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Noting that peace concerns justice and respect for everyone's basic rights, this booklet examines how children, teachers, and parents understand peace, and how they can learn together to respect each other and create peaceful environments for young children. Following introductory remarks, it describes the visions of children, parents, and teachers from the Swanston Street Children's Center in Australia for a peaceful and respectful community and presents the program philosophy. The booklet then lists steps taken at the Center whenever an issue or question about peace and respect is considered. The use of gallery displays to share concerns and differences is also discussed. Next, suggestions are provided for practitioners to build a peaceful and respectful community via dialogue through the arts or to create peaceful places for young children. The booklet then discusses children's right to a safe and secure childhood and the tradition of concern with peace and children's rights within the early childhood community. Ways surroundings can promote peace in children are also listed. Following this, children's understanding of peace at various ages is then detailed. The booklet concludes with suggestions for building policies for peace in children's services and a list of principles to guide policy development. (Contains 10 references and a list of Internet resources.) (KB)

Intraepidermal nerve fiber loss (IENF) is present in many human diseases and is strongly associated with chronic pain. Understanding the mechanisms underlying IENF loss will provide insight into better therapeutic options and improved peripheral nerve health with patients experiencing chronic pain. The reactive dicarbonyl methylglyoxal (MGO) is elevated in chronic pain conditions associated with metabolic dysfunction. We tested how MGO impacts pain and epidermal axon health in various rodent models. A single intraperitoneal injection of MGO (750ng) into C57Bl/6 mice induced acute pain behaviors and long-term mechanical allodynia. Surprisingly, MGO injection significantly decreased IENF density (Control: 55 +3.5, MGO: 40+2.6) in the hind paw. We know consuming a ketogenic diet for one week before an MGO injection prevents MGO-induced pain. Here, we show that seven days of a ketogenic diet prevents IENF loss and can stimulate the regeneration of MGO-damaged axons. Next, we utilized a genetic mouse model (BALB/cByJ) overexpressing glyoxylase 1, an enzyme that breaks down MGO. BALB/cByJ mice injected with MGO had no changes in IENF density. SARM1 is an enzyme involved in axon degeneration. MGO injection in SARM1 null mutant mice did not lead to decreased IENF density. We show a ketogenic diet, overexpression of Glo1, or knockdown of SARM1 in mice combats these effects. We know MGO is a noxious metabolite leading to pain, and we add new evidence that MGO contributes to IENF loss. These findings identify an important link between pain and IENF loss, providing a new tool to investigate this relationship. Grants to be cited: R01NS043314-17 and 5P20GM103418.

•Elderly presented moderate swallowing impairment for consistencies.•There was no difference between clinical and instrumental evaluation.•The assessment of swallowing in the elderly must consider physiological changes.

17β-estradiol (E2)-induced signaling and control of estrogen receptor (ER)α degradation both play a major role in breast cancer cell proliferation. We recently reported the involvement of lysosomal function in both E2-dependent ERα breakdown and E2-induced cell proliferation and thus hypothesized a role for endocytic proteins in ERα signaling. An small interfering RNA screen identified proteins that regulate intracellular endocytic traffic and whose silencing alters E2-induced ERα degradation. One such protein was the clathrin heavy chain (CHC), whose role in E2:ERα signaling to cell proliferation is unknown. Here, we show that CHC physically interacts with ERα in the cytoplasm of breast cancer cells and regulates E2-induced cell proliferation. Surprisingly, the CHC:ERα interaction is required to sustain E2 signaling but is dispensable for ERα degradation. Our data also demonstrate that many membrane trafficking proteins contribute to the regulation of ERα degradation, thus unraveling the contribution of endocytic proteins in E2:ERα signaling.

Research performed during the last decades clearly demonstrated that the endocytic pathways act as a fine spatio-temporal regulator of the cell signaling. It is now accepted that the principal sorting signal for most of the endocytic cargos is the post-translational modification with ubiquitin (Ub). Indeed, nonproteolytic ubiquitination of the cargo protein (e.g., monoubiquitination) triggers its internalization and its incorporation into specific endocytic vesicles through which cargo is destined either to lysosomes for degradation, to plasma membrane for recycling or to other intracellular fates. Thus, cargo ubiquitination and intracellular trafficking are intrinsically connected and contribute to the regulation of many cellular functions. The nuclear receptor estrogen receptor (ER) regulates the physiological effects triggered by 17-estradiol (E2). It is now clear that the ER drives the nuclear (gene transcription) and extra-nuclear (activation of signaling kinase cascades) E2-dependent effects because it has a wide intracellular localization both in the nucleus, in the cytoplasm and at the plasma membrane of the E2 target cells. Remarkably, many laboratories, including our own, have reported that ER is monoubiquitinated and receptor monoubiquitination is required for the receptor- dependent regulation of E2 cellular effects and that an endocytic intracellular trafficking of the ER can occur. Thus, this evidence suggests the possibility of a Ub-based endo-membrane shuttling of the activated ER for the regulation of the E2-triggered effects. In light of these novel discoveries, this review will focus on the role of the endocytic trafficking pathways in E2:ER signaling by particularly highlighting how endocytic proteins and non-degradative ubiquitination could impact on the modulation of E2-dependent physiological processes.

Highly Expressed in Cancer protein 1 (Hec1) is a subunit of the Ndc80 complex, a constituent of the mitotic kinetochore. HEC1has been shown to be over-expressed in many cancers, suggesting that HEC1up-regulation is involved in the generation and/or maintenance of the tumour phenotype. However, the regulation of Hec1 expression in normal and tumour cells and the molecular alterations promoting accumulation of this protein in cancer cells are still unknown. Here we show that elevated Hec1 protein levels are characteristic of transformed cell lines of different origins and that kinetochore recruitment of this protein is also increased in cancer cell lines in comparison with normal human cells. Using different cell synchronization strategies, Hec1 expression was found to be tightly regulated during the cell cycle in both normal and cancer cells. A limited proteasome-dependent degradation of Hec1 cellular content was observed at mitotic exit, with no evident differences between normal and cancer cells. Interestingly, increased expression of HEC1mRNA and Hec1 protein was observed after transient silencing of the retinoblastoma gene  by siRNA or following microRNA-mediated permanent depletion of the retinoblastoma protein in HCT116 cells. Our data provide evidencefor a functional link between Hec1 expression and the pRb pathway. These observations suggest that disruption of pRb function may lead to chromosome segregation errors and mitotic defects through Hec1 overexpression. This may importantly contribute to aneuploidy and chromosomal instability in Rb-defective cancer cells.

Restoration of arm function in the stroke patient has two objectives: (1) to facilitate and exploit natural neurologic recovery to achieve functional gains, and (2) to avoid complications that might limit functional recovery. Disturbances in motor control, alterations in tone, abnormalities in sensation, and derangements in autonomic activity lead to a number of secondary impairments in the hemiplegic shoulder: glenohumeral subluxation, frozen shoulder, impingement syndromes, rotator cuff lesions, brachial plexus neuropathies, and reflex sympathetic dystrophy. This article discusses the causes, diagnosis, prevention, and treatment of each of these conditions.

No formal recommendations exist as to age of cessation of colon cancer screening with flexible sigmoidoscopy. AIM: To determine the relationship between age of patient at time of screening and presence of colonic pathology. MATERIAL AND METHODS: All screening flexible sigmoidoscopies at our institution performed between January 1, and November 10 1999 were reviewed. Patients were stratitfied according to age and need for subsequent colonoscopy. Pathology reports for all patients who underwent polypectomy were then reviewed for presence or absence of significant pathology defined as tubular adenoma, tubulovillous adenoma, or adenocarcinoma. No significant pathology (NSP) was defined as not requiring colonoscopy after screening flexible sigmoidoscopy, or normal colonoscopy. RESULTS: Of 1099 total flexible sigmoidoscopies performed, 656 (59.7%) were for routine screening. Of these, 106 (16.2%) required subsequent colonoscopy. The rate of finding NSP in the different age groups were as follows: =44:10/10 (100%); 45-49: 23/25 (92%); 50-54: 136/147 (92.5%); 55-59: 107/120 (89.1%); 60-64: 105/124 (84.7%); 65-69: 101/124 (81.5%); 70- 74:56/65 (86.2%); =75: 37/41 (90.2%). When age is plotted against NSP rates, a “U” shaped curve emerges. The nadir of this curve represents the point of most frequent pathology. Stopping screening at a point significantly far enough to the right of the nadir so as not to exclude pateints with significant pathology, appears optimal. Age 75 represents such a point, based on our data. CONCLUSIONS: Screening flexible sigmoidoscopy may not be indicated over age 75 based on the low incidence of significant pathology at and beyond this age.