Context sensitivity by development INGOs in Myanmar

This chapter presents analysis of new primary research data collected on INGOs working inside Myanmar. In particular, it looks at the contextualisation they make to common international development approaches, in order to attain greatest effectiveness in this specific context. This research is based on in-depth interviews of forty-seven key informants from INGOs, UN organisations and local NGOs, working within Myanmar. The key finding is that INGO's believe that, with appropriate contextualisation, their effectiveness is not as heavily restricted in Myanmar as is commonly perceived, particularly in addressing the worst impact of extreme poverty in communities, but also in areas such as advocacy and capacity development of the emerging civil society.

Insulin sensitivity in response to a single resistance exercise session in apparently healthy individuals

BACKGROUND: Regular resistance exercise completed for a number of weeks has been shown to increase insulin sensitivity and reduce the risk of diabetes-related complications. However, the acute responses to resistance exercise have not been adequately investigated in relation to training frequency.
AIM: To investigate the changes to insulin sensitivity in apparently healthy individuals following a single session of unaccustomed resistance exercise.
SUBJECTS AND METHODS: Ten sedentary, apparently healthy individuals performed a baseline oral glucose tolerance test and maximal strength testing. Participants then performed a single session of moderate-high intensity resistance exercise which was followed by 4 consecutive days of oral glucose tolerance testing, for which participants replicated their initial diet. Mean estimated insulin sensitivity change scores from baseline values and their 95% confidence intervals were compared to the previously determined values for a clinically meaningful change.
RESULTS: Two participants were identified as having hyperinsulinemia and their data were therefore removed from the main analysis. There was a clinically meaningful increase in insulin response (mean >7237 pmol·l⁻¹·120 min⁻¹) on all days following the exercise session and a clinically meaningful increase in glucose response (mean >81 mmol·l⁻¹·120 min⁻¹) on only the 3rd day following exercise. These changes suggest a potentially adverse short-term effect. Additionally, the 2 individuals with hyperinsulinemia displayed more extreme results.
CONCLUSION: These results suggest that insulin sensitivity may be impaired following a single session of unaccustomed resistance exercise for approximately 4 days in healthy untrained, older individuals. Further research is required for individuals with hyperinsulinemia

Insulin sensitivity not modulated 24 to 78 h after acute resistance exercise in type 2 diabetes patients

Background
The aim of this study was to describe the clinical characteristics, causative pathogens, clinical management and outcomes of patients presenting to a tertiary adult Australian intensive care unit (ICU) with a diagnosis of necrotizing fasciitis (NF).
Methods
This retrospective observational study was conducted in a 19-bed, level III, adult ICU in a 450-bed tertiary, regional hospital. Clinical databases were accessed for patients diagnosed with NF and admitted to The Geelong Hospital ICU between 1 February 2000 and 1 June 2011. Information on severity of sepsis, surgical procedures and microbiological results were collected.
Results
Twenty patients with NF were identified. The median age was 52.5 years and 38% were female. The overall mortality rate was 8.3%. Common co-morbidities were diabetes (21%) and heart failure (17%), although 50% of patients had no co-morbidities. Group A Streptococcus was the identified pathogen in 11 (46%) patients, and Streptococcus milleri group in 5 (21%) patients. Hyperbaric oxygen therapy was not used in the majority of patients. The initial antibiotics administered were active against subsequently cultured bacteria in 83% of patients. Median time to surgical debridement was 20 h. Diagnosis and management was delayed in the nosocomial group.
Conclusions
This study reports physiological data, aetiology and therapeutic interventions in NF for an adult tertiary hospital. We demonstrate one of the lowest reported mortality rates, with early surgical debridement being achieved in the majority of patients. The main delay was found to be in the diagnosis of NF.

The relationship between attachment style, anxiety sensitivity and interpretive bias among adolescent nonclinical panickers

Elevated anxiety sensitivity and the tendency to catastrophically misinterpret ambiguous bodily sensations has been demonstrated in people who experience nonclinical levels of panic (Richards, Austin, & Alvarenga, 2001), and anxiety sensitivity has been shown to be associated with insecure attachment in adolescents and young adults (Weems, Berman, Silverman, and Saavedra, 2001). This study investigated the relationship between attachment style, anxiety sensitivity and catastrophic misinterpretation among 11 nonclinical panickers and 58 nonanxious controls aged 18 to 19 years. Participants completed the Brief Bodily Sensations Interpretation Questionnaire (BBSIQ), Anxiety Sensitivity Index (ASI) and an attachment questionnaire. The hypothesis that insecurely attached individuals would demonstrate greater catastrophic misinterpretation and higher anxiety sensitivity than securely attached individuals was not supported; however, nonclinical panickers gave more anxiety-related interpretations of ambiguous internal stimuli than nonanxious controls. Results do not support the notion that attachment style is related to anxiety sensitivity or catastrophic misinterpretation (regardless of panic experience). Results do, however, support the notion that anxiety-related misinterpretation of ambiguous somatic sensations precedes the onset of panic disorder.

Short term aerobic exercise training in young males does not alter sensitivity to a central serotonin agonist

An increase in the concentration of serotonin in the brain has been shown to cause fatigue during exercise in humans and experimental animals. This type of fatigue is referred to as central fatigue and is likely to be mediated by the concentration of serotonin as well as serotonin receptor sensitivity. Serotonin (5-HT) receptor antagonism in humans and experimental animals has been shown to improve endurance performance. A previous report has shown decreased receptor sensitivity in athletes compared to sedentary controls. It is unclear whether this is due to a training adaptation or if individuals are predisposed to enhanced athletic performance due to their inherent decreased receptor sensitivity. The present study investigated changes in 5-HT receptor sensitivity in response to aerobic exercise. Subjects completed 3 × 30 min of stationary cycling at 70% of their peak aerobic power (V̇O2,peak) for 9 weeks. Serotonin receptor sensitivity was assessed indirectly by measuring the neuroendocrine response following administration of a serotonin agonist (buspirone hydrochloride). The neuroendocrine response following administration of a placebo was also investigated in a blind crossover design. A group of sedentary control subjects was also recruited to control for seasonal variations in central receptor sensitivity. The training caused a significant increase in V̇O2,peak (3.1 ± 0.16 to 3.6 ± 0.15 l min−1, P < 0.05) and endurance capacity (93 ± 8 to 168 ± 11 min, P < 0.05), but there was no change (P > 0.05) in the neuroendocrine response in the presence of a serotonin agonist. However, one-quarter of the subjects in the training group demonstrated decreases in receptor sensitivity. These results suggest that despite increases in V̇O2,peak and endurance performance, there was no measurable change in 5-HT receptor sensitivity in the presence of a serotonin agonist. In addition, it is possible that changes in receptor sensitivity may take longer to occur, that the training stimulus used in the present investigation was inadequate and/or that changes occurred in receptor subtypes that were not probed by the agonist used in the present investigation.

Endurance training in Wistar rats decreases receptor sensitivity to a serotonin agonist

There is mounting evidence that increased brain serotonin during exercise is associated with the onset of CNS-mediated fatigue. Serotonin receptor sensitivity is likely to be an important determinant of this fatigue. Alterations in brain serotonin receptor sensitivity were examined in Wistar rats throughout 6 weeks of endurance training, running on a treadmill four times a week with two exercise tests per week to exhaustion. Receptor sensitivity was determined indirectly as the reduction in exercise time in response to a dose of a serotonin (1A) agonist, m-chlorophenylpiperazine (m-CPP). The two groups of controls were used to examine (i) the effect of the injection per se on exercise performance and (ii) changes in serotonin receptor sensitivity associated with maturation. In the test group, undrugged exercise performance significantly improved by 47% after 6 weeks of training (4518 ± 729 to 6640 ± 903 s, P=0.01). Drugged exercise performance also increased significantly from week 1 to week 6 (306 ± 69–712 ± 192 s, P = 0.04). Control group results indicated that the dose of m-CPP alone caused fatigue during exercise tests and that maturation was not responsible for any decrease in receptor sensitivity. Improved resistance to the fatiguing effects of the serotonin agonist suggests desensitization of central serotonin receptors, probably the 5-HT1A receptors. Endurance training appears to stimulate an adaptive response to the fatiguing effects of increased brain serotonin, which may enhance endurance exercise performance.

Allosteric Modulation of the HIV-1 gp120-gp41 Association Site by Adjacent gp120 Variable Region 1 (V1) N-Glycans Linked to Neutralization Sensitivity

The HIV-1 gp120-gp41 complex, which mediates viral fusion and cellular entry, undergoes rapid evolution within its external glycan shield to enable escape from neutralizing antibody (NAb). Understanding how conserved protein determinants retain functionality in the context of such evolution is important for their evaluation and exploitation as potential drug and/ or vaccine targets. In this study, we examined how the conserved gp120-gp41 association site, formed by the N- and Cterminal segments of gp120 and the disulfide-bonded region (DSR) of gp41, adapts to glycan changes that are linked to neutralization sensitivity. To this end, a DSR mutant virus (K601D) with defective gp120-association was sequentially passaged in peripheral blood mononuclear cells to select suppressor mutations. We reasoned that the locations of suppressors point to structural elements that are functionally linked to the gp120-gp41 association site. In culture 1, gp120 association and viral replication was restored by loss of the conserved glycan at Asn136 in V1 (T138N mutation) in
conjunction with the L494I substitution in C5 within the association site. In culture 2, replication was restored with deletion of the N139INN sequence, which ablates the overlapping Asn141-Asn142-Ser-Ser potential N-linked glycosylation sequons in
V1, in conjunction with D601N in the DSR. The 136 and 142 glycan mutations appeared to exert their suppressive effects by altering the dependence of gp120-gp41 interactions on the DSR residues, Leu593, Trp596 and Lys601. The 136 and/or 142
glycan mutations increased the sensitivity of HIV-1 pseudovirions to the glycan-dependent NAbs 2G12 and PG16, and also pooled IgG obtained from HIV-1-infected individuals. Thus adjacent V1 glycans allosterically modulate the distal gp120-
gp41 association site. We propose that this represents a mechanism for functional adaptation of the gp120-gp41 association site to an evolving glycan shield in a setting of NAb selection.