Regulation of gastric acid secretion by the serum and glucocorticoid inducible kinase isoform SGK3

Background  

The serum and glucocorticoid inducible kinase isoform SGK3 is ubiquitously expressed and has been shown to participate in the regulation of cell survival and transport. Similar to SGK1 and protein kinase B (PKB/Akt) isoforms, SGK3 may phosphorylate glycogen synthase kinase (GSK) 3α,β, which has recently been shown to participate in the regulation of basal gastric acid secretion. The present study thus explored the role of SGK3 in the regulation of gastric acid secretion.     

Importance of Allergy in Asthma: An Epidemiologic Perspective

There has been a global epidemic of asthma during the past half-century. More recently, the prevalence has leveled off or declined in many Western countries, whereas the prevalence in less affluent nations is still increasing. The reasons for this and the different geographical patterns of asthma prevalence remain unclear. This paper provides an epidemiologic perspective on whether allergen exposure and allergies can explain these trends. In particular, the paper discusses 1) geographical and temporal trends in asthma and the role of allergens and allergy, 2) the importance of nonallergic mechanisms, 3) nonallergenic exposures that may modify the risk of allergies and asthma, and 4) new and emerging risk and protective factors. Although allergy and asthma are closely related, allergen exposure and allergy alone cannot explain current time trends and geographical patterns of asthma. Population-based studies focusing on recently identified risk and protective factors may provide further insight.     

Striatal Aβ peptide deposition mirrors dementia and differentiates DLB and PDD from other parkinsonian syndromes

Recent neuropathological studies have described widespread amyloid-β peptide (Aβ) deposition in the striatum of patients with Lewy body disorders, particularly in Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB). However, positron emission tomography (PET) studies using the [(11)C]PIB ligand, binding to Aβ deposits, detects significant striatal pathology only in DLB and not in PDD. Employing immunohistochemistry, we examined striatal Aβ deposition in the caudate nucleus and putamen of 52 PD, 41 PDD, 14 DLB, 7 multiple system atrophy (MSA) and 14 progressive supranuclear palsy (PSP) cases in relation to the presence of dementia. PD, MSA and PSP cases showed little or no Aβ pathology in the striatum. In contrast, both PDD and DLB cases demonstrated significantly greater Aβ deposition in the striatum when compared to PD, MSA and PSP groups. We conclude that striatal Aβ pathology is common in both PDD and DLB and may reflect the development of dementia in these conditions. More detailed examination of the morphology of the Aβ pathology suggests that it is the presence of cored amyloid plaques in DLB, but not PDD, that underlies the differences seen in PET imaging.     

Conservative management of uncomplicated mechanical neck pain in a military aviator

Non-radicular neck pain arising from local musculoskeletal structures, known as mechanical neck pain or somatic dysfunction, is highly prevalent in the fighter jet aviator population. The management of this problem includes both therapeutic and aeromedical decisions. In addition to non-steroidal anti-inflammatory medications, waiver guides recommend therapeutic exercise and manipulative therapy as treatments for somatic spine pain in aviators, and such treatments are employed in many military locations. However, there are currently no published studies that describe the use of manipulative therapy for fighter jet aviators. We report the case of an F/A-18 instructor pilot who experienced long-term relief of uncomplicated mechanical neck pain following interdisciplinary management that included manipulation and a home exercise program. Diagnostic considerations, conservative treatment options, and aeromedical concerns are discussed.     

Bacterial overgrowth syndrome in myotonic muscular dystrophy is potentially treatable

Over one third of patients with myotonic muscular dystrophy type 1 (DM1) have gastrointestinal complaints. The cause is multifactorial, and treatment options are limited. Twenty DM1 patients with gastrointestinal symptoms were screened over a 2-year period using glucose breath hydrogen testing (GBHT) to evaluate the prevalence of small intestinal bacterial overgrowth (SIBO). Sixty-five percent of patients had a positive GBHT, and diarrhea was the most common presenting symptom. Ciprofloxacin was the most common antibiotic used for treatment, and 70% of patients reported a good response to the initial course of treatment. Although the causes of gastrointestinal symptoms in patients with DM1 are multifactorial, small intestinal bacterial overgrowth is an important diagnostic consideration that is easily diagnosed using glucose breath hydrogen testing and often shows a good response to treatment with common antibiotics.     

Models for thermal damage in tissues: processes and applications

Irreversible thermal alterations in tissue function and structure are used in clinical applications to achieve diverse goals, from lower-temperature tumor ablation to higher-temperature tissue fusion and surgical cutting. The typical formulation in tumor hyperthermia studies, the thermal iso-effect dose, derives from cell-survival studies but describes a single process only over a limited range of temperatures and is thus not suitable for multiple higher-temperature events. Many other thermal damage processes have been described using the Arrhenius kinetic rate of formation approach, which has the advantage that it is inherently quantitative in nature and can easily be compared with quantitative markers of injury or histologic section. The vast majority of Arrhenius studies have been directed toward measurable cellular effects at relatively low temperatures. Some emphasis in this paper has been placed on what is known of higher-temperature processes to support the theme of this issue. This review compares and contrasts the two thermal-damage formulations and reviews methods to convert between them.     

Augmentation of bone defect healing using a new biocomposite scaffold: An in vivo study in sheep

Previous studies support resorbable biocomposites made of poly(l-lactic acid) (PLA) and β-tricalcium phosphate (TCP) produced by supercritical gas foaming as a suitable scaffold for tissue engineering. The present study was undertaken to demonstrate the biocompatibility and osteoconductive properties of such a scaffold in a large animal cancellous bone model. The biocomposite (PLA/TCP) was compared with a currently used β-TCP bone substitute (ChronOS?, Dr. Robert Mathys Foundation), representing a positive control, and empty defects, representing a negative control. Ten defects were created in sheep cancellous bone, three in the distal femur and two in the proximal tibia of each hind limb, with diameters of 5 mm and depths of 15 mm. New bone in-growth (osteoconductivity) and biocompatibility were evaluated using microcomputed tomography and histology at 2, 4 and 12 months after surgery. The in vivo study was validated by the positive control (good bone formation with ChronOS?) and the negative control (no healing with the empty defect). A major finding of this study was incorporation of the biocomposite in bone after 12 months. Bone in-growth was observed in the biocomposite scaffold, including its central part. Despite initial fibrous tissue formation observed at 2 and 4 months, but not at 12 months, this initial fibrous tissue does not preclude long-term application of the biocomposite, as demonstrated by its osteointegration after 12 months, as well as the absence of chronic or long-term inflammation at this time point.     

LADD syndrome is caused by FGF10 mutations

Lacrimo-auriculo-dento-digital syndrome [LADD (MIM 149730)] is an autosomal-dominant multiple congenital anomaly disorder characterized by aplasia, atresia or hypoplasia of the lacrimal and salivary systems, cup-shaped ears, hearing loss, and dental and digital anomalies. Loss of function mutations in FGF10 were recently described in aplasia of the lacrimal and salivary glands [ALSG (MIM 180920; MIM 103420)] (Entesarian et al., Nat Genet 2005: 37: 125-127, Milunsky et al., American College of Medical Genetics Annual Meeting, Dallas, TX, 2005: A100). Due to the significant phenotypic overlap between LADD syndrome and ALSG and the variable expressivity of both the disorders, we hypothesized that FGF10 mutations could also result in LADD syndrome. A de novo missense mutation was found in exon 3 of FGF10 in a 3-year-old female (Family 1) with LADD syndrome. This missense mutation, resulting in a non-conservative amino acid change, was confirmed by restriction enzyme digestion and was not found in 500 control chromosomes. A nonsense mutation was also found in exon 2 of FGF10 (Family 2) in a 19-year-old mother with ALSG and her 2-year-old daughter with LADD syndrome. Previous studies of FGF10 mutant mice have demonstrated abnormalities consistent with ALSG and LADD syndrome. We conclude that ALSG and LADD syndrome may represent variable presentations of the same clinical spectrum caused by FGF10 mutations.     

Spatial updating in area LIP is independent of saccade direction

We explore the world around us by making rapid eye movements to objects of interest. Remarkably, these eye movements go unnoticed, and we perceive the world as stable. Spatial updating is one of the neural mechanisms that contributes to this perception of spatial constancy. Previous studies in macaque lateral intraparietal cortex (area LIP) have shown that individual neurons update, or "remap," the locations of salient visual stimuli at the time of an eye movement. The existence of remapping implies that neurons have access to visual information from regions far beyond the classically defined receptive field. We hypothesized that neurons have access to information located anywhere in the visual field. We tested this by recording the activity of LIP neurons while systematically varying the direction in which a stimulus location must be updated. Our primary finding is that individual neurons remap stimulus traces in multiple directions, indicating that LIP neurons have access to information throughout the visual field. At the population level, stimulus traces are updated in conjunction with all saccade directions, even when we consider direction as a function of receptive field location. These results show that spatial updating in LIP is effectively independent of saccade direction. Our findings support the hypothesis that the activity of LIP neurons contributes to the maintenance of spatial constancy throughout the visual field.