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.

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.

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.

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.

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.

Evaluation of an arthritis communication campaign to promote physical activity in two cities.

Two communications campaigns (a "standard" campaign and an "enhanced" campaign linked to a physical activity opportunity) are evaluated to increase physical activity among people with arthritis. A pre- (n = 295) and post- (n = 806) intervention random sample telephone survey is conducted in two cities to measure the population effect of the campaigns. There are no changes in overall message awareness, beliefs, or behaviors related to physical activity and arthritis management in either city. Significant changes in message awareness and exercise frequency are found in subgroups in both cities, but the results do not show an advantage to enhancing the campaign with a local physical activity opportunity. An inability to saturate the market may partly explain why no overall significant increase in message awareness is found after the campaign. A high level of message awareness among respondents before the campaign may also have made it more difficult to affect measured outcomes.

CP violation in B{s} mixing from heavy Higgs boson exchange.

The anomalous dimuon charge asymmetry reported by the D0 Collaboration may be due to the tree-level exchange of some spin-0 particles that mediate CP violation in B{s}-B{s} meson mixing. We show that, for a range of couplings and masses, the heavy neutral states in a two-Higgs doublet model can generate a large charge asymmetry. This range is natural in "uplifted supersymmetry" and may enhance the B{-}→τν and B{s}→µ^{+}µ{-} decay rates. However, we point out that on general grounds the reported central value of the charge asymmetry requires new physics not only in B{s}-B{s} mixing but also in ΔB=1 transitions or in B{d}-B{d} mixing.

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.

Comparison of the level of residual coagulant activity in different cheese varieties.

The coagulant retained in cheese curd is a major contributor to proteolysis during ripening. The objective of this study was to quantify residual coagulant in 9 cheese varieties by measuring its activity on a synthetic heptapeptide (Pro-Thr-Glu-Phe-[NO2-Phe]-Arg-Leu) assayed using reversed-phase HPLC. The level of residual coagulant activity was highest in Camembert cheese, probably due to its low pH at whey drainage and the high moisture content of the cheese, followed in order by Feta=Port du Salut=Cheddar>Gouda>Emmental=Parmigiano Reggiano=low-moisture part-skim Mozzarella=Mozzarella di Bufala Campana. The high cooking temperature (50-54 degrees C) used during the manufacture of Emmental and Parmigiano Reggiano cheeses and the cooking and stretching step in hot water during the manufacture of Mozzarella cheese may be the reasons for the lowest residual coagulant activity in these cheeses. The level of residual coagulant activity was higher in Feta cheese made from milk concentrated by ultrafiltration than in conventional Feta.

Resisting social disenfranchisement: negotiating collective identities and everyday life with memory loss.

Being diagnosed with Alzheimer's disease marks a status passage formally legitimating the incorporation of forgetfulness into daily life. Based on interviews with diagnosed individuals in California, USA, we examine the mechanisms through which an Alzheimer's label is employed to justify forgetfulness, to manage social interactions, and to garner support when deemed necessary, while simultaneously combating the associated demented "master status." For diagnosed individuals, the transition from experience to symptom requires a redefinition of everyday forgetfulness into a medical problem. That is, respondents did not routinely perceive their experiences as pathological but rather were socialised into viewing age-related forgetfulness as symbolic of disease. Support groups sponsored by the Alzheimer's Association and memory clinics have a profound impact not only on the formation of group identity, but also on socialising forgetful individuals into diseased identities. The social disenfranchisement accompanying a diagnosis of dementia transforms forgetful older adults into "Alzheimer's patients," who must manage not only the manifestations of their disease, but also negotiate their interactions and identities. Their adaptation to the "symptoms" of forgetfulness and resultant social relations forms new interactional strategies whereby the diagnosis becomes a resource utilised to get through everyday life. Rather than being passive recipients of a diagnosis, respondents employ the label both as a resource, and as a phenomenon that needs to be incorporated into their self identity.

Commentary: Biases that affect the decision to conditionally release an insanity acquittee.

The care and management of hospitalized insanity acquittees can be quite challenging. As patients progress in treatment, clinicians must invariably address whether the patient is ready to be returned to the community, balancing the liberty interests of the acquittee with the protection of society. The process by which this determination is made is far from simple and involves review of clinical interview and collateral information, identification of indicators of outcome post-discharge, and the use of structured risk assessment instruments. The decision to release an acquittee conditionally is also influenced by an array of factors that emanate from within the clinician, within the institution, the mental health system, the courts, and the broader society. While such biases affect a clinician's objectivity, they are also a natural part of the evaluation process. Their identification is essential so that the degree to which such biases influence the conditional release decision can be more fully understood and addressed.

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.

High pressure-induced changes in bovine milk proteins: a review.

High pressure (HP)-induced changes in the proteins of bovine milk have become an area of considerable research interest in recent years; as a result, there is now a detailed understanding of the effects of HP on casein micelles and whey proteins. HP treatment at pressures >400 or >100 MPa denatures the two most abundant whey proteins, alpha-lactalbumin (alpha-la) and beta-lactoglobulin (beta-lg), respectively. The majority of denatured beta-lg in HP-treated milk associates with the casein micelles, although some denatured beta-lg remains in the serum phase or is attached to the milk fat globule membrane; HP-denatured alpha-la is also associated with the milk fat globules. Casein micelles are disrupted on treatment at pressures >200 MPa; the rate and extent of micellar disruption increases with pressure and is probably due to the increased solubility of calcium phosphate with increasing pressure. On prolonged treatment at 250-300 MPa, reassociation of micellar fragments occurs through hydrophobic bonding; this process does not occur at a pressure >300 MPa, leading to considerably smaller micelles in such milk. As a result of HP-induced changes, the size, number, hydration, composition and light-scattering properties of casein micelles in HP-treated milk differ considerably from those in untreated milk.

Aggregation of rennet-altered casein micelles at low temperatures.

The rennet-induced coagulation of bovine milk at 10 degrees C was investigated. The rate of change of absorbance at 600 nm was higher in milk renneted at 30 degrees C than that at 10 degrees C. The amount of casein sedimented on centrifuging skim milk at 5000g for 1 h at 10 degrees C increased with time after renneting. The viscosity of milk at 10 degrees C at low shear rates did not change significantly until 10 h after rennet addition, but it increased markedly after 20 h. Smaller particles in milk at 10 degrees C disappeared slowly over 36 h after rennet addition and aggregated into larger particles. These results suggested that casein micelles in milk aggregate at low temperatures. Reasons for the slow aggregation of milk renneted at 10 degrees C were investigated by inhibiting chymosin activity by pepstatin A. It is likely that beta-casein, or its hydrolysis, plays a role in aggregation of rennet-altered casein micelles at low temperatures.

Factors affecting the retention of rennet in cheese curd.

The coagulant retained in cheese curd is a major contributor to proteolysis during ripening. The objective of this study was to quantify the effects of several milk-related factors and parameters during cheese manufacture on the retention of coagulant in cheese curd. The amount of coagulant retained in curd was determined by its activity on a synthetic heptapeptide (Pro-Thr-Glu-Phe-[NO2-Phe]-Arg-Leu) using reversed-phase HPLC. The retention of chymosin in cheese curd increased significantly when the pH of milk was reduced at rennet addition below pH 6.1, the pH at whey drainage below pH 5.7, or the average casein micelle size in milk and when the ionic strength of milk was increased. The casein content of milk and the quantity of chymosin added to milk had no significant effect on the retention of chymosin in curd; the quantity of coagulant bound per gram of casein remained unchanged.

Timely follow-up among multicultural women with abnormal mammograms.

OBJECTIVE: To examine factors influencing time from screening to final diagnosis among multicultural women with abnormal mammograms using the precede-proceed model. METHODS: Staff of 58 clinics and a sample of 436 women served by these clinics were interviewed and their medical records examined. RESULTS: Longer duration from screening to diagnosis was associated with speaking Spanish and having clinic staff make appointments. Ease of access to health care, provision of early morning screening services and higher levels of patient anxiety shortened the time to diagnosis. CONCLUSION: The precede-proceed model is useful in delineating personal and structural factors that affect timely diagnosis.