Identifying the Drivers Related to Animal Reservoirs, Environment, and Socio-Demography of Human Leptospirosis in Different Community Types of Southern Chile: An Application of Machine Learning Algorithm in One Health Perspective.

Leptospirosis is a zoonosis with global public health impact, particularly in poor socio-economic settings in tropical regions. Transmitted through urine-contaminated water or soil from rodents, dogs, and livestock, leptospirosis causes over a million clinical cases annually. Risk factors include outdoor activities, livestock production, and substandard housing that foster high densities of animal reservoirs. This One Health study in southern Chile examined Leptospira serological evidence of exposure in people from urban slums, semi-rural settings, and farm settings, using the Extreme Gradient Boosting algorithm to identify key influencing factors. In urban slums, age, shrub terrain, distance to Leptospira-positive households, and neighborhood housing density were contributing factors. Human exposure in semi-rural communities was linked to environmental factors (trees, shrubs, and lower vegetation terrain) and animal variables (Leptospira-positive dogs and rodents and proximity to Leptospira-positive households). On farms, dog counts, animal Leptospira prevalence, and proximity to Leptospira-contaminated water samples were significant drivers. The study underscores that disease dynamics vary across landscapes, with distinct drivers in each community setting. This case study demonstrates how the integration of machine learning with comprehensive cross-sectional epidemiological and geospatial data provides valuable insights into leptospirosis eco-epidemiology. These insights are crucial for informing targeted public health strategies and generating hypotheses for future research.

Confirmation of the invasive American mink (Neogale vison) as carrier of Mycobacterium bovis in southern Chile.

Bovine tuberculosis (bTB) is a chronic infectious-contagious disease with worldwide distribution, caused by the zoonotic pathogen Mycobacterium bovis. It is believed that the existence of wild cycles may hamper the success of bTB control strategies worldwide, where wildlife species could be reservoirs of this bacterial agent across their native (e.g., European badgers, wild boars) or non-indigenous (e.g., brushtail possum in New Zealand) ranges. However, further studies are required to understand the potential risk posed by non-native wildlife in becoming carriers of M. bovis in other neglected latitudes, such as the Southern Cone of South America. In this study, we performed a specific M. bovis-RD4 real-time PCR (qPCR) assay to detect bacterial DNA in tissues from the invasive American mink (Neogale vison) in Los Ríos region, Chile. We detected M. bovis DNA in blood samples collected from 13 out of 186 (7 %) minks with known sex and age. We did not find any significant differences in bacterial DNA detection according to mink sex and age. We found that 92 % (12/13) of specimens were positive in lung, 39 % (5/13) in mediastinal lymph node, and 15 % (2/13) in mesenteric lymph node, which suggest that both respiratory and digestive pathways as possible routes of transmission between infected hosts and minks. Our study is the first report on M. bovis molecular detection in invasive minks in an area where the largest cattle population in the country is located. Furthermore, this area is characterized by a low within-herd prevalence of M. bovis infection in cattle, with a relatively low number of infected herds, and so far, no attempts at eradicating the disease have been successful.

Advances in the Physiology of Transvascular Exchange and A New Look At Rational Fluid Prescription.

The Starling principle is a model that explains the transvascular distribution of fluids essentially governed by hydrostatic and oncotic forces, which dynamically allow vascular refilling according to the characteristics of the blood vessel. However, careful analysis of fluid physiology has shown that the principle, while correct, is not complete. The revised Starling principle (Michel-Weinbaum model) provides relevant information on fluid kinetics. Special emphasis has been placed on the endothelial glycocalyx, whose subendothelial area allows a restricted oncotic pressure that limits the reabsorption of fluid from the interstitial space, so that transvascular refilling occurs mainly from the lymphatic vessels. The close correlation between pathological states of the endothelium (eg: sepsis, acute inflammation, or chronic kidney disease) and the prescription of fluids forces the physician to understand the dynamics of fluids in the organism; this will allow rational fluid prescriptions. A theory that integrates the physiology of exchange and transvascular refilling is the "microconstant model", whose variables include dynamic mechanisms that can explain edematous states, management of acute resuscitation, and type of fluids for common clinical conditions. The clinical-physiological integration of the concepts will be the hinges that allow a rational and dynamic prescription of fluids.

Evidence of Homeostatic Regulation in Mycobacterium avium Subspecies paratuberculosis as an Adaptive Response to Copper Stress.

BACKGROUND: Bacteria are capable of responding to various stressors, something which has been essential for their adaptation, evolution, and colonization of a wide range of environments. Of the many stressors affecting bacteria, we can highlight heavy metals, and amongst these, copper stands out for its great antibacterial capacity. Using Mycobacterium tuberculosis (Mtb) as a model, the action of proteins involved in copper homeostasis has been put forward as an explanation for the tolerance or adaptive response of this mycobacteria to the toxic action of copper. Therefore, the aim of this study was to confirm the presence and evaluate the expression of genes involved in copper homeostasis at the transcriptional level after challenging Mycobacterium avium subsp. paratuberculoisis (MAP) with copper ions. METHODOLOGY: Buffer inoculated with MAP was treated with two stressors, the presence of copper homeostasis genes was confirmed by bioinformatics and genomic analysis, and the response of these genes to the stressors was evaluated by gene expression analysis, using qPCR and the comparative ΔΔCt method. RESULTS: Through bioinformatics and genomic analysis, we found that copper homeostasis genes were present in the MAP genome and were overexpressed when treated with copper ions, which was not the case with H2O2 treatment. CONCLUSION: These results suggest that genes in MAP that code for proteins involved in copper homeostasis trigger an adaptive response to copper ions.

Experimental evidence of the anti-bacterial activity pathway of copper ion treatment on Mycobacterium avium subsp. paratuberculosis.

Copper causes significant damage to the integrity of many bacteria, mainly at the DNA level, through its redox states, as well as its reactive oxygen species (ROS) generating capacity at the cellular level. But whether these mechanisms also apply to Mycobacterium avium subsp. paratuberculosis (MAP) is unknown. In the present study, we have evaluated whether copper ions produce damage at the DNA level of MAP, either through their redox states or through ROS production. MAP-spiked PBS was first supplemented with different copper chelators (2) and ROS antioxidants (3), followed by treatment with copper ions at 942 ppm. MAP DNA integrity (qPCR, magnetic phage separation) was then evaluated. We found that bathocuproine (BCS), as a chelator, and D-mannitol, as an antioxidant of hydroxyl radicals, had a significant protective effect (P < 0.05) on DNA molecules, and that EDTA, as a chelator, and D-mannitol, as an antioxidant had a significant positive effect (P < 0.05) on the viability of this pathogen in contrast to the control and other chelators and anti-oxidants used. In light of the reported findings, it may be concluded that copper ions within MAP cells are directly related to MAP DNA damage.

Development and evaluation of polyclonal antibody-based antigen detection ELISA and dot blot assays as a less costly diagnostic alternative for pathogenic Leptospira infection.

Leptospirosis is an infectious, zoonotic disease of worldwide distribution, the cause of which is infection by pathogenic Leptospira. In Chile, dairy cattle are recognized a significant source in the maintenance and transmission of this infection, which causes economic losses and represents an infection threat to workers in the dairy industry. The infection is underestimated in cattle, due to the lack of clinical, pathognomonic signs, as well as the low efficiency of current diagnostic techniques. In this study, we developed antigen ELISA and dot blot assays, based on polyclonal antibodies, to detect pathogenic Leptospira in the urine samples of dairy cattle. The proposed tests showed an acceptable diagnostic accuracy, based on an analytical sensitivity of 1·104 Leptospira per mL for ELISA, and 3.2·103 for dot blot. These results corresponded with those obtained by qPCR, and the use of urine samples allowed us to propose new diagnostic alternatives for pathogenic Leptospira infection at a low cost, which can provide information on active infection status, which is a key element in control programs both at individual and herd level.

Are Reactive Oxygen Species (ROS) the Main Mechanism by Which Copper Ion Treatment Degrades the DNA of Mycobacterium avium subsp. paratuberculosis Suspended in Milk?

BACKGROUND: Mycobacterium avium subsp. paratuberculosis (MAP) is the causal agent of paratuberculosis. This pathogen is able to survive adverse environmental conditions, including the pasteurization process. Copper, a well-studied metal, is considered an important antibacterial tool, since it has been shown to inactivate even MAP in treated milk through unknown mechanisms. The aim of the present study is to show the effect of copper ions, and reactive oxygen species (ROS) generated in response to oxidative stress, on the damage to MAP DNA when exposed to a copper ion challenge in cow's milk. METHODOLOGY: Spiked milk with different MAP bacterial loads was supplemented with blocking agents. These were either the copper chelators ethylenediaminetetraacetic acid (EDTA) and batocuproin (BCS) or the ROS quenchers D-mannitol, gallic acid and quercetin. The DNA protection, MAP viability and ROS production generated after exposure to a copper challenge were then measured. RESULTS: In a bacterial load of 104 cells mL-1, blocking effects by both the copper chelators and all the ROS quenchers offered significant protection to MAP DNA. In a concentration of 102 cells mL-1, only D-mannitol and a mix of quenchers significantly protected the viability of the bacteria, and only at a concentration of 106 cells mL-1 was there a lower production of ROS when supplementing milk with gallic acid, quercetin and the mix of quenchers. CONCLUSION: Based on these findings, it may be concluded that MAP DNA damage can be attributed to the combined effect of the direct copper ions and ROS generated. Nevertheless, taking into account the antioxidant environment that milk provides, the direct effect of copper could play a prominent role.

Down syndrome: orofacial pain, masticatory muscle hypotonia, and sleep disorders.

The aim of the present study was to investigate orofacial pain in individuals with Down syndrome (DS) and determine possible associations with masticatory muscle hypotonia (MMH), maximum mouth opening (MMO), and sleep disorders. Twenty-three individuals with DS underwent a standardized clinical examination using Axis I of the Diagnostic Criteria for Temporomandibular Disorders, for the diagnosis of pain in the masseter and temporal muscles and temporomandibular joint (TMJ). MMH was investigated using electromyography of the temporal and masseter muscles and the measurement of maximum bite force (MBF). MMO was measured using an analog caliper. Sleep disorders (obstructive sleep apnea [OSA], snoring index [SI], and sleep bruxism index [SBI]) were investigated using type II polysomnography. Statistical analysis was performed. Nonsignificant differences were found in muscle and TMJ pain between the sexes. However, myalgia and referred myofascial pain in the left masseter muscle were more frequent in males (69%) than females (40%). Electrical activity of the temporal (left: p = .002; right: p = .004) and masseter (left: p = .008) muscles was significantly lower in males than in females. MBF range was lower in males than females, indicating the highest MMH among males. OSA, SI, and SBI were identified in both sexes, but with no statistically significant differences. We concluded that myalgia and referred myofascial pain were found in some individuals with DS, especially in males. Arthralgia was found mainly in females. Temporal and masseter myalgia may have exerted an influence on the severity of MMH in males, particularly on the left side.

Síndrome del impacto posterior del tobillo secundario a proceso de Stieda / Posterior Ankle Impingement secondary to a Stieda process

Introducción: El síndrome de impacto posterior es una condición que resulta de la compresión de tejidos blandos entre la cara posterior del astrágalo y el área posteroinferior de la tibia durante el movimiento de flexión plantar del tobillo y provoca inflamación de los tejidos blandos circundantes. Objetivo: Presentar un caso de síndrome de impacto posterior secundario a proceso de Stieda. Presentación de caso: Se presenta el caso de un varón de 53 años, cocinero de profesión que se quejaba de dolor en la región posterior del tobillo derecho, que se exacerbaba con la flexión plantar del tobillo sin traumatismo previo. Se descartaron lesiones de tipo tendinosas y ligamentosas al examen físico, por lo que se indica radiografía convencional. A través de la radiografía de tobillo se define proceso de Stieda el cual justifica la clínica. Por esto no se realizaron otros estudios. Conclusiones: La radiografía convencional en el contexto clínico de un síndrome de impacto posterior del tobillo permite establecer el diagnóstico sin requerir estudios de imagen de mayor complejidad(AU)

Introduction: The posterior impingement syndrome is a condition resulted of compressed posterior soft tissues, between the posterior talus and the calcaneus. Classically, this is seen at activities that cause extreme plantar flexion. Objective: To describe a posterior Ankle Impingement case secondary to a Stieda process. Case report: We report a 53 years old male, cook profession, with a chronic pain history within the posterior ankle, previous trauma was denied. At clinical examination tendon and ligament injuries were not found. Initial evaluation with conventional radiography showed the presence of a Stieda's process as cause of clinical manifestations. No further imaging studies were required. Conclusion: Conventional radiograph allows to clarify diagnosis in the posterior impingement syndrome(AU)

First Molecular Confirmation of Treponema spp. in Lesions Consistent with Digital Dermatitis in Chilean Dairy Cattle.

Digital dermatitis (DD) is a highly contagious and infectious disease in cattle which has a considerable negative economic impact worldwide, and adversely affects animal welfare. Members of the genus Treponema are the only bacterial agents for which there is consistent evidence of participation in DD lesions. In Chile, DD has been described since the 1990s, but only under a clinical approach. To date, the presence of the pathogenic agent has not been confirmed in Chile by any type of confirmatory microbiological diagnosis. The aim of the present study was to detect the presence of Treponema spp. DNA in lesions consistent with DD, in Chilean dairy cattle for the first time. We provide PCR confirmation of Treponema spp. in Chilean dairy cattle affected by DD. The high rate of positive results, as well as the proportion of the main Treponema species involved, is in line with what have been described in published studies elsewhere. Future herd control plans should benefit from the molecular detection of these pathogenic bacteria associated with DD.

Saccharomyces boulardii exerts renoprotection by modulating oxidative stress, renin angiotensin system and uropathogenic microbiota in a murine model of diabetes.

AIMS: We aimed to investigate whether Saccharomyces boulardii strain might exert renoprotective effects by modulating renal renin angiotensin system, oxidative stress and intestinal microbiota in streptozotocin-diabetic mice. MAIN METHODS: Thirty-six C57BL/6 male mice were divided into four groups: control (C), control + probiotic (CP), diabetes (D), diabetes + probiotic (DP). Diabetes was induced by one intraperitoneal injection of streptozotocin and Saccharomyces boulardii was administered by oral gavage for 8 weeks. Blood glucose, albuminuria and urinary volume were measured. Renal levels of angiotensin peptides (angiotensin I, II and 1-7) and the activities of angiotensin-converting enzyme (ACE) and ACE2 were determined, besides that, renal morphology, serotonin and dopamine levels and also microbiota composition were analyzed. KEY FINDINGS: Probiotics significantly increased C-peptide secretion and reduced blood glucose of diabetic animals. Saccharomyces boulardii also improved renal antioxidant defense, restored serotonin and dopamine concentration, and activated the renin-angiotensin system (RAS) vasodilator and antifibrotic axis. The modulation of these markers was associated with a beneficial impact on glomerular structure and renal function of diabetic treated animals. The phenotypic changes induced by Saccharomyces boulardii were also related to modulation of intestinal microbiota, evidenced by the decreased abundance of Proteus and Escherichia-Shigella, considered diabetic nephropathy biomarkers. SIGNIFICANCE: Therefore, probiotic administration to streptozotocin-induced diabetic mice improves kidney structure and function in a murine model and might represent a reasonable strategy to counteract nephropathy-associated maladaptive responses in diabetes.

Understanding the antibacterial mechanisms of copper ion treatment on Mycobacterium avium subsp. paratuberculosis.

Copper and its alloys are natural and very well-proven antimicrobial materials. The mechanisms of action through which copper is highly effective have been described at the molecular and cellular level. However, both the design of the studies carried out and the nature of the microorganisms studied have meant that this research has been of limited scope. In the present study, we examined the action mechanisms of a copper ion treatment on the integrity of Mycobacterium avium subsp. paratuberculosis (MAP), a highly resistant animal pathogen. The copper ion treatment applied to MAP cells, resulted in nucleic acid degradation and disintegration, increased ROS production and protein alteration. However, the observed susceptibility of MAP to copper-based treatment was dose-dependent. Finally, it had no effect on the integrity of the MAP cell wall. This new evidence about the observed tolerance in the MAP cell wall against the copper ions, may help us to understand how we can improve the proposed copper-based treatment, and finally achieve a totally effective alternative to control MAP in calf´s milk.

More Insights about the Efficacy of Copper Ion Treatment on Mycobacterium avium subsp. paratuberculosis (MAP): A Clue for the Observed Tolerance.

BACKGROUND: Scientific evidence is scarce for the antimicrobial effect of copper on bacteria characterized as more resistant. Using Mycobacterium avium subsp. paratuberculosis (MAP), a highly resistant microorganism, as a pathogen model, copper ion treatment has shown a significant bactericidal effect; however, the sustainability of MAP against copper toxicity was also reported in several studies. Accordingly, the present study aimed to evaluate the impacts of copper on MAP. METHODOLOGY: This study considered physicochemical properties and copper concentration in a buffer since it could modulate MAP response during the application of copper treatment. RESULTS: Despite the efficacy of copper ions in significantly reducing the MAP load in Phosphate Buffered Saline, some MAP cells were able to survive. The copper concentration generated by the copper ion treatment device increased significantly with increasing exposure times. MAP bacterial load decreased significantly when treated with copper ions as the exposure times increased. An increase in pH decreased oxygen consumption, and an increase in conductivity was reported after treatment application. CONCLUSIONS: Even with higher concentrations of copper, the efficacy of MAP control was not complete. The concentration of copper must be a key element in achieving control of highly resistant microorganisms.

New teaching strategies in dentistry: an experience in a Brazilian dental school / Novas estratégias de ensino em Odontologia: experiência em uma universidade brasileira

The need for new teaching-learning strategies stems from the great change society is going through. The so-called digital natives are part of a generation that lives in a hyperactive rhythm making it increasingly difficult to adapt to traditional classrooms. In Dentistry Courses, new strategies and pedagogical tools have been used, suchas active learning methodologies. In this context, the Discipline of Histology of the Dentistry Course has been proposing the use of some innovative pedagogical strategies. This work will present the experience with team-based learning (TBL), which articulates individual (iRAT) and group activities (gRAT), stimulates the application of concepts and can articulate with other methodologies such as flipped classroom, case study and problematization. This study alsoanalysedstudents' performance in iRAT and gRAT with the application of TBLand discussed the results achieved. Itwas conducted by analysingthe scoresof 240 first-year students of the Histology course in 2016, 2017 and 2018. Student scores, individually and in groups, were statistically analysedby the paired student t-test. Comparisons were made between the iRAT and gRAT activities about gender and the full-time and night classes by the one-way ANOVA and Kruskal-Wallis test. All students obtained higher group scores when compared to individual test results (p <0.001). There was no significant difference between sexes and study period. Group performanceexceeds individual performance. From this, it can be inferred that TBL can be a good strategy to use in dentistry, as an interaction between students leads to higher performance and problem-solving capacity (AU).

A necessidade de novas estratégias de ensino-aprendizagem decorre da grande mudança pela qual a sociedade está passando. Os chamados nativos digitais fazem parte de uma geração que vive em um ritmo hiperativo tornando cada vez mais difícil a adaptação às salas de aula tradicionais. Nos cursos de Odontologia, novas estratégias e ferramentas pedagógicas têm sido utilizadas, como metodologias ativas de aprendizagem. Nesse contexto, a Disciplina de Histologia do Curso de Odontologia tem proposto a utilização de algumas estratégias pedagógicas inovadoras. Este trabalho apresentará a experiência com a aprendizagem baseada em equipe (TBL), que articula atividades individuais (iRAT) e em grupo (gRAT), estimula a aplicação de conceitos e pode se articular com outras metodologias como aula invertida, estudo de caso e problematização. Este estudo também analisou o desempenho dos alunos no iRAT egRAT com a aplicação da TBL e discutiu os resultados alcançados. Foi realizado por meio da análise das notas de 240 alunos do primeiro ano do curso de Histologia em 2016, 2017 e 2018. As notas dos alunos, individualmente e em grupos, foram analisadas estatisticamente por meio do teste t-student pareado. As comparações foram feitas entre as atividades iRAT e gRAT sobre gênero e as aulas em período integral e noturno pelo teste ANOVA one waye teste de Kruskal-Wallis. Todos os alunos obtiveram pontuações mais altas do grupo quando comparados aos resultados dos testes individuais (p <0,001). Não houve diferença significativa entre os sexos e o período de estudo. O desempenho do grupo excede o desempenho individual. A partir disso, pode-se inferirque o TBL pode ser uma boa estratégia para uso em odontologia, pois uma interação entre os alunos leva a um maior desempenho e capacidade de resolução de problemas (AU).

Dynamic of Mycobacterium avium subspecies paratuberculosis infection in a domestic-wildlife interface: Domestic sheep and guanaco as reservoir community.

Natural herbivore populations have experienced uninterrupted pressures from direct and evident domestic-wildlife interactions and competition, to indirect or less obvious ones such as pathogen transmission. Thus, pathogen spillover between wild and domestic animals is a constant concern because the domestic-wildlife interface represents the ecological frontier in which pathogen transmission takes place in both directions. In Patagonian steppe communities, extensive sheep ranching and guanaco (Lama guanicoe) populations coexist, and guanaco have shown to be infected by pathogens such as Mycobacterium avium subspecies paratuberculosis (MAP) likely transmitted from livestock. MAP causes chronic enteritis and affects mostly domestic ruminants. We evaluated MAP prevalence and pathogen shedding in both species' faeces collected in non-shared and shared sites according to presence/absence of sheep and guanaco along a year, in four different seasons (autumn, winter, and spring 2018, and summer 2019). Our results indicate that MAP circulates in both sheep and guanaco populations with self-sustained transmission; however, both species differ in their levels of competence. We detected higher pathogen shedding in sites occupied by sheep, suggesting that sheep populations may be the main source of infection for susceptible animals due to their large numbers which drive MAP dynamics.

Association between the severity of histopathological lesions and Mycobacterium avium subspecies paratuberculosis (MAP) molecular diversity in cattle in southern Chile.

The objective was to evaluate the association between the severity of histopathological lesions caused by Mycobacterium avium subspecies paratuberculosis (MAP) infection and the molecular diversity of this pathogen. Blood, ileum, and mesenteric lymph node samples were collected at slaughter, from 1,352 adult cattle [source population 1 (SP1)]. In addition, 42 dairy herds (n = 4,963 cows) were followed for 2 years, and samples from compatible paratuberculosis clinical cases [source population 2 (SP2)] were collected. MAP infection was confirmed using an ELISA test, liquid media culture, and PCR. Isolates were genotyped using five MIRU-VNTR markers. Tissues from confirmed samples were subjected to a histopathological examination. A histopathological severity score (HSS) system was developed and used to grade (0 to 5) the magnitude of lesions caused by MAP. In general, the HSS system assesses the number of foci and degree of macrophage infiltration, together with the presence of multinucleated giant cells (MGCs) and acid-fast bacilli (AFB), in addition to the fusion of the intestinal villi and hyperplasia of the crypts. Despite the large sampling effort, only 79 MAP isolates were successfully genotyped, where 19 different haplotypes were described. A mixed-effect Poisson regression model was used to assess the relationship between haplotypes and HSS values. The model was controlled by animal age, and the farm was used as a random effect. Haplotypes were grouped based on their relative frequency: the most frequent haplotype (group i, 49.4%), the second most frequent haplotype (group ii, 12.7%), and all other haplotypes (group iii, 37.9%). Model outputs indicated that group i had significantly higher HSS values than group iii. In addition, group i was also associated with higher optical density (OD) values of the ELISA test. These results support the existence of differences in pathogenicity between MAP haplotypes. However, results were based on a relatively small sample size; thus, these should be taken with caution. Despite this, study findings suggest that haplotypes would be associated with differences in disease progression, where the dominant haplotype tends to generate more severe lesions, which could be linked to a greater shed of MAP cells than non-dominant haplotypes, increasing their chances of transmission.

Carcinoma de mama bilateral sincrónico. Presentación de un caso / Synchronous bilateral breast carcinoma. A case report

Introducción: El carcinoma de mama bilateral sincrónico se define por la aparición de tumores simultáneos en ambas mamas. Estudios indican que la frecuencia de estos carcinomas oscila entre 1,4 y 11,8 %. Actualmente, la ecografía mamaria y la mamografía constituyen los métodos de cribado aconsejables para detectar lesiones iniciales. Objetivo: Presentar un caso infrecuente de carcinoma bilateral simultáneo. Presentación de caso: Se trata de una mujer de 67 años de edad, sin antecedentes personales ni familiares de cáncer de mama, que acude a consulta de mastología por aumento de volumen focal en la mama derecha. En mamografía digital se identifican imágenes nodulares espiculadas de alta densidad en ambas mamas, con clasificación BIRADS-5. Se completó el estudio con citología por aguja fina y biopsia posoperatoria con el resultado de carcinoma ductal bilateral con metástasis al ganglio axilar derecho. Conclusiones: El carcinoma bilateral de mama, a pesar de ser una entidad de aparición excepcional, se puede identificar en estadios clínicos avanzados en pacientes sin antecedentes familiares, por lo que es importante la evaluación de ambas mamas en los estudios de imagen, para descartar lesiones sincrónicas con las pertinentes biopsias bilaterales para su conclusión histopatológica.

Introduction: Synchronous bilateral breast cancer is defined by some authors as the simultaneous appearance of tumors in both breasts. Studies indicate that the frequency of these carcinomas range from 1.4 to 11.8%. Currently, breast ultrasound and mammography are the recommended screening methods to detect initial lesions. Objective: To describe a rare simultaneous bilateral breast carcinoma case. Case report:We present the case of a 67-year-old woman, with no personal or family history of breast cancer, who attended a mastology consultation due to focal volume increase in the right breast. Digital mammography was performed, identifying high-density spiculated nodular images in both breasts with BIRADS-5 classification. A study was completed with fine-needle cytology and postoperative biopsy, obtaining the result of bilateral ductal carcinoma with metastasis to the right axillary node.Conclusions: Bilateral breast carcinoma, despite being an entity of exceptional appearance, can be identified in advanced clinical stages in patients with no family history, so it is important to evaluate both breasts in imaging studies, to rule out synchronous lesions, requesting the relevant bilateral biopsies for histopathological conclusion.

Mechanism of Action and Efficacy of Immunosupressors in Lupus Nephritis.

Approximately 70% of the patients with systemic lupus erythematosus will have clinical evidence of kidney damage during their evolution. Patients with impaired renal function at onset and those with recurrent flares have a poor prognosis. Understanding the mechanism of action of immunosuppressants is essential for proper prescription. Steroids inhibit the DNA sequence that promotes the release of inflammatory cytokines. Phosphoramide mustard, metabolite of cyclophosphamide, cross-link with the DNA, causing the aggregation of an alkyl group, causing cell death. Mycophenolate inhibits inosine monophosphate dehydrogenase, prevents de novo synthesis of guanine, inducing cell arrest in S phase. Azathioprine blocks the synthesis of purines and induces apoptosis. Calcineurin inhibitors prevent the dephosphorylation of NFAT and reduce the production of interleukin 2. Antimalarials alter the enzymatic release of lysosomes by increasing intravesicular pH. The mechanism of action of rituximab is related to complement-dependent cytotoxicity and the elimination of anti-CD20-labeled B cells. Progress in the knowledge and management of low doses of steroids may change the current paradigm and reduce the frequency of related adverse events. Mycophenolate seems to be a better choice than cyclophosphamide for induction, it is also preferred over azathioprine as a maintenance immunosuppressive agent, although azathioprine is preferred in women with a desire for conception, those pregnant, or with low resources. For treatment-resistant cases, tacrolimus, rituximab or belimumab may be effective. Ongoing clinical trials with new drugs offer promising results.

Attempted Control of Paratuberculosis in Dairy Calves by Only Changing the Quality of Milk Fed to Calves.

One of the important routes of Mycobacterium avium subsp. paratuberculosis (MAP) transmission in dairy calves is milk. The aim of the present study was to assess the efficacy of milk treatments to prevent MAP infection transmission to calves. A one-year longitudinal study was carried out. Newborn calves were assigned to one of four experimental groups: 5 calves received naturally MAP-contaminated milk, 5 calves received copper treated milk, 4 calves were fed calf milk replacer, and 3 were fed UHT pasteurized milk. MAP load in milk was estimated. Infection progression was monitored monthly. After one year, calves were euthanized, and tissue samples were cultured and visually examined. MAP was undetectable in milk replacer and UHT milk. Copper ion treatment significantly reduced the number of viable MAP in naturally contaminated milk. Fecal shedding of MAP was observed in all study groups but began earlier in calves fed naturally contaminated milk. Paratuberculosis control programs must place multiple hurdles between the infection source, MAP-infected adult cows, and the most susceptible animals on the farm, young calves. As our study shows, strict dependence on a single intervention to block infection transmission, no matter how important, fails to control this insidious infection on dairy farms.

Saccharomyces boulardii modulates oxidative stress and renin angiotensin system attenuating diabetes-induced liver injury in mice.

Type 1 diabetes (T1DM) is a chronic disease characterized by hyperglycemia due to a deficiency in endogenous insulin production, resulting from pancreatic beta cell death. Persistent hyperglycemia leads to enhanced oxidative stress and liver injury. Several studies have evaluated the anti-diabetic and protective effects of probiotic strains in animal models. In the present study, we investigated, through histopathological and biochemical analyses, the effects of eight weeks of administration of Saccharomyces boulardii (S. boulardii) yeast on the liver of streptozotocin (STZ) induced diabetic C57BL/6 mice. Our results demonstrated that S. boulardii attenuates hepatocytes hydropic degeneration and hepatic vessels congestion in STZ-induced diabetic mice. The treatment attenuated the oxidative stress in diabetic mice leading to a reduction of carbonylated protein concentration and increased activity of antioxidant enzymes superoxide dismutase and glutathione peroxidase, compared to untreated diabetic animals. The results also show the beneficial influence of S. boulardii in regulating the hepatic concentration of renin angiotensin system (RAS) peptides. Therefore, our results demonstrated that S. boulardii administration to STZ-induced diabetic mice reduces oxidative stress and normalizes the concentration of RAS peptides, supporting the hypothesis that this yeast may have a role as a potential adjunctive therapy to attenuate diabetes-induced liver injury.