Spin density wave induced disordering of the vortex lattice in superconducting La2−x_{2-x}Srx_xCuO4_4

We use small angle neutron scattering to study the superconducting vortex lattice in La$_{2-x}$Sr$_x$CuO$_4$ as a function of doping and magnetic field. We show that near optimally doping the vortex lattice coordination and the superconducting coherence length $\xi$ are controlled by a van-Hove singularity crossing the Fermi level near the Brillouin zone boundary. The vortex lattice properties change dramatically as a spin-density-wave instability is approached upon underdoping. The Bragg glass paradigm provides a good description of this regime and suggests that SDW order acts as a novel source of disorder on the vortex lattice.Comment: Accepted in Phys. Rev.

Effect of Stay-at-Home orders and other COVID-related policies on trauma hospitalization rates and disparities in the USA: a statewide time-series analysis

Background To combat the coronavirus pandemic, states implemented several public health policies to reduce infection and transmission. Increasing evidence suggests that these prevention strategies also have had a profound impact on non-COVID healthcare utilization. The goal of this study was to determine the impact of a statewide Stay-at-Home order and other COVID-related policies on trauma hospitalizations, stratified by race/ethnicity, age, and sex. Methods We used the North Carolina Trauma Registry, a statewide registry of trauma hospitalizations for 18 hospitals across North Carolina, including all North Carolina trauma centers, to calculate weekly rates of assault, self-inflicted, unintentional motor vehicle collision (MVC), and other unintentional injury hospitalizations between January 1, 2019, and December 31, 2020. Interrupted time-series design and segmented linear regression were used to estimate changes in hospitalization rates after several COVID-related executive orders, overall and stratified by race/ethnicity, age, and sex. Changes in hospitalization rates were assessed after 1) USA declaration of a public health emergency; 2) North Carolina statewide Stay-at-Home order; 3) Stay-at-Home order lifted with restrictions (Phase 2: Safer-at-Home); and 4) further lifting of restrictions (Phase 2.5: Safer-at-Home). Results There were 70,478 trauma hospitalizations in North Carolina, 2019–2020. In 2020, median age was 53 years old and 59% were male. Assault hospitalization rates (per 1,000,000 NC residents) increased after the Stay-at-Home order, but substantial increases were only observed among Black/African American residents (weekly trend change = 1.147, 95% CI = 0.634 to 1.662) and 18–44-year-old males (weekly trend change = 1.708, 95% CI = 0.870 to 2.545). After major restrictions were lifted, assault rates decreased but remained elevated compared to pre-COVID levels. Unintentional non-MVC injury hospitalizations decreased after the USA declared a public health emergency, especially among women ≥ 65 years old (weekly trend change = -4.010, 95% CI = -6.166 to -1.855), but returned to pre-pandemic levels within several months. Conclusions Statewide Stay-at-Home orders placed Black/African American residents at higher risk of assault hospitalizations, exacerbating pre-existing disparities. Males 18–44 years old were also at higher risk of assault hospitalization. Fear of COVID-19 may have led to decreases in unintentional non-MVC hospitalization rates, particularly among older females. Policy makers must anticipate policy-related harms that may disproportionately affect already disadvantaged communities and develop mitigation approaches

Epidemiologic and Economic Burden of Achalasia in the United States

Background & Aims: Achalasia is a debilitating chronic condition of the esophagus. Currently there are no national estimates on the epidemiologic and economic burden of disease. We sought to estimate trends in incidence and prevalence of achalasia by age-sex strata, and to estimate the total direct medical costs attributed to achalasia in the United States. Methods: We conducted a cohort study using two administrative claims databases: IBM MarketScan Commercial Claims and Encounters database (2001-2018; age <65) and a 20% sample of nationwide Medicare enrollment and claims (2007-2015; age ≥65). Point prevalence was calculated on the first day of each calendar year; the incidence rate captured new cases developed in the ensuing year. Utilization rates of healthcare services and procedures were reported. Mean costs per patient were calculated and standardized to the corresponding U.S. Census Bureau population data to derive achalasia-specific total direct medical costs. Results: The crude prevalence of achalasia per 100,000 persons was 18.0 (95% CI, 17.4, 18.7) in MarketScan and 162.1 (95% CI, 157.6, 166.6) in Medicare. The crude incidence rate per 100,000 person-years was 10.5 (95% CI, 9.9, 11.1) in MarketScan and 26.0 (95% CI, 24.9, 27.2) in Medicare. Incidence and prevalence increased substantially over time in the Medicare cohort, and increased with more advanced age in both cohorts. Utilization of achalasia-specific healthcare was high; national estimates of total direct medical costs exceeded $408 million in 2018. Conclusions: Achalasia has a higher epidemiologic and economic burden in the US than previously suggested, with diagnosis particularly increasing in older patients

Sex-Based Differences in Inpatient Burn Mortality

Background: Among burn patients, research is conflicted, but may suggest that females are at increased risk of mortality, despite the opposite being true in non-burn trauma. Our objective was to determine whether sex-based differences in burn mortality exist, and assess whether patient demographics, comorbid conditions, and injury characteristics explain said differences. Methods: Adult patients admitted with burn injury—including inhalation injury only—between 2004 and 2013 were included. Inverse probability of treatment weights (IPTW) and inverse probability of censor weights (IPCW) were calculated using admit year, patient demographics, comorbid conditions, and injury characteristics to adjust for potential confounding and informative censoring. Standardized Kaplan–Meier survival curves, weighted by both IPTW and IPCW, were used to estimate the 30-day and 60-day risk of inpatient mortality across sex. Results: Females were older (median age 44 vs. 41 years old, p < 0.0001) and more likely to be Black (32% vs. 25%, p < 0.0001), have diabetes (14% vs. 10%, p < 0.0001), pulmonary disease (14% vs. 7%, p < 0.0001), heart failure (4% vs. 2%, p = 0.001), scald burns (45% vs. 26%, p < 0.0001), and inhalational injuries (10% vs. 8%, p = 0.04). Even after weighting, females were still over twice as likely to die after 60 days (RR 2.87, 95% CI 1.09, 7.51). Conclusion: Female burn patients have a significantly higher risk of 60-day mortality, even after accounting for demographics, comorbid conditions, burn size, and inhalational injury. Future research efforts and treatments to attenuate mortality should account for these sex-based differences. The project was supported by the National Institutes of Health, Grant Number UL1TR001111

Risk Factors for Healthcare-Associated Infections in Adult Burn Patients

OBJECTIVE Burn patients are particularly vulnerable to infection, and an estimated half of all burn deaths are due to infections. This study explored risk factors for healthcare-Associated infections (HAIs) in adult burn patients. DESIGN Retrospective cohort study. SETTING Tertiary-care burn center. PATIENTS Adults (≥18 years old) admitted with burn injury for at least 2 days between 2004 and 2013. METHODS HAIs were determined in real-Time by infection preventionists using Centers for Disease Control and Prevention criteria. Multivariable Cox proportional hazards regression was used to estimate the direct effect of each risk factor on time to HAI, with inverse probability of censor weights to address potentially informative censoring. Effect measure modification by burn size was also assessed. RESULTS Overall, 4,426 patients met inclusion criteria, and 349 (7.9%) patients had at least 1 HAI within 60 days of admission. Compared to 6 times as likely to acquire an HAI (HR, 6.38; 95% CI, 3.64-11.17); and patients with >20% TBSA were >10 times as likely to acquire an HAI (HR, 10.33; 95% CI, 5.74-18.60). Patients with inhalational injury were 1.5 times as likely to acquire an HAI (HR, 1.61; 95% CI, 1.17-2.22). The effect of inhalational injury (P=.09) appeared to be larger among patients with ≤20% TBSA. CONCLUSIONS Larger burns and inhalational injury were associated with increased incidence of HAIs. Future research should use these risk factors to identify potential interventions

Burn injury outcomes in patients with pre-existing diabetic mellitus: Risk of hospital-acquired infections and inpatient mortality

Background: Diabetes mellitus (DM) is a major cause of illness and death in the United States, and diabetic patients are at increased risk for burn injury. We therefore sought to examine the impact of pre-existing DM on the risk of inpatient mortality and hospital acquired infections (HAI) among burn patients. Methods: Adult patients (≥18 years old) admitted from 2004 to 2013 were analyzed. Weighted Kaplan–Meier survival curves – adjusting for patient demographics, burn mechanism, presence of inhalation injury, total body surface area, additional comorbidities, and differential lengths of stay – were used to estimate the 30-day and 60-day risk of mortality and HAIs. Results: A total of 5539 adult patients were admitted and included in this study during the study period. 655 (11.8%) had a pre-existing DM. The crude incidence of HAIs and in-hospital mortality for the whole burn cohort was 8.5% (n = 378) and 4.4% (n = 243), respectively. Diabetic patients were more likely to be older, female, have additional comorbidities, inhalational injury, and contact burns. After adjusting for patient and burn characteristics, the 60-day risk of HAI among patients with DM was significantly higher, compared to non-diabetic patients (RR 2.07, 95% CI 1.28, 6.79). However, no significant difference was seen in the 60-day risk of mortality (RR 1.34, 95% CI 0.44, 3.10). Conclusions: Pre-existing DM significantly increases the risk of developing an HAI in patients following burn injury, but does not significantly impact the risk of inpatient mortality. Further understanding of the immune modulatory mechanism of burn injury and DM is imperative to better attenuate the acquisition of HAIs

Incorporation of DPP6a and DPP6K Variants in Ternary Kv4 Channel Complex Reconstitutes Properties of A-type K Current in Rat Cerebellar Granule Cells

Dipeptidyl peptidase-like protein 6 (DPP6) proteins co-assemble with Kv4 channel α-subunits and Kv channel-interacting proteins (KChIPs) to form channel protein complexes underlying neuronal somatodendritic A-type potassium current (ISA). DPP6 proteins are expressed as N-terminal variants (DPP6a, DPP6K, DPP6S, DPP6L) that result from alternative mRNA initiation and exhibit overlapping expression patterns. Here, we study the role DPP6 variants play in shaping the functional properties of ISA found in cerebellar granule (CG) cells using quantitative RT-PCR and voltage-clamp recordings of whole-cell currents from reconstituted channel complexes and native ISA channels. Differential expression of DPP6 variants was detected in rat CG cells, with DPP6K (41±3%)>DPP6a (33±3%)>>DPP6S (18±2%)>DPP6L (8±3%). To better understand how DPP6 variants shape native neuronal ISA, we focused on studying interactions between the two dominant variants, DPP6K and DPP6a. Although previous studies did not identify unique functional effects of DPP6K, we find that the unique N-terminus of DPP6K modulates the effects of KChIP proteins, slowing recovery and producing a negative shift in the steady-state inactivation curve. By contrast, DPP6a uses its distinct N-terminus to directly confer rapid N-type inactivation independently of KChIP3a. When DPP6a and DPP6K are co-expressed in ratios similar to those found in CG cells, their distinct effects compete in modulating channel function. The more rapid inactivation from DPP6a dominates during strong depolarization; however, DPP6K produces a negative shift in the steady-state inactivation curve and introduces a slow phase of recovery from inactivation. A direct comparison to the native CG cell ISA shows that these mixed effects are present in the native channels. Our results support the hypothesis that the precise expression and co-assembly of different auxiliary subunit variants are important factors in shaping the ISA functional properties in specific neuronal populations

Dynamic Changes in the MicroRNA Expression Profile Reveal Multiple Regulatory Mechanisms in the Spinal Nerve Ligation Model of Neuropathic Pain

Neuropathic pain resulting from nerve lesions or dysfunction represents one of the most challenging neurological diseases to treat. A better understanding of the molecular mechanisms responsible for causing these maladaptive responses can help develop novel therapeutic strategies and biomarkers for neuropathic pain. We performed a miRNA expression profiling study of dorsal root ganglion (DRG) tissue from rats four weeks post spinal nerve ligation (SNL), a model of neuropathic pain. TaqMan low density arrays identified 63 miRNAs whose level of expression was significantly altered following SNL surgery. Of these, 59 were downregulated and the ipsilateral L4 DRG, not the injured L5 DRG, showed the most significant downregulation suggesting that miRNA changes in the uninjured afferents may underlie the development and maintenance of neuropathic pain. TargetScan was used to predict mRNA targets for these miRNAs and it was found that the transcripts with multiple predicted target sites belong to neurologically important pathways. By employing different bioinformatic approaches we identified neurite remodeling as a significantly regulated biological pathway, and some of these predictions were confirmed by siRNA knockdown for genes that regulate neurite growth in differentiated Neuro2A cells. In vitro validation for predicted target sites in the 3′-UTR of voltage-gated sodium channel Scn11a, alpha 2/delta1 subunit of voltage-dependent Ca-channel, and purinergic receptor P2rx ligand-gated ion channel 4 using luciferase reporter assays showed that identified miRNAs modulated gene expression significantly. Our results suggest the potential for miRNAs to play a direct role in neuropathic pain