Amyloid and tau in the brain in sporadic Alzheimer's disease: defining the chicken and the egg

In the October 2013 issue of Acta Neuropathologica there were three very interesting articles on: Amyloid or tau: the chicken or the egg? In the first article, David Mann and John Hardy argued that the deposition of aggregated amyloid β (Aβ) protein in the brain is a primary driving force behind the pathogenesis of Alzheimer’s disease with tau pathology following as a consequential or at least a secondary event. In the communication that followed, Braak and Del Tredici presented the contrary argument with accumulation of tau protein as the primary event in sporadic Alzheimer’s disease. Attems and Jellinger questioned the concept of a chicken and egg and suggested that the majority of cases of age-associated dementia are not caused by one single primary pathological mechanism

An ongoing case-control study to evaluate the NHS Bowel Cancer Screening Programme

© 2014 Massat et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

The evolutionary origins of ritualized acoustic signals in caterpillars

Animal communication signals can be highly elaborate, and researchers have long sought explanations for their evolutionary origins. For example, how did signals such as the tail-fan display of a peacock, a firefly flash or a wolf howl evolve? Animal communication theory holds that many signals evolved from non-signalling behaviours through the process of ritualization. Empirical evidence for ritualization is limited, as it is necessary to examine living relatives with varying degrees of signal evolution within a phylogenetic framework. We examine the origins of vibratory territorial signals in caterpillars using comparative and molecular phylogenetic methods. We show that a highly ritualized vibratory signal—anal scraping—originated from a locomotory behaviour—walking. Furthermore, comparative behavioural analysis supports the hypothesis that ritualized vibratory signals derive from physical fighting behaviours. Thus, contestants signal their opponents to avoid the cost of fighting. Our study provides experimental evidence for the origins of a complex communication signal, through the process of ritualization

Room temperature mid-IR single photon spectral imaging

Spectral imaging and detection of mid-infrared (mid-IR) wavelengths are emerging as an enabling technology of great technical and scientific interest; primarily because important chemical compounds display unique and strong mid-IR spectral fingerprints revealing valuable chemical information. While modern Quantum cascade lasers have evolved as ideal coherent mid-IR excitation sources, simple, low noise, room temperature detectors and imaging systems still lag behind. We address this need presenting a novel, field-deployable, upconversion system for sensitive, 2-D, mid-IR spectral imaging. Measured room temperature dark noise is 0.2 photons/spatial element/second, which is a billion times below the dark noise level of cryogenically cooled InSb cameras. Single photon imaging and up to 200 x 100 spatial elements resolution is obtained reaching record high continuous wave quantum efficiency of about 20 % for polarized incoherent light at 3 \mum. The proposed method is relevant for existing and new mid-IR applications like gas analysis and medical diagnostics

Barriers to colorectal cancer screening in community health centers: A qualitative study

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer screening rates are low among disadvantaged patients; few studies have explored barriers to screening in community health centers. The purpose of this study was to describe barriers to/facilitators of colorectal cancer screening among diverse patients served by community health centers.</p> <p>Methods</p> <p>We identified twenty-three outpatients who were eligible for colorectal cancer screening and their 10 primary care physicians. Using in-depth semi-structured interviews, we asked patients to describe factors influencing their screening decisions. For each unscreened patient, we asked his or her physician to describe barriers to screening. We conducted patient interviews in English (n = 8), Spanish (n = 2), Portuguese (n = 5), Portuguese Creole (n = 1), and Haitian Creole (n = 7). We audiotaped and transcribed the interviews, and then identified major themes in the interviews.</p> <p>Results</p> <p>Four themes emerged: 1) Unscreened patients cited lack of trust in doctors as a barrier to screening whereas few physicians identified this barrier; 2) Unscreened patients identified lack of symptoms as the reason they had not been screened; 3) A doctor's recommendation, or lack thereof, significantly influenced patients' decisions to be screened; 4) Patients, but not their physicians, cited fatalistic views about cancer as a barrier. Conversely, physicians identified competing priorities, such as psychosocial stressors or comorbid medical illness, as barriers to screening. In this culturally diverse group of patients seen at community health centers, similar barriers to screening were reported by patients of different backgrounds, but physicians perceived other factors as more important.</p> <p>Conclusion</p> <p>Further study of these barriers is warranted.</p

Mast Cells Express 11 beta-hydroxysteroid Dehydrogenase Type 1: A Role in Restraining Mast Cell Degranulation:a role in restraining mast cell degranulation

Mast cells are key initiators of allergic, anaphylactic and inflammatory reactions, producing mediators that affect vascular permeability, angiogenesis and fibrosis. Glucocorticoid pharmacotherapy reduces mast cell number, maturation and activation but effects at physiological levels are unknown. Within cells, glucocorticoid concentration is modulated by the 11β-hydroxysteroid dehydrogenases (11β-HSDs). Here we show expression and activity of 11β-HSD1, but not 11β-HSD2, in mouse mast cells with 11β-HSD activity only in the keto-reductase direction, regenerating active glucocorticoids (cortisol, corticosterone) from inert substrates (cortisone, 11-dehydrocorticosterone). Mast cells from 11β-HSD1-deficient mice show ultrastructural evidence of increased activation, including piecemeal degranulation and have a reduced threshold for IgG immune complex-induced mast cell degranulation. Consistent with reduced intracellular glucocorticoid action in mast cells, levels of carboxypeptidase A3 mRNA, a glucocorticoid-inducible mast cell-specific transcript, are lower in peritoneal cells from 11β-HSD1-deficient than control mice. These findings suggest that 11β-HSD1-generated glucocorticoids may tonically restrain mast cell degranulation, potentially influencing allergic, anaphylactic and inflammatory responses

Pharmaceutical research in paediatric populations and the new EU Paediatric Legislation: an industry perspective

A large proportion of medicines used in children are prescribed off-label, and children have often been denied access to new or innovative medications. Because such situation is unethical, the need to obtain paediatric information for medicines used in children seems nowadays a matter of consensus on a global basis. Based on this, it was clear in EU, like what has happened in the US, that there was a need for a legal obligation for Pharmaceutical Companies to perform studies. This new European Paediatric Regulation that entered into force in 2007 opens a new era of European drug regulatory history and will offer a major opportunity to improve children's health through advancements in research by providing a new framework for evaluating the efficacy and safety of medicines for children. But, paediatric development remains challenging and the hurdles of conducting research in paediatric population are numerous. The article presents the new European Paediatric Regulation, illustrates its rationale through paediatric psychopharmacology, and discusses some of its consequences on paediatric research from an industry perspective. Recommendations for further international collaboration are also suggested to make global paediatric development plans

Surgical management and outcome of newly diagnosed glioblastoma without contrast enhancement (<i>low-grade appearance</i>):a report of the RANO <i>resect </i>group

BackgroundResection of the contrast-enhancing (CE) tumor represents the standard of care in newly diagnosed glioblastoma. However, some tumors ultimately diagnosed as glioblastoma lack contrast enhancement and have a ‘low-grade appearance’ on imaging (non-CE glioblastoma). We aimed to (a) volumetrically define the value of non-CE tumor resection in the absence of contrast enhancement, and to (b) delineate outcome differences between glioblastoma patients with and without contrast enhancement.MethodsThe RANO resect group retrospectively compiled a global, eight-center cohort of patients with newly diagnosed glioblastoma per WHO 2021 classification. The associations between postoperative tumor volumes and outcome were analyzed. Propensity score-matched analyses were constructed to compare glioblastomas with and without contrast enhancement.ResultsAmong 1323 newly diagnosed IDH-wildtype glioblastomas, we identified 98 patients (7.4%) without contrast enhancement. In such patients, smaller postoperative tumor volumes were associated with more favorable outcome. There was an exponential increase in risk for death with larger residual non-CE tumor. Accordingly, extensive resection was associated with improved survival compared to lesion biopsy. These findings were retained on a multivariable analysis adjusting for demographic and clinical markers. Compared to CE glioblastoma, patients with non-CE glioblastoma had a more favorable clinical profile and superior outcome as confirmed in propensity score analyses by matching the patients with non-CE glioblastoma to patients with CE glioblastoma using a large set of clinical variables.ConclusionsThe absence of contrast enhancement characterizes a less aggressive clinical phenotype of IDH-wildtype glioblastomas. Maximal resection of non-CE tumors has prognostic implications and translates into favorable outcome