Memory support training and lifestyle modifications to promote healthy aging in persons at risk for Alzheimer's disease: a digital application supported intervention (Brain Boosters).

BACKGROUND: Evidence-based interventions to protect against cognitive decline among older adults at risk for Alzheimer's disease and related dementias (ADRD) are urgently needed. Rehabilitation approaches to support memory and behavioral/lifestyle interventions are recognized as promising strategies for preserving or improving cognitive health, although few previous interventions have combined both approaches. This paper describes the protocol of the Brain Boosters intervention, which synergistically combines training in compensatory and healthy lifestyle behaviors and supports implementation and tracking of new behaviors with a digital application. METHODS: The study utilizes a single-site, single-blinded, randomized controlled design to compare a structured lifestyle and compensatory aid intervention to an education-only self-guided intervention. We plan to enroll 225 community-dwelling adults (25% from underrepresented groups) aged 65 + who endorse subjective cognitive decline (SCD) and low baseline levels of healthy lifestyle behaviors. Both interventions will be administered in group format, consisting of 15 two-hour classes that occur weekly for ten weeks and taper to bi-monthly and monthly, for an intervention duration of 6 months. Participants in both interventions will receive education about a variety of memory support strategies and healthy lifestyle behaviors, focusing on physical and cognitive activity and stress management. The structured intervention will also receive support in adopting new behaviors and tracking set goals aided by the Electronic Memory and Management Aid (EMMA) digital application. Primary outcomes include global cognition (composite of memory, attention, and executive function tests) and everyday function (Everyday Cognition Questionnaire). Data will be collected at baseline and outcome visits, at approximately 6, 12, and 18 months. Qualitative interviews, self-report surveys (e.g., indicators of self-determination, health literacy) and EMMA data metrics will also be used to identify what components of the intervention are most effective and for whom they work. DISCUSSION: Successful project completion will provide valuable information about how individuals with SCD respond to a compensation and preventative lifestyle intervention assisted by a digital application, including an understanding of factors that may impact outcomes, treatment uptake, and adherence. The work will also inform development, scaling, and personalization of future interventions that can delay disability in individuals at risk for ADRD. TRIAL REGISTRATION: ClinicalTrials.gov. (NCT05027789, posted 8/30/2021).

Microplastic distribution and characteristics across a large river basin: Insights from the Neuse River in North Carolina, USA.

While microplastics (MP) have been found in aquatic ecosystems around the world, the understanding of drivers and controls of their occurrence and distribution have yet to be determined. In particular, their fate and transport in river catchments and networks are still poorly understood. We identified MP concentrations in water and streambed sediment at fifteen locations across the Neuse River Basin in North Carolina, USA. Water samples were collected with two different mesh sizes, a trawl net (>335 µm) and a 64 µm sieve used to filter bailing water samples. MPs >335 µm were found in all the water samples with concentrations ranging from 0.02 to 221 particles per m3 (p m-3) with a median of 0.44 p m-3. The highest concentrations were observed in urban streams and there was a significant correlation between streamflow and MP concentration in the most urbanized locations. Fourier Transform Infrared (FTIR) analysis indicated that for MPs >335 µm the three most common polymer types were polyethylene, polypropylene, and polystyrene. There were substantially more MP particles observed when samples were analyzed using a smaller mesh size (>64 µm), with concentrations ranging from 20 to 130 p m-3 and the most common polymer type being polyethylene terephthalate as identified by Raman spectroscopy. The ratio of MP concentrations (64 µm to 335 µm) ranged from 35 to 375, indicating the 335 µm mesh substantially underestimates MPs relative to the 64 µm mesh. MPs were detected in 14/15 sediment samples. Sediment and water column concentrations were not correlated. We estimate MP (>64 µm) loading from the Neuse River watershed to be 230 billion particles per year. The findings of this study help to better understand how MPs are spatially distributed and transported through a river basin and how MP concentrations are impacted by land cover, hydrology, and sampling method.

Outcomes of Treatment for Infective Endocarditis Following Transcatheter Pulmonary Valve Replacement.

BACKGROUND: Recipients of transcatheter pulmonary valve replacement (TPVR) have shown increased risk of infective endocarditis (IE). Little is known about the outcomes of different management strategies, particularly surgery, for IE after TPVR. METHODS: We queried the Pediatric Health Information System database for cases of IE after TPVR performed from 2010-2020. We described patient demographics, hospital courses, admission complications, and treatment outcomes based on therapy offered, surgical or medical only. We compared outcomes of initial therapy. Data are expressed as median or percent. RESULTS: Sixty-nine cases of IE were identified, accounting for 98 related hospital admissions; 29% of patients recorded IE-related readmissions. Of those readmitted after initial medical therapy only, 33% had relapse IE. Rates of surgery were 22% during initial admission and 36% overall. Likelihood of surgical intervention increased with each subsequent admission. Renal and respiratory failure were more common in those given initial surgery. Mortality rate was 4.3% overall and 8% in the surgical cohort. CONCLUSION: Initial medical therapy may result in relapses/readmissions and possible delay of surgical therapy, which appears to be most effective for treatment of IE. For those treated only medically, a more aggressive course of therapy may be more likely to prevent relapse. Mortality following surgical therapy for IE after TPVR appears higher than reported for surgical pulmonary valve replacement generally.

Hospital and community care costs for people newly diagnosed of living with HIV in London, UK.

This study of people newly diagnosed of living with HIV (ND-PLHIV) calculated the use, cost and outcome of HIV services at a London HIV centre. ND-PLHIV were followed July 2017-October 2018. Hospital data included inpatient days (IP), outpatient (OP), dayward (DW) visits, tests and procedures, and anti-retroviral drugs (ARVs). Community services were recorded in daily diaries. Mean per patient-year (MPPY) use was multiplied by unit costs. 13.6 MPPY (95%CI 12.4-14.9) OP visits, 0.4 MPPY (95%CI 0.1-0.7) IP days, 0.09 MPPY (95%CI 0.01-0.2) DW visits and 4.6 MPPY community services (95%CI 3.4-5.8). Total annual costs per patient-year (CPPY) was £11,483 (95%CI £10,369-12,597): ARVs comprised 63% and community services 2%. White participants used fewer hospital and more community services compared with minority ethnic community (MEC) participants. Costs for White ND-PLHIV was £10,778 CPPY (95%CI £9629-11,928); £13,214 (95%CI £10,656-15,772) for MEC ND-PLHIV (p < 0.06). Annual costs were inversely related to CD4 count at entry (r = -5.58, p = 0.02); mean CD4 count was 476 cells/mm3 (95%CI 422-531) versus 373 cells/mm3 (95%CI 320-425) for White and MEC participants respectively (p = 0.03). Annual costs for ND-PLHIV with CD4 ≤ 350 cells/mm3 was £2478 PPY higher compared with CD4 count >350 cells/mm3 (p = 0.04).

The influence of frailty on outcomes for older adults admitted to hospital with benign biliary disease: a single-centre, observational cohort study.

INTRODUCTION: The prevalence and complications of biliary disease increase with age. Frailty has been associated with adverse outcomes in the hospital setting. We describe the prevalence of frailty in older patients hospitalised with benign biliary disease and its association with duration of hospital stay, and 90-day and 1-year mortality. METHODS: We performed a retrospective cohort study of patients aged 75 years and over admitted with acute biliary disease between 17 September 2014 and 20 March 2017. Clinical Frailty Scale (CFS) score was recorded on admission. RESULTS: We included 200 patients with a median age of 82 (75-99) years, 60% were female; 154 (77%) were independent for personal activities of daily living (ADLs) and 99 (49.5%) for instrumental ADLs. Cholecystitis was the most common diagnosis (43%) followed by cholangitis (36%) and pancreatitis (21%). Ninety-nine patients were non frail (NF; CFS 1-4) and 101 were frail (F; CFS 5-9). Some 104 patients received medical treatment only. Surgery was more common in NF patients (11% vs F 2%), percutaneous drainage more frequently performed in F patients (15% vs NF 5%) and endoscopic cholangiopancreatography was similar in both groups (F 32% vs NF 31%). Frailty was associated with worse clinical outcomes in F vs NF: functional deconditioning (34% vs 11%), increased care level (19% vs 3%), length of stay (12 vs 7 days), 90-day mortality (8% vs 3%) and 1-year mortality (48% vs 24%). CONCLUSIONS: Half of patients in our cohort were frail and spent longer in hospital, were less likely to undergo surgery and were less likely to remain alive at 1 year after discharge.

Emergency medicine (EM) can safely manage geriatric trauma patients sustaining ground level falls: Fostering EM autonomy while safely offloading a busy trauma service.

OBJECTIVE: Limited data exists regarding different specialties care of geriatric (>74 years-old) trauma patients (GTPs). We created a "Tier-III" designation for ground-level fall (GLF) GTPs to be managed by EM, with a trauma consult as needed. MATERIALS AND METHODS: A single-center comparison of PRE (1/1/2013-4/30/2016) versus POST (5/1/2016-11/30/2019) Tier-III GTP GLFs. The primary outcome was mortality. Secondary outcomes included admissions, trauma bay procedures and length of stay (LOS). RESULTS: 1,652 patients (314-PRE vs. 1,338-POST) were included. The admission rate was lower in the POST (56.9% vs. 88.9%, p < 0.001) cohort. There were no differences in LOS or trauma bay procedures between cohorts (p > 0.05). On multivariable analysis there was similar associated risk of mortality between groups (p = 0.68). CONCLUSION: The associated risk of mortality was similar between GLF GTP cohorts managed initially by EM and trauma surgeons, however the admission rate was lower in the POST group suggesting EM management may improve hospital bed utilization.

Imaging Breast Microcalcifications Using Dark-Field Signal in Propagation-Based Phase-Contrast Tomography.

Breast microcalcifications are an important primary radiological indicator of breast cancer. However, microcalcification classification and diagnosis may be still challenging for radiologists due to limitations of the standard 2D mammography technique, including spatial and contrast resolution. In this study, we propose an approach to improve the detection of microcalcifications in propagation-based phase-contrast X-ray computed tomography of breast tissues. Five fresh mastectomies containing microcalcifications were scanned at different X-ray energies and radiation doses using synchrotron radiation. Both bright-field (i.e. conventional phase-retrieved images) and dark-field images were extracted from the same data sets using different image processing methods. A quantitative analysis was performed in terms of visibility and contrast-to-noise ratio of microcalcifications. The results show that while the signal-to-noise and the contrast-to-noise ratios are lower, the visibility of the microcalcifications is more than two times higher in the dark-field images compared to the bright-field images. Dark-field images have also provided more accurate information about the size and shape of the microcalcifications.

Measuring High-Order Phonon Correlations in an Optomechanical Resonator.

We use single photon detectors to probe the motional state of a superfluid ^{4}He resonator of mass ∼1 ng. The arrival times of Stokes and anti-Stokes photons (scattered by the resonator's acoustic mode) are used to measure the resonator's phonon coherences up to the fourth order. By postselecting on photon detection events, we also measure coherences in the resonator when ≤3 phonons have been added or subtracted. These measurements are found to be consistent with predictions that assume the acoustic mode to be in thermal equilibrium with a bath through a Markovian coupling.

Midterm Outcomes of Heart Transplantation in Children With Genetic Disorders.

BACKGROUND: Many congenital heart diseases (CHD) are associated with genetic defects. Children with complex CHD often have heart failure requiring heart transplant. Given the broad spectrum of genetic pathologies and dearth of transplants performed in these children, little is known regarding their outcomes. METHODS: We conducted a retrospective review of heart transplants performed at a high-volume center from 2007 to 2021. Patients were separated into pathogenic molecular and copy number variants, aneuploidies, and variants of uncertain significance, and compared with patients without known genetic diagnoses. Variables included genetic diagnoses, bridge-to-transplant approach, preoperative comorbidities, operative characteristics, and postoperative complications. Outcomes included intensive care unit-free days to 28 days, hospital mortality, survival, rejection, retransplantation, and educational status at latest follow-up. RESULTS: In all, 223 patients received transplants over the study period: 9.9% (22 of 223) had pathogenic molecular variants; 4.5% (10 of 223) had copy number variants; 1.8% (4 of 223) had aneuploidies; and 9% (20 of 223) had variants of uncertain significance. The most common anomalies were Turner syndrome (n = 3) and 22q11.2 deletion syndrome (n = 2). Children with aneuploidies had higher rates of hepatic dysfunction and hypothyroidism, whereas children with pathogenic copy number variants had higher rates of preoperative gastrostomy and stroke. Children with aneuploidies were intubated longer after transplant, with greater need for reintubation, and had the fewest intensive care unit-free days. Mortality and mean survival did not differ. At median follow-up of 4.4 years (range, 1.9 to 8.8), 89.7% of survivors (26 of 29) with pathogenic anomalies were attending or had graduated school. CONCLUSIONS: Despite more preoperative comorbidities, midterm outcomes after heart transplant in children with genetic syndromes and disorders are promising.

Data registration for multi-method qualification of additive manufactured components.

This work refines surface registration methods for metrological datasets to improve the multi-method qualification accuracy of additively manufactured (AM) lattices. Datasets acquired from X-ray computed tomography and a coordinate measurement machine of an AM lattice were aligned using derived geometry datum features based on a theoretical supplemental surface definition, which has been established in recent draft standards, but has had limited examination using complex AM structures. A refined sampling registration approach for lattice geometry based on spatially-dependent subsampling is derived and shown to statistically decrease variation between measurement sources. This importance of well-defined sampling practice and definition is highlighted. The applicability of this approach for multi-method qualification of complex AM parts is discussed. This work lays the foundation of utilizing specifications under consideration in a new standard with possible verification techniques that can be employed.

Characterizing copper and zinc content in forested wetland soils of North Carolina, USA.

Wetlands are often located in landscape positions where they receive runoff or floodwaters, which may contain toxic trace metals and other pollutants from anthropogenic sources. Over time, this can lead to the accumulation of potentially harmful levels of metals in wetlands soils. To assess the potential risk of Cu and Zn buildup in wetland soils in North Carolina, soil data from 88 wetlands were analyzed. In a subset of 16 wetlands, more intensive sampling was conducted. Samples were analyzed for Mehlich 3 Cu and Zn, and a subset of the samples was analyzed for total Cu and Zn. Overall, Mehlich 3 Cu and Zn were low, with mean values of 0.9 mg/kg for Cu and 3.2 mg/kg for Zn. Warning levels for Mehlich 3 Zn were only exceeded in three of the 88 sites; elevated Mehlich Cu was not observed. Total Cu and Zn were also low, with only a few sites having elevated levels; however, there was not a strong linear relationship between Mehlich 3 and total metals. Mean levels of Mehlich 3 Cu and Zn in wetlands were much lower than for human-impacted upland soils and background threshold concentrations that might be indicative of disturbance were much lower than warning levels for agricultural soils. The very low mobile Zn and Cu in most of these wetlands indicated that these metals do not pose a risk to the biota in most North Carolina wetlands, but wetlands with a direct and significant anthropogenic source of metal contamination could be exceptions.

Evaluation of the reticulorumen pH throughout the feeding period for beef feedlot steers maintained in a commercial feedlot and its association with liver abscesses.

OBJECTIVE: To evaluate the reticulorumen pH of beef feedlot steers throughout the feeding period and to assess the association between the respective durations that the reticulorumen pH was ≤ 5.6 (subacute ruminal acidosis) and ≤ 5.2 (acute ruminal acidosis) and liver abscess severity. ANIMALS: 59 feedlot steers (mean body weight, 349.5 kg). PROCEDURES: On day 0, each steer was orally administered an electronic bolus that monitored the reticulorumen pH every 10 minutes for 150 days. Steers were transitioned from a starter to intermediate ration on day 8 (transition 1) and from the intermediate to finish ration on day 19 (transition 2). The ration carbohydrate and megacalorie contents increased with each transition. During each transition, the lower megacalorie ration was fed at the 8:00 am feeding and the higher megacalorie ration was fed at the 2:00 pm feeding for 3 days before the higher megacalorie ration was fed extensively. Steers were sent to slaughter after 182 days; each carcass was assessed for liver abscesses. RESULTS: The diurnal reticulorumen pH pattern was characterized by a peak at 7:00 am and nadir at 8:00 pm. The mean percentages of time that the reticulorumen pH was ≤ 5.6 and ≤ 5.2 were more than 10-fold greater during transition 1, compared with during transition 2, and were significantly greater for steers with extensive liver abscesses than for steers without extensive liver abscesses. CONCLUSIONS AND CLINICAL RELEVANCE: Efforts to minimize the duration that the reticulorumen pH is ≤ 5.6 might mitigate liver abscess formation in feedlot cattle.

Computerised decision support in veterinary medicine, exemplified in a canine idiopathic epilepsy care pathway.

Computerised decision support is of emerging and increasing importance in human medicine, but as yet has not been thoroughly applied or evaluated in veterinary medicine. In this essay, the authors report on the first example of a veterinary care pathway, a specific form of computerised decision support, which guides clinicians through a clinical workflow and incorporates individual patient data to inform patient-specific decision recommendations. The veterinary care pathway was designed using consensus statements and specialist neurologist opinion to create a decision support tool concerning canine idiopathic epilepsy. The authors evaluated the care pathway by comparing 35 clinical decisions made by referral clinicians in historical cases of idiopathic epilepsy to decisions recommended by the care pathway when presented with the same clinical case. Their results show that in 77.1% (95% confidence interval [59.9, 89.6]) of cases the care pathway recommended a decision that was the same or similar to a specialist neurologist's decision. Whilst further studies are needed to explore the potential use of such technology in clinical practice, the authors believe this first application provides great promise of a new and alternative method of clinical decision support.

Tolerability of four-drug antiretroviral combination therapy in primary HIV-1 infection.

OBJECTIVES: Rapid initiation of antiretroviral therapy (ART) is important for individuals with high baseline viral loads, such as in primary HIV-1 infection (PHI). Four-drug regimens are sometimes considered; however, data are lacking on tolerability. We aimed to evaluate the tolerability of four-drug regimens used in the Research in Viral Eradication of HIV-1 Reservoirs (RIVER) study. METHODS: At enrolment, ART-naïve adult participants or those newly commenced on ART were initiated or intensified to four-drug regimens within 4 weeks of PHI. Rapid start was defined as pre-confirmation or ≤ 7 days of confirmed diagnosis. Primary and secondary outcomes were patient-reported adherence measured by 7-day recall and regimen switches between enrolment and randomization, respectively. RESULTS: Overall, 54 men were included: 72.2% were of white ethnicity, with a median age of 32 years old, 42.6% had a viral load of ≥ 100 000 HIV-1 RNA copies/mL, and in 92.6% sex with men was the mode of acquisition of HIV-1. Twenty (37%) started a four-drug regimen and 34 (63%) were intensified. Rapid ART initiation occurred in 28%, 100% started in ≤ 4 weeks. By weeks 4, 12, and 24, 37.0%, 69.0%, and 94.0% were undetectable (viral load < 50 copies/mL), respectively. Adherence rates of 100% at weeks 4, 12, 22 and 24 were reported in 88.9%, 87.0%, 82.4% and 94.1% of participants, respectively. Five individuals switched to three drugs, four changed their regimen constituents, and two switched post-randomization. CONCLUSIONS: Overall, four-drug regimens were well tolerated and had high levels of adherence. Whilst their benefit over three-drug regimens is lacking, our findings should provide reassurance if a temporarily intensified regimen is clinically indicated to help facilitate treatment.

Adsorption trajectories of nonspherical particles at liquid interfaces.

The adsorption of colloidal particles at liquid interfaces is of great importance scientifically and industrially, but the dynamics of the adsorption process is still poorly understood. In this paper we use a Langevin model to study the adsorption dynamics of ellipsoidal colloids at a liquid interface. Interfacial deformations are included by coupling our Langevin dynamics to a finite element model while transient contact line pinning due to nanoscale defects on the particle surface is encoded into our model by renormalizing particle friction coefficients and using dynamic contact angles relevant to the adsorption timescale. Our simple model reproduces the monotonic variation of particle orientation with time that is observed experimentally and is also able to quantitatively model the adsorption dynamics for some experimental ellipsoidal systems but not others. However, even for the latter case, our model accurately captures the adsorption trajectory (i.e., particle orientation versus height) of the particles. Our study clarifies the subtle interplay between capillary, viscous, and contact line forces in determining the wetting dynamics of micron-scale objects, allowing us to design more efficient assembly processes for complex particles at liquid interfaces.

Biomolecular phenotyping and heterogeneity assessment of mesenchymal stromal cells using label-free Raman spectroscopy.

Easy, quantitative measures of biomolecular heterogeneity and high-stratified phenotyping are needed to identify and characterise complex disease processes at the single-cell level, as well as to predict cell fate. Here, we demonstrate how Raman spectroscopy can be used in the difficult-to-assess case of clonal, bone-derived mesenchymal stromal cells (MSCs) to identify MSC lines and group these according to biological function (e.g., differentiation capacity). Biomolecular stratification is achieved using high-precision measures obtained from representative statistical sampling that also enable quantified heterogeneity assessment. Application to primary MSCs and human dermal fibroblasts shows use of these measures as a label-free assay to classify cell sub-types within complex heterogeneous cell populations, thus demonstrating the potential for therapeutic translation, and broad application to the phenotypic characterisation of other cells.

Combined HIV Adolescent Prevention Study (CHAPS): comparison of HIV pre-exposure prophylaxis regimens for adolescents in sub-Saharan Africa-study protocol for a mixed-methods study including a randomised controlled trial.

BACKGROUND: HIV remains a major public health issue, especially in Eastern and Southern Africa. Pre-exposure prophylaxis is highly effective when adhered to, but its effectiveness is limited by cost, user acceptability and uptake. The cost of a non-inferiority phase III trial is likely to be prohibitive, and thus, it is essential to select the best possible drug, dose and schedule in advance. The aim of this study, the Combined HIV Adolescent PrEP and Prevention Study (CHAPS), is to investigate the drug, dose and schedule of pre-exposure prophylaxis (PrEP) required for the protection against HIV and the acceptability of PrEP amongst young people in sub-Saharan Africa, and hence to inform the choice of intervention for future phase III PrEP studies and to improve strategies for PrEP implementation. METHODS: We propose a mixed-methods study amongst young people aged 13-24 years. The first component consists of qualitative research to identify the barriers and motivators towards the uptake of PrEP amongst young people in South Africa, Uganda and Zimbabwe. The second component is a randomised clinical trial (ClinicalTrials.gov NCT03986970, June 2019) using a novel ex vivo HIV challenge method to investigate the optimal PrEP treatment (FTC-TDF vs FTC-TAF), dose and schedule. We will recruit 144 amongst HIV-negative uncircumcised men aged 13-24 years from voluntary male medical circumcision clinics in two sites (South Africa and Uganda) and randomise them into one of nine arms. One group will receive no PrEP prior to surgery; the other arms will receive either FTC-TDF or FTC-TAF, over 1 or 2 days, and with the final dose given either 6 or 20 h prior to surgery. We will conduct an ex vivo HIV challenge on their resected foreskin tissue. DISCUSSION: This study will provide both qualitative and quantitative results to help decide the optimum drug, dose and schedule for a future phase III trial of PrEP. The study will also provide crucial information on successful strategies for providing PrEP to young people in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT03986970 . Registered on 14 June 2019.

Secukinumab-associated localized granuloma annulare (SAGA): a case report and review of the literature.

Granuloma annulare (GA) is a benign, usually self-limited inflammatory skin dermatosis characterized clinically by pink-red to brown dermal papules or annular plaques. The main histologic feature is the presence of palisading or interstitial granulomas composed of necrobiotic collagen, elastic fibers, and mucin surrounded by a lymphohistiocytic infiltrate. Granuloma annulare is commonly associated with trauma, infections, diabetes mellitus, dyslipidemia, malignancy, thyroid disease, and a variety of medications. Two cases of GA have been reported in association with the use of secukinumab, a monoclonal antibody directed against interleukin 17A (IL17A), for the treatment of moderate-to-severe plaque psoriasis. We report the third case of secukinumab-associated GA in a 52-year-old woman with a history of diabetes mellitus type II, dyslipidemia, and non-alcoholic steatohepatitis. After four months of therapy with secukinumab, she presented with pink papules coalescing to plaques involving the antecubital fossae. Histology demonstrated a lymphohistiocytic palisading granuloma with central necrobiotic collagen and mucin, consistent with GA. Physicians should be aware of the possibility of GA developing in patients receiving secukinumab, especially in those with predisposing factors for GA. A better understanding of secukinumab-associated GA may lead to discoveries in GA pathogenesis and reveal broader immunomodulatory effects of secukinumab.