State health departments leverage pharmacy partnerships across the nation to advance diabetes care initiatives.

BACKGROUND: In 2018, the Centers for Disease Control and Prevention (CDC)'s Division of Diabetes Translation (DDT) initiated a five-year cooperative agreement funding opportunity with departments of health in every state and the District of Columbia. The funded recipients pursued activities that strengthened diabetes management and type 2 diabetes prevention interventions within their jurisdictions. An option to involve the pharmacy sector in their diabetes-related interventions was available. OBJECTIVES: This research aims to understand who public health departments partnered with in the pharmacy sector and identify the types of activities pursued together to expand access to diabetes-related interventions. METHODS: A review of annual work plans and progress reports submitted to CDC by recipients during the first four years of the funding cycle was conducted. Descriptions of work conducted in partnership with pharmacies, pharmacists, or pharmacy organizations were flagged for review, coding, and analysis. RESULTS: Of the 51 public health department recipients, 48 collaborated with pharmacy partners within their jurisdictions. Activities were developed and carried out in ways that utilized the pharmacy workforce to support public health diabetes initiatives, such as the development and delivery of diabetes self-management education and support and type 2 diabetes prevention programs in pharmacies (68.8%), delivery of diabetes-related training for the pharmacy workforce (91.7%), and support of billing and sustainability efforts for pharmacy-based diabetes services (52.1%). CONCLUSION: State public health department diabetes program personnel cultivated productive relationships with a variety of members of the pharmacy workforce. Through these partnerships, they leveraged one another's resources, expertise, and mutual determination to prepare and carry out diabetes-related interventions within their states. This document provides pharmacists and pharmacy decision-makers with foundational knowledge that can lead to increased engagement with public health partners to expand diabetes management and prevention services in pharmacy settings.

Genetic ablation of synaptotagmin-9 alters tomosyn-1 function to increase insulin secretion from pancreatic ß-cells improving glucose clearance.

Stimulus-coupled insulin secretion from the pancreatic islet ß-cells involves the fusion of insulin granules to the plasma membrane (PM) via SNARE complex formation-a cellular process key for maintaining whole-body glucose homeostasis. Less is known about the role of endogenous inhibitors of SNARE complexes in insulin secretion. We show that an insulin granule protein synaptotagmin-9 (Syt9) deletion in mice increased glucose clearance and plasma insulin levels without affecting insulin action compared to the control mice. Upon glucose stimulation, increased biphasic and static insulin secretion were observed from ex vivo islets due to Syt9 loss. Syt9 colocalizes and binds with tomosyn-1 and the PM syntaxin-1A (Stx1A); Stx1A is required for forming SNARE complexes. Syt9 knockdown reduced tomosyn-1 protein abundance via proteasomal degradation and binding of tomosyn-1 to Stx1A. Furthermore, Stx1A-SNARE complex formation was increased, implicating Syt9-tomosyn-1-Stx1A complex is inhibitory in insulin secretion. Rescuing tomosyn-1 blocked the Syt9-knockdown-mediated increases in insulin secretion. This shows that the inhibitory effects of Syt9 on insulin secretion are mediated by tomosyn-1. We report a molecular mechanism by which ß-cells modulate their secretory capacity rendering insulin granules nonfusogenic by forming the Syt9-tomosyn-1-Stx1A complex. Altogether, Syt9 loss in ß-cells decreases tomosyn-1 protein abundance, increasing the formation of Stx1A-SNARE complexes, insulin secretion, and glucose clearance. These outcomes differ from the previously published work that identified Syt9 has either a positive or no effect of Syt9 on insulin secretion. Future work using ß-cell-specific deletion of Syt9 mice is key for establishing the role of Syt9 in insulin secretion.

Loss of Brain Angiogenesis Inhibitor-3 (BAI3) G-Protein Coupled Receptor in Mice Regulates Adaptive Thermogenesis by Enhancing Energy Expenditure.

Effective energy expenditure is critical for maintaining body weight (BW). However, underlying mechanisms contributing to increased BW remain unknown. We characterized the role of brain angiogenesis inhibitor-3 (BAI3/ADGRB3), an adhesion G-protein coupled receptor (aGPCR), in regulating BW. A CRISPR/Cas9 gene editing approach was utilized to generate a whole-body deletion of the BAI3 gene (BAI3-/-). In both BAI3-/- male and female mice, a significant reduction in BW was observed compared to BAI3+/+ control mice. Quantitative magnetic imaging analysis showed that lean and fat masses were reduced in male and female mice with BAI3 deficiency. Total activity, food intake, energy expenditure (EE), and respiratory exchange ratio (RER) were assessed in mice housed at room temperature using a Comprehensive Lab Animal Monitoring System (CLAMS). While no differences were observed in the activity between the two genotypes in male or female mice, energy expenditure was increased in both sexes with BAI3 deficiency. However, at thermoneutrality (30 °C), no differences in energy expenditure were observed between the two genotypes for either sex, suggesting a role for BAI3 in adaptive thermogenesis. Notably, in male BAI3-/- mice, food intake was reduced, and RER was increased, but these attributes remained unchanged in the female mice upon BAI3 loss. Gene expression analysis showed increased mRNA abundance of thermogenic genes Ucp1, Pgc1α, Prdm16, and Elov3 in brown adipose tissue (BAT). These outcomes suggest that adaptive thermogenesis due to enhanced BAT activity contributes to increased energy expenditure and reduced BW with BAI3 deficiency. Additionally, sex-dependent differences were observed in food intake and RER. These studies identify BAI3 as a novel regulator of BW that can be potentially targeted to improve whole-body energy expenditure.

Medium to long-term results of a recessed glenoid for glenoid resurfacing in total shoulder arthroplasty.

BACKGROUND: Recessed mini-glenoid components provide an alternative to total shoulder replacement that may avoid some of the known shortcomings and complications associated with shoulder hemiarthroplasty or standard glenoid components in difficult cases. This study reports survivorship, radiological and clinical outcomes of a recessed mini-glenoid implant in a consecutive cohort. METHODS: Retrospective cohort study reporting outcomes of 28 consecutive shoulders (27 patients) following total shoulder replacement using a recessed, cemented mini-glenoid implant at two sites. RESULTS: The most frequent diagnosis was primary osteoarthritis (79%); glenoid morphology was Walch Type A (67%), B1 15%, B2 10% and C 10%. At final follow-up, pain was 16.3 (SD = 23.1), American Shoulder and Elbow Score was 64.5 (SD = 31.9) and (normalized) Constant score was 83.0 (SD = 20.7). Implant survivorship at average final follow-up of seven years (3-13) was 96.4%. Seven mini-glenoids showed small peripheral radiolucent lines at one-year X-ray follow-up but were non-progressive on subsequent imaging. DISCUSSION: Recessed polyethylene mini-glenoid is an attractive alternative for shoulder arthroplasty and provides an intermediate solution between standard glenoid components and hemiarthroplasty. Our medium to long-term results demonstrate reliable clinical outcomes, absence of glenoid erosion, low complication rate and satisfactory implant survivorship.

Integrated dual optical frequency comb source.

A monolithically integrated dual-channel optical frequency comb source is demonstrated in this paper. Three lasers are integrated on a single chip using a regrowth-free fabrication process in a master-slave-slave configuration. The master laser's power is split equally using a 1x2 multimode interference coupler and injection locks the two slave lasers. The slave lasers are gain-switched to produce dual optical frequency combs at 4.1 GHz and 5 GHz. To the best of our knowledge, this is the first demonstration of a dual optical frequency comb source with all light sources monolithically integrated in a photonic integrated circuit (PIC).

Temporal trends of gestational malaria in the United States.

BACKGROUND: Although regarded as rare in the United States (US), increased global traffic and importation of malaria from endemic countries may lead to a rise in gestational malaria in the US. METHODS: This multi-year retrospective study analyzed trends in diagnosed cases of gestational malaria from 2002 to 2017 using joinpoint regression models. We also assessed the association between gestational malaria and selected maternal-fetal adverse outcomes. RESULTS: Mothers diagnosed with gestational malaria tended to be older, and the majority of diagnosed cases (52.9%) were among Non-Hispanic (NH) Blacks. Diagnosed cases of gestational malaria are on the rise in the US. Mothers diagnosed with gestational malaria were 5 times as likely (OR = 5.05, 95% CI: 4.05-6.29) to be anemic as compared to those without malaria. Compared to NH-Whites, NH-Black mothers were twice as likely to experience stillbirth, had nearly 50% greater adjusted odds of severe preeclampsia, and had about 30% elevated likelihood for preterm labor. CONCLUSIONS: There is a need to dedicate appropriate resources to identify women that are at risk for gestational malaria in order to prevent related pregnancy complications.

Off-Axis Cavity-Enhanced Absorption Spectroscopy of 14NH3 in Air Using a Gain-Switched Frequency Comb at 1.514 µm.

A custom-designed gain-switched frequency comb (GSFC) source was passively coupled to a medium finesse (F ≈ 522) cavity in off-axis configuration for the detection of ammonia (14NH3) in static dry air. The absorption of ammonia was detected in the near infrared spectral region between 6604 and 6607 cm-1 using a Fourier transform detection scheme. More than 30 lines of the GSFC output (free spectral range 2.5 GHz) overlapped with the strongest ro-vibrational ammonia absorption features in that spectral region. With the cavity in off-axis configuration, an NH3 detection limit of ∼3.7 ppmv in 20 s was accomplished in a laboratory environment. The experimental performance of the prototype spectrometer was characterized; advantages, drawbacks and the potential for future applications are discussed.

The effect of vitamin E-enhanced cross-linked polyethylene on wear in shoulder arthroplasty-a wear simulator study.

BACKGROUND: Wear of the polyethylene glenoid component and subsequent particle-induced osteolysis remains one of the most important modes of failure of total shoulder arthroplasty. Vitamin E is added to polyethylene to act as an antioxidant to stabilize free radicals that exist as a byproduct of irradiation used to induce cross-linking. This study was performed to assess the in vitro performance of vitamin E-enhanced polyethylene compared with conventional polyethylene in a shoulder simulator model. METHODS: Vitamin E-enhanced, highly cross-linked glenoid components were compared with conventional ultrahigh-molecular-weight polyethylene glenoids, both articulating with a ceramic humeral head component using a shoulder joint simulator over 500,000 cycles. Unaged and artificially aged comparisons were performed. Volumetric wear was assessed by gravimetric measurement, and wear particle analysis was also subsequently performed. RESULTS: Vitamin E-enhanced polyethylene glenoid components were found to have significantly reduced wear rates compared with conventional polyethylene in both unaged (36% reduction) and artificially aged (49% reduction) comparisons. There were no differences detected in wear particle analysis between the 2 groups. CONCLUSION: Vitamin E-enhanced polyethylene demonstrates improved wear compared with conventional polyethylene in both unaged and artificially aged comparisons and may have clinically relevant benefits.

Association of scapholunate dissociation and two-part articular fractures of the distal radius.

Scapholunate dissociation may occur in association with distal radial fractures and is easily missed at initial presentation. The aim of this study was to examine variances in the scapholunate distance with respect to subtypes of two-part partial articular distal radial fractures. Axial computed tomography (CT) scans of acute two-part intra-articular radial fractures were assessed retrospectively from 80 patients and compared to 20 controls. From each scan, two images were analysed to identify the scaphoid, lunate and articular fracture line in the distal radius for fracture type categorization. The images were overlaid on a standardized distal radius template and the scapholunate distance measured. Significant increase in the scapholunate distance was noted in fracture subtypes: radial styloid oblique; dorsal ulnar column; sagittal ulnar column; and volar coronal. We conclude that these findings support the need for a higher index of suspicion for scapholunate dissociation in these distal radial fracture subtypes. Level of evidence: III.

Atomically Traceable Nanostructure Fabrication.

Reducing the scale of etched nanostructures below the 10 nm range eventually will require an atomic scale understanding of the entire fabrication process being used in order to maintain exquisite control over both feature size and feature density. Here, we demonstrate a method for tracking atomically resolved and controlled structures from initial template definition through final nanostructure metrology, opening up a pathway for top-down atomic control over nanofabrication. Hydrogen depassivation lithography is the first step of the nanoscale fabrication process followed by selective atomic layer deposition of up to 2.8 nm of titania to make a nanoscale etch mask. Contrast with the background is shown, indicating different mechanisms for growth on the desired patterns and on the H passivated background. The patterns are then transferred into the bulk using reactive ion etching to form 20 nm tall nanostructures with linewidths down to ~6 nm. To illustrate the limitations of this process, arrays of holes and lines are fabricated. The various nanofabrication process steps are performed at disparate locations, so process integration is discussed. Related issues are discussed including using fiducial marks for finding nanostructures on a macroscopic sample and protecting the chemically reactive patterned Si(100)-H surface against degradation due to atmospheric exposure.

Ligament origins are preserved in distal radial intraarticular two-part fractures: a computed tomography-based study.

Background Operative fixation of intraarticular distal radius fractures is increasingly common. A greater understanding of fracture patterns will aid surgical fixation strategy. Previous studies have suggested that ligamentous insertions may less commonly be involved, but these have included heterogeneous groups of fractures and have not addressed Lister's tubercle. Purpose We hypothesize that fracture lines of distal radial intraarticular 2-part fractures have reproducible patterns. They propagate through the cortical bone between ligament origins and do not involve Lister's tubercle. Methods Axial CT scans of two-part intraarticular distal radius fractures were assessed independently by two examiners. The fractures were mapped onto a grid and the cortical breaches expressed as a percentile of the total radial width or length. The cortical breaches were compared with the ligamentous insertions on the distal and Lister's tubercle. Associated injuries were also documented. Results The cortical breaches occurred between the ligamentous insertions in 85%. Lister's tubercle was not involved in 95% of the fractures. Three major fracture patterns emerged: radial styloid, dorsal, and volar. Each major pattern had two subtypes. Associated injuries were common. Scapholunate dissociation was associated with all types, not just the radial styloid fracture pattern. Conclusions The fracture patterns of two-part intraarticular fractures mostly involved the interligamentous zones. Three major groups were identified: dorsal, volar, and radial styloid. Lister's tubercle was preserved with fractures tending to propagate radial or ulnar to this structure. We suggest conceptualizing fracture fragments as osseo-ligamentous units to aid prediction of fracture patterns and associated injury. Study Design Diagnostic III Level of Evidence 3.

GeneCards Version 3: the human gene integrator.

GeneCards (www.genecards.org) is a comprehensive, authoritative compendium of annotative information about human genes, widely used for nearly 15 years. Its gene-centric content is automatically mined and integrated from over 80 digital sources, resulting in a web-based deep-linked card for each of >73,000 human gene entries, encompassing the following categories: protein coding, pseudogene, RNA gene, genetic locus, cluster and uncategorized. We now introduce GeneCards Version 3, featuring a speedy and sophisticated search engine and a revamped, technologically enabling infrastructure, catering to the expanding needs of biomedical researchers. A key focus is on gene-set analyses, which leverage GeneCards' unique wealth of combinatorial annotations. These include the GeneALaCart batch query facility, which tabulates user-selected annotations for multiple genes and GeneDecks, which identifies similar genes with shared annotations, and finds set-shared annotations by descriptor enrichment analysis. Such set-centric features address a host of applications, including microarray data analysis, cross-database annotation mapping and gene-disorder associations for drug targeting. We highlight the new Version 3 database architecture, its multi-faceted search engine, and its semi-automated quality assurance system. Data enhancements include an expanded visualization of gene expression patterns in normal and cancer tissues, an integrated alternative splicing pattern display, and augmented multi-source SNPs and pathways sections. GeneCards now provides direct links to gene-related research reagents such as antibodies, recombinant proteins, DNA clones and inhibitory RNAs and features gene-related drugs and compounds lists. We also portray the GeneCards Inferred Functionality Score annotation landscape tool for scoring a gene's functional information status. Finally, we delineate examples of applications and collaborations that have benefited from the GeneCards suite. Database URL: www.genecards.org.

A fowlicidin-1 analog protects mice from lethal infections induced by methicillin-resistant Staphylococcus aureus.

Fowlicidin-1 is a newly identified alpha-helical cathelicidin host defense peptide. We have shown that fowlicidin-1 possesses potent antibacterial activity, but also displays considerable toxicity toward mammalian cells. To further identify fowlicidin-1 analog(s) with enhanced therapeutic potential, a series of amino-terminal truncation analogs were synthesized and functionally evaluated. Relative to the full-length peptide, fowl-1(6-26), an analog with omission of five amino-terminal amino acid residues, maintained the antibacterial potency against a range of Gram-negative and Gram-positive bacteria including antibiotic-resistant strains. Fowl-1(6-26)-NH(2), a carboxyl-terminal amidated form of fowl-1(6-26), retained the antibacterial activity for a minimum of 2h in the presence of 100% serum. In addition, an intraperitoneal administration of 10mg/kg of fowl-1(6-26)-NH(2) led to a 50% increase in the survival of neutropenic mice over a 7-day period from a lethal dose of methicillin-resistant Staphylococcus aureus (MRSA), concomitant with a reduction in the bacterial titer in both peritoneal fluids and spleens of mice 24h post-infection. Fowl-1(6-26)-NH(2) at 20 microM was further found to suppress lipopolysaccharide-mediated production of TNF-alpha and nitric oxide in macrophages by 77% and 96%, respectively. Therefore, with potent endotoxin-neutralizing and bactericidal activities, fowlicidin-1(6-26)-NH(2), may have strong therapeutic potential for drug-resistant infections and sepsis.

Vertebral hemangioma: an important differential in the evaluation of locally aggressive spinal lesions.

STUDY DESIGN: A case report and a discussion of recent published data. OBJECTIVE: To highlight the importance of vertebral hemangioma (VH) as a differential diagnosis in the evaluation of locally aggressive spinal lesions. SUMMARY OF BACKGROUND DATA: VH commonly occur as incidental findings, however, locally aggressive VH have been described. Difficulties in diagnosing these lesions are well reported and relate to changes in fat content causing uncharacteristic appearances on imaging. The management options for these lesions include a combination of observation, embolization, sclerotherapy, surgical decompression, or stabilization and radiotherapy. METHODS: A 45-year-old patient who was previously well presented with back pain and rapidly progressive paraparesis. Imaging confirmed the presence of an extensive lesion centered within the right T3 vertebral pedicle with intrusion into the spinal canal. Urgent surgical decompression was undertaken and was complicated by extensive intraoperative hemorrhage requiring massive transfusion. RESULTS: Histologically, the lesion was shown to be a cavernous VH with no evidence of malignancy. Following radiation oncology review, he was offered adjuvant radiotherapy to minimize the risks of recurrence. He achieved a near full neurologic recovery within 2 weeks and had a full recovery by 12 months. CONCLUSION: VH should be considered in the evaluation of locally aggressive spinal lesions. Angiography is a useful adjunct in the evaluation of these lesions, both as a diagnostic and therapeutic tool. After diagnosed correctly a wide range of treatment options exist that may prevent the patient from undergoing major surgical resection and reconstruction procedures, which may be associated with high rates of morbidity.