Assessment of Y chromosome copy number alterations in non-neoplastic and neoplastic leukocytes of male dogs.

The loss of the Y chromosome (ChrY), also known as LOY, is a common genetic alteration observed in men. It occurs in non-neoplastic cells as an age-related change as well as in neoplastic cells of various cancer types. While well-documented in humans, LOY has not been extensively studied in non-human mammals. In this study, we developed simple digital PCR-based assays to assess the copy number of ChrY relative to the X chromosome (ChrX) and chromosome 8 (Chr8) to evaluate ChrY numerical alterations in male canine DNA specimens. Using these assays, we analyzed non-neoplastic leukocytes from 162 male dogs without hematopoietic neoplasia to investigate the occurrence of age-related LOY in non-neoplastic leukocytes. Additionally, we examined 101 tumor DNA specimens obtained from male dogs diagnosed with various types of lymphoma and leukemia to determine whether copy number alterations of the ChrY occur in canine hematopoietic cancers. Analysis of the 162 non-neoplastic leukocyte DNA specimens from male dogs of varying ages revealed a consistent ∼1:1 ChrY:ChrX ratio. This suggests that age-related LOY in non-neoplastic leukocytes is rare or absent in dogs. Conversely, a decreased or increased ChrY:ChrX ratio was detected in canine neoplastic leukocytes at varying frequencies across different canine hematopoietic malignancies (P = 0.01, Fisher's exact test). Notably, a higher incidence of LOY was observed in more aggressive cancer types. To determine if this relative LOY to ChrX was caused by changes in ChrY or ChrX, we further analyzed their relative copy numbers using Chr8 as a reference. Loss of ChrX relative to Chr8 was found in 21% (9/41) of B-cell lymphomas and 6% (1/18) of non-T-zone/high-grade T-cell lymphomas. In contrast, a subset (29%, 4/14) of T-cell chronic lymphocytic leukemia showed gain of ChrX relative to Chr8. Notably, no relative LOY to Chr8 was detected indolent hematopoietic cancers such as T-zone lymphoma (0/9) and chronic lymphocytic leukemia of B-cell (0/11) and T-cell origins (0/14). However, relative LOY to Chr8 was present in more aggressive canine hematopoietic cancers, with incidences of 24% (10/41) in B-cell lymphoma, 44% (8/18) in non-T-zone/high-grade T-cell lymphoma, and 75% (6/8) in acute leukemia. This study highlights both similarities and differences in LOY between human and canine non-neoplastic and neoplastic leukocytes. It underscores the need for further research into the role of ChrY in canine health and disease, as well as the significance of LOY across various species.

Frequency of arrhythmias detected in 9440 feline electrocardiograms by breed, age, and sex.

OBJECTIVES: The purpose of this study was to describe the frequency of arrhythmias detected in unsedated feline patients from general practice settings. ANIMALS: A total 10,638 feline electrocardiograms (ECGs) were retrospectively collected of which 9440 met the inclusion criteria. METHODS: Recordings were evaluated by a board-certified cardiologist. If an arrhythmia was present in the ECG tracing, the cardiologist categorized the arrhythmia using pre-established keywords. RESULTS: At least one arrhythmia was observed in 249 cases (2.64%, 95% confidence interval (CI): 2.34-2.98, 249/9440), with the most common arrhythmia encountered being ventricular premature complexes (1.63%, 95% CI: 1.39%-1.91%, 154/9440). Ragdoll cats had the highest odds of arrhythmia (odds ratio (OR): 3.17, 95% CI: 1.43-6.17, P=0.036). Both geriatric (Age: 13+ years, OR: 1.70, 95% CI: 1.24-2.34, P=0.013) and senior (Age: 10-13 years, OR: 1.68, 95% CI: 1.19-2.37, P=0.003) cats had higher odds of having an arrhythmia than adult cats. The odds of male cats having an arrhythmia were slightly higher than female (OR: 1.36, 95% CI: 1.06-1.76, P=0.018). CONCLUSIONS AND RELEVANCE: Of the 9440 ECGs included in this study, at least one arrhythmia was detected in 249 distinct cases. Arrhythmias were more common in older cats, male cats and the Ragdoll cat breed. While it is important to note that the presence of an arrhythmia alone does not always indicate the presence of heart disease, further research on the association between breed cardiac health is needed.

Reaction time as a biomarker of aging. A study with women over 65 years / El tiempo de reacción como biomarcador de envejecimiento. Un estudio con mujeres mayores de 65 años

Investigamos los efectos del programa perceptivo-motor en comparación con un programa exclusivamente orientado a la mejora de la fuerza y la condición aeróbica en mujeres mayores de 65 años. Una muestra de 83 mujeres se distribuyó en dos grupos: grupo control y grupo experimental. Se aplicaron tres medidas durante las fases de pretest, retest y postest del programa de período de 1 año: tiempo de reacción simple (SRT-S1), tiempo de reacción de selección (SRT-S4) y tiempo de detección de movimiento (MDT-S1) Los resultados revelan diferencias significativas a favor del grupo experimental (el que practicó con el programa perceptivo-motor) en tiempo de reacción y tiempo de movimiento en todas las pruebas realizadas en el retest y en la mayoría de las pruebas realizadas en el postest ( SERT-S4, SEMT-S4, MDT-S1 y MMT-S1) (AU)

The effect of two anionic membranes (AMI 7001s and Neosepta AMX) on the electrodeposition of manganese from sulphate solutions.

The effect of two different anionic membranes on manganese deposition was studied in a two-compartment electrochemical reactor with a titanium cathode and a dimensionally stable RuO2|Ti anode. Chronopotentiometry, ICP-OES, SEM, XRD and elemental mapping were used to understand the changes in concentration and characteristics of the metallic deposition at different current densities with the anionic membranes AMI 7001s and Neosepta AMX. The results demonstrate that AMI reduces more manganese than AMX below -100 A m-2, generating more metallic deposition but also more low-solubility manganous by-products, whereas both membranes exhibited similar behaviours above -100 A m-2 reaching the maximum current efficiency (63%) at -200 A m-2. It was also observed that the membranes have a significant effect on sulphate consumption since they are anions.

Prospective evaluation of the combined value of physical examination and biomarker variables in screening for preclinical dilated cardiomyopathy in Doberman Pinschers.

INTRODUCTION: Screening to assess likelihood of preclinical dilated cardiomyopathy (PC-DCM) prior to advanced diagnostic tests in Doberman Pinschers (DP) is desirable. OBJECTIVE: To investigate the combined value of physical examination (PE), N-terminal pro B-type natriuretic peptide (NTproBNP) and cardiac troponin I (cTnI) for identifying PC-DCM in DP. ANIMALS, MATERIALS AND METHODS: All dogs underwent: PE, echocardiogram, 3-min ECG and cardiac biomarker measurement. Asymptomatic DP (414) were classified based on 3-min ECG and echocardiogram as: No-DCM/MMVD or myxomatous mitral valve disease (MMVD), PC-DCM based on echocardiogram (PC-DCM-Echo), PC-DCM based on arrhythmias with a normal echocardiogram (PC-DCM-ECG), equivocal DCM (EQ-DCM), and MMVD. Receiver operator characteristic curves and prediction models were derived. RESULTS: Heart murmurs and arrhythmias were rare and gallop sounds were absent in No-DCM/MMVD DP. Dogs ≥ four years old and males had higher probabilities of PC-DCM-Echo. Prediction models incorporating PE variables with NTproBNP had an area under the curve (AUC) of 0.940 for distinguishing between PC-DCM-Echo and all other groups, which was similar to the AUC for NTproBNP (0.939) or cTnI (0.932) alone. Discrimination between No-DCM/MMVD and all other groups was similar for NTproBNP (0.781) and cTnI (0.742) as individual tests, however, models combining PE variables and NTproBNP increased the AUC to 0.812. An NTproBNP cut-off of ≥548 pmol/L, was 100% sensitive and 77.3% specific for detecting PC-DCM-Echo. CONCLUSIONS: Both NTproBNP and cTnI had good utility as sole tests to discriminate PC-DCM-Echo DP from all others. Models differentiating No-DCM/MMVD DP from all other DP were improved by using PE and NTproBNP together.

A review of the underlying genetics and emerging therapies for canine cardiomyopathies.

Cardiomyopathies such as dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are common in large breed dogs and carry an overall poor prognosis. Research shows that these diseases have strong breed predilections, and selective breeding has historically been recommended to reduce the disease prevalence in affected breeds. Treatment of these diseases is typically palliative and aimed at slowing disease progression and managing clinical signs of heart failure as they develop. The discovery of specific genetic mutations underlying cardiomyopathies, such as the striatin mutation in Boxer arrhythmogenic right ventricular cardiomyopathy and the pyruvate dehydrogenase kinase 4 and titin mutations in Doberman Pinschers, has strengthened our ability to screen and selectively breed individuals in an attempt to produce unaffected offspring. The discovery of these disease-linked mutations has also opened avenues for the development of gene therapies, including gene transfer and genome-editing approaches. This review article discusses the known genetics of cardiomyopathies in dogs, reviews existing gene therapy strategies and the status of their development in canines, and discusses ongoing challenges in the clinical translation of these technologies for treating heart disease. While challenges remain in using these emerging technologies, the exponential growth of the gene therapy field holds great promise for future clinical applications.

Exfoliative cheilitis related to psychologic factors uncovered during primary immunodeficiency evaluation.

A 40-year-old previously healthy, non-atopic woman was referred for evaluation of a possible immunodeficiency disorder in the setting of an unusual erosive cheilitis and history of recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection. Extensive work-up was non-diagnostic, including screening for immunologic disorders. She had failed multiple therapeutic modalities, including corticosteroid and immunosuppressive therapy. Tissue biopsy from the lip proved pivotal in demonstrating changes suggestive of factitial disease. This led to further detailed history-taking, yielding evidence of considerable psychologic distress. The patient was diagnosed with exfoliative cheilitis related to factitial disease in association with underlying untreated anxiety and psychologic trauma.

Repeat balloon valvuloplasty for dogs with recurrent or persistent pulmonary stenosis.

INTRODUCTION/OBJECTIVES: Pulmonary stenosis (PS) is a common congenital defect in the dog. Severe valvar PS can be treated with balloon valvuloplasty (BV) to reduce obstruction severity and improve clinical signs. Repeat BV is often unnecessary, as restenosis is uncommon. Repeated pulmonary BV in people is generally successful and safe, but outcomes in dogs with recurrent or persistent stenosis have not been reported. The objectives of this study were to retrospectively evaluate outcomes of repeat BV in dogs. ANIMALS, MATERIALS, AND METHODS: Medical records and stored echocardiographic images were reviewed from dogs that received repeat BV for pulmonary valvar restenosis or persistent stenosis. Echocardiographic variables included maximum systolic ejection velocity (PVmax), velocity-derived maximal pressure gradient (PGmax) and velocity time integral (VTI) across the pulmonary valve, and ratios of pulmonic to aortic maximum velocity (PVmax/AVmax) and VTI (VTIPV/VTIAV). RESULTS: Twenty-three dogs were included; one underwent three BV procedures. The median time between BV procedures was 18.3 months (interquartile range, 6.3-43.6). One dog died during repeat BV, but no others experienced adverse effects. Reductions in PVmax, PGmax, and VTIPV after initial and repeat BV were 1.85 m/s, 76.2 mmHg, and 44.7 cm and 1.33 m/s, 55.6 mmHg, and 30.2 cm, respectively (all p < 0.01). Differences between pre-BV and post-BV PVmax, PGmax, VTIPV, PVmax/AVmax, and VTIPV/VTIAV were not different comparing initial to repeat BV (all p > 0.10). CONCLUSIONS: Repeat BV for recurrent or persistent PS is well tolerated and effective in a majority of dogs.

Selenium and sulphur reactions involved in manganese reduction from sulphate solutions.

Electrochemical reduction of ionic species during manganese deposition from sulphated aqueous solutions has been studied in an electrochemical reactor with two anionic exchange membranes. Thermodynamic analysis, voltammetries, and chronopotentiometries were used to determine the reaction mechanism of the reductions developed, with the results demonstrating that the effect of the elemental selenium on the hydrogen evolution leads to the formation of elemental sulphur by reducing the sulphate ions with both membranes. It was also evident that in the range of -25 to -50 A m-2 the electrodeposition of metallic manganese begins, with minimal interference from parasitic reactions.

Stress in client-owned dogs related to clinical exam location: a randomised crossover trial.

OBJECTIVES: To quantify the effects of wellness examinations conducted in the common treatment area on fear, anxiety and stress indicators in client-owned dogs. MATERIALS AND METHODS: The study was a prospective, non-blinded, randomised, two-period two-treatment crossover trial. Client-owned healthy adult dogs presenting for wellness or dental evaluations at a single veterinary teaching hospital received three consecutive rapid assessment exams; a baseline exam (owner present), followed by two identical physical exams differing in location and presented in random order (isolated exam room with owner present versus common treatment area, owner absent). Primary endpoints were a cumulative fear, anxiety and stress score for five standardised behaviours and heart rate (bpm) measured for each exam. RESULTS: Forty-four dogs were enrolled. Modal fear, anxiety and stress score at baseline was 1 of 5, indicating none to mild stress. Both fear, anxiety and stress and heart rates measured in the common treatment area were clinically elevated relative to assessments conducted in the exam room. Relative to baseline, animals examined in the common treatment area showed increased fear, anxiety and stress (+2.6 units, se 0.5; P<0.0001) and heart rate (20 bpm, 95% confidence interval 13, 28; P<0.0001. Twenty-eight dogs (64%) exhibited fear, anxiety and stress scores ≥3 of 5 (moderate to severe stress) in the common treatment area, compared to 19 (43%) during exam room assessments. CLINICAL SIGNIFICANCE: Stress assessments in this study may have been biased by inability to blind assessors to location. However, stress metrics showed clinically significant, consistent and directionally symmetrical increases when dogs were examined in the common treatment area. When physical exam locations are highly stimulating, dogs may experience increased stress and anxiety, with detrimental effects on clinical assessments and behavioural welfare. Whenever possible, physical exams and procedures should take place in low-stress environments with the owner present.

Diagnostic accuracy of computer aided electrocardiogram analysis in dogs.

OBJECTIVES: Evaluation of a computerised electrocardiogram algorithm compared to the interpretation of a team of board-certified veterinary cardiologists. MATERIALS AND METHODS: This was a cross-sectional retrospective cohort study. A total of 399 electronic canine electrocardiogram recordings screened from 1391 electrocardiograms were enrolled in the study. A panel of seven cardiologists, masked to patient information, evaluated electrocardiograms for the following: P-wave amplitude and duration; PR-interval; R-wave amplitude; QRS duration; heart rate; mean electrical axis; and final overall diagnosis for the detection of arrhythmia and any abnormal electrocardiogram anomaly. RESULTS: The sensitivity of the electrocardiogram algorithm for detecting arrhythmias was 99.7% (95% confidence intervals, CI: 98.5 to 99.9) and the specificity was 99.5% (95% CI: 98.0 to 99.9) compared to the consensus result created by panel of cardiologists. The sensitivity of the algorithm for the detection of any electrocardiogram anomaly, including abnormal measurements, was 71.3% (95% CI: 65.5 to 76.7) and the specificity was 35.1% (95% CI: 27.0 to 43.8) compared to the panel of cardiologists. CLINICAL SIGNIFICANCE: The electrocardiogram algorithm was shown to have high sensitivity for the detection of arrhythmias, but not all electrocardiogram anomalies. The results support the use of this algorithm as a tool to aid in the triage of the electrocardiogram workflow.

Cyclosporine A plus low-dose steroid treatment in COVID-19 improves clinical outcomes in patients with moderate to severe disease: A pilot study.

BACKGROUND: COVID-19 pandemic causes high global morbidity and mortality and better medical treatments to reduce mortality are needed. OBJECTIVE: To determine the added benefit of cyclosporine A (CsA), to low-dose steroid treatment, in patients with COVID-19. METHODS: Open-label, non randomized pilot study of patients with confirmed infection of SARS-CoV-2 hospitalized from April to May 2020 at a single centre in Puebla, Mexico. Patients were assigned to receive either steroids or CsA plus steroids. Pneumonia severity was assessed by clinical, laboratory, and lung tomography. The death rate was evaluated at 28 days. RESULTS: A total of 209 adult patients were studied, 105 received CsA plus steroids (age 55.3 ± 13.3; 69% men), and 104 steroids alone (age 54.06 ± 13.8; 61% men). All patients received clarithromycin, enoxaparin and methylprednisolone or prednisone up to 10 days. Patient's death was associated with hypertension (RR = 3.5) and diabetes (RR = 2.3). Mortality was 22 and 35% for CsA and control groups (P = 0.02), respectively, for all patients, and 24 and 48.5% for patients with moderate to severe disease (P = 0.001). Higher cumulative clinical improvement was seen for the CsA group (Nelson Aalen curve, P = 0.001, log-rank test) in moderate to severe patients. The Cox proportional hazard analysis showed the highest HR improvement value of 2.15 (1.39-3.34, 95%CI, P = 0.0005) for CsA treatment in moderate to severe patients, and HR = 1.95 (1.35-2.83, 95%CI, P = 0.0003) for all patients. CONCLUSION: CsA used as an adjuvant to steroid treatment for COVID-19 patients showed to improve outcomes and reduce mortality, mainly in those with moderate to severe disease. Further investigation through controlled clinical trials is warranted.

Adherence to treatment in children with growth hormone deficiency, small for gestational age and Turner syndrome in Mexico: results of the Easypod™ connect observational study (ECOS).

BACKGROUND: Assessing adherence to growth hormone (GH) is challenging. The Easypod™ connect device delivers pre-set doses of recombinant human GH (r-hGH) and stores a digital record of adherence that can be shared with healthcare provider. We assessed adherence to r-hGH delivered with Easypod™ according to the approved pediatric indications for r-hGH: growth hormone deficiency (GHD), born small for gestational age (SGA) who failed to show catch-up growth and Turner syndrome (TS). METHODS: ECOS (NCT01555528) was a multicenter (24 countries), 5-year, longitudinal, observational study, which aimed to evaluate country-specific adherence to r-hGH therapy prescribed via the Easypod™ electronic injection device. The primary endpoint was yearly adherence. Secondary endpoints were height velocity, height velocity standard deviation scores (SDS), height, height SDS and IGF-1 concentrations. Clinical and auxological data were obtained from medical records and adherence from Easypod™ logs. RESULTS: This study included 147 Easypod™-naïve Mexican children assessed during 3 years (mean age: 9.96 ± 3.41 years, 56.8% boys, mean height SDS at baseline: - 2.17 ± 0.97): 118 with GHD, 24 SGA and 5 with TS. A total of 105 (71.4%) patients were GH naïve. Overall median adherence was > 90% over the first year of treatment and > 80% at 3 years. Adherence was not different by r-hGH indication or between GH-naïve or experienced patients. At 1-year follow-up, mean change in height SDS was 0.57 ± 0.34, whereas mean height velocity SDS was 2.85 ± 2.51. In all, 84.7% patients had normal IGF-1 concentrations at 1-year follow-up. Adherence was associated with change in height SDS (r = 0.239, p = 0.005) and height velocity SDS (r = 0.194, p = 0.027). CONCLUSION: Adherence rates with the Easypod™ device are high and maintained over time in GHD, SGA and TS Easypod™-naïve Mexican patients. High adherence is associated with better outcomes. Easypod™ assists physicians in monitoring adherence to r-hGH.

Technical position on milk and its derivatives in adult health and disease from the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Gerontología y Geriatría. / Posición técnica sobre la leche y derivados lácteos en la salud y en la enfermedad del adulto de la Asociación Mexicana de Gastroenterología y la Asociación Mexicana de Gerontología y Geriatría.

Milk is a liquid food that possesses an important quantity of highly bioavailable macronutrients. In addition, it is readily accessible, as well as relatively inexpensive. Given that the knowledge of physicians about nutrition and food composition is deficient, in general, many of the dietary interventions recommended in diverse clinical settings lack a scientific basis. The aim of the present review was to produce a technical opinion that serves as a frame of reference to best sustain recommendations for consuming milk and dairy products as daily nutrition in the adult and older adult. The effects of milk and dairy products during the pediatric stage are not addressed in the present work. The Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Gerontología y Geriatría jointly discussed and analyzed topics dealing with the legal designation of milk, the classification and nutritional profile of cow's milk, its nutritional characteristics, its consumption in the adult, intolerance to cow's milk, and associations of milk consumption with digestive tract alterations and other conditions. Finally, certain aspects of milk consumption in the older adult and its relation to overall health are briefly discussed.

Design shielding assessment for a nuclear medicine service / Evaluación del diseño de blindaje de un servicio de medicina nuclear

Abstract It is recognized worldwide that the security of radioactive substances is very important and that the design of facilities where these sources are used and stored must cater for the implementation of good security measures, including the shielding of some treatment and diagnostic rooms. The radiation protection assessment of a nuclear medicine facility consists of the evaluation of the annual effective dose both to workers occupationally exposed and to members of the public. This assessment take into account the radionuclides involved, the facility features, the working procedures, the expected number of patients per year, the administered activity, the distribution of rooms, the thickness and physical materials of walls, floors and ceilings and so on. The assessment results were compared to the design requirements established by the Cuban regulatory body in order to determine whether or not, the nuclear medicine facility complies with those requirements, both for workers and for members of the public. The work presented is useful for facility designer that uses unsealed radionuclides and for the regulatory body.

Resumen A nivel mundial se reconoce que la seguridad de las sustancias radiactivas es muy importante y que el diseño de las instalaciones, donde se utilizan y almacenan las mismas, tienen que implementar medidas de seguridad adecuadas, incluyendo el blindaje de algunos locales de tratamiento y diagnóstico. La evaluación de la protección radiológica de una instalación de medicina nuclear consiste en la determinación de la dosis efectiva anual, tanto para los trabajadores ocupacionalmente expuestos a las radiaciones como para los miembros del público. Esta evaluación tuvo en consideración los radionúclidos involucrados, las características de la instalación, los procedimientos de trabajo, la cantidad de pacientes que se espera tratar o diagnosticar por año, la actividad administrada, la distribución de los locales y el espesor de los materiales empleados en las paredes, pisos y techo, entre otros. Los resultados obtenidos de la evaluación fueron comparados con los requerimientos de diseño establecidos por el órgano regulador cubano para determinar si cumplen o no con tales requerimientos para los trabajadores expuestos y miembros del público. El trabajo presentado resulta útil para diseñadores de instalaciones que utilizan sustancias abiertas y para el órgano regulador.

Stent angioplasty for treatment of canine valvular pulmonic stenosis.

Four dogs presented for evaluation and treatment of severe pulmonic valve stenosis and underwent stenting of the pulmonic valve annulus using bare-metal balloon-expandable stents. All dogs survived the procedure with immediate reduction of the transpulmonary valve pressure gradient and increase in activity levels. One dog had a stent fracture and migration 1 month after the intervention. This dog underwent a second procedure, in which multiple stents were used to alleviate the obstruction. The stents that were placed at the level of the right ventricular outflow tract fractured within 1 month of the procedure, and the patient died when a third (surgical) approach was attempted. The other three dogs remain alive 54, 42, and 29 months after the procedure. Stent angioplasty may be a viable option for dogs with valvular pulmonic stenosis in which routine balloon valvuloplasty does not provide a successful outcome. Aggressive attempts to diminish RVOT dynamic obstruction with high-dose beta blockade and avoiding deployment of the stent within the RVOT are recommended to prevent stent fracture and migration.

Transvenous pacing implantation: techniques, tips, and lessons learned along the way.

The right ventricular apex has been the traditional site for lead placement in veterinary patients who require permanent cardiac pacing therapy for atrioventricular block and sick sinus syndrome. Implantation of leads in this location is a straightforward procedure that most veterinary cardiologists perform routinely. Pacing at the right ventricular apex, however, has been demonstrated to have long-term deleterious effects on the left ventricular function in numerous patient populations and animal models. Alternative lead placement sites and pacing system configurations have been developed, and the purpose of this review article is not to review the literature or the decision-making process in selecting a specific pacing system but rather to share the experiences of our group with the use of alternative pacing implantation techniques for veterinary patients in need of permanent cardiac pacing.