Basement membrane charge in human glomerular disease

Fixed anionic charges in the mammalian glomerulus, on both the basement membrane and the epithelial cell foot processes, are believed to form an important part of the glomerular filtration barrier. There is good evidence that their loss causes proteinuria. The charges can be visualized ultrastructurally using cationic dyes, but the requirement of these techniques for perfusion or immersion of fresh tissue has largely confined such studies to experimental models. We have extended the widely used polyethyleneimine technique, to study the charge of glomerular basement membranes in human tissue reprocessed out of paraffin blocks up to 10 years old. We studied selected cases of glomerular disease, where the diagnosis was not in any doubt. In the majority of diseases studied, a continuous charge layer persisted despite severe abnormalities of the basement membrane. Two exceptions were found. In amyloidosis, accumulation of fibrils was associated with a considerable decrease or loss of stainable basement membrane charge. In S.L.E., numerous small defects in the charge layer were noted. The persistence of charge is contrary to reported findings in several animal models of glomerular disease, including puromycin nephrosis, Heymann nephritis and streptozotocin diabetes. Although this method is not subject to precise quantitative analysis, we conclude that in the majority of cases, proteinuria in man is not caused by an extensive loss of glomerular basement membrane anionic charge.     

Amino acid uptake required for long-term memory formation

α-Amino-iso-butyrate (AIB) inhibits long-term, protein synthesis-dependent memory formation by reducing labelled leucine uptake in vivo without affecting leucine incorporation into protein. Unlike the antibiotic cycloheximide, AIB does not block long-term memory formation through inhibition of protein synthesis per se. The behavioural effect of AIB is restricted to times of administration between 5 min before and 5 min after learning a single trial passive avoidance task by day-old chickens. It is concluded that (1) AIB competes with normal amino acids for uptake into cells, and (2) the uptake of amino acids for protein synthesis specific to long-term memory formation takes place in the first few minutes following learning.     

Multiple Micronutrients,Including Zinc,Selenium and Iron,Are Positively Associated with Anemia in New Zealand Aged Care Residents

Anemia is a significant comorbidity for older adults not fully attributable to iron deficiency. Low-grade inflammation and other micronutrient deficiencies also contribute. This cross-sectional study examined the relationships between nutrient and non-nutrient factors with hemoglobin and anemia in 285 residents (>65 years) of 16 New Zealand aged-care facilities. Blood samples were analyzed for hemoglobin, ferritin, sTfR, hepcidin, zinc, selenium, and interleukin-6 (IL-6), (with ferritin, sTfR, zinc and selenium adjusted for inflammation). Linear regression models examined the relationships between micronutrient biomarkers (iron, zinc, selenium, vitamin B-12 and D), age, sex, and health factors with hemoglobin. Thirty-two percent of participants exhibited anemia, although <2% had either depleted iron stores or iron deficiency. Plasma zinc and selenium deficiencies were present in 72% and 38% of participants, respectively. Plasma zinc and total body iron (TBI) were positively associated (p < 0.05) with hemoglobin, while gastric acid suppressing medications, hepcidin, and interleukin-6 were inversely associated. These relationships were maintained after the application of anemia cut-offs. These findings emphasize the importance of considering multiple micronutrient deficiencies as risk factors for anemia.     

Former Foster System Youth: Perspectives on Transitional Supports and Programs

The Journal of Behavioral Health Services & Research - Youth aging out of the foster care system have well-documented challenges when transitioning to adulthood. Multiple transition services...     

Communication Tools to Support Advance Care Planning and Hospital Care During the COVID-19 Pandemic: A Design Process

The COVID-19 pandemic has exposed the medical and social vulnerability of an unprecedented number of people. Consequently, there has never been a more important time for clinicians to engage patients in advance care planning (ACP) discussions about their goals, values, and preferences in the event of critical illness. An evidence-based communication tool—the Serious Illness Conversation Guide—was adapted to address COVID-related ACP challenges using a user-centered design process: convening relevant experts to propose initial guide adaptations; soliciting feedback from key clinical stakeholders from multiple disciplines and geographic regions; and iteratively testing language with patient actors. With feedback focused on sharing risk about COVID-19–related critical illness, recommendations for treatment decisions, and use of person-centered language, the team also developed conversation guides for inpatient and outpatient use. These tools consist of open-ended questions to elicit perception of risk, goals, and care preferences in the event of critical illness, and language to convey prognostic uncertainty. To support use of these tools, publicly available implementation materials were also developed for clinicians to effectively engage high-risk patients and overcome challenges related to the changed communication context, including video demonstrations, telehealth communication tips, and step-by-step approaches to identifying high-risk patients and documenting conversation findings in the electronic health record. Well-designed communication tools and implementation strategies can equip clinicians to foster connection with patients and promote shared decision making. Although not an antidote to this crisis, such high-quality ACP may be one of the most powerful tools we have to prevent or ameliorate suffering due to COVID-19.     

The Sydney AFF Score: A Simple Tool to Distinguish Females Presenting With Atypical Femur Fractures Versus Typical Femur Fractures

Atypical femur fractures (AFF) are a rare but serious complication of long-term bisphosphonate use. Although clearly defined by ASBMR criteria, a proportion of patients with AFFs may go unrecognized and the use of qualitative fracture criteria may lead to uncertainty in AFF diagnosis, with significant therapeutic implications. A score that rapidly and accurately identifies AFFs among subtrochanteric femur fractures using quantitative, measurable parameters is needed. In a retrospective cohort of 110 female patients presenting with AFFs or typical femur fractures (TFFs), multiple logistic regression and decision tree analysis were used to develop the Sydney AFF score. This score, based on demographic and femoral geometry variables, uses three dichotomized independent predictors and adds one point for each: (age ≤80 years) + (femoral neck width <37 mm) + (lateral cortical width at lesser trochanter ≥5 mm), (score, 0 to 3). In an independent validation set of 53 female patients at a different centre in Sydney, a score ≥2 demonstrated 73.3% sensitivity and 69.6% specificity for AFF (area under the receiver-operating characteristic curve [AUC] 0.775, SE 0.063) and remained independently associated with AFF after adjustment for bisphosphonate use. The Sydney AFF score provides a quantitative means of flagging female patients with atraumatic femur fractures who have sustained an AFF as opposed to a TFF. This distinction has clear management implications and may augment current ASBMR diagnostic criteria. © 2021 American Society for Bone and Mineral Research (ASBMR).