Comparative Study of Digital Squamous Cell Carcinoma in Giant, Standard, and Miniature Schnauzers

In schnauzers, a breed predisposition to squamous cell carcinoma of the digit (dSCC) is well known. The aim of this study was to compare the clinical and macroscopic findings of dSCCs in giant (GSs), standard (SSs), and miniature schnauzers (MSs). Methods: Pathology reports of 478 dSCCs from 417 schnauzers (227 GSs, 174 SSs, and 16 MSs) were retrospectively evaluated. Results: The MSs were older than the SSs and GSs (p ≤ 0.01). The male GSs were predisposed to dSCC (p < 0.05). In the GSs, the nodular dSCCs were larger than in the MSs (p ≤ 0.05) and SSs (p ≤ 0.001). The digital SCCs were mostly diagnosed at the forelimbs, especially at digits 1, 2, and 5. At the hindlimbs, the affected toes differed between the GSs and SSs. Multiple dSCCs were more common in SSs than in GSs (p = 0.003). If dSCC was the cause of death, the survival time was shorter than in dogs dying from other diseases (p = 0.004). Metastases occurred in 20% of the cases and led to a significantly shorter survival time in both the GSs and SSs (p < 0.001). Conclusions: The results showed various differences in the dSCC depending on the size variant of the schnauzer

Comparative Study of Digital Squamous Cell Carcinoma in Giant, Standard, and Miniature Schnauzers

In schnauzers, a breed predisposition to squamous cell carcinoma of the digit (dSCC) is well known. The aim of this study was to compare the clinical and macroscopic findings of dSCCs in giant (GSs), standard (SSs), and miniature schnauzers (MSs). Methods: Pathology reports of 478 dSCCs from 417 schnauzers (227 GSs, 174 SSs, and 16 MSs) were retrospectively evaluated. Results: The MSs were older than the SSs and GSs (p ≤ 0.01). The male GSs were predisposed to dSCC (p p ≤ 0.05) and SSs (p ≤ 0.001). The digital SCCs were mostly diagnosed at the forelimbs, especially at digits 1, 2, and 5. At the hindlimbs, the affected toes differed between the GSs and SSs. Multiple dSCCs were more common in SSs than in GSs (p = 0.003). If dSCC was the cause of death, the survival time was shorter than in dogs dying from other diseases (p = 0.004). Metastases occurred in 20% of the cases and led to a significantly shorter survival time in both the GSs and SSs (p < 0.001). Conclusions: The results showed various differences in the dSCC depending on the size variant of the schnauzer

Preeclampsia and long-term risk of cardiovascular disease: what do obstetrician-gynecologists know?

BACKGROUND: Preeclampsia (PE), a hypertensive disorder of pregnancy affects 2-8% of women and is associated with increased cardiovascular disease (CVD) risk later in life. There is little information about the knowledge of obstetrician-gynecologists in German outpatient care setting regarding the future health risk of PE and knowledge of the current guidelines on treatment and counseling patients post PE. This study aimed to assess whether obstetrician-gynecologists are aware of PE’s association with maternal long-term adverse outcomes and providing appropriate counseling. METHODS: A random sample of 500 obstetrician-gynecologists in the federal state of Lower Saxony was mailed a survey and a reminder with a second copy of the survey. The questionnaire elicited both personal information, and knowledge on future disease risks, e.g. cardiovascular disease (CVD) and current guidelines as well as on counseling practice. Descriptive analysis was used to analyze the responses. RESULTS: A total of 212 obstetrician-gynecologists (42.4%) responded to the questionnaire. A large proportion of physicians stated that PE was associated with a higher risk for the development for hypertension (86.6%), stroke (78.5%) and kidney disease (78.0%). Of the participants 75.8% reported that women after PE have a shorter life expectancy. Respondents with knowledge of the current guidelines of the German Association of Obstetrics and Gynecology concerning follow up and risk management of PE (45.2%) were more often aware of the development of CVD and stroke and counseled patients on self -blood-pressure measurement, meaning and long-term-risks of PE and attached importance to family history of PE compared to physicians with no knowledge of the guidelines. CONCLUSION: Although the majority of obstetrician-gynecologists were aware of higher CVD risk after PE, weaknesses exist in the follow up care and counseling of these patients. These deficiencies would be amendable to directed educational activities to improve the implementation of current guidelines

KITLG Copy Number Germline Variations in Schnauzer Breeds and Their Relevance in Digital Squamous Cell Carcinoma in Black Giant Schnauzers

Copy number variations (CNVs) of the KITLG gene seem to be involved in the oncogenesis of digital squamous cell carcinoma (dSCC). The aims of this study were (1) to investigate KITLG CNV in giant (GS), standard (SS), and miniature (MS) schnauzers and (2) to compare KITLG CNV between black GS with and without dSCC. Blood samples from black GS (22 with and 17 without dSCC), black SS (18 with and 4 without dSSC; 5 unknown), and 50 MS (unknown dSSC status and coat colour) were analysed by digital droplet PCR. The results are that (1) most dogs had a copy number (CN) value > 4 (range 2.5–7.6) with no significant differences between GS, SS, and MS, and (2) the CN value in black GS with dSCC was significantly higher than in those without dSCC (p = 0.02). CN values > 5.8 indicate a significantly increased risk for dSCC, while CN values < 4.7 suggest a reduced risk for dSCC (grey area: 4.7–5.8). Diagnostic testing for KITLG CNV may sensitise owners to the individual risk of their black GS for dSCC. Further studies should investigate the relevance of KITLG CNV in SS and the protective effects in MS, who rarely suffer from dSCC

Neuronal Activity, TGFβ-Signaling and Unpredictable Chronic Stress Modulate Transcription of Gadd45 Family Members and DNA Methylation in the Hippocampus

Neuronal activity is altered in several neurological and psychiatric diseases. Upon depolarization not only neurotransmitters are released but also cytokines and other activators of signaling cascades. Unraveling their complex implication in transcriptional control in receiving cells will contribute to understand specific central nervous system (CNS) pathologies and will be of therapeutically interest. In this study we depolarized mature hippocampal neurons in vitro using KCl and revealed increased release not only of brain-derived neurotrophic factor (BDNF) but also of transforming growth factor beta (TGFB). Neuronal activity together with BDNF and TGFB controls transcription of DNA modifying enzymes specifically members of the DNA-damage-inducible (Gadd) family, Gadd45a, Gadd45b, and Gadd45g. MeDIP followed by massive parallel sequencing and transcriptome analyses revealed less DNA methylation upon KCl treatment. Psychiatric disorder-related genes, namely Tshz1, Foxn3, Jarid2, Per1, Map3k5, and Arc are transcriptionally activated and demethylated upon neuronal activation. To analyze whether misexpression of Gadd45 family members are associated with psychiatric diseases, we applied unpredictable chronic mild stress (UCMS) as established model for depression to mice. UCMS led to reduced expression of Gadd45 family members. Taken together, our data demonstrate that Gadd45 family members are new putative targets for UCMS treatments.Sin financiación6.308 JCR (2017) Q1, 24/261 NeurosciencesUE

Neuronal Activity, TGFβ-Signaling and Unpredictable Chronic Stress Modulate Transcription of Gadd45 Family Members and DNA Methylation in the Hippocampus

Neuronal activity is altered in several neurological and psychiatric diseases. Upon depolarization not only neurotransmitters are released but also cytokines and other activators of signaling cascades. Unraveling their complex implication in transcriptional control in receiving cells will contribute to understand specific central nervous system (CNS) pathologies and will be of therapeutically interest. In this study we depolarized mature hippocampal neurons in vitro using KCl and revealed increased release not only of brain-derived neurotrophic factor (BDNF) but also of transforming growth factor beta (TGFB). Neuronal activity together with BDNF and TGFB controls transcription of DNA modifying enzymes specifically members of the DNA-damage-inducible (Gadd) family, Gadd45a, Gadd45b, and Gadd45g. MeDIP followed by massive parallel sequencing and transcriptome analyses revealed less DNA methylation upon KCl treatment. Psychiatric disorder-related genes, namely Tshz1, Foxn3, Jarid2, Per1, Map3k5, and Arc are transcriptionally activated and demethylated upon neuronal activation. To analyze whether misexpression of Gadd45 family members are associated with psychiatric diseases, we applied unpredictable chronic mild stress (UCMS) as established model for depression to mice. UCMS led to reduced expression of Gadd45 family members. Taken together, our data demonstrate that Gadd45 family members are new putative targets for UCMS treatments.Depto. de Medicina Legal, Psiquiatría y PatologíaFac. de MedicinaTRUEpu