Effectiveness of an Intervention to Improve Decision Making for Older Patients With Advanced Chronic Kidney Disease : A Randomized Controlled Trial.

BACKGROUND: Older patients with advanced chronic kidney disease (CKD) face difficult decisions about managing kidney failure, frequently experiencing decisional conflict, regret, and treatment misaligned with preferences. OBJECTIVE: To assess whether a decision aid about kidney replacement therapy improved decisional quality compared with usual care. DESIGN: Multicenter, randomized, controlled trial. (ClinicalTrials.gov: NCT03522740). SETTING: 8 outpatient nephrology clinics associated with 4 U.S. centers. PARTICIPANTS: English-fluent patients, 70 years and older with nondialysis CKD stages 4 to 5 recruited from 2018 to 2020. INTERVENTION: DART (Decision-Aid for Renal Therapy) is an interactive, web-based decision aid for older adults with CKD. Both groups received written education about treatments. MEASUREMENTS: Change in the decisional conflict scale (DCS) score from baseline to 3, 6, 12, and 18 months. Secondary outcomes included change in prognostic and treatment knowledge and change in uncertainty. RESULTS: Among 400 participants, 363 were randomly assigned: 180 to usual care, 183 to DART. Decisional quality improved with DART with mean DCS declining compared with control (mean difference, -8.5 [95% CI, -12.0 to -5.0]; P < 0.001), with similar findings at 6 months, attenuating thereafter. At 3 months, knowledge improved with DART versus usual care (mean difference, 7.2 [CI, 3.7 to 10.7]; P < 0.001); similar findings at 6 months were modestly attenuated at 18 months (mean difference, 5.9 [CI, 1.4 to 10.3]; P = 0.010). Treatment preferences changed from 58% "unsure" at baseline to 28%, 20%, 23%, and 14% at 3, 6, 12, and 18 months, respectively, with DART, versus 51% to 38%, 35%, 32%, and 18% with usual care. LIMITATION: Latinx patients were underrepresented. CONCLUSION: DART improved decision quality and clarified treatment preferences among older adults with advanced CKD for 6 months after the DART intervention. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute (PCORI).

New physics searches at kaon and hyperon factories.

Rare meson decays are among the most sensitive probes of both heavy and light new physics. Among them, new physics searches using kaons benefit from their small total decay widths and the availability of very large datasets. On the other hand, useful complementary information is provided by hyperon decay measurements. We summarize the relevant phenomenological models and the status of the searches in a comprehensive list of kaon and hyperon decay channels. We identify new search strategies for under-explored signatures, and demonstrate that the improved sensitivities from current and next-generation experiments could lead to a qualitative leap in the exploration of light dark sectors.

Testing the Sensitivity of the Galactic Center Excess to the Point Source Mask.

The Fermi Large Area Telescope (Fermi-LAT) Collaboration has an updated point source catalog, referred to as 4FGL. We perform the first template fit using a mask based on this new catalog and find that the excess in gamma rays detected at the Galactic Center in Fermi-LAT data persists. On the other hand, we find that a search for point sources is highly sensitive to the use of the 4FGL catalog: no sizable excess of bright pixels is apparent in the inner Galaxy when we mask out 4FGL point sources. Combining these observations restricts the ability of point sources to contribute to the Galactic Center excess. After identifying which bright sources have no known counterpart, we place strong constraints on any point source luminosity function capable of explaining the smooth emission identified in the template fit.

Dexamethasone after early-life seizures attenuates increased susceptibility to seizures, seizure-induced microglia activation and neuronal injury later in life.

Chronic epilepsy can begin with isolated early-life prolonged seizures followed by remission and the re-emergence of seizures later in life. Seizures are known to trigger a neuroinflammatory response to promote neuronal damage and increase the risk of epilepsy. We examined whether post-seizure anti-inflammatory treatment with dexamethasone after early-life seizures could decrease future seizure susceptibility and ameliorate heightened microglia activation and cell injury in response to later-life seizures. Using a "two-hit" model, early-life seizures (SZ) were induced in rats on postnatal day (P) 25 by systemic kainic acid (KA) injection followed by later-life KA at P39. P25 animals were administered anti-inflammatory drugs for 2 or 7 days after first KA exposure to inhibit seizure-induced inflammation. Hippocampal microglial activation was measured after first or second KA treatments to assay neuroinflammation, and the latency and severity of seizures to the second KA treatment were measured to determine seizure susceptibility. In situ end labeling for DNA fragmentation was used to compare KA-induced neuronal injury between treatment groups after the second KA administration. KA-SZ at P25 caused marked microglia activation within 48 hours. At P39, KA-SZ in rats without prior seizures caused a modest (2-fold) increase in microglia assayed 72 hours after KA. In contrast, microglia were markedly activated (5-fold) in response to a second KA-SZ at P39. Short-course (2 days) dexamethasone significantly decreased seizure-induced microglia activation at P25, and ameliorated the exaggerated microglia activation, cell injury, and heightened susceptibility to second-hit seizures. Although short-course dexamethasone was effective, longer term (7 days) administration of dexamethasone resulted in decreased weight gain and increased mortality in animals with or without KA-induced seizures. These data indicated that acute short-term steroid therapy after SZ could inhibit seizure-induced microglia activation and decrease the long-term damaging effects of early-life SZ. These results further implicate seizure-induced inflammation and activation of innate immunity mediated by microglia in the pathogenesis of childhood epilepsy.

General Solution to the U(1) Anomaly Equations.

The anomaly cancellation equations for the U(1) gauge group can be written as a cubic equation in n-1 integer variables, where n is the number of Weyl fermions carrying the U(1) charge. We solve this Diophantine cubic equation by providing a parametrization of the charges in terms of n-2 integers, and prove that this is the most general solution.

Effect of Beta Cyclodextrin on the Reduction of Cholesterol in Ewe's Milk Manchego Cheese.

Beta-cyclodextrin (ß-CD) is a cyclic oligosaccharide consisting of seven glucose units and is produced from starch using cyclodextrin glycotransferase enzymes to break the polysaccharide chain and forming a cyclic polysaccharide molecule. The use of ß-CD in food research for reduction of cholesterol is increasing due to its affinity for non-polar molecules such as cholesterol. The aim of this study was to evaluate the feasibility of using ß-CD in cholesterol removal from pasteurized ewe's milk Manchego cheese and evaluate the effect on the main components of the milk, lipids, and flavor characteristics. Approximately 97.6% cholesterol reduction was observed in the cheese that was treated using ß-CD. Physicochemical properties (fat, moisture and protein) were not changed by the ß-CD treatment, except the soluble nitrogen and non-protein nitrogen that showed slight differences after the treatment. The amount of the different components of the lipid fraction (fatty acids, triglycerides and phospholipids) were similar in cheeses treated and not treated with ß-CD. Flavor compound and short chain free fatty acids were not mostly significantly influenced by the effect of the ß-CD. ß-CD molecules are edible and nontoxic and as a result they can be used safely for cholesterol removal processing in cheese manufacturing. Therefore, the present study suggests that ß-CD treatment is an effective process for cholesterol removal from Manchego cheese while preserving its properties.

Pediatric Ureteroscopy.

In recent years, the incidence of nephrolithiasis in the pediatric population appears to be increasing. 1 This has placed a new emphasis on surgical management of stones in children. In the past, extracorporeal shockwave lithotripsy was the preferred management technique for stones in children. 2 More recently, though, advances in endoscopy have allowed ureteroscopy to be adapted to the pediatric population and this approach has become more frequently utilized not just for lower ureteral calculi but also for proximal ureteral and renal stones.

Continent Catheterizable Vesicostomy: An Alternative Surgical Modality for Pediatric Patients With Large Bladder Capacity.

OBJECTIVE: To present a modified technique and early outcomes of a continent catheterizable vesicostomy in pediatric patients with either flaccid neurogenic bladder or intractable voiding dysfunction and large capacity bladder. METHODS: Six patients underwent the procedure from October 2014 to December 2015. A 4-cm Pfannenstiel incision was made, avoiding intraperitoneal dissection. After adequate mobilization, a 2-cm vertical flap at the dome of the bladder was identified and tubularized over a 12Fr catheter with 4-0 vicryl suture. The tubularized flap was then intussuscepted into the bladder with four 4-0 polydioxanone sutures, creating a continent mechanism. The catheterizable channel was then tunneled to the umbilicus, the channel ostomy matured, and the cystotomy closed in two layers. RESULTS: The median patient age was 8 (interquartile range [IQR] 12) years. All patients had urinary dysfunction requiring drainage from etiologies that included Eagle-Barrett syndrome (n = 2), Noonan syndrome (n = 1), Lennox-Gastaut syndrome (n = 1), and Spina bifida (n = 2). Median hospital length of stay was 8 (IQR 3) days. One patient had a superficial wound infection treated with antibiotics, and 1 patient required balloon dilation of the catheterizable channel at 3 months postoperatively, secondary to difficulty self-catheterizing. Five patients were successfully self-catheterizing at last follow-up. Median follow-up was 6 (IQR 5) months and there were no intra- or perioperative complications. CONCLUSION: Continent catheterizable vesicostomy is a novel technique for urinary drainage in patients with large bladder capacity that spares use of the appendix or ileum. Early results are encouraging, providing a catheterizable channel through the umbilicus without urinary leakage between catheterization.

A Paratesticular Serous Borderline Tumor in a Pediatric Patient With Proteus Syndrome.

Proteus syndrome is a rare disorder of asymmetric overgrowth of various tissues of the body and is associated with specific tumors appearing before the second decade. Although there have been reports of lesions of the genitourinary tract associated with Proteus syndrome, a case of serous borderline tumor of the paratestis has not been previously recorded. We report the first such case in a 20-month-old child who presented with a left-sided testicular mass that was found on histology to be a serous borderline tumor of the paratestis. Surgical management included a left inguinal radical orchiectomy and surveillance follow-up.

Before it is too late: professional responsibilities in late-onset Alzheimer's research and pre-symptomatic prediction.

The development of a wide array of molecular and neuroscientific biomarkers can provide the possibility to visualize the course of Alzheimer's disease (AD) at early stages. Many of these biomarkers are aimed at detecting not only a preclinical, but also a pre-symptomatic state. They are supposed to facilitate clinical trials aiming at treatments that attack the disease at its earliest stage or even prevent it. The increasing number of such biomarkers currently tested and now partly proposed for clinical implementation calls for critical reflection on their aims, social benefits, and risks. This position paper summarizes major challenges and responsibilities. Its focus is on the ethical and social problems involved in the organization and application of dementia research, as well as in healthcare provision from a cross-national point of view. The paper is based on a discussion of leading dementia experts from neuroscience, neurology, social sciences, and bioethics in the United States and Europe. It thus reflects a notable consensus across various disciplines and national backgrounds. We intend to initiate a debate on the need for actions within the researchers' national and international communities.

Non-ideal effects in indentation testing of soft tissues.

Indentation has several advantages as a loading mode for determining constitutive behavior of soft, biological tissues. However, indentation induces a complex, spatially heterogeneous deformation field that creates analytical challenges for the calculation of constitutive parameters. As a result, investigators commonly assume small indentation depths and large sample thicknesses to simplify analysis and then restrict indentation depth and sample geometry to satisfy these assumptions. These restrictions limit experimental resolution in some fields, such as brain biomechanics. However, recent experimental evidence suggests that conventionally applied limits are in fact excessively conservative. We conducted a parametric study of indentation loading with various indenter geometries, surface interface conditions, sample compressibility, sample geometry and indentation depth to quantitatively describe the deviation from previous treatments that results from violation of the assumptions of small indentation depth and large sample thickness. We found that the classical solution was surprisingly robust to violation of the assumption of small strain but highly sensitive to violation of the assumption of large sample thickness, particularly if the indenter was cylindrical. The ramifications of these findings for design of indentation experiments are discussed and correction factors are presented to allow future investigators to account for these effects without recreating our finite element models.

For whom the bell tolls: Silver Alerts raise concerns regarding individual rights and governmental interests.

The Silver Alert system was initially created to help protect missing persons who have cognitive impairments, particularly the elderly. The Silver Alert is modeled after the Amber Alert, created to help locate and safeguard missing children. Unlike the Amber Alert, however, in most states the Silver Alert applies to the elderly, adults with a mental impairment, or both, depending on the state. The goal of the Silver Alert system is the quick dissemination of information about missing persons to law enforcement personnel as well as to the general public. Previously, states notified law enforcement personnel of missing persons through teletype to other public safety jurisdictions to enlist their assistance in the retrieval of the missing person. Silver Alert programs substantially expand the notification to include the general public, who receive information through radio and television broadcasts as well as highway billboards. The programs serve a legitimate governmental interest by protecting a vulnerable population from possible harm. Yet, the implementation of these alerts can have unintended consequences, including the possible violation of an individual's right to privacy. Such consequences require careful consideration.

Proteomic comparison of equine and bovine milks on renneting.

Rennet-induced coagulation of bovine milk is a complex mechanism in which chymosin specifically hydrolyzes κ-casein, the protein responsible for the stability of the casein micelle. In equine milk, this mechanism is still unclear, and the protein targets of chymosin are unknown. To reveal the proteins involved, the rennetability of equine milk by calf chymosin was examined using gel-free and gel-based proteomic analysis and compared to bovine milk. RP-HPLC analysis of bovine and equine milks showed the release of several peptides following chymosin incubation. The hydrolyses of equine and bovine casein by chymosin were different, and the major peptides produced from equine milk were identified by mass spectrometry as fragments of ß-casein. Using two-dimensional electrophoresis, equine ß-casein was confirmed as the main target of calf chymosin over 24 h at 30 °C and pH 6.5. The gel-based analysis of equine milk discriminated between the different individual proteins and provided information on the range of isoforms of each protein as a result of post-translational modifications, as well as positively identified for the first time several isoforms of κ-casein. In comparison to bovine milk, κ-casein isoforms in equine milk were not involved in chymosin-induced coagulation. The intensity of equine ß-casein spots decreased following chymosin addition, but at a slower rate than bovine κ-casein.

Medication adherence among older adults with schizophrenia.

Older adults with schizophrenia are a growing segment of the population, yet their physical and mental health status is extremely poor. This article presents findings from a qualitative study that explored the understanding older adults with schizophrenia have of their physical health status. The study was conducted among 28 older adults with schizophrenia from a variety of settings using semi-structured interviews and participant observation. Self-management of psychiatric and non-psychiatric medications and its effect on participants' health status was one of the central themes that emerged from the study. Different styles of medication adherence were identified and factors associated with each style are presented. The findings provide insights into the design of clinical interventions aimed at promoting medication adherence among older adults with schizophrenia.

The safe routes to school program in California: an update.

Despite efforts to combat increasing rates of childhood obesity, the problem is worsening. Safe Routes to School (SRTS), an international movement motivated by the childhood obesity epidemic, seeks to increase the number of children actively commuting (walking or biking) to school by funding projects that remove barriers preventing them from doing so. We summarize the evaluation of the first phase of an ongoing SRTS program in California and discuss ways to enhance data collection.

Minocycline attenuates microglia activation and blocks the long-term epileptogenic effects of early-life seizures.

Innate immunity mediated by microglia appears to play a crucial role in initiating and propagating seizure-induced inflammatory responses. To address the role of activated microglia in the pathogenesis of childhood epilepsy, we first examined the time course of microglia activation following kainic acid-induced status epilepticus (KA-SE) in Cx3cr1(GFP/+) transgenic mice whose microglia are fluorescently labeled. We then determined whether this seizure-induced microglia activation primes the central immune response to overreact and to increase the susceptibility to a second seizure later in life. We used an inhibitor of microglia activation, minocycline, to block the seizure-induced inflammation to determine whether innate immunity plays a causal role in mediating the long-term epileptogenic effects of early-life seizure. First status epilepticus was induced at postnatal day (P) 25 and a second status at P39. KA-SE at P25 caused nearly a two-fold increase in microglia activation within 24h. Significant seizure-induced activation persisted for 7 days and returned to baseline by 14 days. P39 animals with prior exposure to KA-SE not only responded with greater microglial activation in response to "second hit" of KA, but shorter latency to express seizures. Inhibition of seizure-induced inflammation by 7 day minocycline post-treatment abrogated both the exaggerated microglia activation and the increased susceptibility to the second seizure later in life. The priming effect of early-life seizures is accompanied by modified and rapidly reactivated microglia. Our results suggest that anti-inflammatory therapy after SE may be useful to block the epileptogenic process and mitigate the long-term damaging effects of early-life seizures.

Medical ideology as a double-edged sword: the politics of cure and care in the making of Alzheimer's disease.

This paper builds on our prior work concerning the emergence of Alzheimer's disease (AD) as a major social and health concern. Our study was conducted in two phases (1985-1987 and 2009-2011). We examined the historical evolution of the concept of AD and the emergence of the AD social movement in the U. S. Sources include interviews with movement leaders and scientists, historical documents of the Alzheimer's Association, Congressional records, and published literature. We identified recurrent themes and salient issues motivating those in the movement, its barriers and facilitators, and the roles of government and NGOs in the creation of an organizational structure to maintain it. The characterization of AD as a leading cause of death among the elderly was crucial to sustaining the movement, but also operated as a "double edged sword". By construing "senility" as a treatable, even curable biomedical entity, the movement substantively contributed to the notion of an impending "crisis" of the aging population to be avoided at all costs, compounding the effect of conservative federal policies that emphasized the treatment or cure of AD, and less so the long-term care service needs of sufferers and caregivers that had given rise to the movement. We also discuss how the continuing hegemony of the medical model establishes a race against the demographic clock, pitting advances in biomedical research against the needs of an aging population. We propose that alternative framings and sources of legitimization are critical to address the needs and preserve the humanity of people living with AD and their caregivers.

Promoting best-care practices in childhood asthma: quality improvement in community health centers.

OBJECTIVE: Outpatient asthma management remains suboptimal. We previously reported significant improvements in asthma guideline adherence and outcomes in children by using quality-improvement processes and community health workers. We hypothesized that a larger project could achieve comparable outcome improvements with streamlined quality-improvement processes and decreased technical assistance. METHODS: Seventeen clinics treating 12 000 children with asthma were evaluated through interviews of a subset of patients with persistent or high-risk asthma (n=761) at baseline and at 12 and 21 months and chart reviews randomly selected from all patients with asthma at baseline and 12 and 24 months (n=2040). Multidisciplinary teams developed data-driven continuous quality-improvement activities. Asthma coordinators provided patient education and were active team members. RESULTS: Study children were predominantly Hispanic (77%) and black (11%); 60% were enrolled in Medicaid, and 9% were uninsured. Comparing results between baseline and the 21-month follow-up, significantly fewer families reported emergency-department visits (29.6% vs 9.3%), hospitalizations (10.9% vs 3.4%), frequent daytime symptoms (44.0% vs 11.7%), and missed school days (28.7% vs 13.6%); significantly more reported confidence in asthma management (70.6% vs 95.5%); and quality-of-life scores increased significantly for both children and caregivers (all P<.05). Cross-sectional data revealed significant clinic-wide improvements in symptom documentation, health care use, and review of action plans. CONCLUSIONS: On a larger scale, this approach realized impressive changes in provider clinical practice associated with major improvements in health outcomes. It holds great potential for significantly reducing asthma-related morbidity among low-income children.