Efficient Digital Workflow to Replace a Missing Denture Tooth for Complete Denture Repair.

Debonded denture teeth is a common complication on a fixed or removable dental prosthesis when denture teeth are fabricated separately from the denture base and bonded together. Missing denture teeth can alter a person's appearance, speech, or ability to eat. Traditionally, denture teeth repair can be a challenge for clinicians or dental laboratory technicians to find the identical tooth mould to meet esthetic and functional demands. This case report describes a digital workflow to scan, design, and mill a well-fitting and esthetic denture tooth to expedite treatment, improve patient satisfaction, and increase troop readiness when traditional methods may not be feasible.

Society of Radiologists in Ultrasound Consensus on Routine Pelvic US for Endometriosis.

Endometriosis is a prevalent and potentially debilitating condition that mostly affects individuals of reproductive age, and often has a substantial diagnostic delay. US is usually the first-line imaging modality used when patients report chronic pelvic pain or have issues of infertility, both common symptoms of endometriosis. Other than the visualization of an endometrioma, sonologists frequently do not appreciate endometriosis on routine transvaginal US images. Given a substantial body of literature describing techniques to depict endometriosis at US, the Society of Radiologists in Ultrasound convened a multidisciplinary panel of experts to make recommendations aimed at improving the screening process for endometriosis. The panel was composed of experts in the imaging and management of endometriosis, including radiologists, sonographers, gynecologists, reproductive endocrinologists, and minimally invasive gynecologic surgeons. A comprehensive literature review combined with a modified Delphi technique achieved a consensus. This statement defines the targeted screening population, describes techniques for augmenting pelvic US, establishes direct and indirect observations for endometriosis at US, creates an observational grading and reporting system, and makes recommendations for additional imaging and patient management. The panel recommends transvaginal US of the posterior compartment, observation of the relative positioning of the uterus and ovaries, and the uterine sliding sign maneuver to improve the detection of endometriosis. These additional techniques can be performed in 5 minutes or less and could ultimately decrease the delay of an endometriosis diagnosis in at-risk patients.

Deep learning automation of radiographic patterns for hallux valgus diagnosis.

Artificial intelligence (AI) and deep learning are becoming increasingly powerful tools in diagnostic and radiographic medicine. Deep learning has already been utilized for automated detection of pneumonia from chest radiographs, diabetic retinopathy, breast cancer, skin carcinoma classification, and metastatic lymphadenopathy detection, with diagnostic reliability akin to medical experts. In the World Journal of Orthopedics article, the authors apply an automated and AI-assisted technique to determine the hallux valgus angle (HVA) for assessing HV foot deformity. With the U-net neural network, the authors constructed an algorithm for pattern recognition of HV foot deformity from anteroposterior high-resolution radiographs. The performance of the deep learning algorithm was compared to expert clinician manual performance and assessed alongside clinician-clinician variability. The authors found that the AI tool was sufficient in assessing HVA and proposed the system as an instrument to augment clinical efficiency. Though further sophistication is needed to establish automated algorithms for more complicated foot pathologies, this work adds to the growing evidence supporting AI as a powerful diagnostic tool.

Vital signs among emergency department trauma patients in the setting of alcohol or drug use.

INTRODUCTION: The incidence of alcohol use among trauma patients has been estimated at 19-55%. This study was undertaken to identify any relationship between vital signs and alcohol and drug use among Emergency Department (ED) patients with trauma. METHODS: In this retrospective case control study, eligible subjects included trauma patients ages 18 and over, with trauma and drug or alcohol use, between 2018 and 2022. The control group was comprised of trauma patients ages 18 and over, with trauma and no drug or alcohol use, who were matched by Injury Severity Score (ISS). Vital signs on ED arrival were compared among patients with and without alcohol use, and with and without recreational drug use. RESULTS: Among 16,159 eligible trauma subjects, 5,323 had tests available for drugs and alcohol of whom 2,750 had complete ISS and vital signs data. 684 subjects were identified with alcohol intoxication, 707 subjects were identified with recreational drug use. Patients with alcohol use had lower mean systolic blood pressure (Mean=133, SD=26.7), compared to patients without alcohol use (Mean=143, SD=29.4) (p < 0.001). Patients with alcohol use had higher mean heart rate (Mean=93, SD=19.9) compared to patients without alcohol use (Mean=91, SD=19.7) (p = 0.01). Patients with recreational drug use had lower mean systolic blood pressure (Mean=137, SD=28.5) compared to patients without drug use (Mean=143, SD=29.6) (p < 0.001). Patients with drug use had higher mean heart rate (Mean=94, SD=22.8), compared to patients without drug use (Mean=91, SD=20.0) (p = 0.002). Cannabinoids were associated with lower SBP (Case Mean=136 (25.4) vs. Control Mean=141 (31.0), p = 0.009). Opioids were associated with lower SBP (Case Mean=138 (28.0) vs. Control Mean=145 (29.4), p = 0.01). Benzodiazepines were associated with increased HR and decreased SBP and RR. CONCLUSIONS: There appear to be no clinically relevant differences in vital signs among trauma patients with drug use and/or alcohol use, compared to patients without drug or alcohol use. Abnormal vital signs should not be prematurely attributed solely to acute substance intoxication before fully evaluating for associated traumatic injuries.

Sociodemographic disparities in ADHD diagnosis and treatment among U.S. elementary schoolchildren.

We examined whether some groups of U.S. elementary schoolchildren are less likely to be diagnosed and treated for ADHD in analyses of a population-based cohort (N = 10,920). We predicted ADHD diagnosis using measures of race and ethnicity, age, socioeconomic status, birthweight, individually assessed academic, behavioral, and executive functioning, family language use, mental health, health insurance coverage, marital status, school composition, and geographic region. We predicted prescription medication use among those diagnosed with ADHD. We stratified additional analyses by biological sex. Black children (aOR, 0.60), girls (aOR, 0.55), and emergent bilinguals (aOR, 0.29) were less likely to have an ADHD diagnosis than observationally similar White children, boys, or those from English-speaking households. Black children's under-diagnosis occurred among boys. Emergent bilingual children's under-diagnosis occurred among both boys and girls. Girls (aOR, 0.52) and emergent bilinguals (aOR, 0.24) with ADHD were less likely to use prescription medication. Sociodemographic disparities in ADHD diagnosis and treatment occur among U.S. elementary schoolchildren. Measured confounds including independently assessed ADHD symptomatology and impairment do not explain the disparities. The findings empirically support cultural, linguistic, and biological sensitivity in the ADHD diagnostic and treatment procedures in use for the U.S. pediatric population.

Association study between drug prescriptions and Alzheimer's disease claims in a commercial insurance database.

In the ongoing effort to discover treatments for Alzheimer's disease (AD), there has been considerable focus on investigating the use of repurposed drug candidates. Mining of electronic health record data has the potential to identify novel correlated effects between commonly used drugs and AD. In this study, claims from members with commercial health insurance coverage were analyzed to determine the correlation between the use of various drugs on AD incidence and claim frequency. We found that, within the insured population, several medications for psychotic and mental illnesses were associated with higher disease incidence and frequency, while, to a lesser extent, antibiotics and anti-inflammatory drugs were associated with lower AD incidence rates. The observations thus provide a general overview of the prescription and claim relationships between various drug types and Alzheimer's disease, with insights into which drugs have possible implications on resulting AD diagnosis.

Real-Time Impedance-Based Monitoring of the Growth and Inhibition of Osteomyelitis Biofilm Pathogen Staphylococcus aureus Treated with Novel Bisphosphonate-Fluoroquinolone Antimicrobial Conjugates.

Osteomyelitis is a limb- and life-threatening orthopedic infection predominantly caused by Staphylococcus aureus biofilms. Bone infections are extremely challenging to treat clinically. Therefore, we have been designing, synthesizing, and testing novel antibiotic conjugates to target bone infections. This class of conjugates comprises bone-binding bisphosphonates as biochemical vectors for the delivery of antibiotic agents to bone minerals (hydroxyapatite). In the present study, we utilized a real-time impedance-based assay to study the growth of Staphylococcus aureus biofilms over time and to test the antimicrobial efficacy of our novel conjugates on the inhibition of biofilm growth in the presence and absence of hydroxyapatite. We tested early and newer generation quinolone antibiotics (ciprofloxacin, moxifloxacin, sitafloxacin, and nemonoxacin) and several bisphosphonate-conjugated versions of these antibiotics (bisphosphonate-carbamate-sitafloxacin (BCS), bisphosphonate-carbamate-nemonoxacin (BCN), etidronate-carbamate-ciprofloxacin (ECC), and etidronate-carbamate-moxifloxacin (ECX)) and found that they were able to inhibit Staphylococcus aureus biofilms in a dose-dependent manner. Among the conjugates, the greatest antimicrobial efficacy was observed for BCN with an MIC of 1.48 µg/mL. The conjugates demonstrated varying antimicrobial activity depending on the specific antibiotic used for conjugation, the type of bisphosphonate moiety, the chemical conjugation scheme, and the presence or absence of hydroxyapatite. The conjugates designed and tested in this study retained the bone-binding properties of the parent bisphosphonate moiety as confirmed using high-performance liquid chromatography. They also retained the antimicrobial activity of the parent antibiotic in the presence or absence of hydroxyapatite, albeit at lower levels due to the nature of their chemical modification. These findings will aid in the optimization and testing of this novel class of drugs for future applications to pharmacotherapy in osteomyelitis.

Fixed Effect Estimates of Student-Teacher Racial or Ethnic Matching in U.S. Elementary Schools.

We used student fixed effects and statistical controls to investigate whether U.S. elementary students (N = 18,170) displayed greater academic achievement, social-emotional behavior, or executive functioning and were more likely to receive gifted or special education services when taught by teachers of the same race or ethnicity. We observed mostly null effects for student-teacher racial or ethnic matching across the study's 12 dependent measures in analyses adjusting for Type 1 error. For the full sample, matching resulted in lower science achievement (effect size [ES] = -.03 SD). For Black students, matching resulted in fewer internalizing problem behaviors (ES = 0.18 SD). We observed null effects for Hispanic students. Robustness checks including those stratified by race or ethnicity and biological sex or by prior levels of low or high level of achievement, behavior, or executive functioning largely supported the study's null findings. Exceptions were that matching resulted in fewer externalizing problem behaviors (ES = 0.22 SD) for Black girls and lower academic achievement (ES range = -0.04 to -0.14 SD) and fewer externalizing and internalizing problem behaviors (ES range = 0.24 to 0.33 SD) for students who had previously displayed low levels of academic, behavioral, or executive functioning. Collectively, the analyses provide limited support for student-teacher racial or ethnic matching as a school-based policy to address educational disparities in U.S. elementary schools.

Disparities in Family-Centered Care Among US Children and Youth with Special Healthcare Needs.

Cross-sectional analyses of 4 nationally representative samples indicate disparities in family-centered care occur among US children and youth with special healthcare needs by race and ethnicity, family income and composition, insurance coverage, and healthcare setting. Measured confounds including children's health and impairment severity do not explain the disparities.

Sensorimotor Cortex GABA Moderates the Relationship between Physical Exertion and Assessments of Effort.

Experiences of physical exertion guide our assessments of effort. While these assessments critically influence our decisions to engage in daily activities, little is known about how they are generated. We had female and male human participants exert grip force and assess how effortful these exertions felt; and used magnetic resonance spectroscopy to measure their brain GABA concentration. We found that variability in exertion (i.e., the coefficient of variation in their force exertion profile) was associated with increases in assessments of effort, making participants judge efforts as more costly. GABA levels in the sensorimotor cortex (SM1) moderated the influence of exertion variability on overassessments of effort. In individuals with higher sensorimotor GABA, exertion variability had a diminished influence on overassessments of effort. Essentially, sensorimotor GABA had a protective effect on the influence of exertion variability on inflations of effort assessment. Our findings provide a neurobiological account of how the brain's GABAergic system integrates features of physical exertion into judgments of effort, and how basic sensorimotor properties may influence higher-order judgments of effort.SIGNIFICANCE STATEMENT Feelings of effort critically shape our decisions to partake in activities of daily living. It remains unclear how the brain translates physical activity into judgments about effort (i.e., "How effortful did that activity feel?"). Using modeling of behavior and neuroimaging, we show how the nervous system uses information about physical exertion to generate assessments of effort. We found that higher variability in exertion was associated with increases in assessments of effort, making participants judge efforts as more costly. GABA, the brain's main inhibitory neurotransmitter, moderated the influence of exertion variability on overassessments of effort. These findings illustrate how low-level features of motor performance and sensorimotor neurochemistry influence higher-order cognitive processes related to feelings of effort.

Bisphosphonates: The role of chemistry in understanding their biological actions and structure-activity relationships, and new directions for their therapeutic use.

The bisphosphonates ((HO)2P(O)CR1R2P(O)(OH)2, BPs) were first shown to inhibit bone resorption in the 1960s, but it was not until 30 years later that a detailed molecular understanding of the relationship between their varied chemical structures and biological activity was elucidated. In the 1990s and 2000s, several potent bisphosphonates containing nitrogen in their R2 side chains (N-BPs) were approved for clinical use including alendronate, risedronate, ibandronate, and zoledronate. These are now mostly generic drugs and remain the leading therapies for several major bone-related diseases, including osteoporosis and skeletal-related events associated with bone metastases. The early development of chemistry in this area was largely empirical and only a few common structural features related to strong binding to calcium phosphate were clear. Attempts to further develop structure-activity relationships to explain more dramatic pharmacological differences in vivo at first appeared inconclusive, and evidence for mechanisms underlying cellular effects on osteoclasts and macrophages only emerged after many years of research. The breakthrough came when the intracellular actions on the osteoclast were first shown for the simpler bisphosphonates, via the in vivo formation of P-C-P derivatives of ATP. The synthesis and biological evaluation of a large number of nitrogen-containing bisphosphonates in the 1980s and 1990s led to the key discovery that the antiresorptive effects of these more complex analogs on osteoclasts result mostly from their potency as inhibitors of the enzyme farnesyl diphosphate synthase (FDPS/FPPS). This key branch-point enzyme in the mevalonate pathway of cholesterol biosynthesis is important for the generation of isoprenoid lipids that are utilized for the post-translational modification of small GTP-binding proteins essential for osteoclast function. Since then, it has become even more clear that the overall pharmacological effects of individual bisphosphonates on bone depend upon two key properties: the affinity for bone mineral and inhibitory effects on biochemical targets within bone cells, in particular FDPS. Detailed enzyme-ligand crystal structure analysis began in the early 2000s and advances in our understanding of the structure-activity relationships, based on interactions with this target within the mevalonate pathway and related enzymes in osteoclasts and other cells have continued to be the focus of research efforts to this day. In addition, while many members of the bisphosphonate drug class share common properties, now it is more clear that chemical modifications to create variations in these properties may allow customization of BPs for different uses. Thus, as the appreciation for new potential opportunities with this drug class grows, new chemistry to allow ready access to an ever-widening variety of bisphosphonates continues to be developed. Potential new uses of the calcium phosphate binding mechanism of bisphosphonates for the targeting of other drugs to the skeleton, and effects discovered on other cellular targets, even at non-skeletal sites, continue to intrigue scientists in this research field.

Toward Real-Time Muscle Force Inference and Device Control via Optical-Flow-Tracked Muscle Deformation.

Despite the utility of musculoskeletal dynamics modeling, there exists no safe, noninvasive method of measuring in vivo muscle output force in real time - limiting both biomechanical insight into dexterous motion and intuitive control of assistive devices. In this paper, we demonstrate that muscle deformation constitutes a promising, yet unexplored signal from which to 1) infer such forces and 2) build novel device control schemes. Through a case study of the elbow joint on a preliminary cohort of 10 subjects, we show that muscle deformation (specifically, thickness change of the brachioradialis, as measured via ultrasound and tracked via optical flow) correlates well with elbow output force to an extent comparable with standard surface electromyography (sEMG) activation during varied isometric elbow contraction. We then show that, given real-time visual feedback, subjects can readily perform a trajectory tracking task using this deformation signal, and that they largely prefer this method to a comparable sEMG-based control scheme and perform the tracking task with similar accuracy. Together, these contributions illustrate muscle deformation's potential utility for both biomechanical study of individual muscle dynamics and device control, in a manner that - thanks to, unlike sEMG, the localized nature of the signal and its tight mechanistic coupling to output force - is readily extensible to multiple muscles and device degrees of freedom. To enable such future extensions, all modeling, tracking, and visualization software described in this paper, as well as all raw and processed data, have been made available on SimTK as part of the Open-Arm project (https://simtk.org/projects/openarm) for general research use.

Prosthodontic and Endodontic Considerations for Treatment of Military Working Dogs.

Military Working Dogs (MWD) are highly trained in substance detection and various phases of controlled aggression to protect military assets and personnel. Dental health is essential to maintain their performance and mission readiness. MWD's dentition is often fractured or worn due to the physically demanding nature of their job. When non-surgical endodontic therapy or full coverage crowns are deemed necessary, good communication between veterinary and dental teams is necessary to provide quality and timely treatment. These two case reports describe important prosthodontic and endodontic procedural steps and treatment considerations for providing care to MWDs.

Comparison of CO2 Reduction Performance with NH3 and H2O between Cu/TiO2 and Pd/TiO2.

The aim of this study is to clarify the effect of doped metal type on CO2 reduction characteristics of TiO2 with NH3 and H2O. Cu and Pd have been selected as dopants for TiO2. In addition, the impact of molar ratio of CO2 to reductants NH3 and H2O has been investigated. A TiO2 photocatalyst was prepared by a sol-gel and dip-coating process, and then doped with Cu or Pd fine particles by using the pulse arc plasma gun method. The prepared Cu/TiO2 film and Pd/TiO2 film were characterized by SEM, EPMA, TEM, STEM, EDX, EDS and EELS. This study also has investigated the performance of CO2 reduction under the illumination condition of Xe lamp with or without ultraviolet (UV) light. As a result, it is revealed that the CO2 reduction performance with Cu/TiO2 under the illumination condition of Xe lamp with UV light is the highest when the molar ratio of CO2/NH3/H2O = 1:1:1 while that without UV light is the highest when the molar ratio of CO2/NH3/H2O = 1:0.5:0.5. It is revealed that the CO2 reduction performance of Pd/TiO2 is the highest for the molar ratio of CO2/NH3/H2O = 1:1:1 no matter the used Xe lamp was with or without UV light. The molar quantity of CO per unit weight of photocatalyst for Cu/TiO2 produced under the illumination condition of Xe lamp with UV light was 10.2 µmol/g, while that for Pd/TiO2 was 5.5 µmol/g. Meanwhile, the molar quantity of CO per unit weight of photocatalyst for Cu/TiO2 produced under the illumination condition of Xe lamp without UV light was 2.5 µmol/g, while that for Pd/TiO2 was 3.5 µmol/g. This study has concluded that Cu/TiO2 is superior to Pd/TiO2 from the viewpoint of the molar quantity of CO per unit weight of photocatalyst as well as the quantum efficiency.

Impact of Microporous Layer on Heat and Mass Transfer in a Single Cell of Polymer Electrolyte Fuel Cell Using a Thin Polymer Electrolyte Membrane and a Thin Gas Diffusion Layer Operated at a High-Temperature Range.

The impact of microporous layer (MPL) on the heat- and mass-transfer characteristics and power generation performance of a polymer electrolyte fuel cell using a thin polymer electrolyte membrane (PEM) and a thin gas diffusion layer (GDL) is investigated in this paper. The power generation is investigated at the operational temperatures of 90 and 100 °C which are the target temperatures from year 2020 to 2025 according to the New Energy and Industrial Technology Development Organization's road map in Japan. The in-plane temperature distributions on the separator back at the anode and the cathode are also measured by a thermograph. As a result, it is found that the voltage drop with the MPL at a high current density is larger compared to that without the MPL irrespective of the initial temperature of the cell and relative humidity conditions. The study also revealed from the anode side observation that the in-plane temperature distribution with the MPL is wider compared to that without the MPL, especially at the initial temperature of 90 °C of the cell . Similarly, from the cathode side observation, the in-plane temperature distributions with the MPL were found to be wider compared to that without the MPL. This study has concluded that the MPL is not effective in obtaining a high performance and even an in-plane temperature distribution for a polymer electrolyte fuel cell with the thin PEM and the thin GDL at a high operational temperature range.

Micronodular pattern organising pneumonia mimicking miliary lung disease: a rare radiological presentation.

Organising pneumonia (OP) is an interstitial lung disease characterised by granulation tissues in alveoli and alveolar ducts. Typical imaging findings are migratory airspace opacities with peripheral or peribronchovascular distribution. Diffuse micronodular OP (MNOP) is a rare imaging manifestation, which has imaging differential diagnosis of endobronchial infection such as tuberculosis, hypersensitivity pneumonitis and respiratory bronchiolitis. Although clinical and ancillary radiological findings may aid in refining the differential diagnosis, histopathological assessment is frequently required for this rare presentation due to implications of treatment and prognosis. We report a case of MNOP and performed a review of the literature.

Clinical targeting of HIV capsid protein with a long-acting small molecule.

Oral antiretroviral agents provide life-saving treatments for millions of people living with HIV, and can prevent new infections via pre-exposure prophylaxis1-5. However, some people living with HIV who are heavily treatment-experienced have limited or no treatment options, owing to multidrug resistance6. In addition, suboptimal adherence to oral daily regimens can negatively affect the outcome of treatment-which contributes to virologic failure, resistance generation and viral transmission-as well as of pre-exposure prophylaxis, leading to new infections1,2,4,7-9. Long-acting agents from new antiretroviral classes can provide much-needed treatment options for people living with HIV who are heavily treatment-experienced, and additionally can improve adherence10. Here we describe GS-6207, a small molecule that disrupts the functions of HIV capsid protein and is amenable to long-acting therapy owing to its high potency, low in vivo systemic clearance and slow release kinetics from the subcutaneous injection site. Drawing on X-ray crystallographic information, we designed GS-6207 to bind tightly at a conserved interface between capsid protein monomers, where it interferes with capsid-protein-mediated interactions between proteins that are essential for multiple phases of the viral replication cycle. GS-6207 exhibits antiviral activity at picomolar concentrations against all subtypes of HIV-1 that we tested, and shows high synergy and no cross-resistance with approved antiretroviral drugs. In phase-1 clinical studies, monotherapy with a single subcutaneous dose of GS-6207 (450 mg) resulted in a mean log10-transformed reduction of plasma viral load of 2.2 after 9 days, and showed sustained plasma exposure at antivirally active concentrations for more than 6 months. These results provide clinical validation for therapies that target the functions of HIV capsid protein, and demonstrate the potential of GS-6207 as a long-acting agent to treat or prevent infection with HIV.

Expression of mRNAs, miRNAs, and lncRNAs in Human Trabecular Meshwork Cells Upon Mechanical Stretch.

Purpose: Intraocular pressure (IOP), the primary risk factor for primary open-angle glaucoma, is determined by resistance to aqueous outflow through the trabecular meshwork (TM). IOP homeostasis relies on TM responses to mechanical stretch. To model the effects of elevated IOP on the TM, this study sought to identify coding and non-coding RNAs differentially expressed in response to mechanical stretch. Methods: Monolayers of TM cells from non-glaucomatous donors (n = 5) were cultured in the presence or absence of 15% mechanical stretch, 1 cycle/second, for 24 hours using a computer-controlled Flexcell unit. We profiled mRNAs and lncRNAs with stranded total RNA sequencing and microRNA (miRNA) expression with NanoString-based miRNA assays. We used two-tailed paired t-tests for mRNAs and long non-coding RNAs (lncRNAs) and the Bioconductor limma package for miRNAs. Gene ontology and pathway analyses were performed with WebGestalt. miRNA-mRNA interactions were identified using Ingenuity Pathway Analysis Integrative miRNA Target Finder software. Validation of differential expression was conducted using droplet digital PCR. Results: We identified 219 mRNAs, 42 miRNAs, and 387 lncRNAs with differential expression in TM cells upon cyclic mechanical stretch. Pathway analysis indicated significant enrichment of genes involved in steroid biosynthesis, glycerolipid metabolism, and extracellular matrix-receptor interaction. We also identified several miRNA master regulators (miR-125a-5p, miR-30a-5p, and miR-1275) that regulate several mechanoresponsive genes. Conclusions: To our knowledge, this is the first demonstration of the differential expression of coding and non-coding RNAs in a single set of cells subjected to cyclic mechanical stretch. Our results validate previously identified, as well as novel, genes and pathways.