Electrochemical Control of Strong Coupling of CdSe Exciton-Polaritons in Plasmonic Cavities.

This work reports in situ (active) electrochemical control over the coupling strength between semiconducting nanoplatelets and a plasmonic cavity. We found that by applying a reductive bias to an Al nanoparticle lattice working electrode the number of CdSe nanoplatelet emitters that can couple to the cavity is decreased. Strong coupling can be reversibly recovered by discharging the lattice at oxidative potentials relative to the conduction band edge reduction potential of the emitters. By correlating the number of electrons added or removed with the measured coupling strength, we identified that loss and recovery of strong coupling are likely hindered by side processes that trap and/or inhibit electrons from populating the nanoplatelet conduction band. These findings demonstrate tunable, external control of strong coupling and offer prospects to tune selectivity in chemical reactions.

Electronic Coding for Abnormal Fecal Immunochemical Test Is Associated With Increased Colonoscopy Completion.

INTRODUCTION: We examined the utility of the International Classification of Disease, Tenth Revision (ICD-10) code, R19.5, for a positive or abnormal fecal immunochemical test (FIT) and its association with colonoscopy completion. METHODS: We identified all patients in a safety-net health system who underwent FITs from January 1, 2020, to August 31, 2021, and extracted the FIT date, FIT result, and ICD-10 code (R19.5) and colonoscopy procedures for each patient. RESULTS: FIT-positive patients who had an R19.5 designation within 90 days (n = 383) were significantly more likely than all other FIT-positive patients (n = 273) to complete a colonoscopy within 6 months (40.9% vs 16.8%, P <0.001). DISCUSSION: We found that less than two-thirds of patients had an ICD-10 code designated in their chart within 30 days of an abnormal FIT. When coding occurred in a timely manner, patients were more likely to complete their colonoscopy within 6 months.

The effect of mailed outreach on FIT completion among patients aged 45-50 in a safety net healthcare system.

PURPOSE: Colorectal cancer screening is recommended starting at age 45, but there has been little research on strategies to promote screening in patients younger than 50. METHODS: An outreach program quasi-randomly assigned patients aged 45-50 without recent fecal immunochemical test (FIT), colonoscopy or contraindications to screening to two intervention arms: electronic outreach with email and text (electronic outreach only) versus electronic outreach plus mailed outreach with FIT, an instructional letter and a prepaid return envelope (mailed + electronic outreach). In response to known disparities in screening uptake, all Black patients were assigned to receive mailed + electronic outreach. RESULTS: Among patients quasi-randomly assigned to an intervention (non-Black patients), the 180-day FIT completion rate was 18.8% in the electronic outreach only group (n = 1,318) and 25.0% in the mailed + electronic outreach group (n = 1,364) (difference 6.2% [95% CI 3.0, 9.4]). FIT completion was 16.6% among Black patients (n = 469), 8.4% (95% CI 4.1, 12.6) lower than among non-Black patients also assigned to mailed + electronic outreach. CONCLUSION: Among patients aged 45-50, mailed + electronic outreach had a greater effect on FIT completion than electronic outreach alone. Crossover between intervention groups likely lead to an underestimation of the effect of mailed outreach.

Liquid lasing from solutions of ligand-engineered semiconductor nanocrystals.

Semiconductor nanocrystals (NCs) can function as efficient gain materials with chemical versatility because of their surface ligands. Because the properties of NCs in solution are sensitive to ligand-environment interactions, local chemical changes can result in changes in the optical response. However, amplification of the optical response is technically challenging because of colloidal instability at NC concentrations needed for sufficient gain to overcome losses. This paper demonstrates liquid lasing from plasmonic lattice cavities integrated with ligand-engineered CdZnS/ZnS NCs dispersed in toluene and water. By taking advantage of calcium ion-induced aggregation of NCs in aqueous solutions, we show how lasing threshold can be used as a transduction signal for ion detection. Our work highlights how NC solutions and plasmonic lattices with open cavity architectures can serve as a biosensing platform for lab-on-chip devices.

Artificial intelligence improves resident detection of pediatric and young adult upper extremity fractures.

PURPOSE: We wished to evaluate if an open-source artificial intelligence (AI) algorithm ( https://www.childfx.com ) could improve performance of (1) subspecialized musculoskeletal radiologists, (2) radiology residents, and (3) pediatric residents in detecting pediatric and young adult upper extremity fractures. MATERIALS AND METHODS: A set of evaluation radiographs drawn from throughout the upper extremity (elbow, hand/finger, humerus/shoulder/clavicle, wrist/forearm, and clavicle) from 240 unique patients at a single hospital was constructed (mean age 11.3 years, range 0-22 years, 37.9% female). Two fellowship-trained musculoskeletal radiologists, three radiology residents, and two pediatric residents were recruited as readers. Each reader interpreted each case initially without and then subsequently 3-4 weeks later with AI assistance and recorded if/where fracture was present. RESULTS: Access to AI significantly improved area under the receiver operator curve (AUC) of radiology residents (0.768 [0.730-0.806] without AI to 0.876 [0.845-0.908] with AI, P < 0.001) and pediatric residents (0.706 [0.659-0.753] without AI to 0.844 [0.805-0.883] with AI, P < 0.001) in identifying fracture, respectively. There was no evidence of improvement for subspecialized musculoskeletal radiology attendings in identifying fracture (AUC 0.867 [0.832-0.902] to 0.890 [0.856-0.924], P = 0.093). There was no evidence of difference between overall resident AUC with AI and subspecialist AUC without AI (resident with AI 0.863, attending without AI AUC 0.867, P = 0.856). Overall physician radiograph interpretation time was significantly lower with AI (38.9 s with AI vs. 52.1 s without AI, P = 0.030). CONCLUSION: An openly accessible AI model significantly improved radiology and pediatric resident accuracy in detecting pediatric upper extremity fractures.

In-Situ Measurement of Magnetoelectric Coupling and Strain Transfer in Multiferroic Nanocomposites of CoFe2O4 and Hf0.5Zr0.5O2 with Residual Porosity.

With increasing applications for voltage-controlled magnetism, the need to more fully understand magnetoelectric coupling and strain transfer in nanostructured multiferroic composites has also increased. Here, multiferroic nanocomposites were synthesized using block copolymer templating to create mesoporous cobalt ferrite (CFO), followed by partly filling the pores with ferroelectric zirconium-substituted hafnia (HZO) using atomic layer deposition (ALD) to produce a porous multiferroic composite with enhanced mechanical flexibility. Upon electrical poling of the nanocomposite, we observed large changes in the magnetization. These changes partly relaxed upon removing the electric field, suggesting a strain-mediated mechanism. Both the anisotropic strain transfer from HZO to CFO and the strain relaxation after the field was removed were confirmed using high-resolution X-ray diffraction measurements collected during in-situ poling. The in-situ observation of both anisotropic strain transfer and large magnetization changes allows us to directly characterize the strong multiferroic coupling that can occur in flexible, nanostructured composites.

Polypharmacy and Cardiovascular Diseases: Consideration for Older Adults and Women.

PURPOSE OF REVIEW: The intent of this review is to provide an update in polypharmacy in older adults and women with a focus on common determinants and strategies to mitigate polypharmacy. RECENT FINDINGS: Polypharmacy is becoming a critical focus in the management of cardiovascular diseases. It may emerge unintentionally while managing multimorbidity in older adults or in the vulnerable subgroup of patients, such as pregnant and lactating females. Clinicians should utilize several approaches such as deprescribing, sex-specific risk assessment, and encouraging healthy lifestyle to minimize inappropriate and unnecessary use of medications. A shared decision-making model along with coordination and collaboration among healthcare providers should be utilized in the selection and management of pharmacotherapies.

Orbital tuberculosis: a case report and update on the role of imaging in treatment.

Orbital tuberculosis is a manifestation of extra-pulmonary tuberculosis that is challenging to diagnose and treat. Here, we describe the pivotal role of serial imaging in the diagnosis and treatment of orbital tuberculosis. A 28-year-old male presented with recurrent right upper eyelid swelling and a supraduction deficit associated with a firm painless orbital mass, seen on initial computed tomography to be an extensive superomedial lesion producing mass effect. Biopsy revealed a tuberculosis-like granulomatous inflammation, which, coupled with a positive QuantiFERON gold test, led to empiric anti-tuberculin treatment. Serial radiologic imaging following initiation of treatment showed progressive reduction in mass size, supporting the diagnosis and determining the length of treatment. This rare case demonstrates the utility of serial radiologic exams in the diagnosis and treatment of orbital tuberculosis.

Comparison of mortality and medical complications between older and younger malignant melanoma inpatients.

Previous studies have identified older age as a negative prognostic factor in malignant melanoma patients. To compare comorbidities, medical complications, and inpatient mortality between younger and older malignant melanoma inpatients. All adult patient encounters with a diagnosis of cutaneous malignant melanoma were identified using the 2003 to 2012 National Inpatient Sample database. Concurrent comorbidities and inpatient medical complications were queried. Comparisons were made between older and younger adults, defined as ≥65 years and 18 to 64 years, respectively. In total, 8153 patient encounters were identified in the database (51.6% older and 48.4% younger). Older adults had a higher prevalence of numerous comorbidities, including chronic pulmonary disease, chronic renal failure, congestive heart failure, diabetes mellitus, hypertension, hypothyroidism, peripheral vascular disease, and pulmonary circulation disorder (P < .001). In contrast, younger adults were more likely to have obesity (P < .001) and coagulopathy (P = .005). On multivariable analysis of medical complications, older adult inpatients were more likely to experience urinary tract infection (OR = 1.54, P = .021), but less likely to experience acute respiratory failure (OR = 0.46, P = .012) and venous thromboembolism (OR = 0.44, P = .026). Notably, inpatient mortality did not significantly differ. Older adult inpatients with malignant melanoma have different comorbidities than younger patients and have a larger overall comorbidity burden. Surprisingly, however, the odds of most inpatient medical complications and mortality were found to be similar in younger vs older patients.

Characterization of Biopsies by Dermatologists and Nonphysician Providers in the Medicare Population: A Rapidly Changing Landscape.

BACKGROUND: Previous studies show that nonphysician providers may require a higher number of biopsies to identify skin malignancies than dermatologists. Therefore, understanding the trends behind the types of providers performing biopsies may help analyze their impact on this vulnerable population. OBJECTIVE: This retrospective study analyzes changes in nationwide, regional, and state-level data on the number and proportion of biopsies performed by dermatologists compared with nonphysician providers. MATERIALS AND METHODS: Biopsy cases were isolated in the Medicare database from 2012 to 2018 using the HCPCS codes 11,100 and 11,101. Cases were limited to biopsies performed by a dermatologist, nurse practitioner (NP), or physician assistant (PA). RESULTS: From 2012 to 2018, national biopsy rates per 100,000 Medicare beneficiaries for dermatologists decreased by 6%, whereas those for NPs and PAs increased by 97% and 82%, respectively. Each state showed variation in both the proportion of biopsies by provider type and the net change in biopsies rates over time. All states saw increases in the number of biopsies per 100,000 Medicare beneficiaries by nonphysician providers. CONCLUSION: As the number of Medicare beneficiaries continues to grow, nonphysician providers are performing an increasing proportion of biopsies, with specific states and regions being affected more than others.

N6-Furfuryladenine is protective in Huntington's disease models by signaling huntingtin phosphorylation.

The huntingtin N17 domain is a modulator of mutant huntingtin toxicity and is hypophosphorylated in Huntington's disease (HD). We conducted high-content analysis to find compounds that could restore N17 phosphorylation. One lead compound from this screen was N6-furfuryladenine (N6FFA). N6FFA was protective in HD model neurons, and N6FFA treatment of an HD mouse model corrects HD phenotypes and eliminates cortical mutant huntingtin inclusions. We show that N6FFA restores N17 phosphorylation levels by being salvaged to a triphosphate form by adenine phosphoribosyltransferase (APRT) and used as a phosphate donor by casein kinase 2 (CK2). N6FFA is a naturally occurring product of oxidative DNA damage. Phosphorylated huntingtin functionally redistributes and colocalizes with CK2, APRT, and N6FFA DNA adducts at sites of induced DNA damage. We present a model in which this natural product compound is salvaged to provide a triphosphate substrate to signal huntingtin phosphorylation via CK2 during low-ATP stress under conditions of DNA damage, with protective effects in HD model systems.

Advanced Notification Calls Prior to Mailed Fecal Immunochemical Test in Previously Screened Patients: a Randomized Controlled Trial.

BACKGROUND: Phone calls as part of multimodal fecal immunochemical test (FIT) outreach are effective but resource-intensive. Previous studies of advanced notification calls before FIT mailing have not differentiated patients' prior screening status. OBJECTIVE: To determine the effectiveness of a phone call preceding mailing of a FIT kit on test completion rate for patients who have completed a prior FIT. DESIGN: Randomized controlled trial nested within a larger study. All patients were assigned to receive organized mailed FIT outreach in the larger study. PARTICIPANTS: Patients in a safety-net health setting ages 50-75 years old with a previously negative FIT. INTERVENTIONS: Patients were assigned to either receive an advanced notification phone call or no phone call preceding a mailed FIT kit. Both groups received an informational postcard prior to the mailed FIT. MAIN MEASURES: The primary outcome was FIT completion rate at 1 year. The secondary outcomes were FIT completion rates at 60, 90, and 180 days, rates stratified by demographic subgroups, and rates according to outcome of the phone call. KEY RESULTS: A total of 1645 patients were assigned to advanced notification calls and 1595 were assigned to no call preceding the FIT mailing. Although FIT completion rate was higher at day 60 (55.5% vs. 50.8%, p < 0.01), an advanced notification call did not significantly improve FIT completion at 1 year (70.9% vs. 69.9%, p = 0.52). Of the patients assigned to receive an advanced notification call, 90.5% were spoken with or left a voicemail; patients who were spoken with were more likely to complete a FIT at 1 year compared with patients who were only left a voicemail or could not be left a voicemail (79.9% vs. 69.2% vs. 49.6%, p < 0.01). CONCLUSIONS: Advanced notification phone calls prior to FIT mailing did not improve rates at 1 year for patients with a previously negative FIT.

Intermittent Hypoxia Enhances Functional Connectivity of Midcervical Spinal Interneurons.

Brief, intermittent oxygen reductions [acute intermittent hypoxia (AIH)] evokes spinal plasticity. Models of AIH-induced neuroplasticity have focused on motoneurons; however, most midcervical interneurons (C-INs) also respond to hypoxia. We hypothesized that AIH would alter the functional connectivity between C-INs and induce persistent changes in discharge. Bilateral phrenic nerve activity was recorded in anesthetized and ventilated adult male rats and a multielectrode array was used to record C4/5 spinal discharge before [baseline (BL)], during, and 15 min after three 5 min hypoxic episodes (11% O2, H1-H3). Most C-INs (94%) responded to hypoxia by either increasing or decreasing firing rate. Functional connectivity was examined by cross-correlating C-IN discharge. Correlograms with a peak or trough were taken as evidence for excitatory or inhibitory connectivity between C-IN pairs. A subset of C-IN pairs had increased excitatory cross-correlations during hypoxic episodes (34%) compared with BL (19%; p < 0.0001). Another subset had a similar response following each episode (40%) compared with BL (19%; p < 0.0001). In the latter group, connectivity remained elevated 15 min post-AIH (30%; p = 0.0002). Inhibitory C-IN connectivity increased during H1-H3 (4.5%; p = 0.0160), but was reduced 15 min post-AIH (0.5%; p = 0.0439). Spike-triggered averaging indicated that a subset of C-INs is synaptically coupled to phrenic motoneurons and excitatory inputs to these "pre-phrenic" cells increased during AIH. We conclude that AIH alters connectivity of the midcervical spinal network. To our knowledge, this is the first demonstration that AIH induces plasticity within the propriospinal network.SIGNIFICANCE STATEMENT Acute intermittent hypoxia (AIH) can trigger spinal plasticity associated with sustained increases in respiratory, somatic, and/or autonomic motor output. The impact of AIH on cervical spinal interneuron (C-IN) discharge and connectivity is unknown. Our results demonstrate that AIH recruits excitatory C-INs into the spinal respiratory (phrenic) network. AIH also enhances excitatory and reduces inhibitory connections among the C-IN network. We conclude that C-INs are part of the respiratory, somatic, and/or autonomic response to AIH, and that propriospinal plasticity may contribute to sustained increases in motor output after AIH.

Synthetic small RNAs: Current status, challenges, and opportunities.

Small regulatory RNAs act at the levels of transcription, posttranscription, and translation, with numerous roles that include binding to protein targets, protein modification, binding to messenger RNA targets, and regulation of gene expression. We discuss the development of a number of riboregulators and riboswitches, highlighting their use in metabolic engineering and genetic control. Riboregulators and riboswitches are self-assembled RNA molecules that can dynamically change their conformation, acting as regulatory switches that affect biological changes. They have currently been designed, characterized, and implemented in a wide range of organisms and cell types, including bacteria, yeast, and mammalian cells. We have identified and examined the recent advances in RNA synthetic biology, underlining the potential future development of their use and capabilities, noting how these can be ultimately expanded and improved into novel biotechnological, biomedical, and industrial applications.

Effects of corticosterone on infection and disease in salamanders exposed to the amphibian fungal pathogen Batrachochytrium dendrobatidis.

Although it is well established that glucocorticoid hormones (GCs) alter immune function and disease resistance in humans and laboratory animal models, fewer studies have linked elevated GCs to altered immune function and disease resistance in wild animals. The chytrid fungal pathogen Batrachochytrium dendrobatidis (Bd) infects amphibians and can cause the disease chytridiomycosis, which is responsible for worldwide amphibian declines. It is hypothesized that long-term exposure to environmental stressors reduces host resistance to Bd by suppressing host immunity via stress-induced release of GCs such as corticosterone (CORT). We tested whether elevation of CORT would reduce resistance to Bd and chytridiomycosis development in the red-legged salamander Plethodon shermani. Plasma CORT was elevated daily in animals for 9 d, after which animals were inoculated with Bd and subsequently tested for infection loads and clinical signs of disease. On average, Bd-inoculated animals treated with CORT had higher infection abundance compared to Bd-inoculated animals not treated with CORT. However, salamanders that received CORT prior to Bd did not experience any increase in clinical signs of chytridiomycosis compared to salamanders not treated with CORT. The lack of congruence between CORT effects on infection abundance versus disease may be due to threshold effects. Nonetheless, our results show that elevation of plasma CORT prior to Bd inoculation decreases resistance to infection by Bd. More studies are needed to better understand the effects of CORT on animals exposed to Bd and whether CORT variation contributes to differential responses to Bd observed across amphibian species and populations.

Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles.

Genistein is a naturally occurring isoflavone phytoestrogen commonly found in plant products such as soybeans, lentils, and chickpeas. Genistein, like other phytoestrogens, has the potential to mimic, enhance, or impair the estradiol biosynthesis pathway, thereby potentially altering ovarian follicle growth. Previous studies have inconsistently indicated that genistein exposure may alter granulosa cell proliferation and hormone production, but no studies have examined the effects of genistein on intact antral follicles. Thus, this study was designed to test the hypothesis that genistein exposure inhibits follicle growth and steroidogenesis in intact antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice were cultured with vehicle (dimethyl sulfoxide; DMSO) or genistein (6.0 and 36µM) for 18-96h. Every 24h, follicle diameters were measured to assess growth. At the end of each culture period, the media were pooled to measure hormone levels, and the cultured follicles were collected to measure expression of cell cycle regulators and steroidogenic enzymes. The results indicate that genistein (36µM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36µM) increases progesterone, testosterone, and dehydroepiandrosterone (DHEA) levels, but decreases estrone and estradiol levels. The results also indicate that genistein alters the expression of steroidogenic enzymes at 24, 72 and 96h, and the expression of cell cycle regulators at 18h. These data indicate that genistein exposure inhibits antral follicle growth by inhibiting the cell cycle, alters sex steroid hormone levels, and dysregulates steroidogenic enzymes in cultured mouse antral follicles.