Temperature and Strain Rate Related Deformation Behavior of UHMWPE Fiber-Reinforced Composites.

As they possess the qualities of high specific strength, high specific modulus, high specific energy absorption, and excellent designability, ultra-high molecular weight polyethylene (UHMWPE) fiber-reinforced composites have gradually replaced traditional materials such as ceramics and steel plates as the main ballistic protection materials. Using an improved test method, the uniaxial tensile tests of UHMWPE fiber-reinforced composites at two strain rates of 10-4 s-1 and 10-2 s-1 and a temperature range from -20 °C to 80 °C are carried out to study the effects of strain rate and temperature on the tensile behavior of UHMWPE fiber-reinforced composites. The experimental results indicate that the tensile responses exhibit nonlinear characteristics and the sensitivity of strain rate and temperature. The yield strength and modulus decrease with increasing temperature and increase with the increase in strain rate. A phenomenological viscoelastic constitutive model composed of a nonlinear spring and a nonlinear Maxwell element is proposed to characterize the temperature and strain rate dependent deformation behavior of UHMWPE fiber-reinforced composites before yielding. The results show that the model can accurately predict the tensile nonlinear viscoelastic responses of UHMWPE fiber-reinforced composites before yielding over a wide temperature range under quasi-static loading.

Thermoregulatory pathway underlying the pyrogenic effects of prostaglandin E2 in the lateral parabrachial nucleus of male rats.

It has been shown that prostaglandin (PG) E2 synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE2 induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE2 in male rats. The core temperature (Tcore) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE2 (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE2. We demonstrated that EP3 receptor was a pivotal receptor for PGE2-induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE2, respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE2 perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE2; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (IA) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE2; however, the IA current density was significantly increased by PGE2 perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of IA currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors.

Do Insurers With Greater Market Power Negotiate Consistently Lower Prices for Hospital Care? Evidence From Hospital Price Transparency Data.

This study examined if greater insurer market power was associated with consistently lower negotiated prices within each hospital for 44 shoppable and emergency procedures, using price transparency data disclosed by 1,506 hospitals in metropolitan areas. We used multi-level fixed effects models to estimate the within-hospital variation in plan-level insurer-negotiated prices (from the largest insurer, the second largest insurer, other major insurers, and nonmajor insurers) and cash-pay prices as a function of insurer market power. For shoppable services, relative to nonmajor insurers, the largest, second largest, and other major insurers negotiated 23%, 16%, and 3% lower prices, respectively, while cash prices were 17% higher. For emergency room visits, while the largest insurers paid 5% less than nonmajor insurers, the second largest and other major insurers did not pay lower prices. Stratified analyses by type of shoppable services found varying magnitudes and patterns of price discounts associated with insurer market power.

Is there an advantage? Considerations for researchers studying the effects of the type of Medicare coverage.

OBJECTIVE: To describe common methodological problems that arise in comparisons of Medicare Advantage (MA) and Traditional Medicare (TM) and within-MA studies and provide suggestions of how researchers can address these issues. STUDY SETTING: Published research evaluating Medicare coverage options in the United States. STUDY DESIGN: We considered key conceptual challenges and promising solutions that have been used thus far and suggest additional directions. DATA COLLECTION: Not available. PRINCIPAL FINDINGS: Many existing studies of MA versus TM include significant limitations, such as failing to account for unobserved confounders driving both beneficiary coverage choice and health outcomes once enrolled, not accounting for variation in benefit generosity, provider networks, or plan design across MA plans, and/or having been conducted at a time when MA enrollment was less than a third of all Medicare beneficiaries. We provide a review of methods that can help researchers to overcome these weaknesses and suggest additional methods and data sources that may aid future research. CONCLUSIONS: The MA program is becoming an essential part of the US healthcare system. By accounting for non-random movement into and out of MA and studying the heterogeneity of beneficiary experience across plan and market characteristics, researchers can provide the high-quality evidence necessary for policymakers to design the program and reform TM in ways that maximize beneficiary outcomes.

Hospital Prices in Medicaid Managed Care.

This cross-sectional study uses hospitals' self-disclosed pricing information to characterize Medicaid managed care hospital prices.

Role of Patient Sorting in Avoidable Hospital Stays in Medicare Advantage vs Traditional Medicare.

Importance: Unlike traditional Medicare (TM), Medicare Advantage (MA) plans limit in-network care to a specific network of Medicare clinicians. MA plans thus play a role in sorting patients to a subset of clinicians. It is unknown whether the performance of physicians who treat MA and TM beneficiaries is different. Objective: To examine whether avoidable hospital stay differences between MA and TM can be explained by the primary care clinicians who treat MA and TM beneficiaries. Design, Setting, and Participants: This was a cross-sectional study of a nationally representative sample of MA and TM beneficiaries in 2019 with any of 5 chronic ambulatory care-sensitive conditions (ACSCs). The relative risk (RR) of avoidable hospital stays in MA compared with TM was estimated with inverse probability of treatment-weighted Poisson regression, both without and with clinician fixed effects. The degree to which the estimated MA vs TM difference could be explained by patient sorting was calculated by comparing the 2 RR estimates. Data were analyzed between February 2022 and April 2023. Exposure: Enrollment in MA. Main Outcome and Measures: Whether a beneficiary had avoidable hospital stays in 2019 due to any of the ACSCs. Avoidable hospital stays included both hospitalizations and observation stays. Results: The study sample comprised 1 323 481 MA beneficiaries (mean [SD] age, 75.4 [7.0] years; 56.9% women; 69.3% White) and 1 965 863 TM beneficiaries (mean [SD] age, 75.9 [7.4] years; 57.1% women; 82.5% White). When controlling for the primary care clinician, the RR of avoidable hospital stays in MA vs TM changed by 2.6 percentage points (95% CI, 1.72-3.50; P < .001), suggesting that compared with TM beneficiaries, MA beneficiaries saw clinicians with lower rates of avoidable hospital stays. This effect size was statistically significant to explain the 2% lower rate of avoidable hospital stays in MA than in TM. Conclusions and Relevance: In this cross-sectional study of MA and TM beneficiaries, the lower rate of avoidable hospital stays among MA beneficiaries than TM beneficiaries was attributable to MA beneficiaries visiting clinicians with lower rates of avoidable hospital stays. The patient sorting that occurs in MA plays a critical role in the lower rates of avoidable hospital stays compared with TM.

The allometric relationship between carbon emission and economic development in Yangtze River Delta: fusion of multi-source remote sensing nighttime light data.

Exploring the allometric relationship between carbon emission and economic development can provide guidance for policy-makers who hope to accelerate carbon emission reduction and achieve high-quality development. First, based on the established DMSP/OLS and NPP/VIIRS nighttime light datasets, this study simulated the carbon emissions of the Yangtze River Delta from 2000 to 2020. Second, our research analyzed the spatiotemporal evolution characteristics of carbon emissions. Third, adopting allometric growth model, we explored the allometric relationship between economic development and carbon emissions in Yangtze River Delta. The main conclusions are as follows. First, four prediction models, namely, linear fitting, support vector machine, random forest, and CNN-BiLSTM deep learning, were compared to simulate the accuracy of carbon emissions. Consequently, the CNN-BiLSTM deep learning estimation model presented the best accuracy. Second, both the carbon emissions in YRD as a whole showed an increasing trend, with the largest growth rate appearing in Shanghai and the smallest growth rate occurring in Lishui. Moreover, the high-carbon emission areas were mainly distributed in the core city cluster, which are enclosed by Shanghai, Nanjing, and Hangzhou. Finally, the allometric relationship between economic development and carbon emissions was dominated by one-level negative during the sample period, and the relative growth rate of carbon emissions is lower than that of the economic development, which made the YRD at a basic coordinate stage of weak expansion of economy.

Different Life-Stage Exposure to Hexafluoropropylene Oxide Trimer Acid Induces Reproductive Toxicity in Adult Zebrafish (Danio rerio).

As a novel alternative to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) has been widely used and has caused ubiquitous water pollution. However, its adverse effects on aquatic organisms are still not well known. In the present study, zebrafish at different life stages were exposed to 0, 5, 50, and 100 µg/L of HFPO-TA for 21 days to investigate reproductive toxicity in zebrafish. The results showed that HFPO-TA exposure significantly inhibited growth and induced reproductive toxicity in zebrafish, including a decrease of the condition factor, gonadosomatic index, and the average number of eggs. Histological section observation revealed that percentages of mature oocytes and spermatozoa were reduced, while those of primary oocytes and spermatocytes increased. In addition, exposure to HFPO-TA at three stages induced a significant decrease in the hatching rate, while the heart rate and normal growth rate of F1 offspring were only significantly inhibited for the exposure from fertilization to 21 days postfertilization (dpf). Compared with the exposure from 42 to 63 dpf, the reproductive toxicity induced by HFPO-TA was more significant for the exposure from fertilization to 21 dpf and from 21 to 42 dpf. Expression of the genes for cytochrome P450 A1A, vitellogenin 1, estrogen receptor alpha, and estrogen receptor 2b was significantly up-regulated in most cases after exposure to HFPO-TA, suggesting that HFPO-TA exhibited an estrogen effect similar to PFOA. Therefore, HFPO-TA might disturb the balance of sex steroid hormones and consequently induce reproductive toxicity in zebrafish. Taken together, the results demonstrate that exposure to HFPO-TA at different life stages could induce reproductive toxicity in zebrafish. However, the underlying mechanisms deserve further investigation. Environ Toxicol Chem 2023;42:2490-2500. © 2023 SETAC.

Hospital Prices For Commercial Plans Are Twice Those For Medicare Advantage Plans When Negotiated By The Same Insurer.

Most major insurers operate in both the commercial health insurance and Medicare Advantage (MA) markets. We investigated the ratio of commercial-to-MA prices negotiated by the same insurer, in the same hospital and for the same services, using 2022 price information disclosed by hospitals in compliance with the hospital price transparency rule. Insurers negotiated median hospital prices for commercial plans that were two to three times higher than their MA prices in the same hospital for the same service. The median commercial-to-MA price ratio in the same hospital varied, from 1.8 for surgery and medicine services to 2.2 for laboratory tests and emergency department visits and 2.4 for imaging services. In multivariable Poisson regression analysis, higher ratios were associated with system-affiliated, nonprofit, and teaching hospitals, as well as with large national insurers. These findings reflect the differences in financial incentives and regulatory policies in the commercial and MA markets. Because insurers respond to differing incentives by obtaining different negotiated prices across markets, policy and practice efforts that alter incentives for insurers may have the potential to lower commercial prices.

A parabrachial-hypothalamic parallel circuit governs cold defense in mice.

Thermal homeostasis is vital for mammals and is controlled by brain neurocircuits. Yet, the neural pathways responsible for cold defense regulation are still unclear. Here, we found that a pathway from the lateral parabrachial nucleus (LPB) to the dorsomedial hypothalamus (DMH), which runs parallel to the canonical LPB to preoptic area (POA) pathway, is also crucial for cold defense. Together, these pathways make an equivalent and cumulative contribution, forming a parallel circuit. Specifically, activation of the LPB → DMH pathway induced strong cold-defense responses, including increases in thermogenesis of brown adipose tissue (BAT), muscle shivering, heart rate, and locomotion. Further, we identified somatostatin neurons in the LPB that target DMH to promote BAT thermogenesis. Therefore, we reveal a parallel circuit governing cold defense in mice, which enables resilience to hypothermia and provides a scalable and robust network in heat production, reshaping our understanding of neural circuit regulation of homeostatic behaviors.

Association of Medicare Program Type with Health Care Access, Utilization, and Affordability among Cancer Survivors.

BACKGROUND: The Medicare Advantage program provides care to nearly half of Medicare beneficiaries, including a rapidly growing population of cancer survivors. Despite its increased adoption, it is still unknown whether or not the program improves healthcare access, outcomes, and affordability for cancer survivors. METHODS: We performed a cross-sectional study of Medicare beneficiaries aged ≥ 65 years with a self-reported history of cancer from the 2019 National Health Interview Survey. We used multivariable logistic regression to evaluate the association between Medicare program type (Medicare Advantage vs. traditional Medicare) and measures of healthcare access, acute care utilization, and affordability. RESULTS: We identified 4451 beneficiaries with a history of cancer, corresponding to 26.6 million weighted cancer survivors in 2019. Of the beneficiaries, 35.8% were enrolled in Medicare Advantage, whereas 64.2% were enrolled in traditional Medicare. The age, sex, racial and ethnic composition, household income, primary site of cancer, and comorbidity burden of Medicare Advantage and traditional Medicare beneficiaries were similar. In the adjusted analysis, there were no differences in healthcare access or acute care utilization between traditional Medicare and Medicare Advantage beneficiaries. However, cancer survivors enrolled in Medicare Advantage were more likely to worry about (34.3% vs. 29.4%; aOR, 1.3 (95% CI, 1.1-1.5)) or have problems paying (13.6% vs. 11.1%; aOR, 1.4 (95% CI, 1.1-1.8)) medical bills. CONCLUSIONS: We found no evidence that Medicare Advantage beneficiaries with cancer had better healthcare access, affordability, or acute care utilization than traditional Medicare beneficiaries did. Furthermore, Medicare Advantage beneficiaries were more likely to report financial strain and have difficulty paying for their medical bills than were those with traditional Medicare. Despite the generous benefits and attractive incentives, Medicare Advantage plans may not be more cost-effective than traditional Medicare is for cancer survivors. Our study informs ongoing congressional deliberations to re-evaluate the role of Medicare Advantage in promoting equity among beneficiaries with cancer.

Comparison of Third-Generation Sequencing Technology and Traditional Microbiological Detection in Pathogen Diagnosis of Lower Respiratory Tract Infection.

BACKGROUND: It is common to obtain a low detection rate and unsatisfactory detection results in complex infection or rare pathogen detection. This retrospective study aimed to illustrate the application value and prospect of the third-generation sequencing technology in lower respiratory tract infection disease. METHODS: This study recruited 70 patients with lower respiratory tract infection (LRTI). Pathogen detection of bronchoalveolar lavage fluid (BALF) from all patients was performed using nanopore metagenomic sequencing technology and traditional culture. BALF culture combined with quantitiative PCR (qPCR) was used as a reference standard to analyze the sensitivity and specificity of nanopore sequencing technology. The current study also collected the examination results of enrolled samples using technical methods sputum culture, tuberculosis DNA (TB-DNA), and Xpert MTB/RIF and analyzed the detection efficiency of nanopore sequencing for Mycobacterium tuberculosis. RESULTS: The positive rates of pathogens in 70 BALF samples detected by conventional culture and nanopore sequencing were 25.71% and 84.29%, respectively. Among the 59 positive BALF cases using nanopore sequencing, a total of 31 pathogens were identified, of which the proportions of bacteria, fungi, viruses, and other pathogens were 50%, 17%, 32%, and 1%, respectively. Using the results combined with culture and qPCR detection methods as the standard, the pathogen detection of BALF using nanopore sequencing had a sensitivity of 70% and a specificity of 91.7%. Additionally, the positive rate of the detection of M. tuberculosis using nanopore sequencing was 33.3% (6/18). The clinical medication plans of 74.3% (52/70) of the patients were referred to the nanopore sequencing results, of which 31 cases changed their treatment strategy, 21 supported the previous treatment plans, and 90% (47/52) of the patients finally had clinical improvement. CONCLUSIONS: BALF detection using nanopore sequencing technology improves the process of detecting pathogens in patients with LRTI, especially for M. tuberculosis, fungi, and viruses, by reducing the report time from three days to six hours. The clinical application prospect of nanopore sequencing technology is promising in the pathogen diagnosis of LRTI.

Atomically Site Synergistic Effects of Dual-Atom Nanozyme Enhances Peroxidase-like Properties.

Pursuing effective and generalized strategies for modulating the electronic structures of atomically dispersed nanozymes with remarkable catalytic performance is exceptionally attractive yet challenging. Herein, we developed a facile "formamide condensation and carbonization" strategy to fabricate a library of single-atom (M1-NC; 6 types) and dual-atom (M1/M2-NC; 13 types) metal-nitrogen-carbon nanozymes (M = Fe, Co, Ni, Mn, Ru, Cu) to reveal peroxidase- (POD-) like activities. The Fe1Co1-NC dual-atom nanozyme with Fe1-N4/Co1-N4 coordination displayed the highest POD-like activity. Density functional theory (DFT) calculations revealed that the Co atom site synergistically affects the d-band center position of the Fe atom site and served as the second reaction center, which contributes to better POD-like activity. Finally, Fe1Co1 NC was shown to be effective in inhibiting tumor growth both in vitro and in vivo, suggesting that diatomic synergy is an effective strategy for developing artificial nanozymes as novel nanocatalytic therapeutics.

Prevalence and Influencing Factors of Mixed Dentition Malocclusion in Children Aged 6-12 Years in Jinzhou, China.

PURPOSE: To investigate the prevalence, clinical manifestations and related risk factors of malocclusion in schoolchildren of Jinzhou City, China. MATERIALS AND METHODS: A total of 2162 children aged 6-12 years were randomly selected from various districts of Jinzhou. Conventional clinical examination was performed by stomatologists, and the results were described based on different clinical manifestations of malocclusion and individual normal occlusion. Further, a questionnaire survey completed by children's parents or guardians provided the demographic data, lifestyle, and oral habits. The distribution of individual normal occlusion and malocclusion was documented in percentage, and Pearson's Χ2 was used for two-factor analysis. The data were statistically analysed using SPSS software (version 25.0) with a significance level of α = 0.05. RESULTS: A total of 1129 boys and 1033 girls were included in this study, i.e. 52.2% and 47.8% of the total number of children, respectively. The prevalence of malocclusion in children aged 6-12 years old in Jinzhou was 67.9%, of which crowded dentition was the most common form, with a prevalence of 71.8%, followed by deep overbite, anterior crossbite, dental spacing, deep overjet, anterior edge-to-edge occlusion, and anterior open bite. In the logistic regression model, the results showed that BMI index had little effect on the occurrence of malocclusion (p > 0.05), while dental caries, bad oral habits, retained primary teeth, and a low labial frenum were all related to the occurrence of malocclusion (p < 0.05). Moreover, the higher frequency and duration of bad oral habits were associated with a higher likelihood of malocclusion. CONCLUSIONS: The prevalence of malocclusion in children aged 6-12 years in Jinzhou is high. In addition, bad oral habits (such as lip biting, tongue thrusting, biting/gnawing objects, unilateral chin supporting, and unilateral mastication) and other related risk factors (such as dental caries, mouth breathing, retention of primary teeth, and low labial frenum, etc) were associated with malocclusion.

Sorafenib regulates c-CBL gene-mediated chemoresistance in acute myeloid leukemia cells.

Chemotherapeutic regimens containing sorafenib are widely used in salvage treatment for patients with relapsed and refractory acute leukemia, especially those with FLT3-ITD mutations. However, the therapeutic effects in individuals are heterogeneous, and the effective maintenance period is relatively short. Our clinical analysis showed patients with high c-kit (CD117) expression in leukemia cells generally had a better response to sorafenib, but the reason for this finding was not clear. c-kit (CD117) is a receptor tyrosine kinase, and its signal inactivation and hydrolytic metabolism are regulated by the CBL protein, a Ring finger E3 ubiquitin ligase, encoded by the c-CBL gene. And we also found that the c-CBL gene expression in refractory and relapsed patients was significantly lower than that in healthy hematopoietic stem cell donors. Therefore, we assumed that there is a relationship among c-CBL gene function, high expression of c-kit (CD117) and a better clinical response to sorafenib. To confirm this hypothesis, we packaged interfering lentiviruses and overexpressed adenoviruses targeting the c-CBL gene respectively, and infected leukemia cell lines with these viruses to regulate the expression of the c-CBL gene, and observed the subsequent changes of these cells in various biological behaviors. Our results showed when the c-CBL gene was silenced, the cells proliferation was accelerated, drug sensitivity to cytarabine or sorafenib was decreased, and apoptosis ratio was decreased. And all these phenomena were reversed when the gene was overexpressed, which confirmed the expression of c-CBL gene was related to drug resistance in leukemia cells. At last, we explored the possible molecular mechanisms underlying these phenomena.

Clinical factors associated with functional outcomes in patients with single subcortical infarction with neurological deterioration.

Objective: Factors that predict poor outcomes in patients with single subcortical infarction (SSI) may differ from those that predict poor outcomes in the SSI subgroup with neurological deterioration (ND). This study aimed to investigate the effect of ND on functional outcomes in patients with SSI and the clinical factors that predict poor outcomes in patients with SSI with ND (SSI-ND) and in all patients with SSI. Methods: Patients with SSI were consecutively enrolled in this study. ND was defined as an increase of ≥2 points in the National Institutes of Health Stroke Scale (NIHSS) total score, an increase of ≥1 point in the NIHSS subscore of consciousness or motor function, or any new neurological deficit. Results: A total of 255 patients were enrolled, and nine (3.53%) were lost to a follow-up. ND [adjusted relative risk (aRR) = 1.37, 95% confidence interval (CI) = 1.22-1.55, p < 0.001], female sex (aRR = 1.13, 95% CI = 1.03-1.24, p = 0.12), initial NIHSS (aRR = 1.08, 95% CI = 1.07-1.10, p < 0.001), and parental arterial disease (PAD) (aRR = 1.16, 95% CI = 1.07-1.26, p = 0.038) were associated with a poor 90-day outcome (the modified Rankin scale (mRS) > 2 points) in patients with SSI. In the SSI-ND subgroup, PAD (aRR = 2.15, 95% CI = 1.20-3.86, p = 0.01), glycosylated hemoglobin (aRR = 1.17, 95% CI = 1.01-1.35, p = 0.035), and severe NIHSS (aRR = 1.15, 95% CI = 1.06-1.25, p = 0.001) were predictive of a poor outcome, and PAD (aRR = 1.87, 95% CI = 1.19-2.95, p = 0.007) was correlated with higher/worsened NIHSS [> 2 points (median)]. For predicting poor outcomes in patients with SSI-ND with PAD, a more severe NIHSS (aRR = 1.09, 95% CI = 1.02-1.17, p = 0.01) was the only determinant, with a cutoff of 4.5 points, a sensitivity of 94.0%, and a specificity of 83.3%. Conclusions: ND is an independent predictor of poor outcomes in patients with SSI, and poor outcome determinants in the SSI-ND subgroup and in all patients with SSI are not identical. For patients with SSI-ND, PAD could aggravate ND and was therefore an essential predictor of poor outcomes.

Part D beneficiaries' incentives and responses under preferred pharmacy networks.

OBJECTIVES: The share of Medicare stand-alone prescription drug plans with a preferred pharmacy network has grown from less than 9% in 2011 to 98% in 2021. This article assesses the financial incentives that such networks created for unsubsidized and subsidized beneficiaries and their pharmacy switching. STUDY DESIGN: We analyzed prescription drug claims data for a nationally representative 20% sample of Medicare beneficiaries from 2010 through 2016. METHODS: We evaluated the financial incentives for using preferred pharmacies by simulating unsubsidized and subsidized beneficiaries' annual out-of-pocket spending differentials between using nonpreferred and preferred pharmacies for all their prescriptions. We then compared beneficiaries' use of pharmacies before and after their plans adopted preferred networks. We also examined the amount of money that beneficiaries left on the table under such networks, based on their pharmacy use. RESULTS: Unsubsidized beneficiaries faced substantial incentives-on average, $147 annually in out-of-pocket spending-and moderately switched toward preferred pharmacies, whereas subsidized beneficiaries were insulated from the incentives and demonstrated little switching. Among those who continued to mainly use nonpreferred pharmacies (half of the unsubsidized and about two-thirds of the subsidized), on average, the unsubsidized paid more out of pocket ($94) relative to if they had used preferred pharmacies, whereas Medicare bore the extra spending ($170) for the subsidized through cost-sharing subsidies. CONCLUSIONS: Preferred networks have important implications for beneficiaries' out-of-pocket spending and the low-income subsidy program. Further research is needed about the impact on the quality of beneficiaries' decision-making and cost savings to fully evaluate preferred networks.

The hyperthermic response to intra-preoptic area administration of agmatine in male rats.

Agmatine is an endogenous biogenic amine that exerts various effects on the central nervous system. The hypothalamic preoptic area (POA, thermoregulatory command center) has high agmatine immunoreactivity. In this study, in conscious and anesthetized male rats, agmatine microinjection into the POA induced hyperthermic responses associated with increased heat production and locomotor activity. Intra-POA administration of agmatine increased the locomotor activity, the brown adipose tissue temperature and rectum temperature, and induced shivering as demonstrated by increased neck muscle electromyographic activity. However, intra-POA administration of agmatine almost had no impact on the tail temperature of anesthetized rats. Furthermore, there were regional differences in the response to agmatine in the POA. The most effective sites for the microinjection of agmatine to elicit hyperthermic responses were localized in the medial preoptic area (MPA). Agmatine microinjection into the median preoptic nucleus (MnPO) and lateral preoptic nucleus (LPO) had a minimal effect on the mean core temperature. Analysis of the in vitro discharge activity of POA neurons in brain slices when perfused with agmatine showed that agmatine inhibited most warm-sensitive but not temperature-insensitive neurons in the MPA. However, regardless of thermosensitivity, the majority of MnPO and LPO neurons were not responsive to agmatine. The results demonstrated that agmatine injection into the POA of male rats, especially the MPA, induced hyperthermic responses, which may be associated with increased BAT thermogenesis, shivering and locomotor activity by inhibiting warm-sensitive neurons.

Sebaceous Carcinoma of the Submandibular Gland a Case Report and Review of the Literature.

Objective: Sebaceous carcinoma (SC) of the submandibular gland is extremely rare. Owing to the low morbidity and nonspecific clinical manifestations, diagnosis is commonly delayed, which increases metastasis and mortality. To date, there have been five reported cases of SC of the submandibular gland. Here, we present a new case and review the relevant literature. Methods and Results: A 36-year-old woman presented with an enlarged left submandibular gland. Clinical features included a non-tender solitary nodular mass with normal overlying skin. There were no special findings on computed tomography or ultrasound examination except for a swollen mass in the left submandibular gland. The patient underwent surgical resection. Pathological examination confirmed the diagnosis of SC with nerve infiltration. Immunohistochemical examination of this case showed positive staining for P63, P40, CK7, CK8/18, MLH1, MSH2, MSH6, and PMS2. The specimen was negative for androgen receptor, CEA, S-100, CK5/6, SOX-10, SOX-11, SMA, and GCDFP-15. The KI-67 labeling index was determined to be 15%. PAS and anti-epithelial membrane antigen were positive in partial area. The patient is still undergoing follow-up, and no metastasis or recurrence has been observed for 2 months. Conclusion: This case highlighted the fact that despite its rarity, SC should be considered as a differential diagnosis for masses located in the head and face. Early and accurate diagnosis, followed by wide surgical excision, has a favorable prognosis. Therefore, clinicians should be familiar with the clinical and pathological features of this disease.

Comparing Medicare Advantage and Traditional Medicare Prices for Hospital Outpatient Services With Hospital Price Transparency Data.

As Medicare Advantage (MA) plans enroll an increasingly large share of Medicare beneficiaries, how much providers charge MA plans relative to Traditional Medicare (TM) has important policy implications. We used new price transparency data from hospitals-which contain the most up-to-date negotiated prices-to evaluate whether and how MA prices differed from TM for hospital outpatient services. We found that among the 1,135 hospitals in our sample, MA prices were close to TM at about half of them, but the other half reported MA prices that deviated considerably from TM, predominantly in the direction of higher rather than lower, and rural hospitals were more likely than urban ones to charge high MA markups. Our findings also suggest that hospital price transparency data hold promise for promoting price shopping among MA beneficiaries. But greater hospital compliance and more standardized reporting are necessary for the data to be a more useful tool.