Anesthesie van kittens: een literatuuroverzicht met nadruk op de mogelijkheden in België

In Belgium, elective surgical procedures in very young small animals are rarely performed. Consequently, most veterinarians have little experience in anesthetizing pediatric patients. This article describes potential problems of anesthesia in kittens, which are mainly linked to their specific anatomy and physiology. Additionally, some practical anesthetic protocols are highlighted. Combinations with ketamine are practical, economical and efficient options

Spatially dense 3D facial heritability and modules of co-heritability in a father-offspring design

Introduction: The human face is a complex trait displaying a strong genetic component as illustrated by various studies on facial heritability. Most of these start from sparse descriptions of facial shape using a limited set of landmarks. Subsequently, facial features are preselected as univariate measurements or principal components and the heritability is estimated for each of these features separately. However, none of these studies investigated multivariate facial features, nor the co-heritability between different facial features. Here we report a spatially dense multivariate analysis of facial heritability and co-heritability starting from data from fathers and their children available within ALSPAC. Additionally, we provide an elaborate overview of related craniofacial heritability studies. Methods: In total, 3D facial images of 762 father-offspring pairs were retained after quality control. An anthropometric mask was applied to these images to establish spatially dense quasi-landmark configurations. Partial least squares regression was performed and the (co-)heritability for all quasi-landmarks (∼7160) was computed as twice the regression coefficient. Subsequently, these were used as input to a hierarchical facial segmentation, resulting in the definition of facial modules that are internally integrated through the biological mechanisms of inheritance. Finally, multivariate heritability estimates were obtained for each of the resulting modules. Results: Nearly all modular estimates reached statistical significance under 1,000,000 permutations and after multiple testing correction (p ≤ 1.3889 × 10-3), displaying low to high heritability scores. Particular facial areas showing the greatest heritability were similar for both sons and daughters. However, higher estimates were obtained in the former. These areas included the global face, upper facial part (encompassing the nasion, zygomas and forehead) and nose, with values reaching 82% in boys and 72% in girls. The lower parts of the face only showed low to moderate levels of heritability. Conclusion: In this work, we refrain from reducing facial variation to a series of individual measurements and analyze the heritability and co-heritability from spatially dense landmark configurations at multiple levels of organization. Finally, a multivariate estimation of heritability for global-to-local facial segments is reported. Knowledge of the genetic determination of facial shape is useful in the identification of genetic variants that underlie normal-range facial variation

Working memory moderates the relation between the brain-derived neurotropic factor (BDNF) and psychotherapy outcome for depression

Background: Insight into patient characteristics that predict response to treatment for major depressive disorder (MDD) may help to personalize treatment and improve outcomes. One mechanism that has been linked to the success of treatment for MDD is brain-derived neurotropic factor (BDNF). BDNF is implicated in learning and memory and may play a role in the effects of psychotherapy that involves changing cognitions and behaviors. In addition, only in individuals with low BDNF, low working memory capacity has been associated with increased symptoms of depression. However, the role of BDNF and working memory capacity in psychotherapy outcome is unclear. The aim of this study was to investigate the role of BDNF and its interaction with working memory capacity in psychotherapy outcomes for MDD. Method: Adult patients with MDD were randomized to weekly or twice weekly sessions of cognitive behavioral therapy or interpersonal psychotherapy. BDNF Val66Met polymorphism (rs6265) (n = 138) was defined and serum BDNF was quantified before (n = 138) and after psychotherapy (n = 82). Results: Baseline serum BDNF and the Val66Met polymorphism were not associated with outcome and associations did not differ between treatment conditions. Working memory capacity significantly moderated the relation between baseline serum BDNF and outcome: high serum BDNF at baseline was related to less depressive symptoms following psychotherapy in the presence of high working memory capacity, but not low working memory capacity. Discussion: These findings, if replicated, might indicate that while BDNF may not be related to psychotherapy outcomes in general, they may play a role in the presence of specific learning processes such as working memory capacity

Six NSCL/P loci show associations with normal-range craniofacial variation

Objectives: Orofacial clefting is one of the most prevalent craniofacial malformations. Previous research has demonstrated that unaffected relatives of patients with non-syndromic cleft lip with/without cleft palate (NSCL/P) show distinctive facial features, which can be an expression of underlying NSCL/P susceptibility genes. These results support the hypothesis that genes involved in the occurrence of a cleft also play a role in normal craniofacial development. In this study, we investigated the influence of genetic variants associated with NSCL/P on normal-range variation in facial shape. Methods: A literature review of genome wide association studies (GWAS) investigating the genetic etiology of NSCL/P was performed, resulting in a list of 75 single nucleotide polymorphisms (SNPs) located in 38 genetic loci. Genotype data were available for 65 of these selected SNPs in three datasets with a combined sample size of 7,418 participants of European ancestry, whose 3D facial images were also available. The effect of each SNP was tested using a multivariate canonical correlation analysis (CCA) against 63 hierarchically-constructed facial segments in each of the three datasets and meta-analyzed. This allowed for the investigation of associations between SNPs known to be involved in NSCL/P and normal-range facial shape variations in a global-to-local perspective, without preselecting specific facial shape features or characteristics. Results: Six NSCL/P SNPs showed significant associations with variation in normal-range facial morphology. rs6740960 showed significant effects in the chin area (p = 3.71 × 10−28). This SNP lies in a non-coding area. Another SNP, rs227731 near the NOG gene, showed a significant effect in the philtrum area (p = 1.96 × 10−16). Three SNPs showed significant effects on the shape of the nose. rs742071 (p = 8.71 × 10−14), rs34246903 (p = 6.87 × 10−12), and rs10512248 (p = 8.4 × 10−9). Respectively, these SNPs are annotated to PAX7, MSX1, and PTCH1. Finally, rs7590268, an intron variant of THADA, showed an effect in the shape of the supraorbital ridge (p = 3.84 × 10−7). Conclusions: This study provides additional evidence NSCL/P-associated genetic variants influence normal-range craniofacial morphology, with significant effects observed for the chin, the nose, the supraorbital ridges and the philtrum area

Prognostic implications of cellular senescence in resected non-small cell lung cancer

Background: Cure and long-term survival for non-small cell lung cancer (NSCLC) remains hard to achieve. Cellular senescence, an emerging hallmark of cancer, is considered as an endogenous tumor suppressor mechanism. However, senescent cancer cells can paradoxically affect the surrounding tumor microenvironment (TME), ultimately leading to cancer relapse and metastasis. As such, the role of cellular senescence in cancer is highly controversial. Methods: In 155 formalin-fixed paraffin-embedded (FFPE) samples from surgically resected NSCLC patients with pathological tumor-node-metastasis (pTNM) stages I-IV (8th edition), cellular senescence was assessed using a combination of four immunohistochemical senescence markers, i.e., lipofuscin, p16INK4a, p21WAF1/Cip1 and Ki67, and correlated to clinicopathological parameters and outcomes, including overall survival (OS) and disease-free survival (DFS). Results: A tumoral senescence signature (SS) was present in 48 out of 155 NSCLC patients, but did not correlate to any clinicopathological parameter, except for p53 mutation status. In a histologically homogenous patient cohort of 100 patients who fulfilled the following criteria: (I) one type of histology, i.e., adenocarcinoma, (II) without known epidermal growth factor receptor (EGFR) mutation, (III) curative (R0) resection and (IV) no neoadjuvant systemic therapy or radiotherapy, the median OS and DFS for patients with a tumoral SS (n=30, 30.0%) compared to patients without a tumoral SS (n=70, 70.0%) was 53 versus 141 months (P=0.005) and 45 versus 55 months (P=0.25), respectively. In multiple Cox proportional hazards (Cox PH) model analysis correcting for age, pTNM stage I-III and adjuvant therapy, a tumoral SS remained a significant prognostic factor for OS (HR =2.03; P=0.014). Conclusions: The presence of a tumoral SS particularly based on high p16INK4a expression significantly affects OS in NSCLC adenocarcinoma. In this light, adjuvant senolytic therapy could be an interesting strategy for NSCLC patients harboring a tumoral SS, ultimately to improve survival of these patients

Study protocol for a randomized controlled trial : prophylactic swallowing exercises in head-and-neck cancer patients treated with (chemo)radiotherapy (PRESTO trial)

Background: Dysphagia is a common and serious complication after (chemo)radiotherapy (CRT) for head-and-neck cancer (HNC) patients. Prophylactic swallowing exercises (PSE) can have a significantly positive effect on post-treatment swallowing function. However, low adherence rates are a key issue in undermining this positive effect. This current randomized trial will investigate the effect of adherence-improving measures on patients' swallowing function, adherence and quality of life (QOL). Methods: This ongoing trial will explore the difference in adherence and swallowing-related outcome variables during and after PSE in HNC patients performing the same therapy schedule, receiving different delivery methods. One hundred and fifty patients treated in various hospitals will be divided into three groups. Group 1 performs PSE at home, group 2 practices at home with continuous counseling through an app and group 3 receives face-to-face therapy by a speech and language pathologist. The exercises consist of tongue-strengthening exercises and chin-tuck against resistance with effortful swallow. The Iowa Oral Performance Instrument and the Swallowing Exercise Aid are used for practicing. Patients are evaluated before, during and after treatment by means of strength measurements, swallowing and QOL questionnaires. Discussion: Since low adherence rates undermine the positive impact of PSE on post-treatment swallowing function, there is need to develop an efficient PSE protocol maximizing adherence rates

Spatially Dense 3D Facial Heritability and Modules of Co-heritability in a Father-Offspring Design

Introduction: The human face is a complex trait displaying a strong genetic component as illustrated by various studies on facial heritability. Most of these start from sparse descriptions of facial shape using a limited set of landmarks. Subsequently, facial features are preselected as univariate measurements or principal components and the heritability is estimated for each of these features separately. However, none of these studies investigated multivariate facial features, nor the co-heritability between different facial features. Here we report a spatially dense multivariate analysis of facial heritability and co-heritability starting from data from fathers and their children available within ALSPAC. Additionally, we provide an elaborate overview of related craniofacial heritability studies.Methods: In total, 3D facial images of 762 father-offspring pairs were retained after quality control. An anthropometric mask was applied to these images to establish spatially dense quasi-landmark configurations. Partial least squares regression was performed and the (co-)heritability for all quasi-landmarks (∼7160) was computed as twice the regression coefficient. Subsequently, these were used as input to a hierarchical facial segmentation, resulting in the definition of facial modules that are internally integrated through the biological mechanisms of inheritance. Finally, multivariate heritability estimates were obtained for each of the resulting modules.Results: Nearly all modular estimates reached statistical significance under 1,000,000 permutations and after multiple testing correction (p ≤ 1.3889 × 10-3), displaying low to high heritability scores. Particular facial areas showing the greatest heritability were similar for both sons and daughters. However, higher estimates were obtained in the former. These areas included the global face, upper facial part (encompassing the nasion, zygomas and forehead) and nose, with values reaching 82% in boys and 72% in girls. The lower parts of the face only showed low to moderate levels of heritability.Conclusion: In this work, we refrain from reducing facial variation to a series of individual measurements and analyze the heritability and co-heritability from spatially dense landmark configurations at multiple levels of organization. Finally, a multivariate estimation of heritability for global-to-local facial segments is reported. Knowledge of the genetic determination of facial shape is useful in the identification of genetic variants that underlie normal-range facial variation

3D facial phenotyping by biometric sibling matching used in contemporary genomic methodologies

The analysis of contemporary genomic data typically operates on one-dimensional phenotypic measurements (e.g. standing height). Here we report on a data-driven, family-informed strategy to facial phenotyping that searches for biologically relevant traits and reduces multivariate 3D facial shape variability into amendable univariate measurements, while preserving its structurally complex nature. We performed a biometric identification of siblings in a sample of 424 children, defining 1,048 sib-shared facial traits. Subsequent quantification and analyses in an independent European cohort (n = 8,246) demonstrated significant heritability for a subset of traits (0.17–0.53) and highlighted 218 genome-wide significant loci (38 also study-wide) associated with facial variation shared by siblings. These loci showed preferential enrichment for active chromatin marks in cranial neural crest cells and embryonic craniofacial tissues and several regions harbor putative craniofacial genes, thereby enhancing our knowledge on the genetic architecture of normal-range facial variation

Six NSCL/P Loci Show Associations With Normal-Range Craniofacial Variation

Objectives: Orofacial clefting is one of the most prevalent craniofacial malformations. Previous research has demonstrated that unaffected relatives of patients with non-syndromic cleft lip with/without cleft palate (NSCL/P) show distinctive facial features, which can be an expression of underlying NSCL/P susceptibility genes. These results support the hypothesis that genes involved in the occurrence of a cleft also play a role in normal craniofacial development. In this study, we investigated the influence of genetic variants associated with NSCL/P on normal-range variation in facial shape.Methods: A literature review of genome wide association studies (GWAS) investigating the genetic etiology of NSCL/P was performed, resulting in a list of 75 single nucleotide polymorphisms (SNPs) located in 38 genetic loci. Genotype data were available for 65 of these selected SNPs in three datasets with a combined sample size of 7,418 participants of European ancestry, whose 3D facial images were also available. The effect of each SNP was tested using a multivariate canonical correlation analysis (CCA) against 63 hierarchically-constructed facial segments in each of the three datasets and meta-analyzed. This allowed for the investigation of associations between SNPs known to be involved in NSCL/P and normal-range facial shape variations in a global-to-local perspective, without preselecting specific facial shape features or characteristics.Results: Six NSCL/P SNPs showed significant associations with variation in normal-range facial morphology. rs6740960 showed significant effects in the chin area (p = 3.71 × 10−28). This SNP lies in a non-coding area. Another SNP, rs227731 near the NOG gene, showed a significant effect in the philtrum area (p = 1.96 × 10−16). Three SNPs showed significant effects on the shape of the nose. rs742071 (p = 8.71 × 10−14), rs34246903 (p = 6.87 × 10−12), and rs10512248 (p = 8.4 × 10−9). Respectively, these SNPs are annotated to PAX7, MSX1, and PTCH1. Finally, rs7590268, an intron variant of THADA, showed an effect in the shape of the supraorbital ridge (p = 3.84 × 10−7).Conclusions: This study provides additional evidence NSCL/P-associated genetic variants influence normal-range craniofacial morphology, with significant effects observed for the chin, the nose, the supraorbital ridges and the philtrum area