Alterations in triad ultrastructure following repetitive stimulation and intracellular changes associated with exercise in amphibian skeletal muscle

This study used Rana temporaria sartorius muscles to examine the effect of fatiguing electrical stimulation on the gap between the T-tubular and sarcoplasmic reticular membranes (T-SR distance) and the T-tubule diameter and compared this with corresponding effects on resting fibres exposed to a range of extracellular conditions that each replicate one of the major changes associated with muscular activity: membrane depolarisation, isotonic volume increase, acidification and intracellular lactate accumulation. Following each treatment, muscles were immersed in isotonic fixative solution and processed for transmission electron microscopy (TEM). Mean T-SR distances were estimated from orthogonal intercepts to provide estimates of diffusion distances between T and SR membranes and T-tubule diameter was estimated by measuring its shortest axis in the sampled J-SR complexes. Measurements from muscles fatigued by low frequency intermittent stimulation showed significant (P << 0.05) reversible increases in both T-SR distance and T-tubule diameter from 15.97 ± 0.37 nm to 20.15 ± 0.56 nm and from 15.44 ± 0.60 nm to 22.26 ± 0.84 nm (n = 40, 30) respectively. Exposure to increasing concentrations of extracellular [K⁺] in the absence of Cl⁻ to produce membrane depolarisation without accompanying cell swelling reduced T-SR distance and increased T-tubule diameter, whilst comparable increases in [K⁺]_e in the presence of Cl⁻ suggested that isotonic cell swelling has the opposite effect. Acidification alone, produced by NH₄Cl addition and withdrawal, also decreased T-SR distance and T-tubule diameter. A similar reduction in T-SR distance occurred following exposure to extracellular Na-lactate where such acidification was accompanied by elevations of intracellular lactate, but these conditions produced a significant swelling of T-tubules attributable to movement of lactate from the cell into the T-tubules. This study thus confirms previous reports of significant increases in T-SR distance and T-tubule diameter following stimulation. However, of membrane depolarisation, isotonic cell swelling, intracellular acidification and lactate accumulation, only isotonic cell swelling increases T-SR distance whilst membrane depolarisation and intracellular lactate likely contribute to the observed increases in T-tubule diameter.     

The impact of group counseling on depression,post-traumatic stress and function outcomes: A prospective comparison study in the Peter C. Alderman trauma clinics in northern Uganda

Background

The effectiveness of group interventions for adults with mental distress in post-conflict settings is less clear in sub-Saharan Africa.

Aim

To assess the impact of group counseling intervention on depression, post-traumatic stress and function outcomes among adults attending the Peter C. Alderman Foundation (PCAF) trauma clinics in northern Uganda.

Methods

631 War affected adults were enrolled into PCAF trauma clinics. Using a quasi-experimental design, assessments were conducted at baseline, at 3 and 6 months following initiation of care. Multivariate longitudinal regression models were used to determine change in depression, post-traumatic stress and function scores over time among group counseling participants and non-participants.

Results

In comparison to non-participants, participants had faster reduction in depression scores during the 6-month follow-up period [β=−1.84, 95%CI (−3.38 to −0.30), p=0.019] and faster reduction in post-traumatic stress scores during the 3-month follow-up period [β=−2.14, 95%CI (−4.21 to −0.10), p=0.042]. At 3-month follow up, participants who attended two or more sessions had faster increase in function scores [β=3.51, 95%CI (0.61–6.40), p=0.018] than participants who attended only one session.

Limitations

Selection bias due to the use of non-random samples. Substantial attrition rates and small sample sizes may have resulted in insufficient statistical power to determine meaningful differences.

Conclusion

The group counseling intervention offered in the PCAF clinics may have considerable mental health benefits over time. There is need for more research to structure, standardize and test the efficacy of this intervention using a randomized controlled trial.     

First report of homoanatoxin-a and associated dog neurotoxicosis in New Zealand.

In November 2005, at least five dogs died rapidly after contact with water from the Hutt River (lower North Island, New Zealand). Necropsy performed 24h later on one of the dogs (a 20-month-old Labrador) revealed few findings of interest, except for copious amounts of froth in the respiratory tract down to the bifurcation of the trachea and large quantities of algal material in the dog's stomach. Low and relatively stable flows in the Hutt River during spring had resulted in the proliferation of benthic cyanobacteria that formed large black/brown mats along the river edge. Samples from the Labrador's stomach contents and cyanobacterial mats were analysed microscopically and screened using chemical and biochemical assays for cyanotoxins: anatoxin-a, homoanatoxin-a, cylindrospermopsins, saxitoxins and microcystins. Liquid chromatography-mass spectrometry (LC-MS) confirmed the presence of the neurotoxic cyanotoxins anatoxin-a and homoanatoxin-a and their degradation products, dihydro-anatoxin-a and dihydro-homoanatoxin-a. This is the first report of homoanatoxin-a and associated degradation product in New Zealand. Based on morphology, the causative species was identified as Phormidium sp. Subsequent phylogenetic analysis of 16S rRNA gene sequences demonstrated that the causative organism was most similar to Phormidium autumnale. Further investigations led to the detection of homoanatoxin-a and anatoxin-a in cyanobacterial mats from four other rivers in the Wellington region (lower North Island, New Zealand). Access restrictions were placed on over 60% of river catchments in the western Wellington region, severely affecting recreational users.     

The Australian longitudinal study of health and relationships

Background  

Ensuring the sexual and reproductive health of the population is essential for the wellbeing of a nation. At least three aspects of sexual and reproductive health are among the key policy issues for present Australian governments: maintaining and increasing the birth rate; reducing the abortion rate; and preventing and controlling Chlamydia infections.     

Umbilical cord blood transplantation: current practice and future innovations

As a source of hematopoietic stem cells (HSCs), umbilical cord blood (UCB) has the advantages of speed of availability, tolerance of 1-2 antigen HLA mismatch, and a low incidence of severe GVHD. Thus, UCB represents a highly convenient HSC source that may significantly extend the HSC donor pool. UCB transplantation (UCBT) has become a standard practice in the treatment of pediatric malignancies. Now, UCBT is being investigated in adults using both conventional and non-myeloablative preparative regimens. As graft cell dose is the major factor determining hematopoietic recovery and survival in URD UCBT, methods to increase cell dose such as multiple-unit transplant and ex vivo expansion are being pursued. This review outlines the current status of UCBT with emphasis on current and future innovations.     

Family therapy and dialectical behavior therapy with adolescents: Part I: Proposing a clinical synthesis

Although the practice of family therapy in dialectical behavior therapy (DBT) with multiproblem suicidal adolescents is common and generally indicated, a particular model has yet to be delineated with this age group. The purpose of this article is to propose a coherent clinical synthesis of the more individually oriented DBT strategies with a broader family-systems orientation that maintains the integrity of both theoretical approaches while addressing the treatment needs of adolescents and their families. First, the authors briefly review the literature. Second, they describe the core dialectic of DBT, balancing acceptance and change, and its relevance to family therapy. Finally, the authors propose several specific acceptance and change strategies useful when implementing DBT family therapy with multi-problem adolescents.     

Endogenous gonadal hormones modulate behavioral and neurochemical responses to acute and chronic cocaine administration

Recent evidence demonstrates that there are sex differences in behavioral responses to cocaine. Further, reproductive gonadal hormones (estrogen, progesterone and testosterone) have been further implicated in mediating some of the cocaine-induced alterations. To better understand sex differences and the role of gonadal hormones in cocaine-induced locomotor and stereotypic behavior, intact and gonadectomized male and female Fischer rats were randomly assigned to either chronic cocaine (15 mg/kg) or saline treatments for 14 days followed by a challenge administration (7 days after the last cocaine/saline administration). Locomotor (ambulatory and rearing) and stereotypic activities were measured on days 1, 7 and 14 as well as after withdrawal/challenge with cocaine. Overall, intact female rats consistently showed a rapid (acquired by day 7) and longer lasting (persistent through the challenge dose) sensitization for all locomotor behaviors than any of the other groups. In contrast, intact males developed sensitization of these locomotor activities only in response to chronic cocaine administration, and after withdrawal and drug challenge the sensitization to cocaine-induced locomotor activity was no longer present. In female rats, gonadectomy affected ambulatory activity but not total and rearing responses after acute, sub-acute, chronic and challenge response to cocaine. On the other hand, castrated male rats were affected in cocaine-induced ambulatory activity but not rearing activity. In intact male rats, cocaine-induced stereotypic activity was rapidly and persistently sensitized after 7 days of cocaine administration, where gonadectomized male rats developed sensitization to cocaine-induced stereotypic activity only after a challenge cocaine administration. Although cocaine induced stereotypic activity, no statistically significant differences were observed between intact and ovariectomized female rats or throughout the different lengths of cocaine administration. After a challenge of cocaine, corticosterone levels were induced in all experimental groups. Moreover, no differences in levels of benzoylecgonine, a cocaine metabolite, were observed. Similar to our previous observations after acute cocaine administration, after challenge of cocaine, an increase in progesterone and a decrease in testosterone levels were observed in intact females and males, respectively. In summary, endogenous hormones seem to be involved in the behavioral activation and development of sensitization to cocaine.     

Complete mapping of a novel HLA A*6801-restricted HIV-1 Tat epitope directly with a rapid modified enzyme-linked immunospot assay

We identified a novel HLA A*6801-restricted HIV-1 Tat-derived cytotoxic T lymphocyte (CTL) epitope using an adapted enzyme-linked immunospot assay that allows the rapid ex vivo identification of CTL epitopes together with their associated HLA Class I restriction elements. The optimal 11 amino acid residue Tat epitope efficiently stabilized the refolding of monomeric peptide-HLA A6801 complexes in vitro and fluorochrome-labelled, tetrameric peptide-HLA A6801 complexes stained CD8 T cells specific for this epitope directly ex vivo.