Haptoglobin genotype is a risk factor for coronary artery disease in prediabetes: A case-control study.

Objective: Coronary artery disease (CAD) prediction remains inconsistent with many unappreciated risk factors. Haptoglobin genotype determines the haptoglobin protein's effectiveness to bind free hemoglobin and prevent oxidative stress, a contributor to atherosclerosis. The haptoglobin 2-2 genotype increases the prevalence of cardiovascular disease (CVD) approximately five times compared to the 1-1 genotype in individuals with diabetes. The risk is unknown in prediabetes. The purpose of this study was to determine an association between haptoglobin genotype and CAD in prediabetes. Methods: The researchers used case-control convenience sampling from two cardiovascular disease prevention clinics in Memphis, TN, and Spokane, WA, from January 1, 2016 to March 31, 2020. Participants were ages 35-70, had prediabetes, and free of chronic inflammatory or infectious diseases. Cases had a history of subclinical or clinical CAD, while controls did not have a history of CAD. Differences between cases and controls and among haptoglobin genotypes were analyzed using t-tests and ANOVA for continuous variables and chi-square or Fisher's exact tests for categorical variables. Associations among Hp genotypes and CAD were estimated using logistic regression. Results: The sample (N = 178; 72 cases and 106 controls) was 96 % white and 64 % male. Cases had lower total cholesterol (p = 0.0001) and high-sensitivity C-reactive protein (p = 0.021). Except for CAD, haptoglobin genotype was independent of any demographic or clinical variable. Haptoglobin 2-2 genotype had 4.0 times higher odds of CAD than haptoglobin 1-1 (p = 0.01). Conclusion: Haptoglobin 2-2 genotype had approximately four times higher odds of having CAD compared to the haptoglobin 1-1 genotype. Cases had more desirable clinical profiles, likely attributable to more aggressive treatment of traditional risk factors than controls. Haptoglobin genotype is a potentially important CAD risk factor in prediabetes (88 million Americans). Further studies are needed for interventions to reduce the oxidative stress associated with the Hp 2-2 genotype and glycosylated hemoglobin and for CAD reduction.

Challenges in managing a remote monitoring device clinic.

BACKGROUND: Recent advances in remote cardiac monitoring technology have created new challenges for clinicians and staff working in device clinics who are left processing large volumes of data. Often, this process is fractured and inefficient, with occurrence of unnecessary alerts that strain staff time and resources. OBJECTIVE: The purpose of this survey was to identify challenges allied health professional clinicians and staff encounter when managing a remote monitoring device clinic. METHODS: A 27-item mixed methods survey was developed using a Qualtrics-encrypted, anonymous Web survey tool. Demographic information and questions rating satisfaction level for remote device clinic issues were obtained using a 5-point Likert scale. Three open-ended questions were included that addressed challenges and successes in managing a remote monitoring clinic and served as a method for identifying common themes. RESULTS: Major themes identified were poor connectivity, staffing issues, and large volume of alerts. Approximately 50% of respondents were either satisfied or unsatisfied with issues surrounding managing remote monitoring device clinics. Strategies for success included optimizing alerts, assigning designated staff, and partnering with third-party platforms. CONCLUSION: This survey confirms these issues as an opportunity for industry and digital health leaders to determine best practices for incorporating these technologies into patient care.

A regional massive hemorrhage protocol developed through a modified Delphi technique.

BACKGROUND: A massive hemorrhage protocol (MHP) enables rapid delivery of blood components in a patient who is exsanguinating pending definitive hemorrhage control, but there is variability in MHP implementation rates, content and compliance owing to challenges presented by infrequent activation, variable team performance and patient acuity. The goal of this project was to identify the key evidence-based principles and quality indicators required to develop a standardized regional MHP. METHODS: A modified Delphi consensus technique was performed in the spring and summer of 2018. Panellists used survey links to independently review and rate (on a 7-point Likert scale) 43 statements and 8 quality indicators drafted by a steering committee composed of transfusion medicine specialists and technologists, and trauma physicians. External stakeholder input from all hospitals in Ontario was sought. RESULTS: Three rounds were held with 36 experts from diverse clinical backgrounds. Consensus was reached for 42 statements and 8 quality indicators. Additional modifications from external stakeholders were incorporated to form the foundation for the proposed MHP. INTERPRETATION: This MHP template will provide the basis for the design of an MHP toolkit, including specific recommendations for pediatric and obstetrical patients, and for hospitals with limited availability of blood components or means to achieve definitive hemorrhage control. We believe that harmonization of MHPs in our region will simplify training, increase uptake of evidence-based interventions, enhance communication, improve patient comfort and safety, and, ultimately, improve patient outcomes.

Intensive Treatment Models to Address Posttraumatic Stress Among Post-9/11 Warriors: The Warrior Care Network.

Since September 11, 2001, more than two million U.S. service members have deployed to Iraq or Afghanistan, many returning home with posttraumatic stress disorder (PTSD) and additional psychological and general medical complaints. Nonetheless, many do not seek care or may not respond to traditional outpatient approaches, warranting innovative, multidisciplinary treatment approaches. To help address these complex needs, the Wounded Warrior Project has funded four academic medical centers to develop a care network across the nation. As part of this Warrior Care Network, the Emory Healthcare Veterans Program in Atlanta; the Home Base Program at Massachusetts General Hospital, in collaboration with the Red Sox Foundation, in Boston; Road Home at Rush Medical Center in Chicago; and Operation Mend at the University of California, Los Angeles, have each developed innovative, intensive programs to treat PTSD among post-9/11 veterans and service members. The programs offer two- to three-week intensive PTSD treatment programs with evidence-based approaches embedded in a broader program. To date, 328 post-9/11 veterans and active-duty service members have received care in these intensive outpatient programs. The average completion rate is approximately 95%, which demonstrates the acceptability of this brief but intensive care model for a complex population who can be challenging to engage or retain in care.

Ultrastructural Identification and Colocalization of Interacting Proteins in the Murine Cochlea by Post-Embedding Immunogold Transmission Electron Microscopy.

Verification of the presence and location of a protein within tissue can be accomplished by western blotting and immunohistochemistry, using either paraffin or frozen sections. Affinity purification by reciprocal coimmunoprecipitations using the tissue of interest can demonstrate the existence of an interacting pair of proteins. Ultimately, the ability to visualize the interaction at the cellular level is desired. Precise location(s) of interacting proteins in situ can be accomplished by ultrastructural localization with high-quality primary antibodies and small-particle-size Au-conjugated secondary antibodies. Visualization can be obtained with a transmission electron microscope fitted with a high-resolution camera permitting magnifications that exceed 2 × 10(5), and, to date, resolution capability of 20+ Mpixels, thus enabling localization of the target protein to within nanometers of the actual location. Here, we report the method by which immunolocalization at the level of the electron microscope is accomplished using the post-embedding technique, i.e., performing antibody labeling of proteins on ultrathin sections of tissue embedded in acrylic resin.

Proximal Hamstring Repair Strength: A Biomechanical Analysis at 3 Hip Flexion Angles.

BACKGROUND: Proximal hamstring repair for complete ruptures has become a common treatment. There is no consensus in the literature about postoperative rehabilitation protocols following proximal hamstring repair. Some protocols describe bracing to prevent hip flexion or knee extension while others describe no immobilization. There are currently no biomechanical studies evaluating proximal hamstring repairs; nor are there any studies evaluating the effect of different hip flexion angles on these repairs. HYPOTHESIS: As hip flexion increases from 0° to 90°, there will be a greater gap with cyclical loading. STUDY DESIGN: Controlled laboratory study. METHODS: Proximal hamstring insertions were detached from the ischial tuberosity in 24 cadavers and were repaired with 3 single-loaded suture anchors in the hamstring footprint with a Krakow suture technique. Cyclic loading from 10 to 125 N at 1 Hz was then performed for 0°, 45°, and 90° of hip flexion for 1500 cycles. Gap formation, stiffness, yield load, ultimate load, and energy to ultimate load were compared between groups using paired t tests. RESULTS: Cyclic loading demonstrated the least amount of gap formation (P < .05) at 0° of hip flexion (2.39 mm) and most at 90° of hip flexion (4.19 mm). There was no significant difference in ultimate load between hip flexion angles (326, 309, and 338 N at 0°, 45°, and 90°, respectively). The most common mode of failure occurred with knot/suture failure (n = 17). CONCLUSION: Increasing hip flexion from 0° to 90° increases the displacement across proximal hamstring repairs. Postoperative bracing that limits hip flexion should be considered. CLINICAL RELEVANCE: Repetitive motion involving hip flexion after a proximal hamstring repair may cause compromise of the repair.

The large conductance calcium-activated K(+) channel interacts with the small GTPase Rab11b.

The transduction of sound by the receptor or hair cells of the cochlea leads to the activation of ion channels found in the basal and lateral regions of these cells. Thus, the processing of these transduced signals to the central nervous system is tied to the regulation of baso-lateral ion channels. The large conductance calcium-activated potassium or BK channel was revealed to interact with the small GTPase, Rab11b, which is one of many Rabs found in various endosomal pathways. Immunoelectron microscopy showed the colocalization of these two proteins in receptor cells and auditory neurons. Using Chinese hamster ovary cells as a heterologous expression system, Rab11b increased or decreased BK expression, depending on the overexpression or RNAi knockdown of Rab, respectively. Additional mutation analyses, using a yeast two-hybrid assay, suggested that this GTPase moderately interacts within a region of BK exclusive of the N- or C-terminal tails. These data suggest that this small GTPase regulates BK in a slow recycling process through the endocytic compartment and to the plasmalemma.

Conserved BK channel-protein interactions reveal signals relevant to cell death and survival.

The large-conductance Ca(2+)-activated K(+) (BK) channel and its ß-subunit underlie tuning in non-mammalian sensory or hair cells, whereas in mammals its function is less clear. To gain insights into species differences and to reveal putative BK functions, we undertook a systems analysis of BK and BK-Associated Proteins (BKAPS) in the chicken cochlea and compared these results to other species. We identified 110 putative partners from cytoplasmic and membrane/cytoskeletal fractions, using a combination of coimmunoprecipitation, 2-D gel, and LC-MS/MS. Partners included 14-3-3γ, valosin-containing protein (VCP), stathmin (STMN), cortactin (CTTN), and prohibitin (PHB), of which 16 partners were verified by reciprocal coimmunoprecipitation. Bioinformatics revealed binary partners, the resultant interactome, subcellular localization, and cellular processes. The interactome contained 193 proteins involved in 190 binary interactions in subcellular compartments such as the ER, mitochondria, and nucleus. Comparisons with mice showed shared hub proteins that included N-methyl-D-aspartate receptor (NMDAR) and ATP-synthase. Ortholog analyses across six species revealed conserved interactions involving apoptosis, Ca(2+) binding, and trafficking, in chicks, mice, and humans. Functional studies using recombinant BK and RNAi in a heterologous expression system revealed that proteins important to cell death/survival, such as annexinA5, γ-actin, lamin, superoxide dismutase, and VCP, caused a decrease in BK expression. This revelation led to an examination of specific kinases and their effectors relevant to cell viability. Sequence analyses of the BK C-terminus across 10 species showed putative binding sites for 14-3-3, RAC-α serine/threonine-protein kinase 1 (Akt), glycogen synthase kinase-3ß (GSK3ß) and phosphoinositide-dependent kinase-1 (PDK1). Knockdown of 14-3-3 and Akt caused an increase in BK expression, whereas silencing of GSK3ß and PDK1 had the opposite effect. This comparative systems approach suggests conservation in BK function across different species in addition to novel functions that may include the initiation of signals relevant to cell death/survival.

A statewide multiagency intervention model for empowering schools to improve indoor environmental quality.

A large population of children and adults is potentially exposed to indoor environmental quality (IEQ) hazards in schools. Those with asthma are particularly at risk because IEQ-related hazards in school buildings can trigger asthma episodes. A multiagency consortium created and led by the Connecticut Department of Public Health has successfully implemented and continues to sustain the U.S. Environmental Protection Agency's (U.S. EPA's) Tools for Schools (TfS) program in the majority of Connecticut public schools. TfS is an action kit and program promoting a low-cost, problem-solving team approach to preventing IEQ hazards or improving IEQ. One key to the consortium's success is the array of services it provides to schools, including aggressive outreach and specialized training and consultation. The consortium is also a platform for launching other school IEQ initiatives. The authors present and analyze the consortium model and their efforts at evaluating the impact of TfS in Connecticut.

Identification and quantification of full-length BK channel variants in the developing mouse cochlea.

Maxi-K(+) (BK) channel diversity is attributed to alternative splicing in the kcnma1 gene. The resultant variants manifest themselves in different cell types, tissues, and functions, such as excitation, metabolism, and signaling. Immunoelectron microscopy revealed immunogold particle labeling of BK in apical and basal regions of inner and outer hair cells, respectively. Additional labeling occurs in Deiters' cells and the inner mitochondrial membrane. Identification of full-length sequences reveals 27 BK variants from embryonic and postnatal mouse inner ear, per classification by tail motif, VYR, DEC, and ERL, and by exon usage. Three predicted start codons are found encoding MAN, MSS, and MDA, of which MDA shows the greatest expression through all stages in development, whereas MAN is undetectable. Complex splice sites occur between exons 9 and 10 and between 21 and 23. Spliced-in/out exons between 8 and 10 reveal a short fragment composed of exons 8 + 10, detectable on postnatal day (PD) 14 and PD30, and a longer fragment composed of exons 8 + 9 + 10 that is upregulated on embryonic day (ED) 14. Spliced-in exons 22 or 23 are expressed on ED14 but decrease over time; however, exon 22 increases again on PD34. Using tail-specific primers, qRT-PCR from ED14, PD4, -14, and -30 shows that BK-VYR and -ERL dominate expression on ED14, whereas DEC dominates after birth in all cochlear regions. The localization of BK and the changes in expression of its exons and tail types, by alternative splicing during development, may contribute to cochlear organization, acquisition of hearing, and intracellular signaling.

Making child care centers SAFER: a non-regulatory approach to improving child care center siting.

Licensed child care centers are generally considered to be safe because they are required to meet state licensing regulations. As part of their licensing requirements, many states inspect child care centers and include an assessment of the health and safety of the facility to look for hazardous conditions or practices that may harm children. However, most states do not require an environmental assessment of the child care center building or land to prevent a center from being placed on, next to, or inside contaminated buildings. Having worked on several sites where child care centers were affected by environmental contaminants, the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry (ATSDR) endeavor to raise awareness of this issue. One of ATSDR's partner states, Connecticut, took a proactive, non-regulatory approach to the issue with the development its Child Day Care Screening Assessment for Environmental Risk Program.