SEROEPIDEMIOLOGICAL SCREENING OF LEISHMANIA INFECTION IN DOGS AND CATS: THE ROLE OF THE VETERINARIAN IN A HIGHLY ENDEMIC AREA IN SICILY

Western Sicily is an active focus for canine and feline leishmaniosis in the Mediterranean area. The results of the present study indicate a high exposure rate to Leishmania (about 33% dogs and 44% cats result positive or suspected) in a random population, suggesting that they are infected with L. infantum. Moreover, 5 dogs and 1 cat previously classified as apparently healthy were seropositive with a titer ≥1:160. In conclusion, veterinary surveillance of dogs/cats could help to control the increase of L. infantum infections, especially in areas of high endemicity

SEROEPIDEMIOLOGICAL SCREENING OF LEISHMANIA INFECTION IN DOGS AND CATS: THE ROLE OF THE VETERINARIAN IN A HIGHLY ENDEMIC AREA IN SICILY

BACKGROUND Leishmaniosis is a zoonotic disease caused by Leishmania spp. with a wide spectrum of clinical signs, lymphadenomegaly, skinocular lesions, weight loss, signs of renal failure [1,2]. Many subclinical cases of leishmaniasis without illness could play an important role in the maintenance of Leishmania infection in endemic areas. Veterinary surveillance of dogs/cats owners could help to update the seroprevalence status of Leishmania infantum infection in a random court of sick and apparently healthy dogs and cats from western Sicily (Bagheria and neighboring areas) using indirect fluorescent antibody test (IFAT). MATERIAL AND METHODS A total of 268 dogs and 9 cats living in western Sicily were randomly sampled during the 2020 year. Specific antibodies to L. infantum were detected using the IFAT against in-house cultured promastigotes. Leishmania strain was used as an antigen fixed on multispot microscope slides. The feline and canine sera were both prepared by serial 2-fold dilutions (1:40 to 1:5120) in phosphate buffered saline and added to the antigen-coated wells. Fluorescent anti-cat/anti-dog immunoglobulin G antibody was used for detection. CONCLUSION Western Sicily is an active focus for canine and feline leishmaniosis in the Mediterranean area. The results of the present study indicate a high exposure rate to Leishmania (about 33% dogs and 44% cats result positive or suspected) in a random population, suggesting that they are infected with L. infantum. Moreover, 5 dogs and 1 cat previously classified as apparently healthy were seropositive with a titer ≥1:160. In conclusion, veterinary surveillance of dogs/cats could help to control the increase of L. infantum infections, especially in areas of high endemicity. RESULTS 49/268 (18.3%) sampled dogs tested positive to IFAT with a titer ≥1:160 and 40/268 (15%) tested suspected (titers 1:40-1:80), for L.infantum infection (Table 1). An additional 2/9 (22.2%) cats were seropositive with a titer of 1:160 and 2/9 (22.2%) cats were seropositive with a titer of 1:80 (Table 1). Figure 1 shows geographical distribution of L. infantum seroprevalenc in dogs/cats sampled from western Sicily. CONCLUSION Western Sicily is an active focus for canine and feline leishmaniosis in the Mediterranean area. The results of the present study indicate a high exposure rate to Leishmania (about 33% dogs and 44% cats result positive or suspected) in a random population, suggesting that they are infected with L. infantum. Moreover, 5 dogs and 1 cat previously classified as apparently healthy were seropositive with a titer ≥1:160. In conclusion, veterinary surveillance of dogs/cats could help to control the increase of L. infantum infections, especially in areas of high endemicity

Improving physical activity levels in primary schools: Slackline Training education strategy

Physical education (PE) can be considered the focus of cognitive and social physical literacy (PL) school programs. In primary school, the PL of children is fundamental, both to raise levels of motivation, confidence and competence and to educate an active lifestyle. Slacklining (SLK) is based on the use of a support band, stretched between two solid fixed supports, which stimulates the balance of the body and provides a high variability of movement. The article proposes situations of SLK with which to increase levels of physical activity to expand curriculum planning, in primary school, and offer children educational experiences in which to solicit both psycho-motor and motivational and social aspects. In other words, it is about involving children, through engaging and fun proposals, in the acquisition of an active lifestyle that will last even in later ages

FELINE LEISHMANIASIS: SEROLOGICAL AND MOLECULAR DETECTION OF AN EMERGENT DISEASE IN A NON-ENDEMIC AREA OF NORTHERN ITALY

In recent decades feline leishmaniosis (FeL) has become an emerging disease, also in non-endemic areas for the canine infection. This study updates the epidemiological status for FeL in cats in northern Italy and compares results with previous studies of the same feline population. Co-infections with feline retroviruses FIV and Field were also investigated. Stray, shelter and owned cats from different cities in the Lombardy region of northern Italy, were prospectively randomly sampled between January 2020 and May 2021. A total of 255 cats were tested for L. infantum: 240/255 for antibodies by IFAT and 234/255 and 198/255 for Leishmania DNA by PCR on whole blood and lymph nodes, respectively. Rapid ELISA test was used to detect FIV or FeLV infection. Overall, 26/255 (10.2%) cats tested positive for L. infantum: in 8/26 cats Leishmania DNA was found in popliteal lymph nodes (Leishmania/ml range from 15 to 60), 6/26 were PCR positive on whole blood (Leishmania/ml range from 5 to 80) and 15/26 IFAT seropositive at titers ranging from 1:80 to 1:320. Two Leishmania infected cats were also FIV+FeLV coinfected, another was FIV positive and one was FeLV positive. A high prevalence of FeL was found in a non-endemic area of northern Italy, with an increasing trend in infection rates

Mutations in Thyroid Hormone Beta Receptor Gene Identified in Children with Clinical Resistance to Thyroid Hormones

Introduction: Patients with resistance to thyroid hormones(RTH) show different clinical features. Several mutations have been identified in them.Objective:To describe patients followed up since 2006 with RTH suspicion evaluated for mutations in thyroid hormone beta receptor(THRß)gene.Methods:Children were followed up in our Endocrinology Department.Patient 1:10-yr-old boy with elevated T3, T4 and free T4, normal TSH in routine thyroid testing requested for overweight. Patient 2:0.7-yr- old boy with Down syndrome and elevated T3, T4 and free T4, normal TSH.Patient 3:Boy with abnormal results on neonatal screening, with elevated T3, T4, free T4 and TSH.Patient 4:4.7?yr-old girl with elevated T3, T4 and free T4, normal TSH in routine thyroid testing requested for low weight.Patient 5: 1-yr- old boy with elevated T3, T4 and free T4, normal TSH in routine thyroid testing requested for low weight.Patient 6:Boy with congenital hypothyroidism diagnosed by screening with elevated T3, T4, free T4 and TSH.Clinical manifestations:Patients 1, 4 and 5 showed palpitations, tachycardia.Familial antecedents: Patient 3 has two brothers with similar RTH profile. Patient 4 had a sister who died at 3 months of age and mother with confirmed RTH. Patient 6 had an aunt with RTH profile.Thyroid ultrasound. All patients had normal gland size except patient 6 who had an hypoplastic gland. Patient 4 showed goiter at follow up.Treatment:Patient 1 received metimazol; patients 1,4 and 5 beta blockers and patient 6 levothyroxine.Molecular biology analysis: genomic DNA was isolated from blood cells and the exons 7-10 of the THRß gene, including the flanking intronic regions were amplified by PCR. DNA sequences from each amplified fragment were performed with the Taq polymerase-based chain terminator method and using the specific forward and reverse THRß primers. Results.Direct sequence analysis revealed a novel missense mutation in exon 10 in patient 3, c.1329G>T transvertion that results in a p.K443N substitution and two known missense mutations: c.1357C>A, p.P453T (Patient 1)in exon 10 and c.949G>A, p.A317T (Patient 4) in exon 9.Conclusion:THRß gene mutations were found in half of the patients with RTH, including a new mutation.Although goiter is a common feature in RTH, only one patient presented it.These findings support the importance of searching THRßgene mutations in suspected individuals to achieve an adequate follow-up and treatment in patients with RHT.Fil: Gonzáles, Viviana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Balbi, Viviana A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Morin, Analía. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Reinoso, Andrea. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Vitale, Laura. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Ricci, Jaime. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Espósito, Mariela. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Martín, Rodrigo. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Tournier, Andrea L.. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Adrover, Ezequiela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Molina, Maricel Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Targovnik, Hector Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Rivolta, Carina Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaXXVIII Congreso Latinoamericano de Endocrinología PediátricaFlorianópolisBrasilSociedad Latinoamericana de Endocrinología Pediátric

Expression of CLAVATA3 fusions indicates rapid intracellular processing and a role of ERAD

The 12 amino acid peptide derived from the Arabidopsis soluble secretory protein CLAVATA3 (CLV3) acts at the cell surface in a signalling system that regulates the size of apical meristems. The subcellular pathway involved in releasing the peptide from its precursor is unknown. We show that a CLV3-GFP fusion expressed in transfected tobacco protoplasts or transgenic tobacco plants has very short intracellular half-life that cannot be extended by the secretory traffic inhibitors brefeldin A and wortmannin. The fusion is biologically active, since the incubation medium of protoplasts from CLV3-GFP-expressing tobacco contains the CLV3 peptide and inhibits root growth. The rapid disappearance of intact CLV3-GFP requires the signal peptide and is inhibited by the proteasome inhibitor MG132 or coexpression with a mutated CDC48 that inhibits endoplasmic reticulum-associated protein degradation (ERAD). The synthesis of CLV3-GFP is specifically supported by the endoplasmic reticulum cha- perone endoplasmin in an in vivo assay. Our results indicate that processing of CLV3 starts intracellularly in an early compartment of the secretory pathway and that ERAD could play a regulatory or direct role in the active peptide synthesis

Initial geoarcheaological study of the formation of rockshelters and their fillings in Punta Pórfido (Río Negro, Argentina)

En la costa semiárida del norte de Patagonia (Golfo San Matías, Río Negro) se observan serranías constituidas por riolitas que ilustran diferentes etapas en la evolución de cavidades rocosas. Un estudio comparativo sobre las mismas en el área de Punta Pórfido permitió comenzar a evaluar los procesos de formación de aleros y sus rellenos sedimentarios. La morfología de las cavidades eneste sector resulta del patrón romboidal de diaclasas que presenta la roca de caja y de procesos de meteorización, principalmente el desarrollo de tafoni. Los rellenos se hallan constituidos principalmente por derrubios tamaño grava y bloque derivados de la meteorización de la riolita, a lo que se suma el aporte de sedimentos finos de origen eólico y de sales marinas que han colaborado en la preservación de restos orgánicos inusuales. En la principal cavidad relevada, el Alero 2, se realizaron dos excavaciones y cuatro dataciones radiocarbónicas que proporcionaron edades sobre carbón entre ca. 2200 y 7500 años cal. AP. En esta contribución se presentan los resultados iniciales del estudio geoarqueológico de estas cavidades en la zona costera de Punta Pórfido, orientado a comprender su desarrollo y algunas propiedades del registro arqueológico y tafonómico que contienen sus rellenos.Along the semi-arid coast of northern Patagonia (Golfo San Matías, Río Negro) mountain ranges composed of rhyolites illustrate different stages in the evolution of rock cavities. A comparative study carried out in the Punta Pórfido area allows us to evaluate rockshelter formation processes and their sedimentary fillings. Cavity morphology in this sector results from the romboidal pattern of joints in the volcanic rock and weathering processes, mainly the development of tafoni. The fillings are made up of gravel and blocks derived from the weathering of the rhyolite, with the contribution of fine sediments originating from wind and marine salts that have collaborated in the preservation of unusual organic remains. At the main cavity surveyed, Alero 2, two excavations were carried out and four radiocarbon dating samples determined the ages on charcoal to be between ca. 2200 and 7500 years cal. AP. In this contribution, we present the initial results of the geoarchaeological study of these cavities in the coastal area of Punta Pórfido to understand their development and some properties of the archaeological and taphonomic record contained in their fillings.Fil: Favier Dubois, Cristian Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano. Universidad Nacional del Centro de la Provincia de Buenos Aires. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano; ArgentinaFil: Herrera Villegas, Dalila Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; ArgentinaFil: Alcaraz, Ana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano. Universidad Nacional del Centro de la Provincia de Buenos Aires. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano; ArgentinaFil: Cardillo, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; ArgentinaFil: Vitale, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano. Universidad Nacional del Centro de la Provincia de Buenos Aires. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano; Argentin

In vitro and in vivo single-agent efficacy of checkpoint kinase inhibition in acute lymphoblastic leukemia

Background: Although progress in children, in adults, ALL still carries a dismal outcome. Here, we explored the in vitro and in vivo activity of PF-00477736 (Pfizer), a potent, selective ATP-competitive small-molecule inhibitor of checkpoint kinase 1 (Chk1) and with lower efficacy of checkpoint kinase 2 (Chk2). Methods: The effectiveness of PF-00477736 as single agent in B-/T-ALL was evaluated in vitro and in vivo studies as a single agent. The efficacy of the compound in terms of cytotoxicity, induction of apoptosis, and changes in gene and protein expression was assessed using different B-/T-ALL cell lines. Finally, the action of PF-00477736 was assessed in vivo using leukemic mouse generated by a single administration of the tumorigenic agent n-ethyl-n-nitrosourea. Results: Chk1 and Chk2 are overexpressed concomitant with the presence of genetic damage as suggested by the nuclear labeling for \u3b3-H2A.X (Ser139) in 68 % of ALL patients. In human B-and T-ALL cell lines, inhibition of Chk1/2 as a single treatment strategy efficiently triggered the Chk1-Cdc25-Cdc2 pathway resulting in a dose-and time-dependent cytotoxicity, induction of apoptosis, and increased DNA damage. Moreover, treatment with PF-00477736 showed efficacy ex vivo in primary leukemic blasts separated from 14 adult ALL patients and in vivo in mice transplanted with T-ALL, arguing in favor of its future clinical evaluation in leukemia. Conclusions: In vitro, ex vivo, and in vivo results support the inhibition of Chk1 as a new therapeutic strategy in acute lymphoblastic leukemia, and they provide a strong rationale for its future clinical investigation

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO