Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 46
Filtrar
1.
Vet Sci ; 11(5)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38787168

RESUMO

(1) The main goals of general anesthesia include pain management and a safe anesthetic protocol for smooth recovery. In this retrospective study, we compared two anesthetic protocols for general anesthesia with isoflurane during emergency laparotomy: sedation with xylazine and the intraoperative infusion of lidocaine (X group) versus medetomidine as a preoperative sedation and intraoperative infusion (M group). (2) The medical records of horses who underwent emergency laparotomies between 2016 and 2023 were reviewed. According to the anesthetic protocol, patients were allocated to the X or M groups. Data about the horse, signalment, history, and anesthetic variables were analyzed. (3) Group X had a significantly higher heart rate (HR), lower respiratory rate (RR) and mean and diastolic arterial pressure (MAP/DAP). A progressive increase in HR and RR was observed in both groups. Group X underwent a decrease in RR and an increase in DAP. In Group M, a decrease in MAP and DAP was observed. Group M exhibited a longer recovery time with similar recovery scores. Both protocols provided safe anesthesia for emergency laparotomy, with minor cardiovascular and respiratory depression. Minor respiratory depression was detected when xylazine was used, while recovery was longer with medetomidine.

2.
Cancer Res Commun ; 4(5): 1296-1306, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38651817

RESUMO

The primary treatment for glioblastoma (GBM) is removing the tumor mass as defined by MRI. However, MRI has limited diagnostic and predictive value. Tumor-associated macrophages (TAM) are abundant in GBM tumor microenvironment (TME) and are found in peripheral blood (PB). FKBP51 expression, with its canonical and spliced isoforms, is constitutive in immune cells and aberrant in GBM. Spliced FKBP51s supports M2 polarization. To find an immunologic signature that combined with MRI could advance in diagnosis, we immunophenotyped the macrophages of TME and PB from 37 patients with GBM using FKBP51s and classical M1-M2 markers. We also determined the tumor levels of FKBP51s, PD-L1, and HLA-DR. Tumors expressing FKBP51s showed an increase in various M2 phenotypes and regulatory T cells in PB, indicating immunosuppression. Tumors expressing FKBP51s also activated STAT3 and were associated with reduced survival. Correlative studies with MRI and tumor/macrophages cocultures allowed to interpret TAMs. Tumor volume correlated with M1 infiltration of TME. Cocultures with spheroids produced M1 polarization, suggesting that M1 macrophages may infiltrate alongside cancer stem cells. Cocultures of adherent cells developed the M2 phenotype CD163/FKBP51s expressing pSTAT6, a transcription factor enabling migration and invasion. In patients with recurrences, increased counts of CD163/FKBP51s monocyte/macrophages in PB correlated with callosal infiltration and were accompanied by a concomitant decrease in TME-infiltrating M1 macrophages. PB PD-L1/FKBP51s connoted necrotic tumors. In conclusion, FKBP51s identifies a GBM subtype that significantly impairs the immune system. Moreover, FKBP51s marks PB macrophages associated with MRI features of glioma malignancy that can aid in patient monitoring. SIGNIFICANCE: Our research suggests that by combining imaging with analysis of monocyte/macrophage subsets in patients with GBM, we can enhance our understanding of the disease and assist in its treatment. We discovered a similarity in the macrophage composition between the TME and PB, and through association with imaging, we could interpret macrophages. In addition, we identified a predictive biomarker that drew more attention to immune suppression of patients with GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Isoformas de Proteínas , Proteínas de Ligação a Tacrolimo , Microambiente Tumoral , Humanos , Glioblastoma/genética , Glioblastoma/patologia , Glioblastoma/imunologia , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Glioblastoma/diagnóstico por imagem , Proteínas de Ligação a Tacrolimo/genética , Proteínas de Ligação a Tacrolimo/metabolismo , Prognóstico , Feminino , Microambiente Tumoral/imunologia , Masculino , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/mortalidade , Pessoa de Meia-Idade , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Imageamento por Ressonância Magnética , Adulto
3.
Front Vet Sci ; 10: 1243325, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37789868

RESUMO

Biosensors applied in veterinary medicine serve as a noninvasive method to determine the health status of animals and, indirectly, their level of welfare. Near infrared spectroscopy (NIRS) has been suggested as a technology with this application. This study presents preliminary in vivo time domain NIRS measurements of optical properties (absorption coefficient, reduced scattering coefficient, and differential pathlength factor) and hemodynamic parameters (concentration of oxygenated hemoglobin, deoxygenated hemoglobin, total hemoglobin, and tissue oxygen saturation) of tissue domestic animals, specifically of skeletal muscle (4 dogs and 6 horses) and head (4 dogs and 19 sheep). The results suggest that TD NIRS in vivo measurements on domestic animals are feasible, and reveal significant variations in the optical and hemodynamic properties among tissue types and species. In horses the different optical and hemodynamic properties of the measured muscles can be attributed to the presence of a thicker adipose layer over the muscle in the Longissimus Dorsi and in the Gluteus Superficialis as compared to the Triceps Brachii. In dogs the absorption coefficient is higher in the head (temporalis musculature) than in skeletal muscles. The smaller absorption coefficient for the head of the sheep as compared to the head of dogs may suggest that in sheep we are indeed reaching the brain cortex while in dog light penetration can be hindered by the strongly absorbing muscle covering the cranium.

4.
Life (Basel) ; 13(9)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37763240

RESUMO

MRE has become a standard imaging test for evaluating patients with small bowel pathology, but a rigorous methodology for describing and interpreting the pathological findings is mandatory. Strictures, abscess, inflammatory activity, sinus tract, wall edema, fistula, mucosal lesions, strictures, and mesentery fat hypertrophy are all indicators of small bowel damage in inflammatory and non-inflammatory small bowel disease, and they are all commonly and accurately explained by MRE. MRE is a non-invasive modality that accurately assesses the intra-luminal, parietal, and extra-luminal small bowel. Differential MRE appearance allows us to distinguish between Crohn's disease and non-inflammatory small bowel disorder. The purpose of this paper is to present the MRE pathological findings of small bowel disorder.

5.
Genes (Basel) ; 14(8)2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37628650

RESUMO

We have developed MAGI-ACMG, a classification algorithm that allows the classification of sequencing variants (single nucleotide or small indels) according to the recommendations of the American College of Medical Genetics (ACMG) and the Association for Clinical Genomic Science (ACGS). The MAGI-ACMG classification algorithm uses information retrieved through the VarSome Application Programming Interface (API), integrates the AutoPVS1 tool in order to evaluate more precisely the attribution of the PVS1 criterion, and performs the customized assignment of specific criteria. In addition, we propose a sub-classification scheme for variants of uncertain significance (VUS) according to their proximity either towards the "likely pathogenic" or "likely benign" classes. We also conceived a pathogenicity potential criterion (P_POT) as a proxy for segregation criteria that might be added to a VUS after posterior testing, thus allowing it to upgrade its clinical significance in a diagnostic reporting setting. Finally, we have developed a user-friendly web application based on the MAGI-ACMG algorithm, available to geneticists for variant interpretation.


Assuntos
Algoritmos , Software , Humanos , Relevância Clínica , Mutação INDEL , Nucleotídeos
6.
Vet Sci ; 10(8)2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37624270

RESUMO

Owner complaints of estrus-related behavior in mares are a common cause of referral for laparoscopic ovariectomy. Granulosa cell tumors are a common neoplastic condition affecting the equine ovary, causing behavioral changes at rest and reduced performance. The reported success rate of ovariectomy in treating behavioral disorders is 64-86%. The aim of this study was to retrospectively evaluate the long-term follow-up of laparoscopic ovariectomy in mares in our case series, focusing on the owner's perspective of the behavior of the mares after surgery. In addition, the histopathological features of the removed ovaries were investigated. The clinical records of mares that underwent laparoscopic ovariectomy between 2015 and 2022 were retrospectively reviewed. Owners complaining of poor behavior were interviewed about the main behavioral problem leading to referral and its eventual resolution after surgery. Eleven mares were included. The most common complaints were increased sensitivity on both flanks (10/11, 91%) and general riding problems (9/11, 82%). In 5/11 cases (45%), both ovaries were removed by laparoscopic ovariectomy. Histopathologic findings consistent with GCT/GTCT were found in five out of six examined ovaries (five granulosa theca cell tumors, GTCT). According to owner interviews, the scores assigned to each behavior improved significantly after surgery, regardless of histological findings. Although many factors can influence the behavior of horses, granulosa cell tumors (GCTs) proved to be a common cause and, as reported by the owners, ovariectomy resulted in improvement or complete resolution of the abnormal behavior.

7.
J Clin Med ; 12(15)2023 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-37568411

RESUMO

In the present study, through a case series, we highlighted the role of magnetic resonance (MR) in the identification and diagnosis of peripheral neuropathies. MR neurography allows the evaluation of the course of nerves through 2D and 3D STIR sequences with an isotropic voxel, whereas the relationship between nerves, vessels, osteo-ligamentous and muscular structures can be appraised with T1 sequences. Currently, DTI and tractography are mainly used for experimental purposes. MR neurography can be useful in detecting subtle nerve alterations, even before the onset of symptoms. However, despite being sensitive, MR neurography is not specific in detecting nerve injury and requires careful interpretation. For this reason, MR information should always be supported by instrumental clinical tests.

8.
Life (Basel) ; 13(8)2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37629548

RESUMO

MRE has become a standard imaging test for evaluating patients with small bowel pathology, but the indications, interpretation of imaging findings, methodology, and appropriate use must be standardized and widely known. Several signs of small bowel damage in inflammatory and non-inflammatory small bowel pathology include strictures, abscess, inflammatory activity, sinus tract, wall edema, fistula, mucosal lesions, and mesentery fat hypertrophy, all of which are widely and accurately explained by MRE. MRE is a non-invasive modality that accurately assesses the intra-luminal, parietal, and extra-luminal small bowel. The differential MRE appearance allows us to distinguish between different small bowel pathologies, such as neoplastic and non-neoplastic small bowel diseases. The purpose of this paper is to present the MRE technique, as well as the interpretation of imaging findings, through the approach of a rigorous stepwise methodology.

9.
Curr Probl Cardiol ; 48(11): 101920, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37392981

RESUMO

Incidental epicardial adipose tissue (EAT) and subepicardial fat infiltration on CT scans are not uncommon and the differential diagnosis can be a challenge. Considering the vastness of the possible disorders, it is important to differentiate physiologic age-related condition from pathologic disease. We present a case of an asymptomatic 81-year-old woman in which according to ECG and CMR findings we considered as possible differential diagnoses arrhythmogenic cardiomyopathy (ACM) dominant-right variant, lipomatosis and physiological growth of epicardial fat. We focus on patient characteristics, location of the fat replacement, heart morphovolumetry, wall motion of the ventricles and absence of late gadolinium enhancement to diagnose pericardial fat hypertrophy and physiological fatty infiltration. The role of EAT is unclear and it could play a part in the development of atherosclerosis and atrial fibrillation. Therefore, the clinicians should not underestimate this condition even if it would be an incidental finding in asymptomatic patients.


Assuntos
Displasia Arritmogênica Ventricular Direita , Fibrilação Atrial , Idoso de 80 Anos ou mais , Feminino , Humanos , Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/patologia , Fibrilação Atrial/patologia , Meios de Contraste , Gadolínio , Miocárdio
10.
J Clin Med ; 11(24)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36556146

RESUMO

Obesity is a chronic disease in which abnormal deposition of fat threatens health, leading to diabetes, cardiovascular diseases, cancer, and other chronic illnesses. According to the WHO, 19.8% of the adult population in Italy is obese, and the prevalence is higher among men. It is important to know the predisposition of an individual to become obese and to respond to bariatric surgery, the most up-to-date treatment for severe obesity. To this purpose, we developed an NGS gene panel, comprising 72 diagnostic genes and 244 candidate genes, and we sequenced 247 adult obese Italian patients. Eleven deleterious variants in 9 diagnostic genes and 17 deleterious variants in 11 candidate genes were identified. Interestingly, mutations were found in several genes correlated to the Bardet-Biedl syndrome. Then, 25 patients were clinically followed to evaluate their response to bariatric surgery. After a 12-month follow-up, the patients that carried deleterious variants in diagnostic or candidate genes had a reduced weight loss, as compared to the other patients. The NGS-based panel, including diagnostic and candidate genes used in this study, could play a role in evaluating, diagnosing, and managing obese individuals, and may help in predicting the outcome of bariatric surgery.

11.
Vet Sci ; 9(10)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36288133

RESUMO

The aim of this clinical trial was to evaluate the impacts of administration via the intrarectal route (IR) in cats on their heart and respiratory rates, blood pressure, body temperature, and sedation quality compared to the intramuscular route (IM). The intramuscular group (IMG) received 0.003 mg kg−1 dexmedetomidine, 2 mg kg−1 ketamine, and 0.2 mg kg−1 midazolam while the intrarectal group (IRG) protocol was 0.003 mg kg−1 dexmedetomidine, 4 mg kg−1 ketamine, and 0.4 mg kg−1 midazolam. Cardiorespiratory values, temperature, and sedation score were measured 2 min after administration and then every 5 min up to the 40th minute. Cats belonging to IRG reacted less strongly to the drug, as opposed to those receiving intramuscular administration (2/10 in IRG vs. 8/10 in IMG). Average time between drug administration and standing position was 44.9 ± 5.79 in IRG and 57 ± 9.88 min in IMG. In IRG, maintenance of SpO2 values is >95% at each time point. Median and range peak of sedation {7 (5)} in IMG occurs at 20th, 25th, and 30th minutes post drug administration while was lower in IRG. Cardiorespiratory values were slightly lower in IMG than in IRG, but always constant in both treatments. Temperature did not differ between groups. At this dosage, although sedation score was higher in IMG, intrarectal route could be efficacious for performing minimally invasive clinical and diagnostic procedures in cats.

12.
Vet Sci ; 9(10)2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36288158

RESUMO

(1) Background: colic syndrome is a multifactorial life-threatening condition in equids. Awareness of predisposing and prognostic indicators is useful to adequately inform the owner of the outcome and plan the best treatment. The aim of the study was to identify the variables associated with short-term survival in a cohort of horses referred for colic to a veterinary teaching hospital; (2) Methods: medical records of horses referred for colic from 2016 to 2022 were retrospectively reviewed. Univariate and multivariate regression models were built to assess the odds ratios of discharge from the hospital, both on the whole sample and in those patients undergoing surgery; (3) Conclusions: Month, time of admission, cardiovascular variables (heart rate on admission and after 3-6 h, packed cell volume, capillary refill time, and mucosal membranes), and presence of gastric reflux were significantly associated with discharge in the univariate regression in all horses and in those surgically treated. In the multivariate regression model, heart rate, packed cell volume, and capillary refill time showed significant association with the outcome in the whole sample. Although comparison between this study and previous studies is difficult due to the number and type of variables included, cardiovascular variables and markers of hypovolemia were also shown to be associated with outcome.

13.
Vet Sci ; 9(9)2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36136694

RESUMO

(1) Two-dimensional shear wave elastography (2D-SWE) employs an ultrasound impulse to produce transversely oriented shear waves, which travel through the surrounding tissue according to the stiffness of the tissue itself. The study aimed to assess the reliability of 2D-SWE for evaluating the elastosonographic appearance of the distal attachment of the fetlock joint capsule (DJC) in sound horses and in horses with osteoarthritis (OA) (2). According to a thorough evaluation of metacarpophalangeal joint (MCPJ), adult horses were divided in a sound Group (H) and in OA Group (P). Thereafter, a 2D-SWE of MCPJs was performed. Shear wave velocity (m/sec) and Young's modulus (kPa) were calculated independently by two operators at each selected ROI. Statistical analysis was performed with R software. (3) Results: 2D-SWE had good-excellent inter-CC and intra-CC in both groups. Differences in m/s and kPa between Groups H and P were found in transverse scans with lower values in Group P. No correlation with age or DJC thickness was found. (4) Conclusions: 2D-SWE was repeatable and reproducible. In Group H, DJC was statistically stiffer than in Group P only in transverse scan. The technique showed poor sensitivity and specificity in differentiating fetlocks affected by OA.

14.
J Equine Vet Sci ; 117: 104087, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35908598

RESUMO

A 7-year-old Friesian stallion with a history of oesophageal stenosis, weight loss, inappetence, and recurrent hyperthermia was referred for gastroscopy. The stomach mucosa surrounding the oesophageal opening showed a large, necrotic, and ulcerated mass. On post-mortem examination, a very large, cauliflower-like neoplasm was seen, affecting non-glandular gastric mucosa. Nodular lesions were observed, scattered on the omentum, the spleen, and the liver. Microscopic findings allowed the diagnosis of gastric squamous cell carcinoma with abdominal metastasis. Biomolecular investigations demonstrated the presence of EcPV-2 genes in neoplastic lesions, thus supporting the role of EcPV-2 in the ethiology of equine gastric cancer.


Assuntos
Carcinoma de Células Escamosas , Doenças dos Cavalos , Neoplasias Gástricas , Animais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/veterinária , Mucosa Gástrica/patologia , Gastroscopia/veterinária , Doenças dos Cavalos/diagnóstico , Cavalos , Masculino , Neoplasias Gástricas/patologia , Neoplasias Gástricas/veterinária
15.
Vet Sci ; 9(2)2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35202295

RESUMO

(1) Background: Laparoscopic surgery replaced traditional invasive techniques for the treatment of common urogenital disorders in equids. The aim of this review is to evaluate applications and the development of urogenital laparoscopy from 2001 to 2021. (2) Methods: A scoping review of literature was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for scoping reviews on three databases (NCBI-PubMed, Web of Science-Thompson Reuters, and SciVerse Scopus). (3) Results: A total of 452 papers were identified. After duplicate removal and title screening, 181 papers underwent abstract screening. Of these, 160 + 10 papers (cited by others) were assessed for eligibility according to the PICOs. A total of 132 papers were considered eligible. Most of the research was focused on ovaries and testes, followed by urinary bladder and general articles about laparoscopy in horses. We identified 43 original studies (33%, RCT, NoRCT, and experimental trials), 39 case series/retrospective studies (29%), 37 case reports (28%), and 13 reviews (10%, narrative or systematic). (4) Conclusions: Gonadal disorders were the most investigated. Hand-Assisted Laparoscopic Surgery (HALS) and laparoscopic-assisted surgery represent valuable options for more challenging conditions (uterine and urinary bladder disorders).

16.
Minerva Endocrinol (Torino) ; 47(1): 4-10, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33988008

RESUMO

BACKGROUND: Infertility is a disorder of the male and/or female reproductive system, characterized by failure to establish a clinical pregnancy after 12 months of regular unprotected sexual intercourse. On a world basis, about one in six couples are affected by infertility during their reproductive lifespan. Despite a comprehensive diagnostic work-up, infertility in about 50% of couples remains idiopathic. In this context, a next-generation sequencing (NGS) approach has been suggested to increase diagnostic yield. Accordingly, this study aimed to evaluate the effectiveness of a custom-made NGS gene panel for the simultaneous genetic diagnosis of both partners of a large population of infertile couples. METHODS: We developed a custom-made NGS panel for 229 genes associated with male and female infertility. The panel targeted exons and their flanking regions and was used to screen 99 couples with idiopathic infertility. RESULTS: NGS sequencing revealed five pathogenic variants in six couples and 17 likely pathogenic variants or variants with uncertain significance (VUS). The pathogenic variants were identified in the following genes: GNRHR, CCDC39, DNAH5, and CCDC103; likely pathogenic variants were identified in TAC3, PROKR2, and CFTR; VUS were identified in CATSPER2, FGFR1, LRRC6, DNAH5, DNAH11, TGFBR3, and DNAI1. CONCLUSIONS: The panel of genes designed for this study allowed the identification of pathogenic gene mutations and the presence of VUS in 6.1% and 17.2%, respectively, of couples with idiopathic infertility. This is the first study to successfully apply an NGS-based genetic screening including 229 genes known to play a role in both male and female infertility.


Assuntos
Infertilidade Feminina , Éxons , Feminino , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Infertilidade Feminina/diagnóstico , Masculino , Mutação
17.
Sci Total Environ ; 806(Pt 4): 151383, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34742796

RESUMO

This study was focused on the metropolitan area of Florence in Tuscany (Italy) with the aim to provide a functional spatial thermal anomaly indicator obtained throughout a thermal summer and winter hot-spot detection. The hot-spot analysis was performed by applying Getis-Ord Gi* spatial statistics to Land Surface Temperature (LST) layers, obtained from Landsat 8 remote sensing data during the 2015-2019 daytime summer and winter period, to delimitate summer hot- and cool-spots, and winter warm- and cold-spots. Further, these ones were spatially combined thus obtaining a comprehensive summer-winter Thermal Hot-Spot (THSSW) spatial indicator. Winter and summer mean daily thermal comfort profiles were provided for the study area assessing the Universal Thermal Climate Index (UTCI) by using meteorological data available from seven local weather stations, located at a maximum distance of 350 m from industrial sites. A specific focus on industrial sites was carried out by analyzing the industrial buildings characteristics and their surrounding areas (50 m buffer), through the following layers: industrial building area (BA), surface albedo of buildings (ALB), impervious area (IA), tree cover (TC), and grassland area (GA). The novel THSSW classification applied to industrial buildings has shown that about 50% of the buildings were located in areas characterized by summer hot-spots. Increases in BA and IA revealed warming effects on industrial buildings, whereas increases in ALB, TC, and GA disclosed cooling effects. A decrease of about 10% of IA replaced by TC and GA was associated with about 2 °C decrease of LST. Very strong outdoor heat stress conditions were observed during summer daytime, whereas moderate winter outdoor cold stress conditions were recorded during nighttime until the early morning. The thermal spatial hot-spot classification in industrial areas provides a very useful source of information for thermal mitigation strategies aimed to reduce the heat-related health risk for workers.


Assuntos
Transtornos de Estresse por Calor , Cidades , Clima , Temperatura Alta , Humanos , Estações do Ano , Temperatura , Tempo (Meteorologia)
18.
Hum Genet ; 141(2): 217-227, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34821995

RESUMO

Cooks syndrome (CS) is an ultrarare limb malformation due to in tandem microduplications involving KCNJ2 and extending to the 5' regulatory element of SOX9. To date, six CS families were resolved at the molecular level. Subsequent studies explored the evolutionary and pathological complexities of the SOX9-KCNJ2/Sox9-Kcnj2 locus, and suggested a key role for the formation of novel topologically associating domain (TAD) by inter-TAD duplications in causing CS. Here, we report a unique case of CS associated with a de novo 1;17 translocation affecting the KCNJ2 locus. On chromosome 17, the breakpoint mapped between KCNJ16 and KCNJ2, and combined with a ~ 5 kb deletion in the 5' of KCNJ2. Based on available capture Hi-C data, the breakpoint on chromosome 17 separated KCNJ2 from a putative enhancer. Gene expression analysis demonstrated downregulation of KCNJ2 in both patient's blood cells and cultured skin fibroblasts. Our findings suggest that a complex rearrangement falling in the 5' of KCNJ2 may mimic the developmental consequences of in tandem duplications affecting the SOX9-KCNJ2/Sox9-Kcnj2 locus. This finding adds weight to the notion of an intricate role of gene regulatory regions and, presumably, the related three-dimensional chromatin structure in normal and abnormal human morphology.


Assuntos
Dedos/anormalidades , Deformidades Congênitas do Pé/genética , Rearranjo Gênico , Deformidades Congênitas da Mão/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Sequências Reguladoras de Ácido Nucleico , Adolescente , Adulto , Pontos de Quebra do Cromossomo , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 17/genética , Fácies , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Canais de Potássio Corretores do Fluxo de Internalização/química , Deleção de Sequência , Translocação Genética , Adulto Jovem
19.
Eat Weight Disord ; 27(5): 1869-1880, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34822136

RESUMO

PURPOSE: The aim of this study was to increase knowledge of genes associated with anorexia nervosa (AN) and their diagnostic offer, using a next generation sequencing (NGS) panel for the identification of genetic variants. The rationale underlying this test is that we first analyze the genes associated with syndromic forms of AN, then genes that were found to carry rare variants in AN patients who had undergone segregation analysis, and finally candidate genes intervening in the same molecular pathways or identified by GWAS or in mouse models. METHODS: We developed an NGS gene panel and used it to screen 68 Italian AN patients (63 females, 5 males). The panel included 162 genes. Family segregation study was conducted on available relatives of probands who reported significant genetic variants. RESULTS: In our analysis, we found potentially deleterious variants in 2 genes (PDE11A and SLC25A13) associated with syndromic forms of anorexia and predicted deleterious variants in the following 12 genes: CD36, CACNA1C, DRD4, EPHX2, ESR1, GRIN2A, GRIN3B, LRP2, NPY4R, PTGS2, PTPN22 and SGPP2. Furthermore, by Sanger sequencing of the promoter region of NNAT, we confirmed the involvement of this gene in the pathogenesis of AN. Family segregation studies further strengthened the possible causative role of CACNA1C, DRD4, GRIN2A, PTGS2, SGPP2, SLC25A13 and NNAT genes in AN etiology. CONCLUSION: The major finding of our study is the confirmation of the involvement of the NNAT gene in the pathogenesis of AN; furthermore, this study suggests that NGS-based testing can play an important role in the diagnostic evaluation of AN, excluding syndromic forms and increasing knowledge of the genetic etiology of AN. LEVEL OF EVIDENCE: Level I, experimental study.


Assuntos
Anorexia Nervosa , Sequenciamento de Nucleotídeos em Larga Escala , 3',5'-GMP Cíclico Fosfodiesterases/genética , Animais , Anorexia Nervosa/diagnóstico , Anorexia Nervosa/genética , Ciclo-Oxigenase 2/genética , Feminino , Humanos , Masculino , Camundongos , Proteínas de Transporte da Membrana Mitocondrial/genética , Mutação , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética
20.
Animals (Basel) ; 11(12)2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34944210

RESUMO

Castration is one of the most frequently performed surgical procedures in livestock. All methods of castration are associated with a significant degree of pain, affecting the patients' welfare. Limited information on species-specific protocols in buffaloes is available. Considering the importance of this species and the scarcity of reports available, the objective of this study was to evaluate the effects of two different intramuscular doses of xylazine for premedication in water buffalo calves undergoing isoflurane maintenance anaesthesia for routine castration surgery. Twenty clinically healthy male water buffaloes undergoing bilateral orchiectomy were randomly assigned to two groups of 10 animals each: Group 1 was premedicated with xylazine 0.1 mg/kg bw i.m. and Group 2 was premedicated with xylazine 0.15 mg/kg bw i.m. Anaesthesia was induced by ketamine (2 mg/kg bw i.v.) and maintained with isoflurane-oxygen-air in both groups. The HR, RR, presence/absence of ataxia, sedation, depth of anaesthesia, muscle relaxation status, response to acoustic and tactile stimuli, eyelid reflex, extent of salivation and stimulus were evaluated every 5 min. Both protocols provided consistent sedation and were safe. Faster and more satisfactory sedation was recorded when xylazine was administered at 0.15 mg/kg bw i.m., leading us to recommend this dose for buffalo orchiectomy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...