First detection of Omicron variant BA.4.1 lineage in dogs, Chile.

SARS-CoV-2's rapid global spread caused the declaration of COVID-19 as a pandemic in March 2020. Alongside humans, domestic dogs and cats are also susceptible to infection. However, limited reports on pet infections in Chile prompted a comprehensive study to address this knowledge gap. Between March 2021 and March 2023, the study assessed 65 pets (26 dogs and 39 cats) from 33 COVID-19+ households alongside 700 nasal swabs from animals in households with unknown COVID-19 status. Using RT-PCR, nasal, fecal, and environmental samples were analyzed for the virus. In COVID-19+ households, 6.06% tested positive for SARS-CoV-2, belonging to 3 dogs, indicating human-to-pet transmission. Pets from households with unknown COVID-19 status tested negative for the virus. We obtained 2 SARS-CoV-2 genomes from animals, that belonged to Omicron BA.4.1 variant, marking the first report of pets infected with this lineage globally. Phylogenetic analysis showed these sequences clustered with human sequences collected in Chile during the same period when the BA.4.1 variant was prevalent in the country. The prevalence of SARS-CoV-2 in Chilean pets was relatively low, likely due to the country's high human vaccination rate. Our study highlights the importance of upholding and strengthening human vaccination strategies to mitigate the risk of interspecies transmission. It underscores the critical role of the One Health approach in addressing emerging zoonotic diseases, calling for further research on infection dynamics and risk factors for a comprehensive understanding.

Waning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination.

Since the emergence of SARS-CoV-2, vaccines targeting COVID-19 have been developed with unprecedented speed and efficiency. CoronaVac, utilising an inactivated form of the COVID-19 virus and the mRNA26 based Pfizer/BNT162b2 vaccines are widely distributed. Beyond the ability of vaccines to induce production of neutralizing antibodies, they might lead to the generation of antibodies attenuating the disease by recruiting cytotoxic and opsonophagocytic functions. However, the Fc-effector functions of vaccine induced antibodies are much less studied than virus neutralization. Here, using systems serology, we follow the longitudinal Fc-effector profiles induced by CoronaVac and BNT162b2 up until five months following the two-dose vaccine regimen. Compared to BNT162b2, CoronaVac responses wane more slowly, albeit the levels remain lower than that of BNT162b2 recipients throughout the entire observation period. However, mRNA vaccine boosting of CoronaVac responses, including response to the Omicron variant, induce significantly higher peak of antibody functional responses with increased humoral breadth. In summary, we show that vaccine platform-induced humoral responses are not limited to virus neutralization but rather utilise antibody dependent effector functions. We demonstrate that this functionality wanes with different kinetics and can be rescued and expanded via boosting with subsequent homologous and heterologous vaccination.

Waning and boosting of functional humoral immunity to SARS-CoV-2.

Since the emergence of the SARS-CoV-2 virus, we have witnessed a revolution in vaccine development with the rapid emergence and deployment of both traditional and novel vaccine platforms. The inactivated CoronaVac vaccine and the mRNA-based Pfizer/BNT162b2 vaccine are among the most widely distributed vaccines, both demonstrating high, albeit variable, vaccine effectiveness against severe COVID-19 over time. Beyond the ability of the vaccines to generate neutralizing antibodies, antibodies can attenuate disease via their ability to recruit the cytotoxic and opsinophagocytic functions of the immune response. However, whether Fc-effector functions are induced differentially, wane with different kinetics, and are boostable, remains unknown. Here, using systems serology, we profiled the Fc-effector profiles induced by the CoronaVac and BNT162b2 vaccines, over time. Despite the significantly higher antibody functional responses induced by the BNT162b2 vaccine, CoronaVac responses waned more slowly, albeit still found at levels below those present in the systemic circulation of BNT162b2 immunized individuals. However, mRNA boosting of the CoronaVac vaccine responses resulted in the induction of significantly higher peak antibody functional responses with increased humoral breadth, including to Omicron. Collectively, the data presented here point to striking differences in vaccine platform-induced functional humoral immune responses, that wane with different kinetics, and can be functionally rescued and expanded with boosting.

First report of porcine respirovirus 1 in South America.

Porcine respirovirus 1 (PRV1) is an emerging virus in pigs that has been previously described in the USA and China. There are no reports of its presence in the rest of the world. The objective of this study was to determine the occurrence of PRV1 in Chile and to determine its phylogeny. Thus, we collected samples (oral fluids, nasal swabs, and lungs) from a swine influenza A virus (IAV) surveillance program, most of which belonged to pigs with respiratory disease. The samples were analyzed by RT-PCR, and the viral sequencing was obtained using RNA whole-genome sequencing approach. Maximum likelihood phylogeny was constructed with the available references. Thirty-one of 164 samples (18.9 %) were RT-PCR positive for PRV1: 62.5 % oral fluids, 19.0 % nasal swabs, and 8.6 % lungs. All 6 farms in this study had at least one positive sample, with 6-40 % of positive results per farm, which suggests that PRV1 is disseminated in Chilean swine farms. Twenty-one of 31 (677%) PRV1-positive samples were also positive for IAV, so the role of PRV1 as secondary pathogen in respiratory disease needs to be further evaluated. Near to complete genome of two PRV1s were obtained from two farms. The phylogenies, in general, showed low bootstrap support, except the concatenated genome and the L gene trees which showed clustering of the Chilean PRV1 with Asian sequences, suggesting a close genetic relationship. This is the first report of PRV1 in the Southern Hemisphere. Further studies are necessary to determine the genetic diversity of this virus in Chile.

Antibody responses to chimeric peptides derived from parasite antigens in mice and other animal species.

Peptide vaccines constitute an interesting alternative to classical vaccines due to the possibility of selecting specific epitopes, easy of production and safety. However, an inadequate design may render these peptides poorly immunogenic or lead to undesirable outcomes (e.g., formation of B neoepitopes). As an approach to vaccine development, we evaluated the antibody response to chimeras composed of two or three known B epitopes from Trichinella and Fasciola, and several linkers (GSGSG, GPGPG and KK) in species as different as mice, sheep and turbot. All these species could mount an effective immune response to the short chimeric peptides. Nevertheless, this response depended on several factors including a favorable orientation of B-cell epitopes, adequateness of linkers and/or probability of formation of T neoepitopes. We also observed that, at least in mice, the inclusion of a decoy epitope may have favorable consequences on the antibody response to other epitopes in the chimera.

Comparative analysis of the incidence of bladder cancer in the communities of Andalusia, Catalonia and Madrid in 2011.

OBJECTIVES: To determine the incidence of bladder cancer (BC) in the autonomous communities that include the largest number of cases in the national hospital BC registry (Andalusia, Catalonia and Madrid) and report the clinical, pathological and diagnostic differences and similarities of BC in these regions. MATERIAL AND METHODS: An observational epidemiological study was performed in 2011 in 12 public hospitals with reference population areas according to the National Health System (Spain). Demographic and clinical variables were collected from new cases and relapses, with histopathologic confirmation of BC. The raw incidence rate was calculated using the number of diagnosed cases in all the participating centers compared with the aggregate total population assigned to each center. The raw rates by age and sex were obtained from the National Institute of Statistics (2011) by weighting the assigned population with the distribution by age and sex. RESULTS: The 3 autonomous communities recorded 51% of the 4285 cases included in the national registration, with relapses corresponding to 42.8% of these cases. The raw annual incidence rate for new episodes was 22.6 (95% CI: 20.7; 24.6) in Andalusia, 23.5 (95% CI: 20.9; 26.0) in Catalonia and 22.0 (95% CI: 19.9; 24.1) in Madrid. CONCLUSIONS: Except for the larger proportion of smokers and lower tumor grade of lesions in Andalusia, the 3 autonomous communities studied are similar in terms of clinical characteristics, comorbidities, patient symptoms and diagnostic processes for BC.

PET imaging of cardiac hypoxia: opportunities and challenges.

Myocardial hypoxia is a major factor in the pathology of cardiac ischemia and myocardial infarction. Hypoxia also occurs in microvascular disease and cardiac hypertrophy, and is thought to be a prime determinant of the progression to heart failure, as well as the driving force for compensatory angiogenesis. The non-invasive delineation and quantification of hypoxia in cardiac tissue therefore has the potential to be an invaluable experimental, diagnostic and prognostic biomarker for applications in cardiology. However, at this time there are no validated methodologies sufficiently sensitive or reliable for clinical use. PET imaging provides real-time spatial information on the biodistribution of injected radiolabeled tracer molecules. Its inherent high sensitivity allows quantitative imaging of these tracers, even when injected at sub-pharmacological (≥pM) concentrations, allowing the non-invasive investigation of biological systems without perturbing them. PET is therefore an attractive approach for the delineation and quantification of cardiac hypoxia and ischemia. In this review we discuss the key concepts which must be considered when imaging hypoxia in the heart. We summarize the PET tracers which are currently available, and we look forward to the next generation of hypoxia-specific PET imaging agents currently being developed. We describe their potential advantages and shortcomings compared to existing imaging approaches, and what is needed in terms of validation and characterization before these agents can be exploited clinically.

[Postsurgical family information: an improvement area. Prospective study after urologic surgery]. / Información posquirúrgica a la familia: un área de mejora. Estudio prospectivo tras cirugía urológica.

OBJECTIVES: Analyzing and quantifying the postoperative retention of information, checking if it could be improved been delivered in an organized way. MATERIAL AND METHODS: After the basic information to relatives of 50 post-surgical patients operated for bladder or prostate, we deliver a questionnaire about what has just been told. It must be completed by a family member. The information is distributed differently: group 1 (30 patients) reported to the family following a script designed by us, written in simple and natural language. In group 2 (20 patients) the doctor informed as usual, not knowing that he is participating in the research. Then the relative is interviewed by one of the researchers. RESULTS: Only 3 (6%) family members matched all the right answers, and 25 (50%) did not hit more than 70% of the issues. The best known concept was the organ involved: 46 (92%). 21(42%) of respondents did not know if the process is basically benign or malignant, getting better results in group 1 but without significance: 20/30 (66.7%) vs 9/20 (45%) (p>0.05). The only item in which there are differences in success rate depending on the group is if a catheter have been set: 29 (96.7%) of successes in group 1, 13(65%) in 2. We found no difference in success rate according to number of family members informed, education, age or number of previous interventions. CONCLUSIONS: Relatives do not retain everything that was said. Organizing the information provided may improve, but other factors have influence. We must improve issues such as personal identification. It may be useful to repeat the information later.

Penile incarceration secondary to a ring.

Penile incarceration by foreign objects for sexual stimulation purposes is a situation described in universal literature, however it is a rare situation that the urologist must face in the emergency room. A 75-year-old male is presented to whom his sexual partner had placed a ring in the coronal sulcus.

Differential centrifugation separates cardiac sarcolemmal and endosomal membranes from Langendorff-perfused rat hearts.

The application of subcellular fractionation protocols developed in soft tissues to fibrous organs such as the heart is unsuitable given the substantial differences in subcellular structure these tissues exhibit. The purpose of this study was to develop a simple method for the separation of sarcolemma and endosomes from isolated Langendorff-perfused rat hearts. Hearts were homogenized with either an Ultra-Turrax homogenizer or a hand-held glass tissue grinder. Quantitative immunoblots assessed the enrichment of the sarcolemmal proteins caveolin 3 and the sodium potassium ATPase and the endosomal proteins rab4 and GLUT4 in different membrane fractions. Application of homogenates to sucrose and Percoll density gradients failed to resolve membranes differentially enriched in sarcolemmal or endosomal marker proteins, indicating little difference in density between the sarcolemma and endosomes. However, successive spins of homogenates from a hand-held glass tissue grinder successfully separated the endosomes from the sarcolemma, indicating differences in masses between the two membrane fractions. Approximately 70% of total caveolin 3 and sodium potassium ATPase immunoreactivity was in membrane pellets up to 20,000g and approximately 85% of rab4 and GLUT4 in pellets from 20,000-100,000g. In addition, 86% of ouabain-sensitive ATPase activity (sodium potassium ATPase activity) was in membrane pellets up to 20,000g. Therefore, sarcolemmal membranes were pelleted up to 20,000g, and endosomal membranes between 20,000 and 100,000g. Regional ischemia (40 min) followed by reperfusion (60 min) caused the translocation of GLUT4 (but not rab4) from the endosomal membranes to the sarcolemma in the area of the heart subjected to ischemia.

Differential uptake of FDG and DG during post-ischaemic reperfusion in the isolated, perfused rat heart.

Fluorine-18 2-fluoro-2-deoxyglucose (FDG) and 2-deoxyglucose (DG) are widely used as tracers of glucose uptake in the myocardium. Although there is agreement that the two analogues behave similarly to glucose under control conditions, there is growing evidence that some interventions (e.g. insulin stimulation or ischaemia/reperfusion) cause differential changes in their behaviour. The addition of a two-surface coil nuclear magnetic resonance (NMR) probe and a dual-perfusion cannula to our recently developed PET and NMR dual-acquisition (PANDA) system allows us to collect PET (FDG) images and phosphorus-31 NMR (2-deoxyglucose-6-phosphate) spectra simultaneously from each independently perfused coronary bed of the heart. We have used this technique to study the effect of regional ischaemia/reperfusion on FDG and DG uptake in the isolated, perfused rat heart. During control perfusion, FDG uptake was almost identical in both coronary beds. When one coronary bed was made ischaemic, FDG uptake ceased on that side but continued on the control side. Reperfusion failed to restore FDG uptake. In contrast, NMR spectra showed that, during reperfusion, the uptake and phosphorylation of DG did not differ between the two coronary beds. The results thus demonstrate that regional myocardial ischaemia/reperfusion has different effects on the uptake of FDG and DG in the isolated, perfused rat heart.

Effect of deoxycorticosterone acetate on blood pressure in relation to accumulation of low-density lipoprotein and fibrinogen by aorta and other tissues of normotensive Wistar rats.

OBJECTIVE: To evaluate the effect of different 4-week doses of deoxycorticosterone acetate (DOCA), together with 0.9% sodium chloride in the drinking water (DOCA-salt) on the blood pressure and on the accumulation of low-density lipoprotein (LDL) and fibrinogen in artery walls ad other tissues in conscious, unrestrained, normotensive Wistar-Kyoto rats. METHODS: The accumulation of LDL labelled with 125I via the adduct tyramine cellobiose ([125I]-TC-LDL) and of fibrinogen similarly labelled with 131I ([131I]-TC-fibrinogen) was compared in aortic walls, heart, liver, kidney, lung. skeletal muscle, and adrenal gland tissues during the final 24 h of a 4-week administration of DOCA-salt, with vehicle-salt and saline as controls. RESULTS: In control and vehicle rats the blood pressure did not change significantly during the last 5 days of treatment. Administration of DOCA-salt produced a dose-dependent increase in blood pressure during the same period. DOCA-salt administration increased LDL accumulation in the aorta and the heart and decreased LDL accumulation in the adrenal gland compared with those in rats of the control and vehicle groups. DOCA-salt administration did not affect fibrinogen accumulation significantly. CONCLUSION: DOCA-salt treatment produces an increase in arterial blood pressure accompanied by an increase in LDL accumulation by the aortic wall and heart and a decrease in LDL accumulation by the adrenal gland. These observations raise the possibility that one mechanism by which hypertension affects atherosclerosis is through increased LDL accumulation in arterial walls.

Minority advantage in diabetic end-stage renal disease survival on hemodialysis: due to different proportions of diabetic type?

The objectives of this study were to identify predictors of survival on hemodialysis in patients with diabetic end-stage renal disease (ESRD) and to explain ethnic differences in survival among non-Hispanic whites, African-Americans, and Mexican-Americans. The study design was a survival analysis of an inception cohort and was conducted in dialysis centers in two urban counties in Texas. A population-based, tri-ethnic cohort of 638 adult patients with diabetic ESRD were studied. Follow-up was completed in 96% of the cohort, with a median length of follow-up of 3.8 years. Survival length on center hemodialysis was the main outcome measure. In a combined model of types I and II diabetes, Mexican-Americans (relative hazard [RH], 0.666; 95% confidence interval [CI], 0.457 to 0.944) and African-Americans (RH, 0.598; 95% CI, 0.414 to 0.864) showed a better survival than non-Hispanic whites. Other predictors independently associated with survival were age (RH, 1.015 per 10 years of age; 95% CI, 1.001 to 1.028), high self-reported physical disability (RH, 1.770; 95% CI, 1.213 to 2.583), coronary artery disease (RH, 1.445; 95% CI, 1.044 to 2.012), lower extremity amputations (RH, 2.049; 95% CI, 1.438 to 2.920), and average blood glucose levels prior to ESRD (RH, 1.002 per 1 mg/dL increment; 95% CI, 1.003 to 1.004). Non-Hispanic whites had a significantly higher rate of type I diabetes, but did not have a greater burden of any of the other predictors. In separate type I and II models, ethnicity was still a significant predictor of survival among type I but not among type II. In conclusion, we have reconfirmed the survival advantage on dialysis of African-Americans and Mexican-Americans over non-Hispanic whites with diabetic ESRD. However, among type II patients, this minority survival advantage disappears. Self-reported physical disability is an important predictor of survival among both diabetes types. Functional status at baseline is an important predictor of survival and should be assessed as an adjunct to measurement of co-morbidities. Macrovascular disease is important for type II, while educational status is important for type I. While amputation may be a marker for the severity of systemic illness, it could be a marker for quality of primary care provided to diabetic patients, since a majority of diabetic lower extremity amputations are thought to be preventable.

NIDDM is the major cause of diabetic end-stage renal disease. More evidence from a tri-ethnic community.

Diabetes is the single largest cause of end-stage renal disease (ESRD) in adults in the U.S. Insulin-dependent diabetes mellitus (IDDM) has been recognized for some time as an important cause of ESRD, but non-insulin-dependent diabetes mellitus (NIDDM) has been assumed, until recently, to rarely cause ESRD. The objective of this study is to determine the incidence of treatment of diabetic ESRD by diabetic type for three ethnic/racial groups: non-Hispanic whites, African-Americans, and Mexican-Americans. A population-based incidence cohort was assembled from all dialysis centers in Bexar (San Antonio) and Dallas counties in Texas. All patients with diabetic ESRD beginning dialysis between 1 December 1987 (Bexar) or 1 December 1988 (Dallas) and 31 July 1991 were identified. All non-hispanic whites and African-Americans and a 1/2 random sample of Mexican-Americans were approached for enrollment. Individuals were confirmed to have diabetes using the World Health Organization criteria. Diabetes typing was done using a computerized historical algorithm. Age-specific and age-adjusted incidence rates were obtained by diabetic type and ethnic/racial group. NIDDM causes the majority of diabetic ESRD: 59.5% for non-Hispanic whites, 92.8% for Mexican-Americans, and 84.3% for African-Americans. Mexican-Americans and African-Americans, respectively, have 6.1 and 6.5 times higher incidence of treatment for diabetic ESRD than non-Hispanic whites. NIDDM results in more ESRD than does IDDM. Minorities (African-Americans and Mexican-Americans) are at increased risk, and programs aimed at prevention of NIDDM-related ESRD must focus on them.

In vivo and in vitro characterization of virulence-deficient mutants of Vibrio cholerae.

In vitro and in vivo interactions between Vibrio cholerae and the infant mouse intestinal environment were examined by using a number of virulence-deficient mutants of strain CA401 which are unable to induce a typical diarrheal response. In vitro interactions with upper bowel sections were evaluated by determining percent association of radiolabeled organisms with sections. In vivo behavior was evaluated in the upper bowel early in infection with radiolabeled inocula. Ths relative degree of mechanical clearance was indicated by the percent recovery of input label. The relative degree of multiplication and killing was determined by changes in the specific activities (counts per minute per colony-forming unit) of inocula compared with recovered viable organisms. The results indicated that, whereas some virulence-deficient mutant classes exhibit net multiplication in the upper bowel, other classes show net killing in and accelerated clearance from the upper bowel. The in vitro association patterns failed to correlate with in vivo upper bowel recovery.

Survival and multiplication of Vibrio cholerae in the upper bowel of infant mice.

The survival and multiplication of Vibrio cholerae strains of varying virulence in the upper bowel of orally challenged infant mice early in infection has been examined. Analysis of changes in the apparent specific activity (counts per minute per colony-forming unit) of the cell population after 4 h compared with the inoculum indicated that strain CA401 established a viable, multiplying cell population, whereas strains VB12 (a rough variant) and 569B were subject to host bactericidal and bacteriolytic mechanisms. An analysis of parameters which may affect the specific activity is included. We have defined the infective potential of the strains in terms of the changes in specific activity. The relative infective potentials are CA401 greater than 569B greater than VB12.