible ("quiescent") and irreversible ("senescent") arrest states. Using this map, we found multiple points of divergence from the proliferative cell cycle; identified stress-specific states of arrest; and resolved the molecular mechanisms governing these fate decisions, which we validated by single-cell, time-lapse imaging. Notably, we found that cells can exit into senescence from either G1 or G2; however, both subpopulations converge onto a single senescent state with a G1-like molecular signature. Cells can escape from this "irreversible" arrest state through the upregulation of G1 cyclins. This map provides a more comprehensive understanding of the overall organization of cell proliferation and arrest.

The New York City Department of Health and Mental Hygiene School Vision Program: A description of program expansion.

OBJECTIVE: This study describes how the School Vision Program (SVP) operates in NYC Public Schools, and how it has expanded to provide screening, follow-up, eye exams, and even glasses to more students in recent years. METHODS: Using administrative data from the SVP, we analyze a population sample of all public-school students with non-missing demographic variables in grades Pre-K through 12, focusing on the most recent year of data, 2018-19. We tabulate rates of screening and other results across students by grade and student characteristics, highlighting the expansion of SVP in community schools beginning in 2015-16. RESULTS: The SVP screens about 87% of students in Pre-K through 1st Grade each school year. Of the 22% of screened students who failed the screening in 2018-19, 69% received follow-up efforts, and 39% completed eye exams. Among students with completed eye exams, 13% of students in Pre-K through 1st grade were diagnosed with amblyopia, and 70% needed glasses. Less advantaged students in terms of race, ethnicity, and socioeconomic status were less likely to pass vision screenings and less likely to receive eye exams after failing the screening. The SVP's expansion to all grades in community schools and its provision of eye exams and glasses increased the rate of eye exams to 90% of students with a failed vision screening and distributed glasses to over 22,000 students in grades Pre-K to 12 in 2018-19. CONCLUSION: The expansion of SVP services in community schools suggests large potential benefits from school districts connecting students who fail vision screenings directly to eye doctors. Otherwise, low rates of follow-up eye exams in younger grades can lead to unidentified and unmet need for vision services in older grades, especially among disadvantaged students.

A do-it-yourself 3D-printed thoracic spine model for anesthesia resident simulation.

Central line placement, cricothyroidotomy, and lumbar epidural placement are common procedures for which there are simulators to help trainees learn the procedures. However, a model or a simulator for thoracic epidurals is not commonly used by anesthesia training programs to help teach the procedure. This brief technical report aims to share the design and fabrication process of a low-cost and do-it-yourself (DIY) 3D-printed thoracic spine model. Ten expert anesthesiology attendings and fifteen novice anesthesiology residents practiced with the model and were subsequently surveyed to assess their attitudes towards its fidelity and usefulness as a teaching tool. Responses were recorded with a Likert scale and found to be positive for both groups. Design files and an assembly manual were developed and made public through an open-source website.

Assessment of Crystal Morphology on Uptake, Particle Dissolution, and Toxicity of Nanoscale Titanium Dioxide on Artemia salina.

Knowledge of nanomaterial toxicity is critical to avoid adverse effects on human and environment health. In this study, the influences of crystal morphology on physico-chemical and toxic properties of nanoscale TiO2 (n-TiO2) were investigated. Artemia salina were exposed to anatase, rutile and mixture polymorphs of n-TiO2 in seawater. Short-term (24 h) and long-term (96 h) exposures were conducted in 1, 10 and 100 mg/L suspensions of n-TiO2 in the presence and absence of food. Anatase form had highest accumulation followed by mixture and rutile. Presence of food greatly reduced accumulation. n-TiO2 dissolution was not significant in seawater (p<0.05) nor was influenced from crystal structure. Highest toxic effects occurred in 96h exposure in the order of anatase > mixture > rutile. Mortality and oxidative stress levels increased with increasing n-TiO2 concentration and exposure time (p<0.05). Presence of food in the exposure medium alleviated the oxidative stress, indicating that deprivation from food could promote toxic effects of n-TiO2 under long-term exposure.

A Case Report of a Giant Tubular Adenoma With a Concurrent Fibroadenoma of the Breast.

Tubular adenomas are rare benign epithelial tumors of the breast. Only a handful of cases have been reported in literature. We describe a very rare case of a giant tubular adenoma with a concurrent fibroadenoma in a young woman.

Hippocampal transcriptome after status epilepticus in mice rendered seizure damage-tolerant by epileptic preconditioning features suppressed calcium and neuronal excitability pathways.

Preconditioning brain with a sub-lethal stressor can temporarily generate a damage-refractory state. Microarray analyses have defined the changes in hippocampal gene expression that follow brief preconditioning seizures, but not the transcriptome after a prolonged and otherwise injurious seizure in previously preconditioned brain. Presently, microarray analysis was performed 24 h after status epilepticus in mice that had received previously either seizure preconditioning (tolerance) or sham-preconditioning (injury). Transcriptional changes in the hippocampal CA3 subfield of >or=2 fold were detected for 1357 genes in the tolerance group compared to a non-seizure control group, with 54% up-regulated. Of these regulated genes, 792 were also regulated in the injury group. Among the remaining 565 genes regulated only in tolerance, 73% were down-regulated. Analysis of the genes differentially suppressed in tolerance identified calcium signaling, ion channels and excitatory neurotransmitter receptors, and the synapse as over-represented among pathways, functions and compartments. Finally, 12 days continuous EEG recordings determined mice with induced tolerance had fewer spontaneous electrographic seizures compared to the injury group. Our data suggest the transcriptional phenotype of neuroprotection in tolerance may be dictated by the biology of the preconditioning stressor, functions by transcriptional reduction of vulnerability to excitotoxicity, and has anti-epileptogenic effects.

Using assessing care of vulnerable elders quality indicators to measure quality of hospital care for vulnerable elders.

OBJECTIVES: To assess the quality of care for hospitalized vulnerable elders using measures based on Assessing Care of Vulnerable Elders (ACOVE) quality indicators (QIs). DESIGN: Prospective cohort study. SETTING: Single academic medical center. PARTICIPANTS: Subjects aged 65 and older hospitalized on the University of Chicago general medicine inpatient service who were defined as vulnerable using the Vulnerable Elder Survey-13 (VES-13), a validated tool based on age, self-reported health, and functional status. MEASUREMENTS: Inpatient interview and chart review using ACOVE-based process-of-care measures referring to 16 QIs in general hospital care and geriatric-prevalent conditions (e.g., pressure ulcers, dementia, and delirium); adherence rates calculated for type of care process (screening, diagnosis, and treatment) and type of provider (doctor, nurse). RESULTS: Six hundred of 845 (71%) older patients participated. Of these, 349 (58%) were deemed vulnerable based on VES-13 score. Three hundred twenty-eight (94%) charts were available for review. QIs for general medical care were met at a significantly higher rate than for pressure ulcer care (81.5%, 95% confidence interval (CI)=79.3-83.7% vs 75.8%, 95% CI=70.5-81.1%, P=.04) and for delirium and dementia care (81.5%, 95% CI=79.3-83.7 vs 31.4% 95% CI=27.5-35.2%, P<.01). According to standard nursing assessment forms, nurses were responsible for high rates of adherence to certain screening indicators (pain, nutrition, functional status, pressure ulcer risk; P<.001 when compared with physicians), although in patients with functional limitations, nurse admission assessments of functional limitations often did not agree with reports of limitations by patients on admission. CONCLUSION: Adherence to geriatric-specific QIs is lower than adherence to general hospital care QIs. Hospital care QIs that focus on screening may overestimate performance by detecting standard nursing or protocol-driven care.

Transferrin receptor 2: evidence for ligand-induced stabilization and redirection to a recycling pathway.

Transferrin receptor 2 (TfR2) is a homologue of transferrin receptor 1 (TfR1), the protein that delivers iron to cells through receptor-mediated endocytosis of diferric transferrin (Fe(2)Tf). TfR2 also binds Fe(2)Tf, but it seems to function primarily in the regulation of systemic iron homeostasis. In contrast to TfR1, the trafficking of TfR2 within the cell has not been extensively characterized. Previously, we showed that Fe(2)Tf increases TfR2 stability, suggesting that trafficking of TfR2 may be regulated by interaction with its ligand. In the present study, therefore, we sought to identify the mode of TfR2 degradation, to characterize TfR2 trafficking, and to determine how Fe(2)Tf stabilizes TfR2. Stabilization of TfR2 by bafilomycin implies that TfR2 traffics to the lysosome for degradation. Confocal microscopy reveals that treatment of cells with Fe(2)Tf increases the fraction of TfR2 localizing to recycling endosomes and decreases the fraction of TfR2 localizing to late endosomes. Mutational analysis of TfR2 shows that the mutation G679A, which blocks TfR2 binding to Fe(2)Tf, increases the rate of receptor turnover and prevents stabilization by Fe(2)Tf, indicating a direct role of Fe(2)Tf in TfR2 stabilization. The mutation Y23A in the cytoplasmic domain of TfR2 inhibits its internalization and degradation, implicating YQRV as an endocytic motif.

Binding of the Bacillus subtilis LexA protein to the SOS operator.

The Bacillus subtilis LexA protein represses the SOS response to DNA damage by binding as a dimer to the consensus operator sequence 5'-CGAACN(4)GTTCG-3'. To characterize the requirements for LexA binding to SOS operators, we determined the operator bases needed for site-specific binding as well as the LexA amino acids required for operator recognition. Using mobility shift assays to determine equilibrium constants for B.subtilis LexA binding to recA operator mutants, we found that several single base substitutions within the 14 bp recA operator sequence destabilized binding enough to abolish site-specific binding. Our results show that the AT base pairs at the third and fourth positions from the 5' end of a 7 bp half-site are essential and that the preferred binding site for a LexA dimer is 5'-CGAACATATGTTCG-3'. Binding studies with LexA mutants, in which the solvent accessible amino acid residues in the putative DNA binding domain were mutated, indicate that Arg-49 and His-46 are essential for binding and that Lys-53 and Ala-48 are also involved in operator recognition. Guided by our mutational analyses as well as hydroxyl radical footprinting studies of the dinC and recA operators we docked a computer model of B.subtilis LexA on the preferred operator sequence in silico. Our model suggests that binding by a LexA dimer involves bending of the DNA helix within the internal 4 bp of the operator.

Overproduction of corticotropin-releasing hormone blocks germinal center formation: role of corticosterone and impaired follicular dendritic cell networks.

Corticotropin-releasing hormone (CRH) is a central mediator in the response to stress, coordinating behavioral, autonomic and neuroendocrine activation. CRH overproduction is implicated in several affective disorders, including major depression, panic-anxiety disorder and anorexia--diseases also associated with altered immune function. We investigated the link between CRH overdrive and immune function using CRH transgenic mice. Following immunization, CRH transgenic mice fail to form germinal centers; chronic glucocorticoid administration recapitulates this effect in wild-type mice. Regulation of germinal centers by glucocorticoids appears to be mediated, in part, through effects on follicular dendritic cells (FDC), providing a novel mechanism by which CRH dysregulation may significantly impair humoral immune responses.

Diferric transferrin regulates transferrin receptor 2 protein stability.

Transferrin receptor 2 (TfR2) is a type 2 transmembrane protein expressed in hepatocytes that binds iron-bound transferrin (Tf). Mutations in TfR2 cause one form of hereditary hemochromatosis, a disease in which excessive absorption of dietary iron can lead to liver cirrhosis, diabetes, arthritis, and heart failure. The function of TfR2 in iron homeostasis is unknown. We have studied the regulation of TfR2 in HepG2 cells. Western blot analysis shows that TfR2 increases in a time- and dose-dependent manner after diferric Tf is added to the culture medium. In cells exposed to diferric Tf, the amount of TfR2 returns to control levels within 8 hours after the removal of diferric Tf from the medium. However, TfR2 does not increase when non-Tf-bound iron (FeNTA) or apo Tf is added to the medium. The response to diferric Tf appears to be hepatocyte specific. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis shows that TfR2 mRNA levels do not change in cells exposed to diferric Tf. Rather, the increase in TfR2 is attributed to an increase in the half-life of TfR2 protein in cells exposed to diferric Tf. Our results support a role for TfR2 in monitoring iron levels by sensing changes in the concentration of diferric Tf.

Effect of flunixin meglumine on selected physiologic and performance parameters of athletically conditioned thoroughbred horses subjected to an incremental exercise stress test.

Twelve clinically sound, healthy, athletically conditioned Thoroughbred horses were subjected to an incremental exercise stress test to determine the effects and period of detection of a single dose of flunixin meglumine (1.1 mg/kg by intravenous injection) in serum and urine by ELISA. Flunixin concentrations, performance, and hematologic and clinical chemical parameters were measured. All horses were rotated through four treatment groups of a Latin-square design providing for each horse to serve as its own control. Flunixin meglumine reduced prostaglandin F(1alpha) and thromboxane concentrations that had been increased by intense exercise. Performance parameters did not improve and prostaglandin concentrations did not significantly correlate with total run time. Exercise did not change the flunixin elimination profile in either serum or urine, and concentrations were found to be below the detection limit of the ELISA test within 36 hours in serum and 120 hours in urine.

Effect of sulfadiazine and pyrimethamine on selected physiologic and performance parameters in athletically conditioned thoroughbred horses during an incremental exercise stress test.

Following the regimen used to treat equine protozoal myeloencephalitis, sulfadiazine (20 mg/kg) and pyrimethamine (1mg/kg) were administered orally once daily to 12 physically conditioned Thoroughbred horses for 4 consecutive days. The horses were randomly assigned to two test groups in a crossover design, with each horse serving as its own control. A stepwise exercise stress test was conducted to exhaustion. No effect on athletic performance was observed, and only marginal effects were noted in some hematologic and serochemical measurements, including decreased total white blood cell counts, red blood cell distribution width, total hemoglobin, serum sodium, and serum chloride. Serum folic acid concentration decreased significantly following sulfadiazine/pyrimethamine treatment.

Proton-gated channels in PC12 cells.

Acid-sensing ion channels (ASICs) are expressed in various sensory and central neurons. The functional role of these channels remains elusive. Complex subunit combinations and lack of specific blockers for native receptors are likely to contribute to the difficulty of resolving the function of ASICs. Finding a neuronal cell line, which expresses a single population of ASICs, should prove to be useful in delineating the function of individual ASICs. Using patch-clamp, Ca(2+)-imaging, and RT-PCR techniques, we have explored the existence of ASICs in PC12 cells, a clonal neuronal cell line. Fast drops of extracellular pH activated transient inward currents in PC12 cells with pH(0.5) at 6.0-6.2. The ASICs in PC12 cells were selective for Na(+) with significant Ca(2+) permeability. Currents in PC12 cells were blocked by the nonselective ASIC blocker amiloride. PcTX1, a specific homomeric ASIC1a blocker, also blocked the ASIC currents with an IC(50) of approximately 1.5 nM. RT-PCR demonstrated the existence of ASIC1a transcript in both undifferentiated and nerve growth factor-differentiated PC12 cells. Our data suggest that PC12 cells likely contain a single population of functional proton-gated channel-homomeric ASIC1a. It might be an ideal neuronal cell line for the study of physiological and potential pathological roles of this key subunit of ASICs.