Depression and Implantable Cardioverter-Defibrillator Implantation in Black Patients at Risk for Sudden Cardiac Death.

BACKGROUND: Black patients meeting indications for implantable cardioverter-defibrillators (ICDs) have lower rates of implantation compared with White patients. There is little understanding of how mental health impacts the decision-making process among Black patients considering ICDs. Our objective was to assess the association between depressive symptoms and ICD implantation among Black patients with heart failure. METHODS AND RESULTS: This is a secondary analysis of the VIVID (Videos to Address Racial Disparities in ICD Therapy via Innovative Designs) randomized trial, which enrolled self-identified Black individuals with chronic systolic heart failure. Depressive symptoms were assessed by the Patient Health Questionnaire-2 and the Mental Component Summary of the 12-Item Short-Form Health Survey. Decisional conflict was measured by an adapted Decisional Conflict Scale (DCS). ANCOVA was used to assess differences in Decisional Conflict Scale scores. Multivariable logistic regression was used to examine the association between depressive symptoms and ICD implantation. Among 306 participants, 60 (19.6%) reported depressed mood, and 142 (46.4%) reported anhedonia. Participants with the lowest Mental Component Summary of the 12-Item Short-Form Health Survey scores (poorer mental health and higher likelihood of depression) had greater decisional conflict regarding ICD implantation compared with those with the highest Mental Component Summary of the 12-Item Short-Form Health Survey scores (adjusted mean difference in Decisional Conflict Scale score, 3.2 [95% CI, 0.5-5.9]). By 90-day follow-up, 202 (66.0%) participants underwent ICD implantation. There was no association between either the Patient Health Questionnaire-2 score or the Mental Component Summary of the 12-Item Short-Form Health Survey score and ICD implantation. CONCLUSIONS: Depressed mood and anhedonia were prevalent among ambulatory Black patients with chronic systolic heart failure considering ICD implantation. The presence of depressive symptoms did not impact the likelihood of ICD implantation in this population.

Aquaporin-0-protein interactions elucidated by crosslinking mass spectrometry.

Aquaporin-0 (AQP0) constitutes 50 % of the lens membrane proteome and plays important roles in lens fiber cell adhesion, water permeability, and lens transparency. Previous work has shown that specific proteins, such as calmodulin (CaM), interact with AQP0 to modulate its water permeability; however, these studies often used AQP0 peptides, rather than full-length protein, to probe these interactions. Furthermore, the specific regions of interaction of several known AQP0 interacting partners, i.e. αA and αB-crystallins, and phakinin (CP49) remain unknown. The purpose of this study was to use crosslinking mass spectrometry (XL-MS) to identify interacting proteins with full-length AQP0 in crude lens cortical membrane fractions and to determine the specific protein regions of interaction. Our results demonstrate, for the first time, that the AQP0 N-terminus can engage in protein interactions. Specific regions of interaction are elucidated for several AQP0 interacting partners including phakinin, α-crystallin, connexin-46, and connexin-50. In addition, two new interacting partners, vimentin and connexin-46, were identified.

Trafficking of mitochondrial double-stranded RNA from mitochondria to the cytosol.

In addition to mitochondrial DNA, mitochondrial double-stranded RNA (mtdsRNA) is exported from mitochondria. However, specific channels for RNA transport have not been demonstrated. Here, we begin to characterize channel candidates for mtdsRNA export from the mitochondrial matrix to the cytosol. Down-regulation of SUV3 resulted in the accumulation of mtdsRNAs in the matrix, whereas down-regulation of PNPase resulted in the export of mtdsRNAs to the cytosol. Targeting experiments show that PNPase functions in both the intermembrane space and matrix. Strand-specific sequencing of the double-stranded RNA confirms the mitochondrial origin. Inhibiting or down-regulating outer membrane proteins VDAC1/2 and BAK/BAX or inner membrane proteins PHB1/2 strongly attenuated the export of mtdsRNAs to the cytosol. The cytosolic mtdsRNAs subsequently localized to large granules containing the stress protein TIA-1 and activated the type 1 interferon stress response pathway. Abundant mtdsRNAs were detected in a subset of non-small-cell lung cancer cell lines that were glycolytic, indicating relevance in cancer biology. Thus, we propose that mtdsRNA is a new damage-associated molecular pattern that is exported from mitochondria in a regulated manner.

The "First daughter" effect: Human rights advocacy and attitudes toward gender equality in Taliban-controlled Afghanistan.

International concern for the human rights of Afghan women has spiked since the Taliban consolidated power in Afghanistan in fall 2021. Yet little is known about how to effectively advocate for women's human rights under this new context. We present findings from a random sample of all adult Afghan internet users' attitudes toward peace, security, gender, and human rights and find significant support for women's human rights as a national priority within Afghanistan, even when controlling for other priorities and even among many men and women aligned with the Taliban. Given that men now have much more political power in Afghan society to protect women's rights, we paid particular attention to men's attitudes toward women's human rights. Our evidence from an embedded survey experiment, building on earlier literature from other countries, demonstrates that fathers of eldest daughters are particularly likely to favor prioritizing women's rights when primed to think about the gender of their eldest children. Thus, the human rights and humanitarian community should spend more time and attention engaging with this demographic, and specifically creating marketing and advocacy strategies that encourage men to think about or act on behalf of their eldest daughters.

First-In-Human Demonstration of High Frequency Electrical Motor Nerve Block: Case Report.

ABSTRACT: This feasibility study tested the capability of high frequency stimulation (HFS) to block muscle contractions elicited by electrical stimulation of the same nerve proximally. During a tendon lengthening surgery in the forearm, the anterior interosseous nerve (AIN) was exposed. A specialized nerve cuff electrode was placed around the nerve, and a stimulating probe held on the nerve 1 cm proximal to the cuff electrode delivered pulses of current causing the pronator quadratus muscle to contract. Through the cuff electrode, 20 kHz HFS was delivered to the nerve for 10 seconds during proximal stimulation. HFS amplitudes between 5 and 10 mA peak-to-peak were tested to determine which produced complete and partial block of the electrically induced contractions. The minimum HFS amplitude that produced complete block was 8 mA, with lower amplitudes producing partial block. In all trials, muscle contractions resumed immediately after HFS was turned off. This demonstration of high frequency electrical nerve block is a milestone in the road to clinical implementation of HFS mediated motor block for spasticity.

Epidemiology and clinical relevance of persistent bacteraemia in patients with Gram-negative bloodstream infection: a retrospective cohort study.

OBJECTIVES: The risk factors and outcomes associated with persistent bacteraemia in Gram-negative bloodstream infection (GN-BSI) are not well described. We conducted a follow-on analysis of a retrospective population-wide cohort to characterize persistent bacteraemia in patients with GN-BSI. METHODS: We included all hospitalized patients >18 years old with GN-BSI between April 2017 and December 2021 in Ontario who received follow-up blood culture (FUBC) 2-5 days after the index positive blood culture. Persistent bacteraemia was defined as having a positive FUBC with the same Gram-negative organism as the index blood culture. We identified variables independently associated with persistent bacteraemia in a multivariable logistic regression model. We evaluated whether persistent bacteraemia was associated with increased odds of 30- and 90-day all-cause mortality using multivariable logistic regression models adjusted for potential confounders. RESULTS: In this study, 8807 patients were included; 600 (6.8%) had persistent bacteraemia. Having a permanent catheter, antimicrobial resistance, nosocomial infection, ICU admission, respiratory or skin and soft tissue source of infection, and infection by a non-fermenter or non-Enterobacterales/anaerobic organism were associated with increased odds of having persistent bacteraemia. The 30-day mortality was 17.2% versus 9.6% in those with and without persistent bacteraemia (aOR 1.65, 95% CI 1.29-2.11), while 90-day mortality was 25.5% versus 16.9%, respectively (aOR 1.53, 95% CI 1.24-1.89). Prevalence and odds of developing persistent bacteraemia varied widely depending on causative organism. CONCLUSIONS: Persistent bacteraemia is uncommon in GN-BSI but is associated with poorer outcomes. A validated risk stratification tool may be useful to identify patients with persistent bacteraemia.

Δ BP-Net: Monitoring "Changes" in Blood Pressure Using PPG with Self-contrastive Masking.

Estimating blood pressure (BP) values from physiological signals (e.g., photoplethysmogram (PPG)) using deep learning models has recently received increased attention, yet challenges remain in terms of models' generalizability. Here, we propose taking a new approach by framing the problem as tracking the "changes" in BP over an interval, rather than directly estimating its value. Indeed, continuous monitoring of acute changes in BP holds promising implications for clinical applications (e.g., hypertensive emergencies). As a solution, we first present a self-contrastive masking (SCM) model, designed to perform pair-wise temporal comparisons within the input signal. We then leverage the proposed SCM model to introduce ΔBPNet, a model trained to detect elevations/drops greater than a given threshold in the systolic blood pressure (SBP) over an interval, from PPG. Using data from PulseDB, 1) we evaluate the performance of ΔBP-Net on previously unseen subjects, 2) we test ΔBP-Net's ability to generalize across domains by training and testing on different datasets, and 3) we compare the performance of ΔBP-Net with existing PPG-based BP-estimation models in detecting over-threshold SBP changes. Formulating the problem as a binary classification task (i.e., over-threshold SBP elevation/ drop or not), ΔBP-Net achieves 75.97%/73.19% accuracy on data from subjects unseen during training. Additionally, the proposed ΔBP-Net outperforms ΔSBP estimations derived from existing PPG-based BP-estimation methods. Overall, by shifting the focus from estimating the value of SBP to detecting overthreshold "changes" in SBP, this work introduces a new potential for using PPG in clinical BP monitoring, and takes a step forward in addressing the challenges related to the generalizability of PPG-based BP-estimation models.

Mechanical or Biological Prosthesis for Aortic Valve Replacement in Patients Aged 45 to 74 Years.

OBJECTIVE: The selection of valve prostheses for patients undergoing surgical aortic valve replacement (SAVR) remains controversial. In this study, we compared the long-term outcomes of patients undergoing aortic valve replacement with biological or mechanical aortic valve prostheses. METHODS: We evaluated late results among 5,762 patients aged 45-74 years who underwent biological or mechanical aortic valve replacement with or without concomitant coronary artery bypass from 1989 to 2019 at four medical centers. The Cox proportional hazards model was used to compare late survival; the age-dependent effect of prosthesis type on long-term survival was evaluated by an interaction term between age and prosthesis type. Incidences of stroke, major bleeding, and reoperation on the aortic valve following the index procedure were compared between prosthesis groups. RESULTS: Overall, 61% (n=3,508) of patients received a bioprosthesis. The 30-day mortality rate was 1.7% (n=58) in the bioprosthesis group and 1.5% (n=34) in the mechanical group (P=0.75). During a mean follow-up of 9.0 years, the adjusted risk of mortality was higher in the bioprosthesis group (HR=1.30, P<0.001). The long-term survival benefit associated with mechanical prosthesis persisted until 70 years of age. Bioprosthesis (vs mechanical prosthesis) was associated with a similar risk of stroke (P=0.20), lower risk of major bleeding (P<0.001), and higher risk of reoperation (P<0.001). CONCLUSIONS: Compared to bioprostheses, mechanical aortic valves are associated with a lower adjusted risk of long-term mortality in patients aged 70 years or younger. Patients <70 years old undergoing SAVR should be informed of the potential survival benefit of mechanical valve substitutes.

Unlocking the unfolded structure of ubiquitin: Combining time-resolved x-ray solution scattering and molecular dynamics to generate unfolded ensembles.

The unfolding dynamics of ubiquitin were studied using a combination of x-ray solution scattering (XSS) and molecular dynamics (MD) simulations. The kinetic analysis of the XSS ubiquitin signals showed that the protein unfolds through a two-state process, independent of the presence of destabilizing salts. In order to characterize the ensemble of unfolded states in atomic detail, the experimental XSS results were used as a constraint in the MD simulations through the incorporation of x-ray scattering derived potential to drive the folded ubiquitin structure toward sampling unfolded states consistent with the XSS signals. We detail how biased MD simulations provide insight into unfolded states that are otherwise difficult to resolve and underscore how experimental XSS data can be combined with MD to efficiently sample structures away from the native state. Our results indicate that ubiquitin samples unfolded in states with a high degree of loss in secondary structure yet without a collapse to a molten globule or fully solvated extended chain. Finally, we propose how using biased-MD can significantly decrease the computational time and resources required to sample experimentally relevant nonequilibrium states.

Infection-nutrition feedbacks: fat supports pathogen clearance but pathogens reduce fat in a wild mammal.

Though far less obvious than direct effects (clinical disease or mortality), the indirect influences of pathogens are difficult to estimate but may hold fitness consequences. Here, we disentangle the directional relationships between infection and energetic reserves, evaluating the hypotheses that energetic reserves influence infection status of the host and that infection elicits costs to energetic reserves. Using repeated measures of fat reserves and infection status in individual bighorn sheep (Ovis canadensis) in the Greater Yellowstone Ecosystem, we documented that fat influenced ability to clear pathogens (Mycoplasma ovipneumoniae) and infection with respiratory pathogens was costly to fat reserves. Costs of infection approached, and in some instances exceeded, costs of rearing offspring to independence in terms of reductions to fat reserves. Fat influenced probability of clearing pathogens, pregnancy and over-winter survival; from an energetic perspective, an animal could survive for up to 23 days on the amount of fat that was lost to high levels of infection. Cost of pathogens may amplify trade-offs between reproduction and survival. In the absence of an active outbreak, the influence of resident pathogens often is overlooked. Nevertheless, the energetic burden of pathogens likely has consequences for fitness and population dynamics, especially when food resources are insufficient.

Revealing the atomic and electronic mechanism of human manganese superoxide dismutase product inhibition.

Human manganese superoxide dismutase (MnSOD) is a crucial oxidoreductase that maintains the vitality of mitochondria by converting superoxide (O2●-) to molecular oxygen (O2) and hydrogen peroxide (H2O2) with proton-coupled electron transfers (PCETs). Human MnSOD has evolved to be highly product inhibited to limit the formation of H2O2, a freely diffusible oxidant and signaling molecule. The product-inhibited complex is thought to be composed of a peroxide (O22-) or hydroperoxide (HO2-) species bound to Mn ion and formed from an unknown PCET mechanism. PCET mechanisms of proteins are typically not known due to difficulties in detecting the protonation states of specific residues that coincide with the electronic state of the redox center. To shed light on the mechanism, we combine neutron diffraction and X-ray absorption spectroscopy of the product-bound, trivalent, and divalent states of the enzyme to reveal the positions of all the atoms, including hydrogen, and the electronic configuration of the metal ion. The data identifies the product-inhibited complex, and a PCET mechanism of inhibition is constructed.

Sutureless Valves, a "Wireless" Option for Patients With Aortic Valve Disease: JACC State-of-the-Art Review.

Transcatheter technologies triggered the recent revision of the guidelines that progressively widened the indications for the treatment of aortic stenosis. On the surgical realm, a technology avoiding the need for sutures to anchor the prosthesis to the aortic annulus has been developed with the aim to reduce the duration of cardiopulmonary bypass and simplify the process of valve implantation. In addition to a transcatheter aortic valve replacement (TAVR)-like stent that exerts a radial force, these so-called "rapid deployment valves" or "sutureless valves" for aortic valve replacement also have cuffs to improve sealing and reduce the risk of paravalvular leak. Despite promising, the actual advantage of sutureless valves over traditional surgical procedures (surgical aortic valve replacement) or TAVR is still debated. This review summarizes the current comparative evidence reporting outcomes of "sutureless valves" for aortic valve replacement to TAVR and surgical aortic valve replacement in the treatment of aortic valve stenosis.

Mailed feedback to primary care physicians on antibiotic prescribing for patients aged 65 years and older: pragmatic, factorial randomised controlled trial.

OBJECTIVES: To evaluate whether providing family physicians with feedback on their antibiotic prescribing compared with that of their peers reduces antibiotic prescriptions. To also identify effects on antibiotic prescribing from case-mix adjusted feedback reports and messages emphasising antibiotic associated harms. DESIGN: Pragmatic, factorial randomised controlled trial. SETTING: Primary care physicians in Ontario, Canada PARTICIPANTS: All primary care physicians were randomly assigned a group if they were eligible and actively prescribing antibiotics to patients 65 years or older. Physicians were excluded if had already volunteered to receive antibiotic prescribing feedback from another agency, or had opted out of the trial. INTERVENTION: A letter was mailed in January 2022 to physicians with peer comparison antibiotic prescribing feedback compared with the control group who did not receive a letter (4:1 allocation). The intervention group was further randomised in a 2x2 factorial trial to evaluate case-mix adjusted versus unadjusted comparators, and emphasis, or not, on harms of antibiotics. MAIN OUTCOME MEASURES: Antibiotic prescribing rate per 1000 patient visits for patients 65 years or older six months after intervention. Analysis was in the modified intention-to-treat population using Poisson regression. RESULTS: 5046 physicians were included and analysed: 1005 in control group and 4041 in intervention group (1016 case-mix adjusted data and harms messaging, 1006 with case-mix adjusted data and no harms messaging, 1006 unadjusted data and harms messaging, and 1013 unadjusted data and no harms messaging). At six months, mean antibiotic prescribing rate was 59.4 (standard deviation 42.0) in the control group and 56.0 (39.2) in the intervention group (relative rate 0.95 (95% confidence interval 0.94 to 0.96). Unnecessary antibiotic prescribing (0.89 (0.86 to 0.92)), prolonged duration prescriptions defined as more than seven days (0.85 (0.83 to 0.87)), and broad spectrum prescribing (0.94 (0.92 to 0.95)) were also significantly lower in the intervention group compared with the control group. Results were consistent at 12 months post intervention. No significant effect was seen for including emphasis on harms messaging. A small increase in antibiotic prescribing with case-mix adjusted reports was noted (1.01 (1.00 to 1.03)). CONCLUSIONS: Peer comparison audit and feedback letters significantly reduced overall antibiotic prescribing with no benefit of case-mix adjustment or harms messaging. Antibiotic prescribing audit and feedback is a scalable and effective intervention and should be a routine quality improvement initiative in primary care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04594200.

Planovalgus Foot Deformity in Patients Undergoing Total Hip Arthroplasty Is Associated With Increased Risk of Falls, Implant-Related Complications, and Revisions: A Case-Control Analysis.

BACKGROUND: Pes planus occurs due to the loss of the longitudinal arch of the foot, resulting in altered gait mechanics. This may lead to increased complications following total hip arthroplasty (THA). Thus, the aim of this study was to assess the effects that pes planus has on rates of falls, implant complications, fall-related injuries, and times to revision among THA patients. METHODS: A retrospective review of a private insurance claims database was conducted from 2010 to 2021. Patients who had a diagnosis of congenital or acquired pes planus and cases of THA were identified. Patients undergoing THA with a diagnosis of pes planus were matched to control patients 1:5 based on age, sex, and comorbidity profiles. Logistic regression was utilized to assess for differences in complication rates. RESULTS: A total of 3,622 pes planus patients were matched to 18,094 control patients. The pes planus group had significantly higher rates of falls than the control group (6.93 versus 2.97%, OR [odds ratio]: 2.43; CI [confidence interval]: 2.09 to 2.84; P < .001). Pes planus patients also had significantly greater odds of dislocation (OR: 1.89; CI: 1.58 to 2.27; P < .001), mechanical loosening (OR: 2.43; CI: 2.09 to 2.84; P = .019), and periprosthetic fracture (OR: 2.43; CI: 2.09 to 2.84; P < .001). The pes planus group had significantly greater rates of proximal humerus fractures (P = .008), but no difference was seen in distal radius fractures (P = .102). The time to revision was significantly shorter in the pes planus group (190 versus 554 days, P < .001). CONCLUSIONS: Pes planus in patients undergoing THA is associated with increased risk of complications and faster time to revision. These findings may allow orthopaedic surgeons to identify those patients at risk and allow for more educated patient counseling and operative planning.

The role of Tyr34 in proton-coupled electron transfer of human manganese superoxide dismutase.

Human manganese superoxide dismutase (MnSOD) plays a crucial role in controlling levels of reactive oxygen species (ROS) by converting superoxide (O 2 •- ) to molecular oxygen (O 2 ) and hydrogen peroxide (H 2 O 2 ) with proton-coupled electron transfers (PCETs). The reactivity of human MnSOD is determined by the state of a key catalytic residue, Tyr34, that becomes post-translationally inactivated by nitration in various diseases associated with mitochondrial dysfunction. We previously reported that Tyr34 has an unusual pK a due to its proximity to the Mn metal and undergoes cyclic deprotonation and protonation events to promote the electron transfers of MnSOD. To shed light on the role of Tyr34 MnSOD catalysis, we performed neutron diffraction, X-ray spectroscopy, and quantum chemistry calculations of Tyr34Phe MnSOD in various enzymatic states. The data identifies the contributions of Tyr34 in MnSOD activity that support mitochondrial function and presents a thorough characterization of how a single tyrosine modulates PCET catalysis.

COVID-19 vaccine uptake among Ontario physicians: a descriptive population-based retrospective cohort study.

OBJECTIVES: To determine COVID-19 vaccine uptake among physicians in Ontario, Canada from 14 December 2020 to 13 February 2022. DESIGN: Population-based retrospective cohort study. SETTING: All registered physicians in Ontario, Canada using data from linked provincial administrative healthcare databases. PARTICIPANTS: 41 267 physicians (including postgraduate trainees) who were Ontario residents and registered with the College of Physicians and Surgeons of Ontario were included. Physicians who were out of province, had not accessed Ontario Health Insurance Plan-insured services for their own care for ≥5 years and those with missing identifiers were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were the proportions of physicians who were recorded to have received at least one, at least two and three doses of a Health Canada-approved COVID-19 vaccine by study end date. Secondary outcomes were how uptake varied by physician characteristics (including age, sex, specialty and residential location) and time elapsed between doses. RESULTS: Of 41 267 physicians, (56% male, mean age 47 years), 39 359 (95.4%) received at least one dose, 39 148 (94.9%) received at least two doses and 35 834 (86.8%) received three doses of a COVID-19 vaccine. Of those who received three doses, the proportions were 90.4% among those aged ≥60 years and 81.2-89.5% among other age groups; 88.7% among family physicians and 89% among specialists. 1908 physicians (4.6%) had no record of vaccination, and this included 3.4% of family physicians and 4.1% of specialists; however, 28% of this group had missing specialty information. CONCLUSIONS: In Ontario, within 14 months of COVID-19 vaccine availability, 86.8% of physicians had three doses of a COVID-19 vaccine, compared with 45.6% of the general population. Findings may signify physicians' confidence in the safety and effectiveness of COVID-19 vaccines.

Fabrication and functional application of zein-based core-shell structures: A review.

Core-shell structures exhibit a number of distinct absorptive properties that make them attractive tools for use in a range of industrial contexts including pharmaceuticals, biotechnology, cosmetics, and food/agriculture. Several recent studies have focused on the development and fabrication of zein-based core-shell structures for a range of functional material deliveries. However, no recent review article has evaluated the fabrication of such core-shell structures for food-based applications. In this paper, we therefore survey current approaches to fabricating different zein-based platforms including particles, fibers, films, and hydrogels that have appeared in a variety of functionally relevant applications. In addition, we highlight certain challenges and future research directions in this field, thereby providing a novel perspective on zein-based core-shell structures.

Preanalytical considerations in quantifying circulating miRNAs that predict end-stage kidney disease in diabetes.

Our previous study identified 8 risk and 9 protective plasma miRNAs associated with progression to end-stage kidney disease (ESKD) in diabetes. This study aimed to elucidate preanalytical factors that influence the quantification of circulating miRNAs. Using the EdgeSeq platform, which quantifies 2,002 miRNAs in plasma, including ESKD-associated miRNAs, we compared miRNA profiles in whole plasma versus miRNA profiles in RNA extracted from the same plasma specimens. Less than half of the miRNAs were detected in standard RNA extraction from plasma. Detection of individual and concentrations of miRNAs were much lower when RNA extracted from plasma was quantified by RNA sequencing (RNA-Seq) or quantitative reverse transcription PCR (qRT-PCR) platforms compared with EdgeSeq. Plasma profiles of miRNAs determined by the EdgeSeq platform had excellent reproducibility in assessment and had no variation with age, sex, hemoglobin A1c, BMI, and cryostorage time. The risk ESKD-associated miRNAs were detected and measured accurately only in whole plasma and using the EdgeSeq platform. Protective ESKD-associated miRNAs were detected by all platforms except qRT-PCR; however, correlations among concentrations obtained with different platforms were weak or nonexistent. In conclusion, preanalytical factors have a profound effect on detection and quantification of circulating miRNAs in ESKD in diabetes. Quantification of miRNAs in whole plasma and using the EdgeSeq platform may be the preferable method to study profiles of circulating cell-free miRNAs associated with ESKD and possibly other diseases.

Comparison of initial dental treatment decisions between in-person and asynchronous teledentistry examinations for people with special health care needs.

BACKGROUND: People with special health care needs in long-term care settings have difficulty accessing a traditional dental office. The goal of the authors was to assess initial treatment decision concordance between dentists conducting traditional in-person examinations using mobile equipment and additional dentists conducting examinations using asynchronous teledentistry technology. METHODS: Six dentists from Access Dental Care, a North Carolina mobile dentistry nonprofit, saw new patients on-site at 12 participating facilities or asynchronously off-site with electronic dental records, radiographs, and intraoral images, all captured by an on-site dental hygienist. Off-site dentists were masked to other dentists' treatment need decisions; 3 through 5 off-site examinations were conducted for each on-site examination. Demographic and binary treatment need category data were collected. For the 3 most prevalent treatment types needed (surgery, restorative, and new removable denture), the authors calculated the percentage agreement and κ statistics with bootstrapped CIs (1,000 replicates). RESULTS: The 100 enrolled patients included 47 from nursing homes, 45 from Programs of All-Inclusive Care for the Elderly, and 8 from group homes for those with intellectual and developmental disabilities. Mean (SD) age was 73.9 (16.5) years. Among dentate participants, the percentage agreement and bootstrapped κ (95% CI) were 87% and 0.74 (0.70 to 0.78) for surgery and 78% and 0.54 (0.50 to 0.58) for restorative needs, respectively, and among dentate and edentulous participants, they were 94% and 0.78 (0.74 to 0.83), respectively, for new removable dentures. CONCLUSIONS: The authors assessed the initial dental treatment decision concordance between on-site dentists conducting in-person examinations with a mobile oral health care delivery model and off-site dentists conducting examinations with asynchronous dentistry. Concordance was substantial for surgery and removable denture treatment decisions and moderate for restorative needs. Patient characteristics and facility type were not significant factors in the levels of examiner agreement. PRACTICAL IMPLICATIONS: This evidence supports teledentistry use for patients with special health care needs and could help improve their access to oral health care.

Characterization of Taxonomic and Functional Dynamics Associated with Harmful Algal Bloom Formation in Recreational Water Ecosystems.

Harmful algal bloom (HAB) formation leads to the eutrophication of water ecosystems and may render recreational lakes unsuitable for human use. We evaluated the applicability and comparison of metabarcoding, metagenomics, qPCR, and ELISA-based methods for cyanobacteria/cyanotoxin detection in bloom and non-bloom sites for the Great Lakes region. DNA sequencing-based methods robustly identified differences between bloom and non-bloom samples (e.g., the relative prominence of Anabaena and Planktothrix). Shotgun sequencing strategies also identified the enrichment of metabolic genes typical of cyanobacteria in bloom samples, though toxin genes were not detected, suggesting deeper sequencing or PCR methods may be needed to detect low-abundance toxin genes. PCR and ELISA indicated microcystin levels and microcystin gene copies were significantly more abundant in bloom sites. However, not all bloom samples were positive for microcystin, possibly due to bloom development by non-toxin-producing species. Additionally, microcystin levels were significantly correlated (positively) with microcystin gene copy number but not with total cyanobacterial 16S gene copies. In summary, next-generation sequencing-based methods can identify specific taxonomic and functional targets, which can be used for absolute quantification methods (qPCR and ELISA) to augment conventional water monitoring strategies.