Mathematical Modelling of Glucose‐Dependent Insulinotropic Polypeptide and Glucagon‐like Peptide‐1 following Ingestion of Glucose

The incretin hormones, glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1), play an important role in glucose homeostasis by potentiating glucose‐induced insulin secretion. Furthermore, GLP‐1 has been reported to play a role in glucose homeostasis by inhibiting glucagon secretion and delaying gastric emptying. As the insulinotropic effect of GLP‐1 is preserved in patients with type 2 diabetes (T2D), therapies based on GLP‐1 have been developed in recent years, and these have proven to be efficient in the treatment of T2D. The endogenous secretion of both GIP and GLP‐1 is stimulated by glucose in the small intestine, and the release is dependent on the amount. In this work, we developed a semimechanistic model describing the release of GIP and GLP‐1 after ingestion of various glucose doses in healthy volunteers and patients with T2D. In the model, the release of both hormones is stimulated by glucose in the proximal small intestine, and no differences in the secretion dynamics between healthy individuals and patients with T2D were identified after taking differences in glucose profiles into account.     

Added value of interpreter experience in occult and suspect hip fractures: a retrospective analysis of 254 patients

The influence of experience in categorizing suspect and occult fractures on radiography compared to MRI and clinical outcome has not been studied. The aim of this study is to evaluate the importance of experience in diagnosing normal or suspect hip radiographs compared to MRI. Primarily reported normal or suspect radiography in 254 patients with low-energy hip trauma and subsequent MRI was re-evaluated by two experienced reviewers. Primary readings and review were compared. The prevalence of fractures among normal and suspect radiographic studies was assessed. Clinical outcome was used as reference. At review of radiography, 44 fractures (17 %) were found. Significantly more fractures were found among suspect cases than among normal cases. At MRI, all 44 fractures were confirmed, and further 64 fractures were detected (25 %). MRI detected all fractures with no missed fractures revealed at follow-up. There were a significantly higher proportion of fractures at MRI among the suspect radiographic diagnoses for both the primary report and at review than among occult cases. The more experienced reviewers classified radiography examinations with higher accuracy than primary reporting general radiologists. There was almost complete agreement on MRI diagnoses.     

The Communication Supports Inventory-Children & Youth (CSI-CY), a new instrument based on the ICF-CY

Purpose: Two studies are presented that evaluated the Communication Supports Inventory-Children & Youth (CSI-CY), an instrument designed to facilitate the development of communication-related educational goals for students with complex communication needs (CCN). The CSI-CY incorporates a code set based on the ICF-CY. The studies were designed to determine the effect of using the CSI-CY on IEP goals for students with CCN and to evaluate consumer satisfaction.

Method: In Study 1, sixty-one educators and speech–language pathologists were randomly assigned to either (a) provide a student’s current IEP (control group) or (b) complete the CSI-CY prior to preparing a student’s next IEP and to submit the new IEP (experimental group). Study 2 was a field test to generate consumer satisfaction data.

Results: Study 1 showed that IEP goals submitted by participants in the experimental group referenced CSI-CY-related content significantly more frequently than did those submitted by control participants. Study 2 revealed high satisfaction with the instrument.

Conclusions: The code set basis of the CSI-CY extends the common language of the ICF-CY to practical educational use for children with CCN across diagnostic groups. The CSI-CY is well regarded as an instrument to inform the content of communication goals related to CCN.

• Implications for Rehabilitation

• The CSI-CY will guide rehabilitation professionals to develop goals for children with complex communication impairments.

• The CSI-CY is a new instrument that is based on the ICF-CY for documentation of communication goals.

     

Exploring central and peripheral diversity in antibody evolution

The antigen-binding site, the paratope, of an antibody can be seen as being composed of a central core and a more peripheral area situated at its rim. Naturally these regions acquire their diversity using different mechanisms and they also have dissimilar roles, as they contribute differently to the binding interaction. Also, antigens of different size utilize these regions differently; while haptens mainly interact with the central core, larger antigens have additional interactions in more peripheral regions. Since haptens do not occupy the entire available paratope we hypothesized that hapten-specific antibodies, as they develop naturally or in the laboratory, have an imprint of the carrier protein they were once selected on. By using combinatorial library and phage display technologies on a hapten-specific antibody we were able to demonstrate that a peripheral carrier imprint indeed exists. We further show that such an imprint can act as a seed in the evolution of binders that recognize the carrier protein even in the absence of the hapten modification. The observed results provide a plausible mechanism for how haptenization of self-antigens can lead to the development of autoimmunity.     

Microarray-based molecular detection of foot-and-mouth disease, vesicular stomatitis and swine vesicular disease viruses, using padlock probes

The World Organization for Animal Health (Office International des Epizooties, OIE) includes the diseases caused by foot-and-mouth disease virus (FMDV), swine vesicular disease virus (SVDV), and vesicular stomatitis virus (VSV), as "Diseases Notifiable to the OIE". Foot-and-mouth disease (FMD) outbreaks have severe economical as well as social effects and cannot be differentiated from the diseases caused by the other two viruses on the basis of clinical symptoms. Efficient laboratory techniques are therefore required for detection and identification of the viruses causing similar vesicular symptoms in swine. A rapid method is described using padlock probes and microarrays to detect simultaneously and differentiate the three viruses in a single reaction, as well as providing serotype information in cases of VSV infection. The padlock probe/microarray assay detected successfully and identified 39 cDNA samples of different origin representing the three viruses. The results were in complete agreement with identities and serotypes determined previously. This novel virus detection method is discussed in terms of usefulness and further development.     

Forces applied by anterior and posterior teeth and roles of periodontal afferents during hold-and-split tasks in human subjects

Hold-and-split tasks were performed by 20 subjects (12 females and 8 males) using the right central incisors, canines, 2nd premolars, and 1st molars, respectively. Half a peanut was positioned on a transducer-equipped plate and the subject was instructed to hold the plate with the peanut between two antagonistic teeth, and not using more force than necessary. After ca. 3 s the subject was instructed to split the peanut in a natural manner. Each session consisted of a series of three in which the subject performed the hold-and-split task five times for each tooth. Thus, in total, data were obtained from 60 trials for each subject. The magnitude of the forces and the force rates used to split the peanut increased distally along the dental arch. However, the duration of the split phase was similar for the various teeth examined. During anesthesia of the periodontal ligament (four subjects), no significant changes were seen in the split phase. The forces used to hold the peanut between the teeth also increased distally along the dental arch: 0.60 N for the incisor, 0.77 N for the canine, 1.15 N for the 2nd premolar, and 1.74 N for the 1st molar. The difference in hold forces for the various teeth can be explained by the different sensitivity characteristics of the periodontal afferents innervating anterior and posterior teeth. During periodontal anesthesia, the magnitude and variability of the hold forces increased for all types of teeth, thus supporting the suggestion that periodontal afferent information is used in the regulation of the level of forces used to hold and manipulate morsels between the teeth.     

Long-term effect of hand-arm vibration on thermotactile perception thresholds

Background

Occupational exposure to hand-transmitted vibration (HTV) is known to cause neurological symptoms such as numbness, reduced manual dexterity, grip strength and sensory perception. The purpose of this longitudinal study was to compare thermotactile perception thresholds for cold (TPT_C) and warmth (TPT_W) among vibration exposed manual workers and unexposed white collar workers during a follow-up period of 16 years to elucidate if long-term vibration exposure is related to a change in TPT over time.

Methods

The study group consisted of male workers at a production workshop at which some of them were exposed to HTV. They were investigated in 1992 and followed-up in 2008. All participants were physically examined and performed TPT bilaterally at the middle and distal phalanges of the second finger. Two different vibration exposure dosages were calculated for each individual, i.e. the individual cumulative lifetime dose (mh/s²) or a lifetime 8-h equivalent daily exposure (m/s²).

Results

A significant mean threshold difference was found for all subjects of about 4–5 °C and 1–2 °C in TPT_W and TPT_C, respectively, between follow-up and baseline. No significant mean difference in TPT_C between vibration exposed and non-exposed workers at each occasion could be stated to exist. For TPT_W a small but significant difference was found for the right index finger only. Age was strongly related to thermotactile perception threshold. The 8-h equivalent exposure level (A (8)) dropped from about 1.3 m/s² in 1992 to about 0.7 m/s² in 2008.

Conclusions

A lifetime 8-h equivalent daily exposure to hand-transmitted vibration less than 1.3 m/s² does not have a significant effect on thermotactile perception. Age, however, has a significant impact on the change of temperature perception thresholds why this covariate has to be considered when using TPT as a tool for health screening.

     

Reconstruction of the atrophic edentulous maxilla with free iliac crest grafts and implants: a 3-year report of a prospective clinical study

Purpose: The purpose of this study was to perform a longitudinal follow-up study of implant stability in grafted maxillae with the aid of clinical, radiological, and resonance frequency analysis (RFA) parameters. Materials and Methods: The atrophic edentulous maxillae in 29 patients were reconstructed with free iliac crest grafts using onlay/inlay or interpositional grafting techniques. The endpoint of the resorption pattern in the maxilla determined the grafting technique used. Endosteal implants were placed after 6 months of bone-graft healing. Implant stability was measured four times using RFA: when the implants were placed, after 6 to 8 months of healing, after 6 months and 3 years of bridge loading. Individual checkups were performed at the two later RFA registrations after removal of the supraconstructions (Procera® Implant Bridge, Nobel Biocare AB, Göteborg, Sweden). Radiological follow up of marginal bone level was performed annually. Results: Twenty-five patients remained for the follow-up period. A total of 192 implants were placed and with a survival rate of 90% at the 3-year follow up. Women and an implant position with a class 6 resorption prior to reconstruction were factors with significant increased risk for implant failure (multivariate logistic regression). Twelve of the 20 failed implants were lost before loading (early failures). The change in the marginal bone level was 0.3 ± 0.3 mm between baseline (bridge delivery) and the 3-year follow up. The implant stability quotient (ISQ) value for all implants differed significantly between abutment connection (60.2 ± 7.3) and after 6 months of bridge loading (62.5 ± 5.5) (Wilcoxon signed ranks test for paired data, p=.05) but were nonsignificant between 6 months of bridge loading and 3 years of bridge loading (61.8 ± 5.5). There was a significant difference between successful and failed implants when the ISQ values were compared for individual implants at placement (Mann-Whitney U test, p=.004). All 25 patients were provided with fixed implant bridges at the time of the 3-year follow up. Conclusion: This clinical follow up using radiological examinations and RFA measurements indicates a predictable and stable long-term result for patients with atrophic edentulous maxillae reconstructed with autogenous bone and with delayed placement of endosteal implants. The ISQ value at the time of placement can probably serve as an indicator of level of risk for implant failure.