Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice.

Tyrosine protein-kinase 2 (TYK2), a member of the Janus kinase family, mediates inflammatory signaling through multiple cytokines, including interferon-α (IFNα), interleukin (IL)-12, and IL-23. Missense mutations in TYK2 are associated with protection against type 1 diabetes (T1D), and inhibition of TYK2 shows promise in the management of other autoimmune conditions. Here, we evaluated the effects of specific TYK2 inhibitors (TYK2is) in pre-clinical models of T1D.

AMPA receptors play an important role in the biological consequences of spinal cord injury: Implications for AMPA receptor modulators for therapeutic benefit.

Spinal cord injury (SCI) afflicts millions of individuals globally. There are few therapies available to patients. Ascending and descending excitatory glutamatergic neural circuits in the central nervous system are disrupted by SCI, making α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) a potential therapeutic drug target.

Colon Age: A Metric for Whether and How to Screen Male Veterans for Early-Onset Colorectal Cancer.

We aimed to develop a metric for estimating risk for early-onset colorectal cancer (EOCRC) to help decide whether and how to screen persons < age 50. We used risk prediction models derived and validated on male Veterans to calculate the relative risks (RRs) for 6 scenarios: one low-risk scenario (no risk factors present), four intermediate risk scenarios (some factors present), and one high-risk scenario (all factors present) for three age groups (35-39, 40-44, and 45-49 years). For each scenario, we estimated absolute CRC risk using SEER CRC incidence rates and each scenario's RR.

Self-reported dental pain in Mexican schoolchildren: a national ecological study.

The objective of this study was to quantify the prevalence of and identify the factors associated with dental pain among elementary- and middle-school students in Mexico. An ecological study was carried out with data from the 2008 National School-based Student-Health Survey. Information on dental pain from schoolchildren (aged 5 to 16 years) was collected from public schools across the 32 states of Mexico.

Deep Trans-Omic Network Fusion for Molecular Mechanism of Alzheimer's Disease.

Background: There are various molecular hypotheses regarding Alzheimer's disease (AD) like amyloid deposition, tau propagation, neuroinflammation, and synaptic dysfunction. However, detailed molecular mechanism underlying AD remains elusive. In addition, genetic contribution of these molecular hypothesis is not yet established despite the high heritability of AD.

Peripherally targeted analgesia via AAV-mediated sensory neuron-specific inhibition of multiple pronociceptive sodium channels.

This study reports that targeting intrinsically disordered regions of the voltage-gated sodium channel 1.7 (NaV1.7) protein facilitates discovery of sodium channel inhibitory peptide aptamers (NaViPA) for adeno-associated virus-mediated (AAV-mediated), sensory neuron-specific analgesia.

Long-term Musculoskeletal Consequences of Chemotherapy in Pediatric Mice.

Thanks to recent progress in cancer research, most children treated for cancer survive into adulthood. Nevertheless, the long-term consequences of anticancer agents are understudied, especially in the pediatric population. We and others have shown that routinely administered chemotherapeutics drive musculoskeletal alterations, which contribute to increased treatment-related toxicity and long-term morbidity.

Electromagnetic Field Stimulation Therapy for Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative dementia worldwide. AD is a multifactorial disease that causes a progressive decline in memory and function precipitated by toxic beta-amyloid (Aβ) proteins, a key player in AD pathology. In 2022, 6.

Six months of voluntary alcohol consumption in male cynomolgus macaques reduces intracortical bone porosity without altering mineralization or mechanical properties.

Chronic heavy alcohol consumption is a risk factor for low trauma bone fracture. Using a non-human primate model of voluntary alcohol consumption, we investigated the effects of 6 months of ethanol intake on cortical bone in cynomolgus macaques (Macaca fascicularis). Young adult (6.

Variations in surface area and biogeochemistry of subarctic-arctic lakes established through satellite and in-situ observations: An overview of published research from the past 30 years.

Human activities have strongly impacted the global climate, and during the last few decades the global average temperature has risen at a rate faster than at any time on record. High latitude lakes in the subarctic and arctic permafrost regions have particularly been vulnerable given the "Arctic amplification" phenomenon and acceleration in warming rate in the northern hemisphere (0.2-0.

Early Chronic Fluoxetine Treatment of Ts65Dn Mice Rescues Synaptic Vesicular Deficits and Prevents Aberrant Proteomic Alterations.

Down syndrome (DS) is the most common form of inherited intellectual disability caused by trisomy of chromosome 21, presenting with intellectual impairment, craniofacial abnormalities, cardiac defects, and gastrointestinal disorders. The Ts65Dn mouse model replicates many abnormalities of DS. We hypothesized that investigation of the cerebral cortex of fluoxetine-treated trisomic mice may provide proteomic signatures that identify therapeutic targets for DS.

Occupational Noise Exposure in the Pediatric Dental Setting.

To evaluate the noise levels recorded in a hospital-based pediatric dental clinic and evaluate the occupational exposure personnel have to potentially hazardous levels of noise. A SoundAdvisor™ Sound Level Meter Model 831C was used to gather 19 days of background sound data (equivalent continuous sound levels, measured as LAeq) in the open bay, quiet room, sedation suite, and operating room settings. A Spartan™ Wireless Noise Dosimeter Model 730 (Larson Davis) was utilized to capture data about personal noise exposure of pediatric dental residents over 81 clinic sessions.

Paper Spray Mass Spectrometry with On-Paper Electrokinetic Manipulations: Part-Per-Trillion Detection of Per/Polyfluoroalkyl Substances in Water and Opioids in Urine.

We developed a simple, paper-based device that enables sensitive detection by mass spectrometry (MS) without solid phase extraction or other sample preparation. Using glass fiber filter papers within a 3D printed holder, the device employs electrokinetic manipulations to stack, separate, and desalt charged molecules on paper prior to spray into the MS. Due to counter-balanced electroosmotic flow and electrophoresis, charged analytes stack on the paper and desalting occurs in minutes.

The Impact of Non-bone Metastatic Cancer on Musculoskeletal Health.

Purpose Of Review: The purpose of this review is to discuss the musculoskeletal consequences of cancer, including those that occur in the absence of bone metastases.

Recent Findings: Cancer patients frequently develop cachexia, a debilitating condition reflected by weight loss and skeletal muscle wasting. The negative effects that tumors exert on bone health represents a growing interest amongst cachexia researchers.

Treatment of carbon electrodes with TiCT MXene coating and thermal method for vanadium redox flow batteries: a comparative study.

One of the significant challenges of vanadium redox flow batteries is connected to the negative electrode where the main reaction of V(ii)/V(iii) and the side reaction of hydrogen evolution compete. To address this issue, we used titanium carbide (TiCT) MXene coating drop-casting to introduce oxygen functional groups and metals on the carbon electrode surface. Characterization through scanning electron microscopy and X-ray photoelectron spectroscopy confirmed the even distribution of TiCT MXene on the electrodes and the presence of titanium and termination groups (-O, -Cl, and -F).

TopDIA: A Software Tool for Top-Down Data-Independent Acquisition Proteomics.

Top-down mass spectrometry is widely used for proteoform identification, characterization, and quantification owing to its ability to analyze intact proteoforms. In the last decade, top-down proteomics has been dominated by top-down data-dependent acquisition mass spectrometry (TD-DDA-MS), and top-down data-independent acquisition mass spectrometry (TD-DIA-MS) has not been well studied. While TD-DIA-MS produces complex multiplexed tandem mass spectrometry (MS/MS) spectra, which are challenging to confidently identify, it selects more precursor ions for MS/MS analysis and has the potential to increase proteoform identifications compared with TD-DDA-MS.

Combining anabolic loading and raloxifene improves bone quantity and some quality measures in a mouse model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) increases fracture risk due to changes in bone quantity and quality caused by mutations in collagen and its processing proteins. Current therapeutics improve bone quantity, but do not treat the underlying quality deficiencies. Male and female G610C+/- mice, a murine model of OI, were treated with a combination of raloxifene and in vivo axial tibial compressive loading starting at 10 weeks of age and continuing for 6 weeks to improve bone quantity and quality.

Perspective: The complex relationship between charge, mobility, and gas-phase protein structure.

Ion mobility spectrometry coupled to mass spectrometry (IMS/MS) is a widely used tool for biomolecular separations and structural elucidation. The application of IMS/MS has resulted in exciting developments in structural proteomics and genomics. This perspective gives a brief background of the field, addresses some of the important issues in making structural measurements, and introduces complementary techniques.

Legislative Health Notes: Preliminary Learnings From Piloting a New Policy Analysis Tool.

Context: In 2018, the Health Impact Project (the Project) developed and tested a new health in all policies (HiAP) tool called "legislative health notes" to provide state and local legislators with peer-reviewed evidence, public health data, and local data that illustrate potential positive and negative health and equity effects of proposed bills.

Objectives: The Project sought to refine the health note methodology while piloting the tool in the Colorado and Indiana General Assemblies, and with the Council of the District of Columbia, and worked with affiliates to introduce them in North Carolina, Ohio, and California.

Design And Participants: External partners solicited feedback on health notes via semistructured interviews and surveys from legislators, legislative staff, and expert reviewers who were familiar with health notes in each of these jurisdictions.

The Political Embeddedness of Voluntary Action: The Case of Local Philanthropic COVID-19 Relief Funds.

Scholars and policymakers have long been interested in the complex relationships between political institutions and voluntary collective action. However, the reciprocal nature of their relationships complicates empirical analysis: voluntary action supports democratic institutions and political institutions enable voluntary action. This article examines the relationship between political institutions and the activation of local voluntary action in the context of COVID-19 funds managed by community philanthropic organizations.

Datawiz-IN: Summer Research Experience for Health Data Science Training.

Background: Good science necessitates diverse perspectives to guide its progress. This study introduces Datawiz-IN, an educational initiative that fosters diversity and inclusion in AI skills training and research. Supported by a National Institutes of Health R25 grant from the National Library of Medicine, Datawiz-IN provided a comprehensive data science and machine learning research experience to students from underrepresented minority groups in medicine and computing.