Impaired spatial representation in CA1 after lesion of direct input from entorhinal cortex

Place-specific firing in the hippocampus is determined by path integration-based spatial representations in the grid-cell network of the medial entorhinal cortex. Output from this network is conveyed directly to CA1 of the hippocampus by projections from principal neurons in layer III, but also indirectly by axons from layer II to the dentate gyrus and CA3. The direct pathway is sufficient for spatial firing in CA1, but it is not known whether similar firing can also be supported by the input from CA3. To test this possibility, we made selective lesions in layer III of medial entorhinal cortex by local infusion of the neurotoxin gamma-acetylenic GABA. Firing fields in CA1 became larger and more dispersed after cell loss in layer III, whereas CA3 cells, which receive layer II input, still had sharp firing fields. Thus, the direct projection is necessary for precise spatial firing in the CA1 place cell population.     

Rationale and design of EXPLORE: a randomized, prospective, multicenter trial investigating the impact of recanalization of a chronic total occlusion on left ventricular function in patients after primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

Background

Hypothyroidism is a prevalent endocrine condition. Individuals with this disease are commonly managed through supplementation with synthetic thyroid hormone, with the aim of alleviating symptoms and restoring normal thyroid stimulating hormone levels. Generally this management strategy is effective and well tolerated. However, there is research to suggest that a significant proportion of hypothyroid sufferers are being inadequately managed. Furthermore, hypothyroid patients are more likely to have a decreased sense of well-being and more commonly experience constitutional and neuropsychiatric complaints, even with pharmacological intervention. The current management of hypothyroidism follows a biomedical model. Little consideration has been given to a biopsychosocial approach to this condition. Within the chiropractic profession there is growing support for the use of a biopsychosocial-based intervention called Neuro-Emotional Technique (NET) for this population.

Methods/Design

A placebo-controlled, single-blinded, randomised clinical pilot-trial has been designed to assess the influence of Neuro-Emotional Technique on a population with primary overt hypothyroidism. A sample of 102 adults (≥18 years) who meet the inclusion criteria will be randomised to either a treatment group or a placebo group. Each group will receive ten treatments (NET or placebo) over a six week period, and will be monitored for six months. The primary outcome will involve the measurement of depression using the Depression, Anxiety and Stress Scale (DASS). The secondary outcome measures to be used are; serum thyroid stimulating hormone, serum free-thyroxine, serum free-triiodothyronine, serum thyroid peroxidase auto-antibodies, serum thyroglobulin auto-antibodies as well as the measurement of functional health and well-being using the Short-Form-36 Version 2. The emotional states of anxiety and stress will be measured using the DASS. Self-measurement of basal heart rate and basal temperature will also be included among the secondary outcome measures. The primary and secondary measures will be obtained at commencement, six weeks and six months. Measures of basal heart rate and basal temperature will be obtained daily for the six month trial period, with recording to commence one week prior to the intervention.

Discussion

The study will provide information on the influence of NET when added to existing management regimens in individuals with primary overt hypothyroidism.

Trial Registration

ANZCTR Number: 12607000040460     

Effect of low-level laser (Ga-Al-As 655 nm) on skeletal muscle fatigue induced by electrical stimulation in rats.

We investigated whether low-level laser therapy (LLLT) can reduce muscular fatigue during tetanic contractions in rats. Thirty-two male Wistar rats were divided into four groups receiving either one of three different LLLT doses (0.5, 1.0, and 2.5 J/cm2) or a no-treatment control group. Electrical stimulation was used to induce six tetanic muscle contractions in the tibial anterior muscle. Contractions were stopped when the muscle force fell to 50% of the initial value for each contraction (T50%). There was no significant difference between the 2.5 J/cm2 laser-irradiated group and the control group in mean T50% values. Laser-irradiated groups (0.5 and 1.0 J/cm2) had significantly longer T50% values than the control group. The relative peak force for the sixth contraction in the laser-irradiated groups were significantly higher at 92.2% (SD 12.6) for 0.5 J/cm2, 83.2% (SD 20.5) for 1.0 J/cm2, and 82.9% (SD 18.3) for 2.5 J/cm2 than for the control group [50% (SD 15)]. Laser groups receiving 0.5 and 1.0 J/cm2 showed significant increases in mean performed work compared with both the control group and their first contraction values. Muscle damage was indirectly measured by creatine kinase levels in plasma. A distinct dose-response pattern was found in which 1.0 and 2.5 J/cm2 LLLT groups had significantly lower creatine kinase levels than the 0.5 J/cm2 LLLT group and the control group. We conclude that LLLT doses of 0.5 and 1.0 J/cm2 can prevent development of muscular fatigue in rats during repeated tetanic contractions.     

Relationship between autonomic cardiovascular control,case definition,clinical symptoms,and functional disability in adolescent chronic fatigue syndrome: an exploratory study

Chronic Fatigue Syndrome (CFS) is characterized by severe impairment and multiple symptoms. Autonomic dysregulation has been demonstrated in several studies. We aimed at exploring the relationship between indices of autonomic cardiovascular control, the case definition from Centers for Disease Control and Prevention (CDC criteria), important clinical symptoms, and disability in adolescent chronic fatigue syndrome. 38 CFS patients aged 12–18 years were recruited according to a wide case definition (ie. not requiring accompanying symptoms) and subjected to head-up tilt test (HUT) and a questionnaire. The relationships between variables were explored with multiple linear regression analyses. In the final models, disability was positively associated with symptoms of cognitive impairments (p<0.001), hypersensitivity (p<0.001), fatigue (p=0.003) and age (p=0.007). Symptoms of cognitive impairments were associated with age (p=0.002), heart rate (HR) at baseline (p=0.01), and HR response during HUT (p=0.02). Hypersensitivity was associated with HR response during HUT (p=0.001), high-frequency variability of heart rate (HF-RRI) at baseline (p=0.05), and adherence to the CDC criteria (p=0.005). Fatigue was associated with gender (p=0.007) and adherence to the CDC criteria (p=0.04). In conclusion, a) The disability of CFS patients is not only related to fatigue but to other symptoms as well; b) Altered cardiovascular autonomic control is associated with certain symptoms; c) The CDC criteria are poorly associated with disability, symptoms, and indices of altered autonomic nervous activity.     

Neurogenic inflammation in mice deficient in heparin-synthesizing enzyme

Mast cell activation, or neurogenic inflammation, is known to induce lowering of interstitial fluid pressure (P(if)) and plasma protein extravasation (PPE) in several tissues from both rats and mice. To examine a possible role of connective tissue mast cells (CTMCs) in these inflammatory responses, we used mice with dysfunctional CTMCs due to lack of the N-deacetylase/N-sulfotransferase-2 enzyme (NDST-2(-/-)). P(if) and PPE were measured after challenge with compound 48/80 (C48/80), and P(if) alone was measured after treatment either with capsaicin, substance P (SP), or calcitonin gene-related peptide (CGRP). Measurements of P(if) in anesthetized (fentanyl/fluanison and midazolam, 1:1) mice were performed in paw skin with glass capillaries connected to a servo-controlled counterpressure system. PPE was measured with microdialysis by using hollow plasmapheresis fibers (cutoff at 3,000 kDa) placed subcutaneously on the back. Intravenous administration of C48/80 lowered P(if) significantly (P < 0.05) in NDST-2(-/-) mice (-1.67 +/- 0.42 mmHg) compared with vehicle (-0.57 +/- 0.17 mmHg) but the lowering was significantly (P < 0.05) less compared with that of the NDST-2(+/+) mice (-2.31 +/- 0.47 mmHg). PPE was increased 300% after treatment with C48/80 in NDST-2(+/+) mice, whereas there was no increase in PPE in NDST-2(-/-) mice. Capsaicin, SP, and CGRP lowered P(if) significantly (P < 0.05) compared with vehicle and to the same extent in both NDST-2(+/+) and NDST-2(-/-) mice. We can conclude that although NDST-2(-/-) mice demonstrate an altered response in P(if) after mast cell activation, there was no similar alteration after neurogenic inflammation. Therefore, we suggest that neurogenic inflammation in mouse skin is not exclusively dependent on intact CTMCs.     

Effects of herbivory on N-cycling and distribution of added 15NH 4 + in N-limited low-alpine grasslands

Many rangelands around the world are degraded by severe overgrazing with resulting loss of nutrients and reduced productivity. However, grazing may also increase nutrient cycling and enhance ecosystem productivity. The aim of this study was to determine effects of grazing on availability of nitrogen (N), sources of N utilized by plants and cycling and distribution of N at a low-alpine site, Southern Norway. The study was part of a sheep grazing experiment with three density levels of sheep (no sheep, 25 km^?2 and 80 km^?2) since 2001. The N-content of plants was determined in June 2008, August 2008 and August 2009. Indirect effects of herbivory on sources of N and N-cycling were assessed by δ¹⁵N natural abundance and the system’s distribution of added ¹⁵NH₄-N. We found little evidence for grazing induced effects on availability, sources or cycling of N based on N content of plants and δ¹⁵N natural abundance. The organic soil horizon was the largest sink for the added ¹⁵NH₄-N. Proportional tracer recoveries and tracer enrichments indicate a somewhat greater N cycling at grazed than at non-grazed sites. We conclude that the experimental levels of grazing have limited impact on distribution and cycling of N and thus represent sustainable ecosystem management in terms of N dynamics in the long-term.     

A predatory mechanism dramatically increases the efficiency of lateral gene transfer in Streptococcus pneumoniae and related commensal species

Bacteria that are competent for natural genetic transformation, such as pneumococci and their commensal relatives Streptococcus mitis and Streptococcus oralis , take up exogenous DNA and incorporate it into their genomes by homologous recombination. Traditionally, it has been assumed that genetic material leaking from dead bacteria constitutes the sole source of external DNA for competent streptococci. Here we describe a mechanism for active acquisition of homologous DNA that dramatically increases the efficiency of gene exchange between and within the streptococcal species mentioned above. This mechanism gives competent streptococci access to a common gene pool that is significantly larger than their own genomes, a property representing a considerable advantage when these bacteria are subjected to external selection pressures, such as vaccination and treatment with antibiotics.