Increased fMRI responses during encoding in mild cognitive impairment

Structural and functional magnetic resonance imaging (fMRI) was performed on 21 healthy elderly controls, 14 subjects with mild cognitive impairment (MCI) and 15 patients with mild Alzheimer's disease (AD) to investigate changes in fMRI activation in relation to underlying structural atrophy. The fMRI paradigm consisted of associative encoding of novel picture-word pairs. Structural analysis of the brain was performed using voxel-based morphometry (VBM) and hippocampal volumetry. Compared to controls, the MCI subjects exhibited increased fMRI responses in the posterior hippocampal, parahippocampal and fusiform regions, while VBM revealed more atrophy in MCI in the anterior parts of the left hippocampus. Furthermore, the hippocampal volume and parahippocampal activation were negatively correlated in MCI, but not in controls or in AD. We suggest that the increased fMRI activation in MCI in the posterior medial temporal and closely connected fusiform regions is compensatory due to the incipient atrophy in the anterior medial temporal lobe.     

The human GIMAP5 gene has a common polyadenylation polymorphism increasing risk to systemic lupus erythematosus

Background

Several members of the GIMAP gene family have been suggested as being involved in different aspects of the immune system in different species. Recently, a mutation in the GIMAP5 gene was shown to cause lymphopenia in a rat model of autoimmune insulin‐dependent diabetes. Thus it was hypothesised that genetic variation in GIMAP5 may be involved in susceptibility to other autoimmune disorders where lymphopenia is a key feature, such as systemic lupus erythematosus (SLE).

Material and methods

To investigate this, seven single nucleotide polymorphisms in GIMAP5 were analysed in five independent sets of family‐based SLE collections, containing more than 2000 samples.

Result

A significant increase in SLE risk associated with the most common GIMAP5 haplotype was found (OR 1.26, 95% CI 1.02 to 1.54, p = 0.0033). In families with probands diagnosed with trombocytopenia, the risk was increased (OR 2.11, 95% CI 1.09 to 4.09, p = 0.0153). The risk haplotype bears a polymorphic polyadenylation signal which alters the 3′ part of GIMAP5 mRNA by producing an inefficient polyadenylation signal. This results in higher proportion of non‐terminated mRNA for homozygous individuals (p<0.005), a mechanism shown to be causal in thalassaemias. To further assess the functional effect of the polymorphic polyadenylation signal in the risk haplotype, monocytes were treated with several cytokines affecting apoptosis. All the apoptotic cytokines induced GIMAP5 expression in two monocyte cell lines (1.5–6 times, p<0.0001 for all tests).

Conclusion

Taken together, the data suggest the role of GIMAP5 in the pathogenesis of SLE.     

Effects of tissue-engineered articular disc implants on the biomechanical loading of the human temporomandibular joint in a three-dimensional finite element model

The purpose of this study was to evaluate biomechanical loading of the temporomandibular joint when using a biodegradable laminate implant to replace the articular disc and to test the hypothesis that the use of the implant reduces stress distribution in the condyle, implant, and glenoid fossa. A finite element model of a female human mandible, including the temporomandibular joint, which had two standard endosseous implants inserted bilaterally in the premolar region, was constructed from computed tomography scan images using a commercially available finite element software. The disc, condyle, and glenoid fossa were arbitrarily divided into five regions: the anterior, posterior, medial, lateral, and central. The disc was then replaced with a poly-L/DL-lactide biodegradable laminate. The finite element model was then used to predict principal and Von Mises stresses. The use of poly-L/DL-lactide implant resulted in remarkable reduction in Von Mises stresses (approximately threefold) in the anterior, central, and medial regions of the mandibular condyle in comparison with slight to moderate stress reductions in the corresponding regions of the implant and glenoid fossa. The mandibular condyle also demonstrated the largest total displacement in all directions followed by the implant and glenoid fossa. The use of an alloplastic implant such as the bioresorbable, poly-L/DL-lactide laminate to replace the articular disc reduces loading of the mandibular condyle rather than the implant and glenoid fossa. These findings lead to support the hypothesis that the mandibular condyle more likely functions as a shock absorber than the disc. The use of bioresorbable laminate implants might prove an efficient technique to replace the articular disc and promote normal function of the temporomandibular joint.     

Dual contrast in computed tomography allows earlier characterization of articular cartilage over single contrast

Cationic computed tomography contrast agents are more sensitive for detecting cartilage degeneration than anionic or non-ionic agents. However, osteoarthritis-related loss of proteoglycans and increase in water content contrarily affect the diffusion of cationic contrast agents, limiting their sensitivity. The quantitative dual-energy computed tomography technique allows the simultaneous determination of the partitions of iodine-based cationic (CA4+) and gadolinium-based non-ionic (gadoteridol) agents in cartilage at diffusion equilibrium. Normalizing the cationic agent partition at diffusion equilibrium with that of the non-ionic agent improves diagnostic sensitivity. We hypothesize that this sensitivity improvement is also prominent during early diffusion time points and that the technique is applicable during contrast agent diffusion. To investigate the validity of this hypothesis, osteochondral plugs (d = 8 mm, N = 33), extracted from human cadaver (n = 4) knee joints, were immersed in a contrast agent bath (a mixture of CA4+ and gadoteridol) and imaged using the technique at multiple time points until diffusion equilibrium. Biomechanical testing and histological analysis were conducted for reference. Quantitative dual-energy computed tomography technique enabled earlier determination of cartilage proteoglycan content over single contrast. The correlation coefficient between human articular cartilage proteoglycan content and CA4+ partition increased with the contrast agent diffusion time. Gadoteridol normalized CA4+ partition correlated significantly (P < .05) with Mankin score at all time points and with proteoglycan content after 4 hours. The technique is applicable during diffusion, and normalization with gadoteridol partition improves the sensitivity of the CA4+ contrast agent.     

A Meta‐Analysis of the Association of Fracture Risk and Body Mass Index in Women

Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20–105) years and follow up of 2.2 million person‐years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m²) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non‐obese women. Compared to a BMI of 25 kg/m², the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m² was 0.87 (95% confidence interval [CI], 0.85–0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09–1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored. © 2014 American Society for Bone and Mineral Research.     

Central Nervous System and Ocular Manifestations in Puumala Hantavirus Infection

Puumala hantavirus (PUUV), carried and spread by the bank vole (Myodes glareolus), causes a mild form of hemorrhagic fever with renal syndrome (HFRS) called nephropathia epidemica (NE). Acute high fever, acute kidney injury (AKI), thrombocytopenia, and hematuria are typical features of this syndrome. In addition, headache, blurred vision, insomnia, vertigo, and nausea are commonly associated with the disease. This review explores the mechanisms and presentations of ocular and central nervous system involvement in acute NE.     

Clinical value of ultrasound in the evaluation of dyspepsia in primary health care

OBJECTIVE: In general practice, upper abdominal ultrasound (US) is widely used in the evaluation of patients with dyspepsia. However, there is a dearth of published data on the role of US in the dyspepsia work-up. There are no data on the use of US as a follow-up study in functional dyspepsia. The aims of this study were to assess the role of US in evaluating dyspepsia, and to assess the long-term clinical relevance of minor findings revealed by US in patients with functional dyspepsia. MATERIAL AND METHODS: Four hundred consecutive dyspeptic patients were recruited. At baseline, all patients underwent gastroscopy and US. Patients were divided into two groups: "endoscopy-negative patients" and "endoscopy-positive patients". "The endoscopy-negative" group included all cases in which the final diagnoses could not be settled after gastroscopy. US was repeated after 6-7 years in patients who had functional dyspepsia. RESULTS: In the endoscopy-negative group, gallstones were detected in 21 patients, but this was considered to be a cause of symptoms in 9 patients. No malignant lesions were detected by US in the endoscopy-negative group. In the endoscopy-positive group, a malignant tumor in the kidney was suspected in 3 patients. Only one of these tumors turned out to be an incidental small carcinoma. Moreover, several minor findings were shown by US: usually these consisted of abnormal echogenicity of the liver. During the follow-up period, 6 patients developed gallstones. At the end of the follow-up period, two clinically significant findings were diagnosed: a small renal cancer and hydronephrosis. CONCLUSIONS: This study shows that the wide, untargeted use of abdominal US in the evaluation of patients with dyspepsia following a gastroscopy is not necessary. Repeated US examination in cases of functional dyspepsia is not recommended, and rarely changes the diagnosis.