Amyloid-β aggregates activate peripheral monocytes in mild cognitive impairment

\ua9 The Author(s) 2024. The peripheral immune system is important in neurodegenerative diseases, both in protecting and inflaming the brain, but the underlying mechanisms remain elusive. Alzheimer’s Disease is commonly preceded by a prodromal period. Here, we report the presence of large Aβ aggregates in plasma from patients with mild cognitive impairment (n = 38). The aggregates are associated with low level Alzheimer’s Disease-like brain pathology as observed by 11C-PiB PET and 18F-FTP PET and lowered CD18-rich monocytes. We characterize complement receptor 4 as a strong binder of amyloids and show Aβ aggregates are preferentially phagocytosed and stimulate lysosomal activity through this receptor in stem cell-derived microglia. KIM127 integrin activation in monocytes promotes size selective phagocytosis of Aβ. Hydrodynamic calculations suggest Aβ aggregates associate with vessel walls of the cortical capillaries. In turn, we hypothesize aggregates may provide an adhesion substrate for recruiting CD18-rich monocytes into the cortex. Our results support a role for complement receptor 4 in regulating amyloid homeostasis

State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy

Evidence based practice guidelines for the nutritional management of cancer cachexia and chronic kidney disease

The purpose of these guidelines is to provide dietitians in Australia with a user-friendly summary of the evidence to support the nutritional management of adult patients with cancer cachexia. This best available evidence is presented and used as a basis for providing recommendations about clinical practice.\ud \ud The clinical questions were as follows:\ud • How should patients be identified for referral to the dietitian in order to maximise nutritional intervention opportunities?\ud • How should nutritional status be assessed?\ud • What are the goals of nutrition intervention for patients with cancer cachexia?\ud • What is the nutrition prescription to achieve these goals?\ud • Should eicosapentaenoic acid be included in the prescription?\ud • What are effective methods of implementation to ensure positive outcomes?\ud • Does nutrition intervention improve outcomes in patients with cancer cachexia?\ud \ud This document is a general guide to appropriate practice to be followed only subject to the dietitian’s judgement in each individual case. The guidelines are designed to provide information to assist decision-making and are based on the best information available at the date of compilation. The guidelines recommend intensive nutrition therapy. This has potential resource implications that may include additional staff, change to staff roles and increased use of high/protein energy supplements if they are considered. Therefore, in applying the guidelines these potential organisational and cost\ud barriers need to be considered. These guidelines for practice are provided with the express understanding that they do not establish or specify particular standards\ud of care, whether legal, medical or other

In situ Characterisation of Practical Heterogeneous Catalysts

In situ methods are considered as a curiosity within the standard methodology of practical catalyst characterization. The methods are not commercially available and need to be adapted and validated for each specific problem. The great advantage of these methods is, however, that they deliver immediately relevant characteristics of the working state of a heterogeneous catalyst and allow justified structure-function relations to be deduced. To achieve this it is essential that the experiments are planned and conducted in such away that the proven to be active state of the catalyst is investigated. This can only be ascertained if simultaneous kinetic and spectroscopic data are acquired. The contribution lists a selection of methods with their main characteristics that allows to choose from the wide spectrum of information those that are most relevant for the given problem. A tabulated selection of case studies from the literature gives some insight in the current practice