Short-term outcome after treatment of talocrural instability in cats using modified type II transarticular external skeletal fixation.

Transarticular external skeletal fixation (TESF) is repeatedly used for temporary stabilisation of tarsal joint in cats. Hence, this study aimed to evaluate the use of temporary modified type II TESF for management of talocrural instability (TCI) in cats without joint arthrodesis and to rate short-term outcomes and complications. Medical records of all cats treated for TCI between January 2012 and December 2021 were reviewed. Information was collected including signalment, degree of lameness, type of TCI, accompanying soft tissue and bone injuries, and post-operative follow-up assessment including time of frame removal, complications, degree of lameness, range of joint motion and ankylosis. Surgical management didn't involve debridement of the articular cartilage. Eighty-five percent of cats had satisfactory joint stability at the time of frame removal. Eighteen cats exhibited minor complications, six cats had major complications, and 8 cats showed persistent lameness. All cats showed reduction of joint motion range by 20°-30° directly after frame removal while returned to normal in 79% of cats 4 weeks later. Variable degrees of joint ankylosis were reported. In conclusion, this study supports the use of temporary modified type II TESF for management of TCI in cats without joint involvement as an excellent alternative to tarsal arthrodesis.

Dilated perivascular spaces can present incidental CSF-isointense foci within the ventral forebrain of dogs and cats in transverse MR images.

Objective: Virchow-Robin-Spaces (VRS) are cerebrospinal fluid (CSF)-containing perivascular spaces encompassing brain vessels while coursing through the parenchyma. VRS can enlarge and become visible in magnetic resonance imaging (MRI). While dilatated VRS are mostly incidental findings, they were associated with degenerative brain disease in humans. This study aimed to evaluate their occurrence and MRI morphology within the ventral forebrain of structurally normal canine and feline brains and physiological cerebrospinal fluid analysis. Sample: Retro- and prospective, observational study reviewing medical records of client-owned dogs and cats which underwent MRI brain scans for unrelated reasons between 2011 and 2021. We comprised studies with various magnetic field strengths (1 Tesla/3 Tesla). Out of 2500 brain scans, three hundred thirty-five patients (293 dogs, 42 cats) presented with absent intracranial pathology and physiological CSF analysis and were included. Procedure: The ventral forebrain of the included animals was assessed for bi- or unilateral CSF-isointense foci in the transverse plane. Statistical correlations were evaluated between dilated VRS presence, field strength, age, gender, weight, and cranium conformation. Additionally, a post-mortem histopathologic analysis of one dog and one cat showing dilated VRS on MRI was performed to confirm perforating arteries in the gray matter of the ventral forebrain. Results: 57% of patients presented dilated VRS (N = 191: 170 dogs, 21 cats). 43% did not display dilated VRS (control group; N = 144: 123 dogs, 21 cats). A significant relation between increased magnetic field strength and detection of dilated VRS was observed in dogs; there was a 2.4 increase (p = 0.0001) in detection using 3 Tesla vs. 1 Tesla. There was a 2.4-fold increase in dilated VRS occurrence in male dogs compared to female dogs. Detection also increased with the rise of body weight. We detected no statistically significant difference between dilated VRS and the control group in age, species or cranium conformation. Conclusion and Clinical Relevance: Dilated VRS can be seen within the ventral forebrain at the level of the rostral commissure on transverse MR images as symmetrical or unilateral, dot-like, CSF-isointense areas. Understanding their signal intensity features and localization prevents misinterpretation and helps differentiate them from various pathological conditions.

Results at the 1-Year Follow-Up of a Prospective Cohort Study with Short, Zirconia Implants.

The objective of this study was to clinically and radiologically evaluate the performance of a short (8 mm), 1-piece, zirconia implant after an observation period of 1 year in function. A total of 47 patients with 1 missing tooth in the position of a premolar or molar were recruited. Short (8 mm), 1-piece, zirconia implants were placed and loaded after a healing period of 2 to 4 months with monolithic crowns made of 3 different materials. Implants were followed up for one year and clinically and radiologically assessed. A total of 46 implants were placed. One was excluded since no primary stability was achieved at implant placement. At the 1-year follow-up, mean marginal bone loss 1 year after loading was 0.05 ± 0.47 mm. None of the implants showed marginal bone loss greater than 1 mm or clinical signs of peri-implantitis. A total of 2 implants were lost during the healing phase and another after loading, resulting in a survival rate of 93% after 1 year. All lost implants showed a sudden increased mobility with no previous signs of marginal bone loss or peri-implant infection. The short, 8 mm, zirconia implants showed stable marginal bone levels over the short observation period of 1 year. Although they revealed slightly lower survival rates, they can be suggested for the use in sites with reduced vertical bone. Scientific data are very limited, and long-term data are not yet available, and therefore, they are needed.

The Structural and the Functional Aspects of Intercellular Communication in iPSC-Cardiomyocytes.

Recent advances in the technology of producing novel cardiomyocytes from induced pluripotent stem cells (iPSC-cardiomyocytes) fuel new hope for future clinical applications. The use of iPSC-cardiomyocytes is particularly promising for the therapy of cardiac diseases such as myocardial infarction, where these cells could replace scar tissue and restore the functionality of the heart. Despite successful cardiogenic differentiation, medical applications of iPSC-cardiomyocytes are currently limited by their pronounced immature structural and functional phenotype. This review focuses on gap junction function in iPSC-cardiomyocytes and portrays our current understanding around the structural and the functional limitations of intercellular coupling and viable cardiac graft formation involving these novel cardiac muscle cells. We further highlight the role of the gap junction protein connexin 43 as a potential target for improving cell-cell communication and electrical signal propagation across cardiac tissue engineered from iPSC-cardiomyocytes. Better insight into the mechanisms that promote functional intercellular coupling is the foundation that will allow the development of novel strategies to combat the immaturity of iPSC-cardiomyocytes and pave the way toward cardiac tissue regeneration.

Artemisinin-treatment in pre-symptomatic APP-PS1 mice increases gephyrin phosphorylation at Ser270: a modification regulating postsynaptic GABAAR density.

Artemisinins, a group of plant-derived sesquiterpene lactones, are efficient antimalarial agents. They also share anti-inflammatory and anti-viral activities and were considered for treatment of neurodegenerative disorders like Alzheimer's disease (AD). Additionally, artemisinins bind to gephyrin, the multifunctional scaffold of GABAergic synapses, and modulate inhibitory neurotransmission in vitro. We previously reported an increased expression of gephyrin and GABAA receptors in early pre-symptomatic stages of an AD mouse model (APP-PS1) and in parallel enhanced CDK5-dependent phosphorylation of gephyrin at S270. Here, we studied the effects of artemisinin on gephyrin in the brain of young APP-PS1 mice. We detected an additional increase of gephyrin protein level, elevated gephyrin phosphorylation at Ser270, and an increased amount of GABAAR-γ2 subunits after artemisinin-treatment. Interestingly, the CDK5 activator p35 was also upregulated. Moreover, we demonstrate decreased density of postsynaptic gephyrin and GABAAR-γ2 immunoreactivities in cultured hippocampal neurons expressing gephyrin with alanine mutations at two CDK5 phosphorylation sites. In addition, the activity-dependent modulation of synaptic protein density was abolished in neurons expressing gephyrin lacking one or both of these phosphorylation sites. Thus, our results reveal that artemisinin modulates expression as well as phosphorylation of gephyrin at sites that might have important impact on GABAergic synapses in AD.

Comparison of Dorsal-to-Ventral Ratios of the Cervical Paraspinal Musculature in French Bulldogs With and Without Cervical Intervertebral Disk Disease and Two Other Breeds Based on CT Scan Measurements.

Objective: To objectively assess the cervical paraspinal musculature of French bulldogs (FBs) using computed tomography (CT) scan-based measurements, outline differences in other breeds published in the literature, and investigate the potential influence of its cervical paraspinal musculature on predisposed sites for intervertebral disk disease. Animals: Thirty FBs that underwent CT scans of the cervical spine from the skull to C7/T1 were enrolled. Fifteen dogs were patients suffering from intervertebral disk herniation (IVDH group), and 15 dogs underwent CT scans due to brachycephalic obstructive airway syndrome (BOAS group). Methods: At the level of each cervical intervertebral disk from C2/C3 to C7/T1, measurements were performed and statistically analyzed. On the sagittal CT scan reconstruction, the height ratio of the dorsal to ventral paraspinal musculature and the angle of the disk axis to vertebral body length were assessed. On the transverse plane, the area ratio of the dorsal and ventral paraspinal musculature and the ratio of force moments were determined at each intervertebral disk level. Finally, ratios were compared to the values of Labrador retrievers and dachshunds published by Hartmann et al. (1). Results: Comparing the two FB groups, one significant difference was detected in the mean height ratio of the dorsal to ventral paraspinal musculature at the level of C5/C6 (P = 0.0092) and C6/C7 (P = 0.0076), with IVDH FBs having the more prominent dorsal paraspinal musculature. At the level of C3/C4, a significantly less prominent dorsal paraspinal musculature in FBs than in dachshunds (P = 0.0058) and a significantly steeper disk to vertebral body angulation were observed (P = 0.0005). Conclusion: Although some incidental differences were found, most parameters did not significantly differ between the BOAS and IVDH FBs. Significant conformational differences in the cervical paraspinal musculature and disk to vertebral body length angulation were found between FBs and two other breeds (chondrodystrophic and non-chondrodystrophic). This study's findings suggest that the paraspinal musculature is an additional biomechanical influencing factor on the preferential sites of IVDH in the cervical spine and that other major factors exist in IVDH development, especially in FBs.

CT-Scan Based Evaluation of Dorsal-to-Ventral Ratios of Paraspinal Musculature in Chondrodystrophic and Non-chondrodystrophic Dogs.

Objective: To assess and objectively quantify, with CT-scan exams, differences in cervical paraspinal musculature and vertebrae angulation that might influence the different predisposed sites for intervertebral disk disease observed in chondrodystrophic and non-chondrodystrophic breeds. Sample: Retrospective evaluation and analysis of cervical spine CT-scans performed on 30 dogs presented for clinical reasons unrelated to a cervical disk problem. 15 chondrodystrophic (Dachshunds) and 15 non-chondrodystrophic dogs (Labrador Retrievers) were included. Procedures: Height measurements of dorsal and ventral paraspinal musculature were performed on sagittal CT-scan reconstructions to generate dorsal-to-ventral height ratios. Additionally, disk angulation to the floor of the vertebral canal was determined for each cervical disk. On transverse plane images the areas of the dorsal and the ventral paraspinal musculature were measured and ratios calculated. Furthermore, estimations of moments exerted on the disk were evaluated through calculation of a dorsal-to-ventral ratio of moments applied at the level of each disk. Results: Dachshunds showed a relatively more prominent dorsal paraspinal musculature than Labrador Retrievers with statistically significant higher dorsal-to-ventral height ratios at C3/C4, C4/C5, C7/T1 (p = 0.034*, p = 0,004**, p = 0.004**) and a dorsal-to-ventral area ratio at C3/C4 (p < 0.001**). Regarding the disk angle to the spinal canal floor along the cervical spine, Labrador Retrievers had a less steep conformation compared to Dachshunds with a significant difference at C2/C3 (p < 0.001**). Relation of moments calculations revealed statistically significant differences at C2/C3 (p = 0.021*). Conclusion and Clinical Relevance: Significant differences have been found in the cervical spine of chondrodystrophic and non-chondrodystrophic dogs, regarding paraspinal musculature height and area ratios along with ratio of moments and vertebrae angulation. These differences may affect the anatomical and biomechanical dorsal-to-ventral paraspinal muscle relationship and potentially influence the load on intervertebral disks, especially in the upper cervical spine. Our findings could play a role in understanding the development of intervertebral disk disease.

A Non-Cytotoxic Resin for Micro-Stereolithography for Cell Cultures of HUVECs.

Three-dimensional (3D) printing of microfluidic devices continuously replaces conventional fabrication methods. A versatile tool for achieving microscopic feature sizes and short process times is micro-stereolithography (µSL). However, common resins for µSL lack biocompatibility and are cytotoxic. This work focuses on developing new photo-curable resins as a basis for µSL fabrication of polymer materials and surfaces for cell culture. Different acrylate- and methacrylate-based compositions are screened for material characteristics including wettability, surface roughness, and swelling behavior. For further understanding, the impact of photo-absorber and photo-initiator on the cytotoxicity of 3D-printed substrates is studied. Cell culture experiments with human umbilical vein endothelial cells (HUVECs) in standard polystyrene vessels are compared to 3D-printed parts made from our library of homemade resins. Among these, after optimizing material composition and post-processing, we identify selected mixtures of poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) methyl ethyl methacrylate (PEGMEMA) as most suitable to allow for fabricating cell culture platforms that retain both the viability and proliferation of HUVECs. Next, our PEGDA/PEGMEMA resins will be further optimized regarding minimal feature size and cell adhesion to fabricate microscopic (microfluidic) cell culture platforms, e.g., for studying vascularization of HUVECs in vitro.

In vivo tooth-color measurement with a new 3D intraoral scanning system in comparison to conventional digital and visual color determination methods.

STATEMENT OF PROBLEM: Three-dimensional (3D) intraoral scanning systems allow for the simultaneous acquisition of 3D information about tooth surfaces and a photorealistic view of the patient's tooth colors. AIM: The goal of this study was the in vivo comparison of a new 3D scanner with a color acquisition mode and conventional visual and digital color measurements. MATERIALS AND METHODS: The colors of 40 teeth of 20 patients were evaluated in seven ways: 1) By dentists using the Vita 3D-Master; 2) By dental technicians using the Vita 3D-Master; 3) With the 3Shape Trios device; 4) With the Vita Easyshade device; 5) With the Vita Easyshade Advance device; 6) With the SpectroShade device; and 7) With the SpectroShade Micro device. Digital measurements of Groups 3 to 7 were repeated three times for each tooth. For all groups, both the CIE Lab values and the Vita 3D-Master values were recorded. The repeatability and relative accuracy of the Vita 3D-Master values were analyzed statistically using Pearson's chi-squared test (α < 0.05). ΔE values were calculated from the CIE Lab values, which served as a basis for performing multidimensional scaling (MDS) and evaluating differences between the groups using the one-way ANOVA with post hoc Tamhane's test (α < 0.05). RESULTS: The results of the ΔE values showed that clinically relevant differences between the evaluation by dentists, dental technicians, and the intraoral scanning device (3Shape) are negligible. The intraoral 3D scanning device (Group 3) and the digital systems (Groups 4 to 7) did not differ significantly in the repeatability of color shade management. The SpectroShade Micro (Group 7) had significantly better relative accuracy than the other devices. CONCLUSIONS: The results demonstrate that intraoral scanning systems can be used to measure both tooth color and tooth surface in 3D. CLINICAL IMPLICATIONS: Intraoral optical scanning devices allow for the acquisition of accurate 3D surface data. Tooth color can be evaluated simultaneously and can be used to determine the color of restorations without requiring additional conventional color-measurement methods.

Efficacy and safety of betahistine treatment in patients with Meniere's disease: primary results of a long term, multicentre, double blind, randomised, placebo controlled, dose defining trial (BEMED trial).

STUDY QUESTION: What is the long term efficacy of betahistine dihydrochloride on the incidence of vertigo attacks in patients with Meniere's disease, compared with placebo? METHODS: The BEMED trial is a multicentre, double blind, randomised, placebo controlled, three arm, parallel group, phase III, dose defining superiority trial conducted in 14 German tertiary referral centres (for neurology or ear, nose, and throat). Adults aged 21-80 years (mean age 56 years) with definite unilateral or bilateral Meniere's disease were recruited from March 2008 to November 2012. Participants received placebo (n=74), low dose betahistine (2 × 24 mg daily, (n=73)), or high dose betahistine (3 × 48 mg daily, (n=74)) over nine months. The primary outcome was the number of attacks per 30 days, based on patients' diaries during a three month assessment period at months seven to nine. An internet based randomisation schedule performed a concealed 1:1:1 allocation, stratified by study site. Secondary outcomes included the duration and severity of attacks, change in quality of life scores, and several observer-reported parameters to assess changes in audiological and vestibular function. STUDY ANSWER AND LIMITATIONS: Incidence of attacks related to Meniere's disease did not differ between the three treatment groups (P=0.759). Compared with placebo, attack rate ratios were 1.036 (95% confidence interval 0.942 to 1.140) and 1.012 (0.919 to 1.114) for low dose and high dose betahistine, respectively. The overall monthly attack rate fell significantly by the factor 0.758 (0.705 to 0.816; P<0.001). The population based, mean monthly incidence averaged over the assessment period was 2.722 (1.304 to 6.309), 3.204 (1.345 to 7.929), and 3.258 (1.685 to 7.266) for the placebo, low dose betahistine, and high dose betahistine groups, respectively. Results were consistent for all secondary outcomes. Treatment was well tolerated with no unexpected safety findings. Without a control group of patients who did not receive any intervention to follow the natural course of the disease, the placebo effect could not be accurately assessed and differentiated from spontaneous remission and fluctuation of symptoms. WHAT THIS STUDY ADDS: Current evidence is limited as to whether betahistine prevents vertigo attacks caused by Meniere's disease, compared with placebo. The trial provides information on symptom relief on placebo intervention which is relevant for the design of future studies on potential disease modifying treatments in patients with Meniere's disease. FUNDING, COMPETING INTERESTS, DATA SHARING: Support from the German Federal Ministry of Education and Research (BMBF support code 01KG0708). Potential competing interests have been reported in full at the end of the paper on thebmj.com. Data are available from the corresponding author (Michael.Strupp@med.uni-muenchen.de) or biostatistician (mansmann@ibe.med.uni-muenchen.de). Study registration EudraCT no 2005-000752-32; ISRCTN no ISRCTN44359668.

The takeaway Frenzel goggles: a Fresnel-based device.

OBJECTIVE: To develop and evaluate new thin and light glasses for the examination of patients with nystagmus and to compare them with Frenzel goggles. METHODS: First, we designed new examination glasses: a Fresnel-based device with a short focal length that is not as heavy or bulky as Frenzel goggles. Second, visual-fixation suppression of postrotatory nystagmus with Frenzel goggles and the Fresnel-based device, the latter with 2 different magnifications (2- and 4-fold), was compared in 13 healthy subjects. Third, the intensity of the peripheral vestibular spontaneous nystagmus-in 6 patients with acute vestibular neuritis-with the Frenzel goggles and the Fresnel-based device with the 4-fold magnification was compared. Fourth, the visibility and clinical applicability were evaluated. RESULTS: The Fresnel-based device weighs 6 g (dimensions 12 × 8 × 0.3 cm). There was no significant difference in the intensity of postrotatory nystagmus between the Fresnel-based device with 4-fold magnification (37.3 ± 17.9°/s) and the Frenzel goggles (39.0 ± 18.3°/s). There was also no significant difference between the intensity of peripheral vestibular spontaneous nystagmus in the patients with acute vestibular neuritis. The Fresnel-based device can be easily applied. CONCLUSION: For suppression of nystagmus, the new Fresnel-based device or so-called M glasses is not inferior to Frenzel goggles. Doctors can carry it in their pocket, it is inexpensive, and easy to handle and to fix to the patient's nose so that it can be used in daily practice for the bedside examination. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that, in subjects with nystagmus, a Fresnel-based device identifies a similar intensity of nystagmus as that identified by Frenzel goggles.

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds.

N-Arylated aliphatic and aromatic amines are important substituents in many biologically active compounds. In the last few years, transition-metal-mediated N-aryl bond formation has become a standard procedure for the introduction of amines into aromatic systems. While N-arylation of simple aromatic halides by simple amines works with many of the described methods in high yield, the reactions may require detailed optimization if applied to the synthesis of complex molecules with additional functional groups, such as natural products or drugs. We discuss and compare in this review the three main N-arylation methods in their application to the synthesis of biologically active compounds: Palladium-catalysed Buchwald-Hartwig-type reactions, copper-mediated Ullmann-type and Chan-Lam-type N-arylation reactions. The discussed examples show that palladium-catalysed reactions are favoured for large-scale applications and tolerate sterically demanding substituents on the coupling partners better than Chan-Lam reactions. Chan-Lam N-arylations are particularly mild and do not require additional ligands, which facilitates the work-up. However, reaction times can be very long. Ullmann- and Buchwald-Hartwig-type methods have been used in intramolecular reactions, giving access to complex ring structures. All three N-arylation methods have specific advantages and disadvantages that should be considered when selecting the reaction conditions for a desired C-N bond formation in the course of a total synthesis or drug synthesis.

Influence of the menstrual cycle on the oral microbial flora in women: a case-control study including men as control subjects.

UNLABELLED: Changes in the levels of female sex hormones during the menstrual cycle may cause cyclic differences in subgingival bacterial colonization patterns. The purpose of the present study was to test the hypothesis that hormonal changes in the menstrual cycle cause changes in the oral microbiota. METHODS: Bacterial plaque samples were collected in 20 systemically and periodontally healthy women using no hormonal contraceptives (test group) over a period of 6 weeks. Twenty age-matched systemically and periodontally healthy men were assigned to the control group. Samples were processed by checkerboard DNA-DNA hybridization assay, and 74 species were analyzed. RESULTS: No cyclic pattern of bacterial colonization was identified for any of the 74 species studied in women not using hormonal contraceptives. Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) (Y4) was common at the beginning of menstruation (mean: 32%) and increased during the following 2 weeks (36%) in women (P <0.05). No cyclic differences in bacterial presence were found among the men (P values varied between 0.14 and 0.98). Men presented with significantly higher bacterial counts for 40 of 74 species (P <0.001), including Staphylococcus aureus and Pseudomonas aeruginosa but not Porphyromonas gingivalis (P = 0.15) or Tannerella forsythia (previously T. forsythensis) (P = 0.42). CONCLUSIONS: During a menstruation period, cyclic variation in the subgingival microbiota of periodontally healthy women of child-bearing age who were not using oral hormonal contraceptives could not be confirmed. Male control subjects presented with higher levels of many species but also without a cyclic pattern.

Inflammatory regulation of extracellular matrix remodeling in calcific aortic valve stenosis.

BACKGROUND: Calcific aortic stenosis (AS), the most frequent heart valve disorder in developed countries, leads to the calcification and fibrous thickening of the valve. While several studies have addressed the process of valvular calcification, the molecular pathomechanisms of the extensive matrix remodeling remain unclear. Because inflammation is present in stenotic valves, we hypothesized that the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) might influence cell proliferation and regulate the expression and activation of matrix metalloproteinases (MMPs)--enzymes that are thought to be involved in calcific AS. METHODS: Immunohistochemistry for leukocytes, TNFalpha, MMP-1, and the endogenous MMP inhibitor tissue inhibitor of metalloproteinase (TIMP)-1 was performed on human stenotic (n = 19) and control (n = 8) valves. Primary cultures of human aortic valve myofibroblasts were incubated with and without TNFalpha, and cell proliferation was assessed. The expression and activation of MMP-1 were detected by Western blotting and a specific MMP-1 activity assay. RESULTS: Control valves showed scattered macrophages and low expression of TNFalpha, MMP-1, and TIMP-1. In stenotic valves, leukocyte infiltration and a strong, colocalized expression of TNFalpha and MMP-1 were present, while TIMP-1 remained unchanged. Double-label immunofluorescence localized TNFalpha mainly to macrophages. In cultured human aortic valve myofibroblasts, TNFalpha stimulated proliferation and induced a time-dependent increase in MMP-1 expression and activation, while TIMP-1 remained unchanged. CONCLUSION: The results indicate that matrix remodeling in calcific AS involves the expression and activation of MMPs. Activated leukocytes, by the secretion of TNFalpha, may stimulate valvular myofibroblasts to proliferate and express MMPs, thus regulating actively the matrix remodeling in calcific AS.