Editing the Human Genome with CRISPR/Cas: A Review of its Molecular Basis, Current Clinical Applications, and Bioethical Implications.

Abstract: CRISPR/Cas genes evolved in prokaryotic organisms as a mechanism of defense designed to identify and destroy genetic material from threatening viruses. A breakthrough discovery is that CRISPR/Cas system can be used in eukaryotic cells to edit almost any desired gene. This comprehensive review addresses the most relevant work in the CRISPR/Cas field, including its history, molecular biology, gene editing capability, ongoing clinical trials, and bioethics. Although the science involved is complex, we intended to describe it in a concise manner that could be of interest to diverse readers, including anyone dedicated to the treatment of patients who could potentially benefit from gene editing, molecular biologists, and bioethicists. CRISPR/Cas has the potential to correct inherited diseases caused by single point mutations, to knock-in the promoter of a gene whose expression is highly desirable or knockout the gene coding for a deleterious protein. CRISPR/Cas technique can also be used to edit ex vivo immune cells and reinsert them in patients, improving their efficiency in attacking malignant cells, limiting the infectious potential of viruses or modulating xenotransplant rejection. Very important bioethical considerations on this topic include the need to internationally regulate its use by ad hoc expert committees and to limit its use until safety and bioethical issues are satisfactorily resolved.

Attitude Synchronization of a Group of Rigid Bodies Using Exponential Coordinates.

Currently, managing a group of satellites or robot manipulators requires coordinating their motion and work in a cooperative way to complete complex tasks. The attitude motion coordination and synchronization problems are challenging since attitude motion evolves in non-Euclidean spaces. Moreover, the equation of motions of the rigid body are highly nonlinear. This paper studies the attitude synchronization problem of a group of fully actuated rigid bodies over a directed communication topology. To design the synchronization control law, we exploit the cascade structure of the rigid body's kinematic and dynamic models. First, we propose a kinematic control law that induces attitude synchronization. As a second step, an angular velocity-tracking control law is designed for the dynamic subsystem. We use the exponential coordinates of rotation to describe the body's attitude. Such coordinates are a natural and minimal parametrization of rotation matrices which almost describe every rotation on the Special Orthogonal group SO(3). We provide simulation results to show the performance of the proposed synchronization controller.

Microbiological contaminations of laboratory mice and rats in conventional facilities in Argentina.

Routine microbiological monitoring of rodent colonies in animal facilities is essential to evaluate the health status of the animals used in research studies. In the present study, animals were examined for the presence of selected microbial infections. In order to determine the contamination rates of mice and rats in Argentina, animals from 102 conventional facilities were monitored from 2012 to 2016. The most frequent bacteria isolated were Pseudomonas aeruginosa and Proteus spp. The common parasites identified were Syphacia spp. and Tritrichomonas spp. Serological assays demonstrated the highest prevalence for Mouse hepatitis virus in mice and Sialodacryoadenitis virus in rats. The results indicate that there is a high incidence of infections, so it is suggested that an efficient management system and effective sanitary barriers should be implemented in conventional facilities in Argentina in order to improve sanitary standards.

A recombinant iron transport protein from Bordetella pertussis confers protection against Bordetella parapertussis.

Whooping cough, which is caused by Bordetella pertussis and B. parapertussis, is a reemerging disease. New protective antigens are needed to improve the efficacy of current vaccines against both species. Using proteomic tools, it was here found that B. parapertussis expresses a homolog of AfuA, a previously reported new vaccine candidate against B. pertussis. It was found that this homolog, named AfuABpp , is expressed during B. parapertussis infection, exposed on the surface of the bacteria and recognized by specific antibodies induced by the recombinant AfuA cloned from B. pertussis (rAfuA). Importantly, the presence of the O-antigen, a molecule that has been found to shield surface antigens on B. parapertussis, showed no influence on antibody recognition of AfuABpp on the bacterial surface. The present study further showed that antibodies induced by immunization with the recombinant protein were able to opsonize B. parapertussis and promote bacterial uptake by neutrophils. Finally, it was shown that this antigen confers protection against B. parapertussis infection in a mouse model. Altogether, these results indicate that AfuA is a good vaccine candidate for acellular vaccines protective against both causative agents of whooping cough.

Zigzag Sc2C2 Carbide Cluster inside a [88]Fullerene Cage with One Heptagon, Sc2C2@Cs(hept)-C88: A Kinetically Trapped Fullerene Formed by C2 Insertion?

A non-isolated pentagon rule metallic carbide clusterfullerene containing a heptagonal ring, Sc2C2@Cs(hept)-C88, was isolated from the raw soot obtained by electric arc vaporization of graphite rods packed with Sc2O3 and graphite powder under a helium atmosphere. The Sc2C2@Cs(hept)-C88 was purified by multistage high-performance liquid chromatography (HPLC), cocrystallized with Ni-(octaethylporphyrin), and characterized by single-crystal X-ray diffraction. The diffraction data revealed a zigzag Sc2C2 unit inside an unprecedented Cs(hept)-C88 carbon cage containing 13 pentagons, 32 hexagons, and 1 heptagon. Calculations suggest that the observed nonclassical fullerene could be a kinetically trapped species derived from the recently reported Sc2C2@C2v(9)-C86 via a direct C2 insertion.

In vitro and in vivo antitumor effects of the VO-chrysin complex on a new three-dimensional osteosarcoma spheroids model and a xenograft tumor in mice.

Osteosarcoma (OS) is the most common primary tumor of bone, occurring predominantly in the second decade of life. High-dose cytotoxic chemotherapy and surgical resection have improved prognosis, with long-term survival for patients with localized disease. Vanadium is an ultra-trace element that after being absorbed accumulates in bone. Besides, vanadium compounds have been studied during recent years to be considered as representative of a new class of non-platinum antitumor agents. Moreover, flavonoids are a wide family of polyphenolic compounds that display many interesting biological effects. Since coordination of ligands to metals can improve the pharmacological properties, we report herein, for the first time, the in vitro and in vivo effects of an oxidovanadium(IV) complex with the flavonoid chrysin on the new 3D human osteosarcoma and xenograft osteosarcoma mice models. The pharmacological results show that VOchrys inhibited the cell viability affecting the shape and volume of the spheroids and VOchrys suppressed MG-63 tumor growth in the nude mice without inducing toxicity and side effects. As a whole, the results presented herein demonstrate that the antitumor action of the complex was very promissory on human osteosarcoma models, whereby suggesting that VOchrys is a potentially good candidate for future use in alternative antitumor treatments.

Beyond the Butterfly: Sc2C2@C(2v)(9)-C86, an Endohedral Fullerene Containing a Planar, Twisted Sc2C2 Unit with Remarkable Crystalline Order in an Unprecedented Carbon Cage.

The synthesis, isolation, and characterization of a new endohedral fullerene, Sc2C88, is reported. Characterization by single crystal X-ray diffraction revealed that it is the carbide Sc2C2@C(2v)(9)-C86 with a planar, twisted Sc2C2 unit inside a previously unseen C(2v)(9)-C86 fullerene cage.

Eugenol as anesthetic for Cnesterodon decemmaculatus (Cyprinodontiformes, Poeciliidae).

Anesthetics are commonly used in fish for surgery and to facilitate capture, handling and transport in aquaculture and experimental procedures. In research, the selection of the anesthetic depends on its properties and on the recovery time. Eugenol has been pointed out as an effective anesthetic for fish, alternative to traditional drugs. Although Cnesterodon decemmaculatus is widely used as a model in ecological bioassays, no anesthetic protocol has been reported for this species. The aim of the present study was to evaluate the induction time (i.e. time to reach anesthetic stage VI) and recovery time in individuals of C. decemmaculatus subjected to eugenol at a fixed concentration, according to sex and pregnancy status. Forty-one fish were divided into three groups: males, pregnant females and non-pregnant females. They were measured for total length, standard length and weight, and the condition factor (K) was calculated. No significant differences in induction and recovery times were found for sex, pregnancy status and K between groups. Results are a contribution toward the development protocol of a standard anesthetic protocol for C. decemmaculatus.

Novel genotyping assay for the nt230 (del4) ABCB1 gene mutation and its allele frequency in Border Collie dogs in Mexico.

A 4-bp deletion in the ATP-binding cassette subfamily B member 1 (ABCB1) gene, also referred to as the multidrug resistance gene (MDR1), produces stop codons that cause premature termination of P-glycoprotein 1 (P-gp) synthesis. Dogs with the homozygous mutation do not express functional P-gp, which increases their sensitivity markedly to many common veterinary drugs. We detected the nt230 (del4) ABCB1 mutation in Border Collie dogs in western Mexico with a simple and affordable primer-introduced restriction analysis PCR (PIRA-PCR). PIRA-PCR clearly identified all genotypes in our sample of 104 dogs. Genotype frequencies were 0.952 (wild/wild), 0.029 (wild/mut) and 0.019 (mut/mut). Allele frequencies were 0.033 (mutant alleles) and 0.966 (wild-type alleles). In this small subset of the Mexican dog population, we found a higher prevalence of the nt230 (del4) MDR1/ABCB1 gene mutation than reported in other countries.

SARS-CoV-2-Related Subacute Thyroiditis, Myocarditis, and Hepatitis After Full Resolution of COVID-19 Serum Markers.

BACKGROUND Subacute thyroiditis, myocarditis, and hepatitis are inflammatory disorders that may develop after viral infections, including SARS-CoV-2. These entities may appear after resolution of the respiratory syndrome. CASE REPORT A previously healthy 64-year-old male patient came to the hospital reporting severe chest pain. He had a history of a COVID-19 pneumonia with PCR confirmation 4 weeks before. On admission to the Coronary Care Unit (CCU), the patient had a negative PCR for SARS-CoV-2; the following tests were performed: total T3 643.4 ng/dl (reference 35-193 ng/dl), total thyroxine 12.0 µg/dl (reference 4.8-11.7 µg/dl), free T4 1.85 ng/dl (reference 0.7-1.48 ng/dl), TSH 0.01 µIU/ml (reference 0.35-4.94 µIU/ml); total bilirubin 0.76 mg/dl (reference 0.0-1.5 mg/dl), alkaline phosphatase 185 U/L (reference 40-150 U/L), alanine aminotransferase 194.6 U/L (reference 6-66 U/L), aspartate aminotransferase 93.4 U/L (reference 9-55 U/L); on admission to the CCU high-sensitivity troponin I 548.3 pg/ml (reference 0.0-34.2 pg/ml), after 24 h in the CCU 801 pg/ml, and after 11 days (as an outpatient) 4.5 pg/ml. A thyroid gammagram revealed absent uptake of the radionuclide. Normal cardiac gammagraphy and cardiac enzymes ruled out myocardial ischemia and infarction. The following diagnoses were made: myocarditis, subacute thyroiditis, and reactive hepatitis due to SARS-CoV-2 infection. CONCLUSIONS COVID-19 has been demonstrated to be a multisystemic inflammatory disorder. The serious illness that developed in our patient after relief of his pulmonary disease underlines this nature. We suggest close follow-up of patients even after apparent clinical resolution, and performing thyroid, myocardial, and liver tests if clinically indicated.

IgG4-Related Fibrous Thyroiditis (Riedel's Thyroiditis): A Case Report.

BACKGROUND Riedel's thyroiditis is a rare form of immunoglobulin G (IgG) 4-related invasive fibrosis of the thyroid gland; given its scarce incidence, standardized therapeutic guidelines are unavailable. Although complications are unusual, obstructive symptoms produced by the stony-hard goiter may put patients' lives at risk. The diagnosis must be biopsy-proven, and treatment consists of thyroid hormone replacement and anti-inflammatory drugs, although sometimes thyroidectomy may be required. CASE REPORT A 69-year-old woman presented with a 7-month history of progressive hypothyroidism and obstructive dysphagia. On physical examination, she had a large, stony-hard goiter. A Doppler ultrasound study revealed a massive, avascular enlargement of the thyroid gland. A computed tomography scan failed to demonstrate any extrathyroidal extension of the abnormal tissue. A Tru-Cut biopsy of the thyroid was performed. Extensive replacement of thyroid follicles by prominent bands of fibrous tissue was observed, with follicular obliteration and mild focal occlusive phlebitis. A lymphoplasmacytic infiltrate was clearly identified; no oxyphilic nor giant cells were found. On immunohistochemistry, the immunoglobulin G (IgG) 4/IgG ratio in the plasma cell infiltrate was 40%; increased serum IgG4 levels were also found, supporting the diagnosis of Riedel's thyroiditis. The patient was successfully treated with levothyroxine replacement and tamoxifen with prompt resolution of obstructive symptoms. CONCLUSIONS Fibrous thyroiditis should be considered in the differential diagnosis of primary hypothyroidism in a patient with a stony-hard goiter. Although steroids are often used as a therapeutic strategy for this disease, our patient had an excellent therapeutic response to tamoxifen, avoiding adverse effects associated with steroid therapy, the higher cost of monoclonal antibody therapy, and surgery-associated risks.

Non-aversive photographic measurement method for subcutaneous tumours in nude mice.

We have developed a new method for the measurement of subcutaneous tumour volume which consists in taking photographs of mice in their home cages, to refine the standard method of measurement with calipers. We consider this new method to be non-aversive, as it may be more compatible with mice behavioural preferences and, therefore, improve their welfare. Photographs are captured when mice voluntarily go into an acrylic tube containing graph paper that is later used as a scale. Tumour volumes measured with the caliper and the non-aversive photographic method were compared to those obtained by water displacement volume and weight. Behavioural and physiological changes were evaluated to assess animal welfare. Significant differences were found between measurements obtained with the caliper and the non-aversive photographic method, v. the reference volume acquired by water displacement (P < 0.001). Nevertheless, there was good consistency for these measurements when tumours were measured repeatedly, with all Intra-Class Correlation Coefficients above 0.95. Mice on which the non-aversive photographic method was employed were significantly less reluctant to establish contact with the experimenter (P < 0.001) and behaved less anxiously in a modified-Novelty Suppressed Feeding test. Particularly, statistically significant differences were found in connection with the latency to eat an almond piece (P < 0.05), the frequency of grooming (P < 0.001) and the frequency of defecation (P < 0.001). Corticosterone concentration in faeces and blood glucose were determined and no significant changes were found. Therefore, we propose the non-aversive photographic method to measure subcutaneous tumours as a way to refine methodologies in the field of experimental oncology.

In vitro and in vivo anticancer effects of two quinoline-platinum(II) complexes on human osteosarcoma models.

Platinum-based drugs, mainly cisplatin, are used for the treatment of several solid tumors such as OS. However, cisplatin treatment often results in the development of chemoresistance, leading therapeutic failure. We have previously reported that platinum complexes containing 8-hydroxyquinoline ligands have good antitumor activity against different cancer cell lines and with a different and better cytotoxic profile than cisplatin. Here, the anticancer properties of two different quinoline-platinum complexes [Pt(Cl)2(quinoline)(dmso)] (1) [PtCl(8-O-quinoline)(dmso)] (2) on in vitro (2D and 3D) and in vivo models (xenograft tumor of human osteosarcoma in mice) are presented. In this order, [PtCl(8-O-quinoline)(dmso)] (2) impaired cell viability to have a more pronounced antitumor effect than cisplatin on MG-63 osteosarcoma cells (IC50 4 µM vs. 39 µM). Besides, [PtCl(8-O-quinoline)(dmso)] (2) increased ROS production in a dose-manner response and this compound induced early and late apoptotic fractions of human osteosarcoma cells. Finally, [PtCl(8-O-quinoline)(dmso)] (2) decreased the cell viability of multicellular spheroids and reduced the tumor volume on athymic nude mice N:NIH(S) Fox1nu without inducing side effects. In this way, [PtCl(8-O-quinoline)(dmso)] (2) did not alter the normal cytoarchitecture of liver and kidney and the blood biomarkers (GPT, GOT, uremia, and creatinine) did not suffer modifications. Taken together, our data indicate that these compounds showed a better anticancer performance than cisplatin on in vitro and in vivo studies. These results showed the importance of chelation in the antitumor properties, suggesting that the [PtCl(8-O-quinoline)(dmso)] (2) might be a promising agent for the treatment of human osteosarcoma tumors resistant to cisplatin.

Editing the Human Genome with CRISPR/Cas: A Review of its Molecular Basis, Current Clinical Applications, and Bioethical Implications

ABSTRACT CRISPR/Cas genes evolved in prokaryotic organisms as a mechanism of defense designed to identify and destroy genetic material from threatening viruses. A breakthrough discovery is that CRISPR/Cas system can be used in eukaryotic cells to edit almost any desired gene. This comprehensive review addresses the most relevant work in the CRISPR/Cas field, including its history, molecular biology, gene editing capability, ongoing clinical trials, and bioethics. Although the science involved is complex, we intended to describe it in a concise manner that could be of interest to diverse readers, including anyone dedicated to the treatment of patients who could potentially benefit from gene editing, molecular biologists, and bioethicists. CRISPR/Cas has the potential to correct inherited diseases caused by single point mutations, to knock-in the promoter of a gene whose expression is highly desirable or knockout the gene coding for a deleterious protein. CRISPR/Cas technique can also be used to edit ex vivo immune cells and reinsert them in patients, improving their efficiency in attacking malignant cells, limiting the infectious potential of viruses or modulating xenotransplant rejection. Very important bioethical considerations on this topic include the need to internationally regulate its use by ad hoc expert committees and to limit its use until safety and bioethical issues are satisfactorily resolved.

Características de los días de descanso otorgados a pacientes atendidos en una Red Asistencial de Salud de Perú / Characteristics of days of rest granted to patients treated at the health care network in Peru

Introducción: El descanso médico es una figura legal otorgada para reposar ante una lesión que incapacite, sin necesidad de que el trabajador se vea privado de sus haberes o remuneraciones laborales. Objetivo: Caracterizar los días de descanso médico según el tipo de diagnóstico en los pacientes atendidos en la seguridad social de Trujillo, Perú. Material y Métodos: Estudio transversal analítico de datos secundarios, a partir del uso de la base del otorgamiento por incapacidades temporales laborales se obtuvieron las características de los descansos médicos (medido en días), de 2009-2015 en un hospital de la seguridad social del norte del Perú. Se realizó la caracterización según el tipo de patología y la estadística analítica mediante la regresión lineal. Resultados: De los 145 077 descansos otorgados, el falso trabajo de parto fue la condición más frecuente. Los accidentes comunes, la fractura de maléolo externo, la fractura de radio y el trastorno de discos intervertebrales tuvieron más días de descanso, con un promedio superior en relación con otras incapacidades. La diarrea, la faringitis y la deshidratación generaron menos días de descanso con un promedio menor en comparación con otras patologías. En cuanto al sexo, en general, a los hombres se les otorgó más descansos laborales. Todo esto fue estadísticamente significativo. Conclusiones: Existen diferencias marcadas en la asignación de días de descanso según las características de a quién se le dio, esto debería ser evaluado con estudios que permitan encontrar valores estándar(AU)

Introduction: Medical rest is a legal figure granted to rest in the presence of an incapacitating injury, without depriving the worker of receiving the incomes from work. Objective: To characterize the days of medical rest according to the type of diagnosis in patients treated at the social security in Trujillo, Peru. Material and Methods: Analytical cross-sectional study involving secondary data, and using the basis of medical breaks (measured in days) due to temporary incapacity from 2009 to 2015 in a social security hospital in northern Peru. Characterization was obtained according to the type of pathology, and analytical statistics was performed using linear regression. Results: Of the 145077 rest days granted, false labor was the most frequent condition. However, common accidents such as external malleolus fracture, radius fracture, and intervertebral disc disorder had more days of rest, being above average for other disabilities. On the other hand, those that generated fewer days of rest were diarrhea, pharyngitis and dehydration, being below average for other pathologies. In terms of sex, in general, men were granted more medical rest. All this was statistically significant. Conclusions: There are marked differences in the allocation of days of rest according to the characteristics of the persons to whom they were given; this should be evaluated in further studies to find standard values(AU)

Formación de profesionales mediante simulación clínica durante la primera ola de covid-19 / Training professionals through clinical simulation during the first covid-19 wave

En este artículo se comparte la experiencia de la formación de profesionales sanitarios del Hospital General Universitario de Ciudad Real (HGUCR) mediante la formación teórico-práctica con simulación clínica y la valuación de sus resultados. Se plantearon sesiones con simulación de baja y alta compleji-dad para 40 personas y en grupos reducidos. La evolución de las necesidades hizo aumentar el número de sesiones y la supresión de la sala de simulación avanzada.Se realizó un programa de 64 sesiones entre marzo y abril de 2020 en turnos de mañana y tarde, en grupos de 15 personas.Participó el 41,5% (n= 852) del personal sanitario de la Gerencia de Atención Integrada de Ciudad Real. Respondieron el cuestionario de evaluación 91 personas que refirieron una alta satisfacción con la actividad (4,32 puntos sobre 5 a nivel global), valoraron especialmente la utilidad para el trabajo, la claridad de la información y la parte práctica de la sesión (simulación). Así mismo, el 80,6% manifestó haber aumentado su confianza y el 65,9% una disminución de la ansiedad en el manejo de pacientes con COVID. Si bien habría que analizar otras causas, el porcentaje de contagios entre los profesionales (10%) fue similar al de la población general. Disponer de espacios de formación con simulación y profesionales formados en el diseño de este tipo de actividades supone un recurso útil y flexible a las demandas sanitarias que puedan surgir.(AU)

In this article, we share the experience in training healthcare professionals from the Hospital General Universitario of Ciudad Real (HGUCR) through theoretical-practical training with clinical simulation, and the evaluation of its results.Sessions were set with high and low complexity simulation for 40 persons and in reduced groups. The evolution of needs led to an increase in the number of sessions, and the suppression of the Advanced Simulation Room.A 64-session program was held between March and April 2020, in morning and afternoon shifts and for groups of 15 persons, with participation by 41.5% (n= 852) of the healthcare staff from the Integrated Care Management of Ciudad Real. The evaluation questionnaire was answered by 91 persons, who reported high satisfaction with the activity (4.32 scores over 5 at overall level); they valued particularly its utility for work, the clarity of the information, and the practical aspect of the session (simulation). Likewise, 80.6% reported an increase in confidence, and 65.9% reported a reduction in anxiety regarding management of patients with COVID. Even though other causes should be analysed, the proportion of contagion among professionals (10%) was similar to that among the general population.The availability of training spaces with simulation and professionals trained in the design of this type of activities represents a useful and flexible resource for any healthcare demands that might arise.(AU)

Medicina Traslacional en el Perú, generación de políticas y mejoras basadas en la evidencia / Translational medicine in Peru, policy making and evidence-based improvement

Introducción: la investigación traslacional es una rama de la ciencia de reciente creación, su objetivo principal es la aplicación del conocimiento que se genera de las investigaciones, que no quede formando parte de la literatura gris, en el papel o para unos pocos, sino que pueda servir a la mayor cantidad posible de individuos y/o poblaciones. Objetivo: determinar los avances que se han dado a lo largo de los últimos años en la aplicación de la medicina traslacional en Perú. Métodos: se realizó una búsqueda por conveniencia en bases de datos (Google Scholar, Pubmed). Se han brindado ejemplos de cómo la investigación traslacional en Perú puede aportar en gran medida a la mejora de realidades y problemáticas específicas, esto refuerza la necesidad de que las decisiones políticas deben basarse en la medicina basada en la evidencia. Resultados: la medicina traslacional en Perú enfrenta muchas dificultades, como lo son los recursos limitados, tiempo escaso para implementar la investigación formativa, carencia de modelos pedagógicos actualizados, docentes preparados en escuelas antiguas y con capacidad limitada para la educación médica continua; obstáculos que deben de superarse para poder asegurar que la ciencia -y por ende la sociedad- progresen. Conclusiones: en Perú, el avance de la medicina traslacional ha derivado en la generación de personal de salud más capacitado que ha proporcionado los medios para el desarrollo de múltiples políticas públicas. Dichas políticas en muchos casos han terminado plasmadas en normas, reglamentos y hasta leyes en el país(AU)

Introduction: translational research is a branch of science of recent creation. Its main aim is the application of the knowledge generated by research so that it will not become grey literature printed on paper or for the use of a chosen few, but serve as many people and/or populations as possible. Objective: determine the progress made in recent years in the application of translational medicine in Peru. Methods: a convenience search was conducted in the databases Google Scholar and PubMed. Examples are offered of the way in which translational research may greatly contribute to improve specific realities and problems in Peru. This reinforces the need that political decisions be based on evidence-based medicine. Results: translational medicine is faced with many difficulties in Peru, such as limited resources, scant time to implement training research, lack of updated pedagogical models, and teachers trained in old schools and with a limited capacity for continuing medical education. These hurdles should be overcome to ensure the progress of science and therefore of society as well. Conclusions: progress of translational medicine in Peru has resulted in the training of more skilled health personnel, providing the means for the development of multiple public policies. In many cases those policies have been included in standards, regulations and even laws in the country(AU)

Microbiological contaminations of laboratory mice and rats in conventional facilities in ArgentinaContaminations in mice and rats facilities in Argentina / Contaminaciones microbiológicas de ratones y ratas de laboratorio en bioterios convencionales de Argentina

Abstract Routine microbiological monitoring of rodent colonies in animal facilities is essential to evaluate the health status of the animals used in research studies. In the present study, animals were examined for the presence of selected microbial infections. In order to determine the contamination rates of mice and rats in Argentina, animals from 102 conventional facilities were monitored from 2012 to 2016. The most frequent bacteria isolated were Pseudomonas aeruginosa and Proteus spp. The common parasites identified were Syphacia spp. and Tritrichomonas spp. Serological assays demonstrated the highest prevalence for Mouse hepatitis virus in mice and Sialodacryoadenitis virus in rats. The results indicate that there is a high incidence of infections, so it is suggested that an efficient management system and effective sanitary barriers should be implemented in conventional facilities in Argentina in order to improve sanitary standards.

Resumen Los controles microbiológicos de rutina en colonias de roedores en bioterios son esenciales para evaluar el estado de salud de los animales que se utilizan en las investigaciones. En el presente estudio se examinaron animales de bioterios de Argentina con el objeto de detectar la presencia de infecciones microbianas seleccionadas. Con el fin de determinar los porcentajes de contaminaciones en estos individuos, se controlaron animales de 102 bioterios convencionales entre 2012 y 2016. Las bacterias más frecuentes aisladas fueron Pseudomonas aeruginosa y Proteus spp. Los parásitos comunes identificados fueron Syphacia spp. y Tritrichomonas spp. Los ensayos serológicos demostraron la mayor prevalencia del virus de hepatitis del ratón en ratones y del virus de la Syalodacryoadenitis en ratas. Los resultados indican que hay una alta incidencia de infecciones, por lo que se sugiere que se debe implementar un sistema de gestión eficiente y barreras sanitarias eficaces en instalaciones convencionales en Argentina con el objeto de mejorar los estándares sanitarios.

Diabetes insípida central debida a histiocitosis de células de Langerhans / Central diabetes insipidus due to Langerhans cell histiocytosis

Resumen La diabetes insípida central es un trastorno ocasionado por la deficiencia total o parcial de la síntesis, secreción o ambas de la hormona antidiurética, causada por una disfunción hipotálamo-hipofisaria que resulta en un síndrome poliúrico con polidipsia severa. Este trastorno puede ser primario, debido a anormalidades genéticas, o secundario a lesiones posquirúrgicas, traumáticas, infecciosas o tumorales. Describimos el caso de un paciente de 15 años de edad al momento del diagnóstico. En la primera visita el paciente tenía un claro síndrome poliúrico. La resonancia magnética de cráneo mostró únicamente un aracnoidocele selar; sin embargo, en el estudio de seguimiento realizado ocho meses después se encontró engrosamiento del tallo hipofisario y una lesión osteolítica en el hueso parietal izquierdo. El paciente fue tratado con resección quirúrgica de la lesión lítica, seguida de 12 ciclos de quimioterapia. Dos años después se confirmó hipogonadismo hipogonadotrópico. La ausencia de lesiones al momento del diagnóstico no excluye la posibilidad de que se hagan aparentes las lesiones tumorales clásicas, como en nuestro caso, en el que únicamente aparecía un aracnoidocele inicial y pocos meses después se hizo evidente el engrosamiento del tallo hipofisario y la metástasis osteolítica.

Abstract Central diabetes insipidus is a disorder produced by total or partial deficiency in the synthesis or secretion of antidiuretic hormone caused by hypothalamic-hypophyseal dysfunction, which results in a polyuric syndrome with severe polydipsia. This disorder may be primary when it is caused by genetic abnormalities, or secondary to postoperative, traumatic, infectious or tumoral lesions. This paper reports the case of a male patient, admitted at the endocrine clinic at the age of 15 with a severe polyuric syndrome. At the time of diagnosis of diabetes insipidus, a magnetic resonance was performed demonstrating only a sellar arachnoidocele; however, in the follow-up study conducted eight months later, we found a marked thickening of the hypophyseal stalk and an osteolytic lesion on the left parietal bone. The patient was treated by surgical resection of the lytic parietal bone lesion, followed by 12 cycles of chemotherapy. Two years later, we confirmed the diagnosis of hypogonadotropic hypogonadism. Absent lesions at moment of diagnosis do not exclude the possibility of the appearance of classic tumoral lesions on follow-up studies, like in our case in which only the initial aracnoidocele appeared, but few months later a thickening of the hypophyseal stalk and bone metastasis became evident.