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End-stage heart failure (ESHF) is characterized by severe cardiac dysfunction with persistent disabling symptoms and recurrent acute decompensated heart failure (ADHF), despite guideline-directed medical therapy. The aim of this study was to evaluate the efficacy and safety of intravenous diuretics administration at home through a peripherally inserted central venous catheter (PICC) in ESHF patients.Forty-one ESHF patients received PICC implantation for intravenous diuretic administration at home. The primary efficacy endpoint was the patient-level number of HF hospitalizations in the short (1-3 months), medium (six months), and long term (1 year), before and after PICC implantation. Pre- and post-PICC ADHF-free days were also evaluated as co-primary endpoint. Secondary endpoints comprised changes in clinical, laboratory and echocardiographic parameters, and device safety. A cost-effectiveness analysis was performed to estimate the economic impact of using PICC. For each time frame analyzed, a significant reduction in the number of hospitalizations due to ADHF was observed, resulting in a significant increase in ADHF-free days (71 ± 44 vs. 163 ± 136, p = 0.003). In matched patients' analysis, significant decrease in body weight (68 ± 16 kg vs. 63 ± 10 kg, p = 0.041) and mitral regurgitation grade 3/4 (55% vs. 18%, p 0.001) were also observed. Freedom from PICC-related complications was observed in 61% of patients. A significant reduction in overall ADHF-hospitalizations cost was observed.This proof-of-concept study demonstrates the effectiveness and safety of home administration of intravenous diuretic therapy via PICC in ESHF patients. This palliative cost-effective strategy can be taken in consideration for selected end-stage patients no longer responsive to conventional therapies.

Cavalier King Charles Spaniels (CKCS) are predisposed to developing myxomatous mitral valve disease (MMVD), with radiographs frequently used to screen for evidence of left-sided cardiomegaly secondary to MMVD. Vertebral heart size (VHS), vertebral left atrial size (VLAS), modified VLAS (M-VLAS), and radiographic left atrial dimension (RLAD) are reported as objective measurements of global heart size and left atrial size. Normal VHS in CKCS (10.6 ± 0.5) is reportedly higher than the non-breed-specific value (9.7±0.5). Breed-specific VLAS, M-VLAS, and RLAD cut-offs have not been reported in CKCS. The aim of this prospective reference interval study was to describe the VHS, VLAS, M-VLAS, and RLAD values for 30 clinically healthy adult CKCS. Inclusion criteria were unremarkable physical examination, normal echocardiography, and thoracic radiographs without malposition/abnormalities. There were 22 female and eight male dogs. Ages ranged from 1 to 6 years. The VHS mean value in our sample was 10.08 ± 0.56 (95% range, 9.87-10.29). This was significantly greater than a previously published general canine reference value of 9.7 ± 0.5 and significantly less than a previously published CKCS breed-specific value of 10.6 ± 0.5 (P < 0.01). Mean VLAS, M-VLAS, and the RLAD values in our study were 1.79 ± 0.3 (95% range, 1.68-1.9), 2.23 ± 0.44 (95% range, 2.06-2.39), and 1.2 ± 0.34 (95% range, 1.07-1.33), respectively. These were significantly less than previously published reference interval values (P < 0.001). The VHS, M-VLAS, and the RLAD were not affected by sex, body weight, or BCS; whereas the VLAS was moderately affected by body weight. Findings from this study can be used as background for future thoracic radiographic assessments in CKCS.

Echocardiographic evaluation is a diagnostic tool for the in vivo diagnosis of heart diseases. Specific and unique anatomical characteristics of the ophidian heart such as the single ventricular cavity, a tubular sinus venosus opening into the right atrium, the presence of three arterial trunks and extreme mobility in the coelomic cavity during the cardiac cycle directly affect echocardiographic examination. Twenty‐one awake, healthy ball pythons (Python regius) were analysed based on guidelines for performing echocardiographic examinations. Imaging in the sagittal plane demonstrated the caudal vena cava, sinus venosus valve (SVV) and right atrium and the various portions of the ventricle, horizontal septum, left aortic arch and pulmonary artery. Transverse imaging depicted the spatial relationship of the left and right aortic arches, the pulmonary artery and the horizontal septum. Basic knowledge of cardiac blood flow in reptiles is necessary to understand the echocardiographic anatomy. The flow of the arterial trunks and SVV was analysed using pulsed‐wave Doppler based on the approach used for humans and companion mammals. The walls and diameters of the cavum arteriosum, cavum venosum and cavum pulmonale were also evaluated. This study should improve the veterinarian's knowledge of ophidian heart basal physiology and contribute to the development of cardiology in reptiles., Echocardiography improves the opportunity to diagnose before necropsy, thanks to the evaluation of intracardiac flows. Physiological range allow the clinician an ante‐mortem diagnosis and an appropriate treatment for the individual subject.

The objectives of this retrospective, observer agreement study were to (a) test variability of radiographic left atrial dimension (RLAD) and vertebral left atrial size (VLAS) measurements among observers with different levels of expertise in thoracic radiology and cardiology, (b) assess whether one method is better than the other in detecting left atrial enlargement (LAE), and (c) assess the agreement among RLAD, VLAS, and American College of Veterinary Internal Medicine (ACVIM) classes. Seventy-four dogs (eight healthy and 66 with mitral valve disease) with thoracic radiographs and echocardiography performed on the same day were reviewed. Thirty showed echocardiographic LAE. Left atrial dimension was quantified using RLAD and VLAS by six different operators with three levels of clinical experience in veterinary cardiology/radiology. Vertebral heart score and fourth thoracic vertebra (T4) were also measured. Differences in T4, vertebral heart score (VHS), RLAD, and VLAS measurements were found among six operators and among the three levels of clinical expertise as well as between veterinary cardiology readers and veterinary radiology readers (P < .05). The area under the receiver operating characteristic (AUC) curve for VHS showed good performances for all observers and level and type of expertise; the AUC for RLAD and VLAS was suboptimal only for the radiology student. Our RLAD and VLAS cutoffs (1.9 and 2.43 v, respectively) were better related to qualitative radiographic than quantitative echocardiographic LAE evaluation. Radiographic LA dimension and VLAS showed an increase proportional to the worsening of the ACVIM class. In conclusion, these results allow us to affirm that RLAD and VLAS are reproducible measurements for detecting LAE. Better performances are associated with clinical expertise and background.

The need for a quick and radical green transition gives a key role to the financial system as the main source to fund the change. This debate also involves the development of banking regulation tools able to serve the transition. Building on previous works, we propose a method to weight banks’ assets that combines conventional financial risks and environmental risks to calculate prudential capital requirements, and we apply it to the EU Taxonomy’s technical screening criteria to build an environmental risk indicator based on the buildings’ energy consumptions. We show how to calculate the tool endogenously for the taxonomy sections related to buildings (new construction, purchase of building, renovation), thus proving its immediate enforceability, using data from the Lombardy’s housing stocks. Finally, we conduct a stress test for the Italian banking system showing that our proposal would be an effective incentive for the banks to fund the green transition of the construction sector. Disclaimer: The views expressed are those of the authors and do not involve the responsibility of the Bank of Italy or RSE.

The aim of this work was to retrospectively evaluate the influence of different therapeutic protocols (loop diuretics, ACE-inhibitors, spironolactone +/- pimobendan) on the survival time (ST) of dogs with myxomatous mitral valve disease at different stages using an Inverse Probability Weighting (IPW) analysis. An IPW method was used to minimize confounding and IPW weighted time-repeated logistic model was used to approximate survival curves (SCs) and calculate survival differences. Subjects were allocated into cases (CA) and controls (CO). Dogs in American College of Veterinary Internal Medicine (ACVIM) B2 class treated with pimobendan (+/- ACE-inhibitors) were selected for the CA group, as well as symptomatic patients (ACVIM class C) threated with triple (furosemide, ACE-inhibitor, pimobendan) or quadruple (furosemide, ACE-inhibitor, pimobendan and spironolactone) therapy. The CO group included ACVIM class B2 dogs not treated with any medication and ACVIM C dogs treated with a combination of furosemide and ACE-inhibitor/spironolactone without pimobendan.The SC of the CA group crossed the CO group at 1634 days. The difference between the two SCs at the time of maximum survival difference in favour of the CO group was 11.3% (CI 1.7%–20.9%) (significant), in favour of the CA group was 3.9% (CI -8.6%–16.4%) (not significant) and at the mean ST was 3.6% (CI -8.5%–15.7%) (not significant) in favour of the CA group. For times greater than 1634 days the survival was in favour of the CA group, there were no statistically significant differences in survival in favour of the CA group in this clinical population.

Development and progression of myxomatous mitral valve disease (MMVD) in Cavalier King Charles Spaniels (CKCS) are difficult to predict. Identification at a young age of dogs with a morphotype associated with more severe mitral disease is desirable. The aims of this study were to: 1) describe the physical, morphometric, and echocardiographic features of MMVD affected Cavalier King Charles Spaniels (CKCS) in American College of Veterinary Internal Medicine (ACVIM) class B1; 2) evaluate the influence of morphometric physical measurements on murmur intensity, mitral valve prolapse (MVP), regurgitant jet size and indexed mitral valve and annulus measurements. Fifty-two MMVD affected CKCS in ACVIM class B1 were included. This is a prospective clinical cross-sectional study. Morphometric measurements, which included body, thorax, and the head sizing of each dog, have been investigated to establish the association with heart murmur intensity, valvular and annular echocardiographic measurements, MVP and regurgitant jet size using inverse probability weighting (IPW) analyses to adjust for confounding. The IPW analyses showed that when head length and nose length decreased, dogs had more severe regurgitant jet size. Furthermore, subjects with more pronounced head stop angle had thicker anterior mitral valve leaflets. A brachycephalic morphotype, with dogs more similar to King Charles Spaniel breed in cephalic morphology, is associated with a more severe regurgitant jet size and with valvular characteristics related to worse forms of MMVD.

The epidemiology of Congenital Heart Diseases (CHDs) has changed over the past twenty years. This study aimed to evaluate the prevalence of CHDs in the population of dogs recruited in a single referral center (RC); compare the epidemiological features of CHDs in screened breeds (Boxers) versus non-screened (French and English Bulldogs, German Shepherds); investigate the association of breeds with the prevalence of CHDs; determine the popularity and volatility of breeds over a 20-year period; analysed the trends of the most popular breeds in the overall population of new-born dogs registered in the Italian Kennel Club (IKC) from 1st January 1997 to 31st December 2017. The RC's cardiological database was analysed, and 1,779 clinical records were included in a retrospective observation study. Descriptive statistics and frequencies regarding the most representative breeds and CHDs were generated. A logistic regression model was used to analyse the trends of the most common CHDs found in single and in cluster of breeds. The relationship between breed popularity and presence of CHDs was studied. The most common CHDs were Pulmonic Stenosis, Patent Ductus Arteriosus, Subaortic Stenosis, Ventricular Septal Defect, Aortic Stenosis, Tricuspid Dysplasia, Atrial Septal Defect, Double Chamber Right Ventricle, Mitral Dysplasia, and others less frequent. The most represented pure breeds were Boxer, German Shepherd, French Bulldog, English Bulldog, Maltese, Newfoundland, Rottweiler, Golden Retriever, Chihuahua, and others in lower percentage. Chihuahuas, American Staffordshire Terriers, Border Collies, French Bulldogs, and Cavalier King Charles Spaniel were the most appreciated all of which showed a high value of volatility. This study found evidence for the value of the screening program implemented in Boxers; fashions and trends influence dog owners' choices more than the worries of health problems in a breed. Effective breeding programs are needed in order to control the diffusion of CHDs without impoverishing the genetic pool.

The coexistence of renal and cardiac disease has been defined in dogs and cats as cardiovascular-renal disorders (CvRD). In humans, renal function is affected by recurrent episodes of acute congestive heart failure (CHF). The aim of this prospective, case-control study was to evaluate the appearance and influence of worsening cardiac disease (WCD), defined on echocardiographic and radiographic parameters, on renal function (defined as worsening renal function [WRF], on the basis of serum creatinine level and presence of proteinuria) in two population: 21 dogs with chronic mitral valve disease (CMVD) and 20 healthy dogs. Dogs were sorted into groups according to the presence/absence of WRF or WCD. Statistical analysis was performed between CMVD dogs and healthy dogs and inside the CMVD dogs group. There was no statistically significant difference in developing WRF between dogs with/without WCD and no statistical evidence to support a difference in WRF parameters in dogs experiencing CHF and dogs not experiencing it. The prevalence of azotemia in CMVD dogs was significantly higher than the prevalence of azotemia previously reported in the general population of dogs. Diuretics therapy didn’t affect renal function. No difference in survival time was seen between groups. In conclusion, CHF, WCD and diuretics therapy didn’t directly induce WRF. However, considering the prevalence of azotemia, data suggests a link between heart and kidney function (despite we didn’t excluded aged-related coexistence of organ damage). A bigger number of dogs at inclusion is required to reach statistical significance.

The epidemiology of Congenital Heart Diseases (CHDs) has changed over the past twenty years.We evaluated the prevalence of CHDs in the population of dogs recruited in a single referral center (RC); compared the epidemiological features of CHDs in screened breeds (Boxers) versus nonscreened (French and English Bulldogs and German Shepherds), investigated the association of breeds with the prevalence of CHDs, determined the popularity and volatility of breeds over a 20-year period; and analysed the trends of the most popular breeds in the overall population of new-born dogs registered in the Italian Kennel Club from 1st January 1997 to 31st December 2017.This was a retrospective observational study, the cardiological database of the RC was analysed, and 1,779 clinical records fulfilled the inclusion criteria.Descriptive statistics and frequencies regarding the most representative breeds and CHDs were generated. A logistic regression model was used to analyse the trends of the most common CHDs found in single breeds (French Bulldog, English Bulldog, Boxer, and German Shepherd), and in groups of breeds (brachycephalic breeds and the most represented large breeds). The relationships between the breed popularity and the presence of CHDs was studied.The most common CHDs were Pulmonic Stenosis (34,1%), Patent Ductus Arteriosus (26,4%), Subaortic Stenosis (14,6%), Ventricular Septal Defect (4,8%), Aortic Stenosis (4,7%), Tricuspid Dysplasia (3,4%), Atrial Septal Defect (1,9%), Double Chamber Right ventricle (1,8%), Mitral Dysplasia (1,6%), and reverse Patent Ductus Arteriosus (0,7%). The most represented pure breeds were Boxer (19,4%), German Shepherd (9,4%), French Bulldog (6,2%), English Bulldog (4,9%), Maltese (3,7%), Newfoundland (3,1%), Rottweiler (3,1%), Golden Retriever (3,0%), Chihuahua (2,8%), Poodle (2,5%), Cavalier King Charles Spaniel (2,2%), American Staffordshire Terrier (2,1%), Labrador Retriever (2,3%), Dobermann (2,1%), Miniature Pinscher (2,0%), Cocker Spaniel (2,0%), Yorkshire Terrier (1,7%), Dogue de Bordeaux (1,6%), Dachshund (1,6%), and Bull Terrier (1,5%). Chihuahuas, American Staffordshire Terriers, Border Collies, French Bulldogs, and Cavalier King Charles Spaniel were the most appreciated small and medium breeds, all of which showed a high value of volatility.In conclusion, this study found evidence for the value of the screening program implemented in Boxers, which decreased the prevalence of Subaortic Stenosis and Pulmonic Stenosis. However, fashions and trends influence dog owners’ choices more than the worries of health problems frequently found in a breed. Effective breeding programs are needed in order to control the diffusion of CHDs without impoverishing the genetic pool; in addition, dog owners should be educated, and the breeders supported by a network of veterinary cardiology centers.

The most common cause of heart failure in the canine population is myxomatous mitral valve disease, sometimes complicated by chronic kidney disease. Many studies have been done on the use of symmetric dimethylarginine as biomarker of renal impairment in dogs affected by chronic kidney disease, few studies have examined his reliability as biomarker in dogs affected by heart diseases. Aim of this study was to evaluate symmetric dimethylarginine in dogs affected by mitral valve disease in order to assess his reliability in heart diseases. This was a retrospective case-control study on a clinical population of dogs affected by mitral valve disease (cases) vs healthy dogs (controls). Both groups underwent a complete physical evaluation, echocardiographic examination, complete blood count, biochemical panel, including serum creatinine and urea and urine analysis with protein-to-creatinine ratio. Serum was frozen and sent to IDEXX laboratories for symmetric dimethylarginine determination. General linear model was applied to data. A total number of 24 cases and 7 controls were included. Symmetric dimethylarginine value was in the reference value in the 75% (n=18) of cases, and in the 43% (n=3) of controls. Once set symmetric dimethylarginine as dependent variable, no statistical significant differences were found for each variable considered (breed, age, sex, weight, class of cardiomyopathy, presence/absence of valvular disease, presence/absence of congestive heart failure, pharmacological therapy, creatinine and urea concentration). Blood concentration of SDMA resulted not influenced by the variables mentioned above, so it could be considered a reliable marker of early renal impairment in dogs affected by mitral valve disease.Keywords: Biomarker, Cardiovascular-renal disorder, Dog, Myxomatous mitral valve disease, Symmetric dimethylarginine

BACKGROUND: Hypertrophic cardiomyopathy is the most prevalent heart disorder in cats and principal cause of cardiovascular morbidity and mortality. Yet, the impact of preclinical disease is unresolved.HYPOTHESIS/OBJECTIVES: Observational study to characterize cardiovascular morbidity and survival in cats with preclinical nonobstructive (HCM) and obstructive (HOCM) hypertrophic cardiomyopathy and in apparently healthy cats (AH).ANIMALS: One thousand seven hundred and thirty client-owned cats (430 preclinical HCM; 578 preclinical HOCM; 722 AH).METHODS: Retrospective multicenter, longitudinal, cohort study. Cats from 21 countries were followed through medical record review and owner or referring veterinarian interviews. Data were analyzed to compare long-term outcomes, incidence, and risk for congestive heart failure (CHF), arterial thromboembolism (ATE), and cardiovascular death.RESULTS: During the study period, CHF, ATE, or both occurred in 30.5% and cardiovascular death in 27.9% of 1008 HCM/HOCM cats. Risk assessed at 1, 5, and 10 years after study entry was 7.0%/3.5%, 19.9%/9.7%, and 23.9%/11.3% for CHF/ATE, and 6.7%, 22.8%, and 28.3% for cardiovascular death, respectively. There were no statistically significant differences between HOCM compared with HCM for cardiovascular morbidity or mortality, time from diagnosis to development of morbidity, or cardiovascular survival. Cats that developed cardiovascular morbidity had short survival (mean ± standard deviation, 1.3 ± 1.7 years). Overall, prolonged longevity was recorded in a minority of preclinical HCM/HOCM cats with 10% reaching 9-15 years.CONCLUSIONS AND CLINICAL IMPORTANCE: Preclinical HCM/HOCM is a global health problem of cats that carries substantial risk for CHF, ATE, and cardiovascular death. This finding underscores the need to identify therapies and monitoring strategies that decrease morbidity and mortality.

Objectives Large studies focusing on restrictive cardiomyopathy (RCM) in the cat are scarce. The aims of this retrospective study were to describe epidemiological characteristics and to analyse prognostic factors affecting survival in cats with RCM. Methods The clinical archives of the Gran Sasso Veterinary Clinic (Milan, Italy) and of the cardiology unit of the Department of Veterinary Medicine (University of Milan, Italy) from 1997–2015 were reviewed for all cats diagnosed with RCM based on an echocardiographic examination (left atrial/biatrial enlargement, normal left ventricle wall thickness, normal or mildly decreased systolic function and restrictive left ventricle filling pattern with pulsed Doppler echocardiography). Results The study population comprised 90 cats (53 male, 37 female) with an echocardiographic diagnosis of RCM. Most were domestic shorthairs (n = 60) with a mean ± SD age of 10.0 ± 4.3 years and a median weight of 3.8 kg (interquartile range 3.2–5 kg). Most cats were symptomatic (n = 87). The most common clinical sign was respiratory distress (n = 75). Follow-up was available for 60 cats and the median survival time (MST) was 69 days (95% confidence interval [CI] 0–175 days). Cardiac-related death occurred in 50 cats. In the multivariate Cox analysis only respiratory distress showed a statistically significant effect on survival. The cats without respiratory distress showed an MST of 466 days (95% CI 0–1208); cats with respiratory distress showing an MST of 64 days (95% CI 8–120; P = 0.011). Conclusions and relevance RCM can be considered an end-stage condition associated with a poor prognosis, with few cats not showing clinical signs and surviving >1 year. Most cats died of cardiac disease within a very short time.

Clinical records of dogs with spontaneous degenerative mitral valve disease (DMVD) with clinical signs related to congestive heart failure (CHF) recruited during routine clinical practice between 2001 and 2018 at the Cardiology Unit of the Veterinary Teaching Hospital (University of Milan) were included in this retrospective cohort study. Baseline echocardiographic data were evaluated. Median survival time (MST) was calculated. Data on therapeutic treatment, ISACHC (International Small Animal Cardiac Health Council) or ACVIM (American College of Veterinary Internal Medicine) classes were reviewed based on the inclusion period and type of endpoint (i.e. cardiac death or death for other causes). A univocal classification was needed, and the patients classified in ISACHC classes II, IIIa and IIIb, visited before 2009, were reallocated to ACVIM class C. The main goal of this data review was to retrospectively evaluate 259 clinical records of subjects belonging to ACVIM C class examined between 2001 to 2018 and 202 dogs examined between 2010 to 2018. In this way, in the second group, the bias of the reclassification was avoided. The MST (median survival time) of these subjects was 531 d (2001-2018) and 335.5 d (2010-2018), respectively. Univariate survival regression analysis for subjects included from 2010 to 2018 showed as significantly related to cardiac death (CD): left atrium to aorta ratio (LA/Ao) (HR 2.754, p=0.000), E wave (HR 2.961, p=0.000), E/A ratio (HR 1.372, p=0.000), end-diastolic (HR 1.007, p=0.000) (EDVI) and end-systolic (HR 1.012, p=0.026) (ESVI) volume indexes, allometric diastolic (HR 4.018, p=0.000) (LVIDdN) and systolic (HR 2.674, p=0.049) (LVIDsN) left ventricular internal diameters, age (HR 1.006, p=0.009) and pulmonary hypertension severity (HR=1.309, p=0.012) (PH). Multivariate analysis, adjusted for age, showed that the only variable that determined a statistically significant difference in MST was PH severity (HR 1.334, p=0.033). The type of therapeutic treatment within this class was not significant for the MST of the subjects.

Background Patent ductus arteriosus (PDA) is one of the most common congenital heart defects in dogs. Advanced echocardiographic techniques such as speckle-tracking echocardiography (STE) have not been extensively used to evaluate cardiac function in affected dogs. Hypothesis Advanced echocardiographic techniques are more sensitive than standard echocardiographic techniques in analyzing systolic function in dogs with PDA. Animals Forty-four client-owned dogs: 34 dogs with PDA (preoperative evaluation) and 10 healthy sex- and weight-matched controls. Methods Prospective study. Dogs were recruited over a 2-year period. Complete echocardiographic evaluation was performed, including conventional (end-diastolic volumes indexed to body surface area in B and M-mode [EDVIB/M], end-systolic volumes indexed to body surface area in B and M-mode [ESVIB/M], allometric scaling in diastole and systole [AlloD/S], pulmonary flow to systemic flow [Qp/Qs], ejection fraction [EF] and fractional shortening [FS]) and speckle-tracking echocardiography ([STE]: global longitudinal, radial and circumferential strain [S] and strain rate [SR]). Results Dogs with PDA had significantly different EDVIB/M, ESVIB/M, AlloD/S, Qp/Qs and all STE-derived parameters (global longitudinal S and SR, global circumferential S and SR, global radial S and SR)compared to healthy dogs. No correlation was found between standard techniques (EDVIB/M, ESVIB/M, AlloD/S, Qp/Qs) and STE-derived parameters (global longitudinal, circumferential and radial S and SR). Conclusion and Clinical Importance Conventional parameters routinely used to assess systolic function (EF and FS) were not different between the groups; STE-derived parameters identified subtle changes in cardiac systolic function and contractility between the 2 groups of dogs. Based on these findings, STE may be a more appropriate tool to assess cardiac contractility in dogs with PDA.

Background Patent ductus arteriosus (PDA) is 1 of the most common congenital heart defects in dogs and percutaneous closure is effective in achieving ductal closure; PDA closure is associated with abrupt hemodynamic changes. Hypothesis A marked decrease in standard parameters of systolic function as assessed by M- or B-mode echocardiography after PDA closure was identified in previous studies. Speckle tracking echocardiography can provide further insight into the effect of PDA closure on cardiac mechanics in dogs affected by PDA. Animals Twenty-five client-owned dogs with PDA. Methods Prospective study. Dogs were recruited over a 2-year period. Complete echocardiographic evaluation was performed before and 24 hours after PDA closure, including standard (end-diastolic volumes indexed to body surface area in B- and M-mode [EDVIB/M], end-systolic volumes indexed to body surface area in B- and M-mode [ESVIB/M], allometric scaling in diastole [AlloD] and systole [AlloS], pulmonary flow to systemic flow [Qs/Qp], ejection fraction [EF], and fractional shortening [FS]), and advanced speckle-tracking echocardiography (STE): global longitudinal, radial, circumferential and transverse strain (S), and strain rate (SR). Results Patent ductus arteriosus closure was associated with statistically significant decreases in EDVIM/B and ESVIM/B, AlloD and AlloS, SI, EF, and FS. A statistically significant decrease in the absolute values of radial, transverse, and circumferential S and SR was observed, whereas longitudinal S and SR did not change significantly. Conclusion and Clinical Importance Patent ductus arteriosus closure by percutaneous approach is associated with marked decreases of conventional echocardiographic parameters as a result of the changes in loading conditions, but no evidence of systolic dysfunction was identified by means of STE, as none of the S and SR values were below reference ranges. In the short term, contractility is enhanced in the long axis (long S/SR values were not statistically different before and after closure) and decreases to normal values in short axis (circumferential, radial, and transversal S/SR decreased to normal reference range).

Advanced two-dimensional echocardiographic techniques allow strain (S) analysis of regional function and thus can provide information on regional myocardial deformation. Feature-tracking echocardiography (FTE) is based on a mono-dimensional technology and may offer more detailed information about septal deformation because it can analyse the activity of left- and right-sided septal fibres separately. The present study aimed to quantify global and regional (free wall and septal) right ventricular (RV) longitudinal S and strain rate (SR). We also investigated the relationships of S and SR with age, sex, weight, breed (sighthound breed vs other breeds), and heart rate. Cine loops were acquired from the left apical four-chamber view, optimized for the RV, in 60 dogs. The within-day and between-day intra-observer coefficient of variation for global RV S and SR in normal dogs using FTE was acceptable (

Bronchial and upper respiratory diseases have been associated with hypoxia and subsequent development of pulmonary arterial hypertension (PAH). However, there are no known studies assessing the prevalence of PAH in dogs with these conditions. The aim of this study was to assess the frequency of PAH in dogs with bronchial and upper respiratory diseases. Medical records of dogs with confirmed diagnosis (by endoscopic examination) of bronchial and/or upper respiratory diseases referred for cardiovascular investigation (January 2009 - May 2013) were retrospectively reviewed. Diagnosis of PAH was made by echocardiography (tricuspid regurgitation > 2.8 m/s and/or pulmonic regurgitation > 2.2 m/s); possible PAH was diagnosed when two or more specific echocardiographic findings were present. 52 dogs (30 with upper respiratory diseases, 17 with bronchial disease and 5 with both) were included. Diagnosis of PAH was performed in 3 dogs (5.7%). Two dogs were considered as probably affected by PAH; a total of 5 dogs (9.4%) resulted in being affected or probably affected by PAH. Our study shows that the prevalence of PAH in dogs with bronchial and/or upper respiratory diseases is low; PAH seems to occur mostly in older dogs and/or with very advanced disease: echocardiography may therefore be a useful tool in this category of patients.

Background Epidemiologic knowledge regarding noncardiovascular and all‐cause mortality in apparently healthy cats (AH) and cats with preclinical hypertrophic cardiomyopathy (pHCM) is limited, hindering development of evidence‐based healthcare guidelines. Objectives To characterize/compare incidence rates, risk, and survival associated with noncardiovascular and all‐cause mortality in AH and pHCM cats. Animals A total of 1730 client‐owned cats (722 AH, 1008 pHCM) from 21 countries. Methods Retrospective, multicenter, longitudinal, cohort study. Long‐term health data were extracted by medical record review and owner/referring veterinarian interviews. Results Noncardiovascular death occurred in 534 (30.9%) of 1730 cats observed up to 15.2 years. Proportion of noncardiovascular death did not differ significantly between cats that at study enrollment were AH or had pHCM (P = .48). Cancer, chronic kidney disease, and conditions characterized by chronic weight‐loss‐vomiting‐diarrhea‐anorexia were the most frequently recorded noncardiovascular causes of death. Incidence rates/risk of noncardiac death increased with age in AH and pHCM. All‐cause death proportions were greater in pHCM than AH (65% versus 40%, respectively; P

Objectives Feline cardiomyopathies (CMs) represent a heterogeneous group of myocardial diseases. The most common CM is hypertrophic cardiomyopathy (HCM), followed by restrictive cardiomyopathy (RCM). Studies comparing survival and outcome for different types of CM are scant. Furthermore, little is known about the cardiovascular consequences of systemic diseases on survival. The aim of this retrospective study was to compare survival and prognostic factors in cats affected by HCM, RCM or secondary CM referred to our institution over a 10 year period. Methods The study included 94 cats with complete case records and echocardiographic examination. Fifty cats presented HCM, 14 RCM and 30 secondary CM. Results A statistically significant difference in survival time was identified for cats with HCM (median survival time of 865 days), RCM (273 days) and secondary CM (Conclusions and relevance Primary CMs in cats share some common features (ie, LA dimension and hypercoagulable state) linked to feline cardiovascular physiology, which influence survival greatly in end-stage CM. The presence of clinical signs has to be regarded as a marker of disease severity, regardless of the underlying CM. Secondary CMs are more benign conditions, but if the primary disease is not properly managed, the prognosis might also be poor in this group of patients.

Objective A proportion of multiple sclerosis (MS) patients experience disease activity despite treatment. The early identification of the most effective drug is critical to impact long-term outcome and to move toward a personalized approach. The aim of the present study is to identify biomarkers for further clinical development and to yield insights into the pathophysiology of disease activity. Methods We performed a genome-wide association study in interferon-β (IFNβ)-treated MS patients followed by validation in 3 independent cohorts. The role of the validated variant was examined in several RNA data sets, and the function of the presumed target gene was explored using an RNA interference approach in primary T cells in vitro. Results We found an association between rs9828519G and nonresponse to IFNβ (pdiscovery = 4.43 × 10−8) and confirmed it in a meta-analysis across 3 replication data sets (preplication = 7.78 × 10−4). Only 1 gene is found in the linkage disequilibrium block containing rs9828519: SLC9A9. Exploring the function of this gene, we see that SLC9A9 mRNA expression is diminished in MS subjects who are more likely to have relapses. Moreover, SLC9A9 knockdown in T cells in vitro leads an increase in expression of IFNγ, which is a proinflammatory molecule. Interpretation This study identifies and validates the role of rs9828519, an intronic variant in SLC9A9, in IFNβ-treated subjects, demonstrating a successful pharmacogenetic screen in MS. Functional characterization suggests that SLC9A9, an Na+-H+ exchanger found in endosomes, appears to influence the differentiation of T cells to a proinflammatory fate and may have a broader role in MS disease activity, outside of IFNβ treatment. Ann Neurol 2015;78:115–127

Purpose Peripherally inserted central catheters (PICCs) are associated with some adverse events, the most frequent are thrombosis, tip catheter malposition and spontaneous late migration. However, the cause of spontaneous late migration in most cases remains unknown. We carried out this study to add data to the literature on PICCs late spontaneous migration. Methods We conducted a systematic review of all manuscripts describing PICC spontaneous late migration in adult populations and we also described two cases of late PICCs migration. Results We identified five studies for a total of 58 cases of PICC late migration. In our two cases, patients' activity is an important contributing factor for late spontaneous PICC migration. Conclusions To avoid late catheter misplacement, initial malposition should be immediately identified and promptly corrected and a detailed patients training should be carried out.

Successful veterinary treatment of animals requires owner adherence with a prescribed treatment plan. The aim of our study was to evaluate and compare the level of adherence of the owners of patients presented for behavioural, cardiological, urological, and oncological problems. At the end of the first examination, each owner completed a questionnaire. Then, the owners were called four times to fill out another questionnaire over the phone. With regard to the first questionnaire, statistically significant data concern behavioral medicine and cardiology. In the first area the owner’s worry decreases during the follow-up and the number of owners who would give away the animal increases. In cardiology, owners who think that the pathology harms their animal’s quality of life decreased significantly over time. With regard to the 9 additional follow-up questions, in behavioural medicine and urology the owner’s discomfort resulting from the animal’s pathology significantly decreases over time. Assessment of adherence appears to be an optimal instrument in identifying the positive factors and the difficulties encountered by owners during the application of a treatment protocol.

Background Quantitative and semiquantitative methods have been proposed for the assessment of MR severity, and though all are associated with limitations. Measurement of vena contracta width (VCW) has been used in clinical practice. Objective To measure the VCW in dogs with different levels of MR severity. Animals Two hundred and seventy‐nine dogs were classified according to 5 levels of MR severity. Methods This was a retrospective study. EROA and regurgitant volume calculated by the PISA method, were measured and indexed to BSA. Descriptive statistics were calculated for VCW and VCW index for all categories of MR severity. Spearman's rank correlation coefficients (ρs) were calculated to compare the results of the different methods (VCW and VCW index vs RV PISA, RV PISA index, EROA, EROA index), and between VCW and VCW index versus MR severity. Results All Spearman's rank correlation coefficients were significant (P

Signals that promote myelination must be tightly modulated to adjust myelin thickness to the axonal diameter. In the peripheral nervous system, axonal neuregulin 1 type III promotes myelination by activating erbB2/B3 receptors and the PI3K/AKT/mTOR pathway in Schwann cells. Conversely, PTEN (phosphatase and tensin homolog on chromosome 10) dephosphorylates PtdIns(3,4,5)P3and negatively regulates the AKT pathway and myelination. Recently, the DLG1/SAP97 scaffolding protein was described to interact with PTEN to enhance PIP3dephosphorylation. Here we now report that nerves from mice with conditional inactivation ofDlg1in Schwann cells display only a transient increase in myelin thickness during development, suggesting that DLG1 is a transient negative regulator of myelination. Instead, we identified DDIT4/RTP801/REDD1 as a sustained negative modulator of myelination. We show that DDIT4 is expressed in Schwann cells and its maximum expression level precedes the peak of AKT activation and of DLG1 activity in peripheral nerves. Moreover, loss of DDIT4 expression bothin vitroandin vivoinDdit4-null mice provokes sustained hypermyelination and enhanced mTORC1 activation, thus suggesting that this molecule is a novel negative regulator of PNS myelination.

Objectives To assess survival and risk factors in dogs with pulmonic stenosis. Methods A retrospective review of medical case records of all cases of pulmonic stenosis >50 mmHg, undergoing pulmonary balloon valvuloplasty or not. Survival curves and multivariate analysis were calculated in the overall population and in subgroups. Results One hundred and seventy-two cases were included. Factors negatively affecting survival were clinical signs [hazard ratio (HR) 3 · 44, P

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an inherited disorder that causes progressive kidney damage and renal failure. Mutations in the UMOD gene, encoding uromodulin, lead to ADTKD-UMOD related. Uromodulin is a GPI-anchored protein exclusively produced by epithelial cells of the thick ascending limb of Henle’s loop. It is released in the tubular lumen after proteolytic cleavage and represents the most abundant protein in human urine in physiological condition. We previously generated and characterized a transgenic mouse model expressing mutant uromodulin (Tg UmodC147W) that recapitulates the main features of ATDKD-UMOD. While several studies clearly demonstrated that mutated uromodulin accumulates in endoplasmic reticulum, the mechanisms that lead to renal damage are not fully understood. In our work, we used kidney transcriptional profiling to identify early events of pathogenesis in the kidneys of Tg UmodC147W mice. Our results demonstrate up-regulation of inflammation and fibrosis and down-regulation of lipid metabolism in young Tg UmodC147W mice, before any functional or histological evidence of kidney damage. We also show that pro-inflammatory signals precede fibrosis onset and are already present in the first week after birth. Early induction of inflammation is likely relevant for ADTKD-UMOD pathogenesis and related pathways can be envisaged as possible novel targets for therapeutic intervention.

The aim of the present study is to investigate the molecular pathways underlying amyotrophic lateral sclerosis (ALS) pathogenesis within the peripheral nervous system. We analyzed gene expression changes in human motor nerve diagnostic biopsies obtained from eight ALS patients and seven patients affected by motor neuropathy as controls. An integrated transcriptomics and system biology approach was employed. We identified alterations in the expression of 815 genes, with 529 up-regulated and 286 down-regulated in ALS patients. Up-regulated genes clustered around biological process involving RNA processing and protein metabolisms. We observed a significant enrichment of up-regulated small nucleolar RNA transcripts (p = 2.68*10-11) and genes related to endoplasmic reticulum unfolded protein response and chaperone activity. We found a significant down-regulation in ALS of genes related to the glutamate metabolism. Interestingly, a network analysis highlighted HDAC2, belonging to the histone deacetylase family, as the most interacting node. While so far gene expression studies in human ALS have been performed in postmortem tissues, here specimens were obtained from biopsy at an early phase of the disease, making these results new in the field of ALS research and therefore appealing for gene discovery studies.

International audience; Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.

Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channels of nociceptor fibers, and find application in the management of acute and chronic pain. Despite the key role they play in modern medicine, their cardio and neurotoxicity (together with their short half-life) stress the need for developing implantable devices for tailored local drug release, with the aim of counterbalancing their side effects and prolonging their pharmacological activity. This review discusses the evolution of the physical forms of local anesthetic delivery systems during the past decades. Depending on the use of different biocompatible materials (degradable polyesters, thermosensitive hydrogels, and liposomes and hydrogels from natural polymers) and manufacturing processes, these systems can be classified as films or micro- or nanostructured devices. We analyze and summarize the production techniques according to this classification, focusing on their relative advantages and disadvantages. The most relevant trend reported in this work highlights the effort of moving from microstructured to nanostructured systems, with the aim of reaching a scale comparable to the biological environment. Improved intracellular penetration compared to microstructured systems, indeed, provides specific drug absorption into the targeted tissue and can lead to an enhancement of its bioavailability and retention time. Nanostructured systems are realized by the modification of existing manufacturing processes (interfacial deposition and nanoprecipitation for degradable polyester particles and high- or low-temperature homogenization for liposomes) or development of novel strategies (electrospun matrices and nanogels). The high surface-to-volume ratio that characterizes nanostructured devices often leads to a burst drug release. This drawback needs to be addressed to fully exploit the advantage of the interaction between the target tissues and the drug: possible strategies could involve specific binding between the drug and the material chosen for the device, and a multiscale approach to reach a tailored, prolonged drug release.

Type 1 diabetes mellitus (T1DM), celiac disease (CD) and autoimmune thyroid disease (ATD) are autoimmune conditions relatively common in paediatric age and frequently occur in association in the same subject. This event is not by chance and requires an explanation. Here, we studied the distribution of HLA-DQ αβ heterodimers in 334 Italian children with T1DM, ATD and CD alone or in association and in 224 Italian healthy controls. In particular, 164 patients had T1DM (133 alone, 20+ATD, 7+CD and 4+CD+ATD), 118 had ATD (110 alone, 8+CD) and 52 had CD (40 alone, 11+ATD and 1+T1DM). 51 patients suffered from multiple autoimmune diseases. The risk for multiple autoimmune diseases was significantly associated with the increased number of HLA-DQ markers of susceptibility for both T1DM (p = 0.003) and CD (p = 0.006). The presence of one or more diabetogenic DQ molecules significantly increased the probability of developing not only T1DM (p0.001) but also CD (p0.001) and ATD (p = 0.001). Similarly, the presence of one or more celiac HLA-DQ heterodimers significantly increased the likelihood of developing not only CD (p0.001), but also T1DM (p0.001) and ATD (p0.001). We confirm that the sharing of the immunogenetic background is responsible for the development of multiple autoimmune diseases although with a different risk according to the number and type of susceptible HLA-DQ heterodimers as reported in the algorithm proposed here. It is likely that combinations of DQA1 and DQB1 alleles are the real culprits of the progression towards multiple autoimmune diseases and HLA-DQ genomic typing will improve the capability to predict associated autoimmune diseases in infancy.

Identification of novel targets and biomarkers, such as microRNAs, is extremely helpful to understand the pathogenetic mechanisms in a disease like multiple sclerosis (MS). We tested the expression profile of 1145 microRNAs in peripheral blood mononuclear cells (PBMCs) of 19 MS patients and 14 controls, and we further explored their function by performing a whole-genome mRNA profiling in same subjects and using bioinformatic prediction tool. A total of 104 miRNAs have been identified as deregulated in MS patients; 2/10 which ranked highest (let-7g and miR-150) have been validated in a replication sample, leading to the identification of putative target genes.

To retrospectively compare and contrast the clinical presentation, diagnostic findings and survival in Boxer dogs with cardiomyopathy, with or without left ventricular (LV) systolic failure.Medical records of Boxers referred between 1993 and 2008 in which a diagnosis of ventricular arrhythmias and/or cardiomyopathy was made, were reviewed. Dogs were divided into two groups according to their left ventricular (LV) systolic diameter, group A normal (20 dogs) or group B dilated (59 dogs).Dogs in group A had a better outcome than dogs in group B (median survival time of 124 and 17 weeks respectively, p 0.001). In group B, dogs with a history of collapse had a worse outcome (median survival time of 10 weeks) compared with dogs not showing collapse (median survival time 24 weeks) (p = 0.031).The majority of dogs, in this UK study, presented with the myocardial dysfunction form of the disease, with LV dilation and congestive heart failure signs. The prognosis was worse in dogs with LV dilation compared to dogs with a normal LV and ventricular arrhythmias. In the Boxers with LV dilation, dogs with collapse had a worse prognosis than those without.

MGAT5 was demonstrated to be associated to multiple sclerosis (MS) severity. We evaluated its role in progressive MS. We studied 11 SNPs mapping to MGAT5 in an Italian cohort of primary progressive or progressive-relapsing patients. The rs1257169(G) allele is associated with lower disease severity (p-value = 0.02). Adding the age of onset as covariate, another SNP, rs539588, is nominally significant. None of the SNPs survived after multiple testing correction. These results, even if suggestive of MGAT5 involvement also in progressive MS severity, require a bigger sample size to confirm and better explore the role of this locus in this rare disease course.

Background: Phenotypic accuracy and specificity are essential for a successful genetic association study. Blood pressure (BP) measurements show heterogeneity depending on the method and time of measurement, sexual dimorphism and measurement errors, making genetic dissection difficult. Methods and Results: We studied 1550 adults aged 25-74 years, not on any antihypertensive treatment, resident in Monza, Italy (PAMELA study) all of whom had home, clinic and ambulatory BPs measured. We analysed 3705 single nucleotide polymorphisms (SNPs) (1324 typed and 2381 imputed) across 168 genes for association with these traits. No SNP achieved an experiment wide significance level of P less than 3 × 10 for any of the phenotypes studied. We selected 28 top candidate SNPs for further analysis of phenotypic heterogeneity and sexual dimorphism using a gene-centric strategy calculating empirical P values by permutations within each gene by including genic SNPs with an r less than 0.5. The association signals were not consistent across all the BP phenotypes, whether compared by genes or by physiological pathways. The top SNPs in WNK1, ADRA1A, ADRA1B, DRD1, NOS1 and PON3 showed significant sex interaction for BP and when analysed separately by sex showed evidence of dimorphism with opposite direction of effect for the same allele in the two sexes. Conclusion: In the largest study of its kind, we show that sex and BP measurement methods have a significant impact on association signals. These findings might explain previous inconsistencies in studies on cardiovascular candidate genes and should have major implications for the design and interpretation of association studies. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

In this work we investigated which mitral valve leaflet was most often involved in mitral valve prolapse with degenerative mitral valve disease and whether there was an association with breed, age, gender, or weight. Five hundred and thirty-seven dogs with mitral valve prolapse-degenerative mitral valve disease were assessed; the cross-breed dog was the most represented breed (248 dogs, 46.2%). Mitral valve prolapse was more common in male dogs, and the average age was 11.3 +/- 2.8 years. Prolapse of the anterior leaflet was present in 48.4% of dogs, prolapse of the the posterior leaflet in 7.1%, and bileaflet prolapse was present in 44.5%; this distribution is different than that typically found in humans. There was a significant correlation between severity of mitral regurgitation and severity of mitral valve prolapse or ISACHC class, and between severity of mitral valve prolapse and ISACHC class. There was no relationship between the particular affected leaflet(s) and severity of mitral regurgitation, severity of mitral valve prolapse, or ISACHC class. Our findings suggest that the susceptibility to the mitral valve prolapse-degenerative mitral valve disease is not confined to a specific breeds and that the specific leaflet prolapsing is different in dogs compared with humans.

This article discusses environmental penalties in Italy with a particular focus on their history. Furthermore, it discusses the non-cohesion of penalties, Italian law on environmental crimes, administrative penalties in Italy, assignment of jurisdiction to Italian courts, the statute of limitation in Italy, jurisdiction profiles in Italy and the compensation for environmental damage.

The human Arg (Abl2) nonreceptor tyrosine kinase has a role in cytoskeletal rearrangements by its C-terminal F-actin- and microtubule-binding sequences. We have previously identified Arg transcripts with different 5′- and 3′-ends, named respectively long and short 1A and 1B (1AL, 1AS, 1BL, 1BS) and long and short C-termini (CTL and CTS), that have different expression patterns in various cell types. The combination of the different ends permits to predict eight putative full-length Arg transcripts and corresponding proteins. By Reverse Transcription-Long PCR we show here that all eight full-length transcripts are endogenously expressed in Caki-1 cells and the two bands, ≃10 kDa different, shown by 1-D Western blots of Hek293T and Caki-1 lysates correspond to the full-length Arg protein isoforms with different C-termini. 2-D Western blot analysis evidenced different high molecular weight and slight acidic specific spots in Hek293T and Caki-1 lysates. The cellular localization of two Arg isoforms (1BLCTL and 1BLCTS) transfected in Caki-1 and Hek293T cells was cytoplasmic, and some differences in cytoskeleton interactions have been evidenced. Moreover, in Hek293T cells only the transfected 1BLCTS isoform gives rise to a large intracytoplasmic cylindrical structure containing phalloidin-positive amorphous actin aggregates. The presence of eight full-length Arg isoforms with different cellular expression may imply a diverse functional role in normal and neoplastic cells. J. Cell. Biochem. 105: 1219–1227, 2008. © 2008 Wiley-Liss, Inc.

Hypoxia-inducible transcription factors (HIFs) regulate a wide array of adaptive responses to hypoxia and are often activated in solid tumors and hematologic malignancies due to intratumoral hypoxia and emerging new layers of regulation. We found that in chronic lymphocytic leukemia (CLL), HIF-1α is a novel regulator of the interaction of CLL cells with protective leukemia microenvironments and, in turn, is regulated by this interaction in a positive feedback loop that promotes leukemia survival and propagation. Through unbiased microarray analysis, we found that in CLL cells, HIF-1α regulates the expression of important chemokine receptors and cell adhesion molecules that control the interaction of leukemic cells with bone marrow and spleen microenvironments. Inactivation of HIF-1α impairs chemotaxis and cell adhesion to stroma, reduces bone marrow and spleen colonization in xenograft and allograft CLL mouse models, and prolongs survival in mice. Of interest, we found that in CLL cells, HIF-1α is transcriptionally regulated after coculture with stromal cells. Furthermore, HIF-1α messenger RNA levels vary significantly within CLL patients and correlate with the expression of HIF-1α target genes, including CXCR4, thus further emphasizing the relevance of HIF-1α expression to CLL pathogenesis.

Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Its accumulation in the fetal brain takes place mainly during the last trimester of pregnancy and continues at very high rates up to the end of the second year of life. Since the endogenous formation of DHA seems to be relatively low, DHA intake may contribute to optimal conditions for brain development. We performed a narrative review on research on the associations between DHA levels and brain development and function throughout the lifespan. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling. Most data from human studies concern the contribution of DHA to optimal visual acuity development. Accumulating data indicate that DHA may have effects on the brain in infancy, and recent studies indicate that the effect of DHA may depend on gender and genotype of genes involved in the endogenous synthesis of DHA. While DHA levels may affect early development, potential effects are also increasingly recognized during childhood and adult life, suggesting a role of DHA in cognitive decline and in relation to major psychiatric disorders.