Loxosceles deserta Spider Venom Induces the Expression of Vascular Endothelial Growth Factor (VEGF) in Keratinocytes

Evenomation by arachnids of the genus Loxosceles frequently results in disfiguring necrotic skin lesions. The cellular and molecular mechanisms which contribute to lesion development are incompletely defined but appear to involve participation of several pro-inflammatory mediators. We have recently observed that Loxosceles deserta venom induces the production of chemokines in human umbilical vein endothelial cells (HUVECs) and human pulmonary epithelial cells. In the present study we observed that Loxosceles deserta venom induces the expression of vascular endothelial growth factor (VEGF) in human keratinocytes but little in smooth muscle cells and none in pulmonary epithelial cells. A potent endothelial cell-specific mitogen, VEGF induces angiogenesis and vascular permeability in vivo. RNase protection assay data indicate that VEGF mRNA concentrations in keratinocytes are significantly increased at 2 h following venom exposure. These data suggest that keratinocyte-derived VEGF may contribute to the vasodilation, edema and erythema which occur following Loxosceles evenomation.     

Emotion Perception in Music in High-Functioning Adolescents With Autism Spectrum Disorders

Individuals with Autism Spectrum Disorders (ASD) succeed at a range of musical tasks. The ability to recognize musical emotion as belonging to one of four categories (happy, sad, scared or peaceful) was assessed in high-functioning adolescents with ASD (N = 26) and adolescents with typical development (TD, N = 26) with comparable performance IQ, auditory working memory, and musical training and experience. When verbal IQ was controlled for, there was no significant effect of diagnostic group. Adolescents with ASD rated the intensity of the emotions similarly to adolescents with TD and reported greater confidence in their responses when they had correctly (vs. incorrectly) recognized the emotions. These findings are reviewed within the context of the amygdala theory of autism.     

An immunodominant 30-kDa antigen of a candidate anti-leprosy vaccine,Mycobacterium w,shares T and B cell determinants withM. leprae andM. tuberculosis

Earlier we reported that vaccination of leprosy patients withMycobacterium w induces an immune response directed predominantly against low molecular weight antigens. One of these antigens, with a molecular mass of 30-kDa, was recognized by a majority of the vaccinated subjects as well as the tuberculoid leprosy patients and healthy contacts. In the present communication we report further characterization of this antigen. Immunofluorescence and Western blot studies with antibodies raised against this antigen demonstrate that it is associated with the cell surface and has homologues present inM. leprae andM. tuberculosis. Delayed-type hypersensitivity studies carried out in guinea pigs immunized with the 30-kDa antigen show that in addition to sharing B cell determinants, this immunodominant antigen ofM. w also shares T cell determinants withM. leprae andM. tuberculosis.     

The increase in dural sac area is maintained at 2 years after X-stop implantation for the treatment of spinal stenosis with no significant alteration in lumbar spine range of movement

Background contextThe X-stop interspinous process decompression (IPD) device has been used effectively in the management of symptomatic spinal stenosis. This study examines the radiological outcomes at 2 years postoperatively after X-stop implantation.PurposeTo measure the effect of X-stop IPD device on the dural sac and foraminal areas at 24 months postoperatively at instrumented level in symptomatic lumbar canal stenosis. We also aimed to assess its effect on change in lumbar spine movement.Study designProspective observational study.Patient sampleForty-eight patients treated with X-stop had preoperative positional magnetic resonance imaging (MRI) scans, 40 of whom had 2 years postoperative positional MRI scans. Complete scans were available for 39 of these patients.Outcome measuresPositional MRI scans were performed pre- and postoperatively. Measurements were done on these scans and are presented as the outcome measures.MethodsAll patients had a multipositional MRI scan preoperatively and at 6 and 24 months postoperatively. Foraminal area was measured in flexion and extension. Dural cross-sectional area was measured in standing erect and in sitting neutral, flexion, and extension (sitting) positions. The total range of movement (ROM) of the lumbar spine and individual segments was also measured.ResultsComplete scan data for 39 patients' scans were available. An increase in mean dural sac area was found in all positions. At 24 months after surgery, the mean dural sac area increased significantly in all four postures mentioned above. A small increase in mean foraminal area was noted, but this was not statistically significant. Mean anterior disc height reduced from 5.9 to 4.1 mm (p=.006) at 24 months at the instrumented level in single-level cases, from 7.7 to 6.1 mm (p=.032) in double-level cases caudally, and from 8.54 to 7.91 (p=.106) mm cranially. We hypothesize that the reduction in anterior disc heights could be a result of the natural progression of spinal stenosis with aging. There was no significant change in posterior disc heights at instrumented level or adjacent levels. The mean lumbar spine motion was 21.7° preoperatively and 23° at 24 months (p=.584) in single-level cases. This was 32.1° to 31.1° (p=.637) in double-level cases. There was no significant change in the individual segmental range of motion at instrumented and adjacent levels.ConclusionX-stop interspinous device remains effective in decompressing the stenosed spinal segment by increasing the anatomic dural cross-sectional area and foraminal area of spinal canal. It does not significantly alter the ROM of lumbar spine at instrumented and adjacent levels at 24 months postoperatively.     

General practitioners’ experiences and perceptions of mild moderate depression management and factors influencing effective service delivery in rural Australian communities: a qualitative study

Background

Rural communities in Australia face significant disadvantages relating to geographical isolation and limited access to mental health services. Documenting general practitioners’ (GP) experiences and perception of mental health services in rural Australia may be useful to gain insight into rural GP management of mild to moderate depression.

Aims

To explore GPs’ experience and views on which factors influence access to mental health services for mild to moderate depression.

Method

This qualitative study was conducted in 2014 in the Northern Rivers, NSW, Australia. Data were obtained from semi-structured in-depth face-to-face interviews with ten GPs, and analyses were performed using a general inductive method of thematic analysis.

Results

Most GPs believed that the current services for managing mild-moderate depression were adequate, however they also identified the need for better access and more services that were free for patients. GPs had a positive perception of management of depression in a rural setting, identifying advantages including better doctor-patient relationships, continuity of care and the proximity of services. However, GPs also identified several barriers to access to mental health services in a rural setting, including long waiting-times, inadequate patient rapport with referred professionals, cost of treatment, transportation, geographical location, stigma, and lack of education about available mental health services. As a result, GPs frequently self-managed patients in addition to referring them to other community mental health service providers where possible.

Conclusion

Overall, GPs appeared relatively satisfied with the resources available in their communities but also identified numerous barriers to access and room for improvement. Rural GPs often self-managed patients in addition to referring patients to other mental health services providers. This should be taken into account when designing mental health policies, developing new services or re-designing current services in rural communities.

     

Brain-derived neurotrophic factor genotype impacts the prenatal cocaine-induced mouse phenotype

Prenatal cocaine exposure leads to persistent alterations in the growth factor brain-derived neurotrophic factor (BDNF), particularly in the medial prefrontal cortex (mPFC) and hippocampus, brain regions important in cognitive functioning. BDNF plays an important role in the strengthening of existing synaptic connections as well as in the formation of new contacts during learning. A single nucleotide polymorphism in the BDNF gene (Val66Met), leading to a Met substitution for Val at codon 66 in the prodomain, is common in human populations, with an allele frequency of 20-30% in Caucasians. To study the interaction between prenatal cocaine exposure and BDNF, we have utilized a line of BDNF Val66Met transgenic mice on a Swiss Webster background in which BDNF(Met) is endogenously expressed. Examination of baseline levels of mature BDNF protein in the mPFC of prenatally cocaine-treated wild-type (Val66Val) and Val66Met mice revealed significantly lower levels compared to prenatally saline-treated mice. In contrast, in the hippocampus of prenatally saline- and cocaine-treated adult Val66Met mice, there were significantly lower levels of mature BDNF protein compared to Val66Val mice. In extinction of a conditioned fear, we found that prenatally cocaine-treated Val66Met mice had a deficit in recall of extinction. Examination of mature BDNF protein levels immediately after the test for extinction recall revealed lower levels in the mPFC of prenatally cocaine-treated Val66Met mice compared to saline-treated mice. However, 2 h after the extinction test, there was increased BDNF exons I, IV, and IX mRNA expression in the prelimbic cortex of the mPFC in the prenatally cocaine-treated BDNF Val66Met mice compared to prenatally saline-treated mice. Taken together, our results suggest the possibility that prenatal cocaine-induced constitutive alterations in BDNF mRNA and protein expression in the mPFC differentially poises animals for alterations in behaviorally induced gene activation, which are interactive with BDNF genotype and differentially impact those behaviors. Such findings in our prenatal cocaine mouse model suggest a gene X environment interaction of potential clinical relevance.     

Changes in human brain glutamate concentration during hypoglycemia: insights into cerebral adaptations in hypoglycemia-associated autonomic failure in type 1 diabetes

Hypoglycemia-associated autonomic failure (HAAF) is a condition in which patients with type 1 diabetes (T1D) who experience frequent hypoglycemia develop defective glucose counter-regulation and become unable to sense hypoglycemia. Brain glutamate may be involved in the mechanism of HAAF. The goal of this study was to follow the human brain glutamate concentration during experimentally induced hypoglycemia in subjects with and without HAAF. ¹H magnetic resonance spectroscopy was used to track the occipital cortex glutamate concentration throughout a euglycemic clamp followed immediately by a hypoglycemic clamp. T1D patients with HAAF were studied in comparison to two control groups, i.e., T1D patients without HAAF and healthy controls (n=5 per group). Human brain glutamate concentration decreased (P⩽0.01) after the initiation of hypoglycemia in the two control groups, but a smaller trend toward a decrease in patients with HAAF did not reach significance (P>0.05). These findings are consistent with a metabolic adaptation in HAAF to provide higher glucose and/or alternative fuel to the brain, eliminating the need to oxidize glutamate. In an exploratory analysis, we detected additional metabolite changes in response to hypoglycemia in the T1D patient without HAAF control group, namely, increased aspartate and decreased lactate.     

Frontal and temporal contributions to understanding the iconic co‐speech gestures that accompany speech

In everyday conversation, listeners often rely on a speaker's gestures to clarify any ambiguities in the verbal message. Using fMRI during naturalistic story comprehension, we examined which brain regions in the listener are sensitive to speakers' iconic gestures. We focused on iconic gestures that contribute information not found in the speaker's talk, compared with those that convey information redundant with the speaker's talk. We found that three regions—left inferior frontal gyrus triangular (IFGTr) and opercular (IFGOp) portions, and left posterior middle temporal gyrus (MTGp)—responded more strongly when gestures added information to nonspecific language, compared with when they conveyed the same information in more specific language; in other words, when gesture disambiguated speech as opposed to reinforced it. An increased BOLD response was not found in these regions when the nonspecific language was produced without gesture, suggesting that IFGTr, IFGOp, and MTGp are involved in integrating semantic information across gesture and speech. In addition, we found that activity in the posterior superior temporal sulcus (STSp), previously thought to be involved in gesture‐speech integration, was not sensitive to the gesture‐speech relation. Together, these findings clarify the neurobiology of gesture‐speech integration and contribute to an emerging picture of how listeners glean meaning from gestures that accompany speech. Hum Brain Mapp 35:900–917, 2014. © 2012 Wiley Periodicals, Inc.