Dry mouth: saliva substitutes which adsorb and modify existing salivary condition films improve oral lubrication

Clinical Oral Investigations - The aims of this study are to assess different saliva substitutes for their efficacy to lubricate the oral cavity, and to relate this oral lubrication to the ability...     

Facilitating interaction between rauwolscine and angiotensin in the mesenteric artery of the rabbit

Summary The interaction between rauwolscine and angiotensin II was investigated in the isolated mesenteric artery of the rabbit. Rauwolscine, known as an antagonist at ₂-adrenoceptors, did not induce contraction itself but interacted with angiotensin to produce a facilitated response of the vascular tissue. In the presence of rauwolscine, the contractile response of the tissue to angiotensin was markedly enhanced. The degree of facilitation appeared to be dependent on the rauwolscine concentration used rather than that of angiotensin. Moreover, rauwolscine induced a concentration-dependent increase in tension (pD₂=6.8) in the presence of even subcontractile concentrations of angiotensin (10^–10 mol/l). This effect was not attributable to an indirect action involving presynaptic catecholamines, as revealed by the use of tissue strips from animals pretreated with reserpine or after chemical sympathectomy. Furthermore, an interaction via the prostaglandin system was excluded by negative results obtained with indomethacin. The agonistic effect of rauwolscine was significantly attenuated by phentolamine (₁/₂) but not by prazosin (₁) or phenoxybenzamine when applied for only a short time. The ₂-antagonist BDF 6143 behaved like rauwolscine whereas the ₁-antagonist corynanthine, a stereoisomer of rauwolscine, did not. The results indicate that the rauwolscine effect is mediated by a receptor with ₂-characteristics. In general, angiotensin appears to interfere with some process which determines the expression of a drug's intrinsic effect.This study was supported by a grant of the Deutsche Forschungsgemeinschaft     

Hearing loss and cognitive decline in the general population: a prospective cohort study

Journal of Neurology - Previous studies identifying hearing loss as a promising modifiable risk factor for cognitive decline mostly adjusted for baseline age solely. As such a faster cognitive...     

Combined NGS Approaches Identify Mutations in the Intraflagellar Transport Gene IFT140 in Skeletal Ciliopathies with Early Progressive Kidney Disease

Ciliopathies are genetically heterogeneous disorders characterized by variable expressivity and overlaps between different disease entities. This is exemplified by the short rib‐polydactyly syndromes, Jeune, Sensenbrenner, and Mainzer‐Saldino chondrodysplasia syndromes. These three syndromes are frequently caused by mutations in intraflagellar transport (IFT) genes affecting the primary cilia, which play a crucial role in skeletal and chondral development. Here, we identified mutations in IFT140, an IFT complex A gene, in five Jeune asphyxiating thoracic dystrophy (JATD) and two Mainzer‐Saldino syndrome (MSS) families, by screening a cohort of 66 JATD/MSS patients using whole exome sequencing and targeted resequencing of a customized ciliopathy gene panel. We also found an enrichment of rare IFT140 alleles in JATD compared with nonciliopathy diseases, implying putative modifier effects for certain alleles. IFT140 patients presented with mild chest narrowing, but all had end‐stage renal failure under 13 years of age and retinal dystrophy when examined for ocular dysfunction. This is consistent with the severe cystic phenotype of Ift140 conditional knockout mice, and the higher level of Ift140 expression in kidney and retina compared with the skeleton at E15.5 in the mouse. IFT140 is therefore a major cause of cono‐renal syndromes (JATD and MSS). The present study strengthens the rationale for IFT140 screening in skeletal ciliopathy spectrum patients that have kidney disease and/or retinal dystrophy.     

Correction to: Dry mouth: saliva substitutes which adsorb and modify existing salivary condition films improve oral lubrication

Clinical Oral Investigations - After publication of this paper, the authors observed that that figure 6 appears before figure 5.     

Saturating Nonlinearities of Contrast Response in Human Visual Cortex

Response nonlinearities are ubiquitous throughout the brain, especially within sensory cortices where changes in stimulus intensity typically produce compressed responses. Although this relationship is well established in electrophysiological measurements, it remains controversial whether the same nonlinearities hold for population-based measurements obtained with human fMRI. We propose that these purported disparities are not contingent on measurement type and are instead largely dependent on the visual system state at the time of interrogation. We show that deploying a contrast adaptation paradigm permits reliable measurements of saturating sigmoidal contrast response functions (10 participants, 7 female). When not controlling the adaptation state, our results coincide with previous fMRI studies, yielding nonsaturating, largely linear contrast responses. These findings highlight the important role of adaptation in manifesting measurable nonlinear responses within human visual cortex, reconciling discrepancies reported in vision neuroscience, re-establishing the qualitative relationship between stimulus intensity and response across different neural measures and the concerted study of cortical gain control.SIGNIFICANCE STATEMENT Nonlinear stimulus–response relationships govern many essential brain functions, ranging from the sensory to cognitive level. Certain core response properties previously shown to be nonlinear with nonhuman electrophysiology recordings have yet to be reliably measured with human neuroimaging, prompting uncertainty and reconsideration. The results of this study stand to reconcile these incongruencies in the vision neurosciences, demonstrating the profound impact adaptation can have on brain activation throughout the early visual cortex. Moving forward, these findings facilitate the study of modulatory influences on sensory processing (i.e., arousal and attention) and help establish a closer link between neural recordings in animals and hemodynamic measurements from human fMRI, resuming a concerted effort to understand operations in the mammalian cortex.     

The role of the adenoid in allergic sensitisation

Allergic sensitisation of the airways occurs in the mucosa of the shock organ, or in the lymphatic stations draining these structures. The lymphatic structure closest to the nasal mucosa in humans is the adenoid and in mice the nasal mucosa associated lymphoid tissue (NALT). In this study we tried to find evidence for our hypothesis that allergic sensitisation can occur in the adenoid (NALT). The first part of the investigation was set up to determine possible cellular changes in the adenoid of allergic children compared to non-allergic controls using immunohistochemical staining techniques. We found CD1a (Langerhans cells) and eosinophils to be more numerous in the adenoid of allergic children. In the second part of this study we used a murine model to determine if an intranasally applied 'allergen' is processed in the NALT and/or cervical lymph nodes (CLN). An auto fluorescent dye (Di I) was applied into the nasal cavity of mice. At subsequent time intervals mice were terminated. NALT and CLN tissue sections were placed under fluorescent microscopy. We found that Di I transported to both the NALT and CLN. However, the dye remained in the NALT at least 2 days longer than in the CLN. In these studies we found evidence that the lymphoid compartment in the upper respiratory tract (adenoid and NALT) are involved in the processes of allergic diseases.     

A comparison of methods of analysing exercise tests for diagnosis of coronary artery disease

The diagnostic accuracy of the following methods of analysing exercise tests were evaluated: (a) the cumulative area of ST segment depression during exercise normalised for workload and heart rate (exercise score); (b) discriminant analysis of electrocardiographic exercise variables, workload, and symptoms; and (c) ST segment amplitude changes during exercise adjusted for heart rate. Three hundred and forty five men without a history of myocardial infarction were studied. One hundred and twenty three were apparently healthy. Less than half (170) had coronary artery disease. All had a normal electrocardiogram at rest. A Frank lead electrocardiogram was computer processed during symptom limited bicycle ergometry. The accuracy of the exercise score (a) was low (sensitivity 67%, specificity 90%). Discriminant analysis (b) and ST segment amplitude changes adjusted for heart rate (c) had excellent diagnostic characteristics (sensitivity 80%, specificity 90%), which were little affected by concomitant use of beta blockers. Both methods seem well suited for diagnostic application in clinical practice.     

Effect of catheter placement on 3-D velocity profiles in curved tubes resembling the human coronary system.

Novel measurement techniques based on intravenous ultrasound (IVUS) technology ('IVUS-Flowmetry') require the location of a catheter inside the coronary bed. The present study quantifies disturbances in the 3-D velocity profile induced by catheter placement inside a tube, applying computational fluid dynamics. Two curved, circular meshes (radius K = 0.025 m and K = 0.035 m) with and without a catheter inside the lumen were applied. The catheter was located at the inner curve, the outer curve and at the top position. Boundary conditions were: no slip on the wall, zero stress at the outlet, uniform inflow with entrance velocities of 0.1, 0.2 and 0.4 m/s. Curvature-associated centrifugal forces shifted the maximal velocity to the outer curve and introduced two symmetrical vortices. Additional catheter placement redistributed the 3-D axial velocity field away from the catheter, which was accompanied by the appearance of multiple low-strength vortices. In addition, peak axial velocity increased, peak secondary velocities decreased, axial pressure drop increased and shear stress increased. Flow calculations simulated to resemble IVUS-based flowmetry changed by only 1% after considering secondary velocity. In conclusion, placement of a catheter inside a curved tube resembling the human coronary system changes the velocity field and reduces secondary patterns. The present study supports the usefulness of catheter-based flowmetry during resting flow conditions. During hyperemic flow conditions, flow measurements might be accompanied by large axial pressure drops because the catheter, itself, might act as a significant stenosis.