Food and water intake in rats after transections of fibers en passage in the tegmentum

A 145 micron diameter wire knife was used to transect fibers en passage in ventral, medial, and dorsal aspects of the tegmentum. Data from 74 rats with bilaterally symmetric cuts indicate that the interruption of fibers which course through the central region of the tegmentum result in hyperdipsia. Three distinct syndromes were observed: (a) extreme hyperdipsia beginning on the first or second day after surgery and persisting for 4–6 days; (b) a smaller increase in water intake beginning on the first or second day after surgery and persisting for the duration of the experiment; and (c) normal or subnormal water intake for several days after surgery followed by a sharp increase which persisted for 4–6 days. Cuts through the dorsolateral tegmentum consistently produced hyperphagia in male rats maintained on a dry pellet diet. The magnitude of the effects was comparable to that seen in male rats after ventromedial hypothalamic (VMH) lesions. These cuts, as well as others which did not result in hyperphagia, abolished the normal feeding responses to 2-deoxy-D-glucose (2-DG) without affecting the feeding response to insulin. Some of our cuts produced significant overeating but no commensurate weight gain, suggesting that metabolic disturbances may have occurred. Knife cuts of comparable size through the ventral third of the tegmentum, the pons, or the ventral aspects of the central grey, failed to affect either food or water intake reliably. Histological evidence of minimal direct damage to cellular components of the region of the behaviorally effective cuts and their extensive rostro-caudal distribution indicate that direct damage to perikarya of tegmental neurons probably is not responsible for the effects of the cuts.     

Attack stress induces gastrointestinal pathology in domesticated rats

An established group of domesticated rats readily attached unfamiliar male conspecifics. The intruder animals developed gastric ulcers and mucosal degeneration of the small intestine within 21 hr. This attack stress is the first example of social behavior inducing the physiologic and/or psychologic precursors of gastrointestinal pathology in animals.     

Konservative Dermatologie und ihre Beziehung zur Kosmetik

Ohne Zusammenfassung     

The effects of concentrated barley beta-glucan on blood lipids in a population of hypercholesterolaemic men and women

Barley, like oats, is a rich source of the soluble fibre beta-glucan, which has been shown to significantly lower LDL-cholesterol (LDL-C). However, barley foods have been less widely studied. Therefore, we evaluated the LDL-C-lowering effect of a concentrated barley beta-glucan (BBG) extract as a vehicle to deliver this potential health benefit of barley. In a 10-week blinded controlled study, subjects were randomized to one of four treatment groups or control. Treatment groups included either high molecular weight (HMW) or low molecular weight (LMW) BBG at both 3 and 5 g doses. Treatment was delivered twice per day with meals in the form of two functional food products: a ready-to-eat cereal and a reduced-calorie fruit juice beverage. Levels of total cholesterol, LDL-C, HDL-cholesterol (HDL-C), and TAG were determined at baseline and after 6 weeks of treatment. The study group comprised 155 subjects. All treatments were well tolerated and after 6 weeks of treatment the mean LDL-C levels fell by 15 % in the 5 g HMW group, 13 % in the 5 g LMW group and 9 % in both the 3 g/d groups, versus baseline. Similar results were observed for total cholesterol. HDL-C levels were unchanged by treatment. Concentrated BBG significantly improves LDL-C and total cholesterol among moderately dyslipidaemic subjects. Food products containing concentrated BBG should be considered an effective option for improving blood lipids.     

Mutations in RNU7-1 Weaken Secondary RNA Structure,Induce MCP-1 and CXCL10 in CSF,and Result in Aicardi-Goutières Syndrome with Severe End-Organ Involvement

Background

Aicardi-Goutières syndrome (AGS) is a type I interferonopathy usually characterized by early-onset neurologic regression. Biallelic mutations in LSM11 and RNU7-1, components of the U7 small nuclear ribonucleoprotein (snRNP) complex, have been identified in a limited number of genetically unexplained AGS cases. Impairment of U7 snRNP function results in misprocessing of replication-dependent histone (RDH) pre-mRNA and disturbance of histone occupancy of nuclear DNA, ultimately driving cGAS-dependent type I interferon (IFN-I) release.

Objective

We performed a clinical, genetic, and immunological workup of 3 unrelated patients with uncharacterized AGS.

Methods

Whole exome sequencing (WES) and targeted Sanger sequencing of RNU7-1 were performed. Primary fibroblasts were used for mechanistic studies. IFN-I signature and STAT1/2 phosphorylation were assessed in peripheral blood. Cytokines were profiled on serum and cerebrospinal fluid (CSF). Histopathology was examined on brain and kidney tissue.

Results

Sequencing revealed compound heterozygous RNU7-1 mutations, resulting in impaired RDH pre-mRNA processing. The 3′ stem-loop mutations reduced stability of the secondary U7 snRNA structure. A discrete IFN-I signature in peripheral blood was paralleled by MCP-1 (CCL2) and CXCL10 upregulation in CSF. Histopathological analysis of the kidney showed thrombotic microangiopathy. We observed dysregulated STAT phosphorylation upon cytokine stimulation. Clinical overview of all reported patients with RNU7-1-related disease revealed high mortality and high incidence of organ involvement compared to other AGS genotypes.

Conclusions

Targeted RNU7-1 sequencing is recommended in genetically unexplained AGS cases. CSF cytokine profiling represents an additional diagnostic tool to identify aberrant IFN-I signaling. Clinical follow-up of RNU7-1-mutated patients should include screening for severe end-organ involvement including liver disease and nephropathy.

     

Postweaning social experience and adult aggression in rats

One group of male rats was reared continuously in small, stable colonies of three animals each during a ten-week period beginning when they were 46 days old. A second group of animals was also reared in small groups of three animals each but membership within these colonies was randomly changed at weekly intervals. Thereafter, all subjects were housed in individual cages. A 24 hr test of the subjects' aggression toward an unfamiliar male conspecific at 130-133 days of age indicated that only the heaviest animal in each of the stable colonies was aggressive. In contrast, all animals in the random-composition group were aggressive toward intruders. Scores on a second test of intruder-directed aggression administered when the subjects were nine months old were significantly related to scores on the first aggression test. Subtle variations in social experience during development are critical in establishing long-term patterns of aggression toward conspecifics in laboratory rats.     

The influence of clinical assessment (including age) and geriatric assessment on treatment decisions in older patients with cancer

ObjectivesThe aim of this prospective study in older patients with cancer was to evaluate how clinical assessment (including age) determines the physician's treatment decisions, and how geriatric assessment (GA) further influences these decisions.Patients and MethodsPatients aged ≥ 70 years old with cancer were included if a new therapy was considered. All patients underwent a GA and results were communicated to the treating physician. After the final treatment decision, a predefined questionnaire was completed by the physician.ResultsIn total, 937 patients with median age of 76 years old were included. A total of 902 (96.3%) questionnaires were completed by the treating physicians. In 381/902 patients (42.2%) clinical assessment led to a different treatment decision compared to younger patients without co-morbidities. This difference was most prominent for chemotherapy/targeted therapy decisions. In 505/902 cases (56%) the treating physician consulted GA results before the final treatment decision. In these patients, the treatment decision was influenced by clinical assessment in 44.2%. In 31/505 patients (6.1%) the GA further influenced treatment, mostly concerning chemotherapy/targeted therapy. In eight patients GA influenced the physician to choose a more aggressive chemotherapy.ConclusionsPhysicians use different treatment regimens in older versus younger patients, based on clinical assessment, including age. GA results further influence treatment decisions in a minority of patients and may trigger the use of less aggressive as well as more aggressive treatments. GA information is not always utilized by oncologists, indicating the need for better education and sensitization.