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The vaccine against SARS-CoV-2 has demonstrated proven efficacy to control the disease, rare adverse effects due to this therapy are still being studied, some of them renal. It is suggested that an inadequate immune response could be the cause of glomerular diseases associated with vaccination.We describe a 26-year-old patient, with no significant history, received immunity from the SARS-CoV-2 vaccine (Sinopharm), after which he began with proteinuria in the nephrotic range. Proteinuria: 24g in 24 hours. Albumin: 2.36 mg/dl. COVID-19 test negative. Renal biopsy was performed with ultrasound guidance, with anatomopathological result of Focal and Segmental Glomerulosclerosis, tip variant, observing 17 glomeruli. The patient was hospitalized and received immunosuppression with pulses of methylprednisolone, oral prednisone 1mg/kg/day, atorvastatin 20mg/day, antiplatelet therapy with ASA 100mg/day, omeprazole 20mg/day, and trimethoprim-sulfamethoxazole prophylaxis. Two weeks later, the patient had a weight loss (10 kg), the edemas decreased significantly. Four weeks after starting treatment, she presented proteinuria <500 mg/day, which at the moment is within normal values. The development of de Novo focal segmental glomerulosclerosis is possible, after administration of the SARS-CoV-2 vaccine, and that responds to the use of corticosteroids., La vacuna contra el SARS-CoV-2 ha demostrado eficacia comprobada para el control de la enfermedad, sin embargo, aún se encuentra en estudio los efectos adversos no comunes debido a esta terapia, algunos de tipo renal. Se plantea que una respuesta inmunológica no adecuada podría ser la causa de enfermedades glomerulares asociada a la vacunación. Se reporta el caso de una paciente de 26 años, sin antecedentes de importancia, recibió la inmunidad por la vacuna de SARS-CoV-2 (Sinopharm), posterior a ello inició con proteinuria en rango nefrótico (proteinuria: 24gr en 24 horas), además tuvo albúmina de 2,36 mg/dL y tuvo prueba COVID-19 negativo. Se le realizó biopsia renal con guía ecográfica, con resultado anatomo-patológico de glomeruloesclerosis focal y segmentaria, variante de punta, observándose 17 glomérulos. La paciente fue hospitalizada y recibió inmunosupresión con pulsos de metilprednisolona, prednisona vía oral (1mg/kg/día), atorvastatina (20mg/día), antiagregación plaquetaria con AAS (100mg/día), omeprazol (20mg/día) y profilaxis con trimetoprima-sulfametoxazol. Dos semanas después, la paciente, tuvo una baja de peso (10 kg) y los edemas disminuyeron notoriamente. Cuatro semanas de iniciar el tratamiento, presentó proteinuria < 500 mg/día, la cual al momento se encuentra en valores normales. Es posible el desarrollo de una glomeruloesclerosis focal y segmentaria de novo, tras la administración de la vacuna contra el SARS-CoV-2, y que respondió al uso de corticoides.

High-risk childhood leukemia has a poor prognosis because of treatment failure and toxic side effects of therapy. Drug encapsulation into liposomal nanocarriers has shown clinical success at improving biodistribution and tolerability of chemotherapy. However, enhancements in drug efficacy have been limited because of a lack of selectivity of the liposomal formulations for the cancer cells. Here, we report on the generation of bispecific antibodies (BsAbs) with dual binding to a leukemic cell receptor, such as CD19, CD20, CD22, or CD38, and methoxy polyethylene glycol (PEG) for the targeted delivery of PEGylated liposomal drugs to leukemia cells. This liposome targeting system follows a "mix-and-match" principle where BsAbs were selected on the specific receptors expressed on leukemia cells. BsAbs improved the targeting and cytotoxic activity of a clinically approved and low-toxic PEGylated liposomal formulation of doxorubicin (Caelyx) toward leukemia cell lines and patient-derived samples that are immunophenotypically heterogeneous and representative of high-risk subtypes of childhood leukemia. BsAb-assisted improvements in leukemia cell targeting and cytotoxic potency of Caelyx correlated with receptor expression and were minimally detrimental in vitro and in vivo toward expansion and functionality of normal peripheral blood mononuclear cells and hematopoietic progenitors. Targeted delivery of Caelyx using BsAbs further enhanced leukemia suppression while reducing drug accumulation in the heart and kidneys and extended overall survival in patient-derived xenograft models of high-risk childhood leukemia. Our methodology using BsAbs therefore represents an attractive targeting platform to potentiate the therapeutic efficacy and safety of liposomal drugs for improved treatment of high-risk leukemia.

Dogs are uniquely associated with human dispersal and bring transformational insight into the domestication process. Dingoes represent an intriguing case within canine evolution being geographically isolated for thousands of years. Here, we present a high-quality de novo assembly of a pure dingo (CanFam_DDS). We identified large chromosomal differences relative to the current dog reference (CanFam3.1) and confirmed no expanded pancreatic amylase gene as found in breed dogs. Phylogenetic analyses using variant pairwise matrices show that the dingo is distinct from five breed dogs with 100% bootstrap support when using Greenland wolf as the outgroup. Functionally, we observe differences in methylation patterns between the dingo and German shepherd dog genomes and differences in serum biochemistry and microbiome makeup. Our results suggest that distinct demographic and environmental conditions have shaped the dingo genome. In contrast, artificial human selection has likely shaped the genomes of domestic breed dogs after divergence from the dingo.

Objective: To assess the relationship between metabolic control and peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (DM2) in Maria Auxiliadora Hospital (MAH). Material and methods: This is a sex-matched case-control study with a secondary analysis based on data from the endocrinology service of MAH, Lima, Peru. Cases with PAD were defined as those with <0.9 ankle-to-arm index (ATAI). Controls were those subjects with ATAI between 0.9 and 1.3, under a 4:1 relationship with respect to cases. Poor metabolic control was defined as follows: glycated hemoglobin ≥7%, systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, HDL cholesterol <40 mg/dL (males) or >50 mg/dL (females), LDL cholesterol ≥100 mg/dL and triglycerides ≥150 mg/dL. Odds ratio values for poor metabolic control were calculated, both crude and adjusted, according to the presence or PAD, by using logistic regression. Results: We included 39 cases and 157 controls. A great majority of cases (94.9%) and of controls (82.2%) had poor metabolic control, respectively (p<0.05). When adjusting for age, time with diabetes, body mass index, and history of tobacco use, patients with poor metabolic control had OR at 5.45 (95% CI: 1.17 – 25.2) and p= 0.030 for having peripheral arterial disease, as defined by ATAI <0.9.Conclusion: Poor metabolic control showed and independent relationship with PAD in DM2 patients in Maria Auxiliadora Hospital. If therapy was only centered in glycemic control, it would increase the burden of disease of macrovascular complications, Objetivo: Evaluar la relación entre control metabólico y enfermedad arterial periférica (EAP) en pacientes con diabetes mellitus tipo 2 (DM2) del hospital María Auxiliadora (HMA). Material y métodos: Estudio caso-control pareado para sexo, de un análisis secundario basado en datos del servicio de endocrinología del HMA, Lima-Perú. Los casos con EAP, fueron aquellos con índice tobillo-brazo (ITB) < 0,9. Los controles fueron aquellos con ITB entre 0,9 y 1,3 en una relación 4:1 con respecto a los casos. Se definió como mal control metabólico si presentaron al menos uno de las siguientes: hemoglobina glicosilada ≥ 7 %, presión arterial sistólica ≥ 140 mm Hg, presión arterial diastólica ≥ 90 mm Hg, colesterol HDL< 40 mg/dl (varón) o < 50 mg/dl (mujer), colesterol LDL ≥ 100 mg/dl y triglicéridos ≥ 150 mg/dl. Se calculó el Odds ratio (OR) de mal control metabólico, tanto crudo como ajustado, según presencia de EAP mediante regresión logística. Resultados: Incluimos a 39 casos y 157 controles. Un 94,9 % y 82,2 % de los casos y controles presentaron mal control metabólico respectivamente (p<0,05). Al ajustar a edad, tiempo de diabetes, índice de masa corporal y antecedente de tabaco, los pacientes con mal control metabólico presentaron un OR de 5,45; (IC 95 % 1,17 – 25,2); p=0,030 de presentar enfermedad arterial periférica definido por ITB<0,9. Conclusión: El mal control metabólico presenta una relación independiente con EAP en pacientes con DM2 del Hospital María Auxiliadora. Metas terapéuticas centradas solo en la glicemia, elevarían la carga de enfermedad de complicaciones macrovasculares.

This chapter compares contextual factors and employer related CSR and non-CSR preferences of young job seekers in three Anglo countries: Australia, Ireland, and the United States of America (US). Country specific preferences are compared to the average preferences of the global sample, which includes all countries evaluated in this book. The results indicate higher concern by the Australian and the US sample for all areas of CSR when compared to the global sample. Moreover, while Australian respondents and, to a lesser degree US respondents attach a relatively high importance to attributes related to corporate socio-ecological responsibility and ethics and governance, Irish students value general workplace and company related attributes higher when making employment decisions.

La aplicación de la biotecnología permite aumentar la eficiencia reproductiva y el progreso genético del ganado vacuno. La presente investigación tuvo como objetivo comparar la capacidad de desarrollo de embriones producidos in vitro provenientes de Bos indicus y Bos taurus. Se evaluaron ovocitos colectados en los mismos periodos y épocas del año de estas subespecies; las donadoras estuvieron bajo las mismas condiciones de manejo, tanto sanitarias como nutricionales y sin estimulo hormonal. Se aplicó la prueba de Fisher para comparar el porcentaje de ovocitos viables y el porcentaje de embriones producidos por ambas subespecies y prueba t-student con nivel de significancia p:<0.05. Hubo diferencias estadísticamente significativas en la producción de embriones (28.6 % vs 38.6 %) para Bos taurus y Bos indicus, respectivamente. Se concluye a partir de los resultados obtenidos, que la subespecie Bos indicus tienen mayor capacidad de producción de embriones en comparación con la subespecie Bos Taurus.

The dingo is Australias iconic top order predator and arrived on the continent between 5,000 8,000 years ago. To provide an unbiased insight into its evolutionary affiliations and biological interactions, we coupled long-read DNA sequencing with a multiplatform scaffolding approach to produce an ab initio genome assembly of the desert dingo (85X coverage) we call CanLup_DDS. We compared this genome to the Boxer (CanFam3.1) and German Shepherd dog (CanFam_GSD) assemblies and characterized lineage specific and shared genetic variation ranging from single to megabase pair sized variants. We identified 21,483 dingo-specific and 16,595 domestic dog-specific homozygous structural variants mediating genic and putative regulatory changes. Comparisons between the dingo and domestic dog builds detected unique inversions on Chromosome 16, structural variations in genes linked with starch metabolism, and seven differentially methylated genes. To experimentally assess genomic differences 17 dingoes and 15 German Shepherd dogs were fed parallel diets for 14 days. In dingoes, low AMY2B copy number and serum amylase levels are linked with high cholesterol and LDL levels. Gut microbiome analyses revealed enrichment of the family Clostridiaceae, which can utilize complex resistant starch, while scat metabolome studies identified high phenylethyl alcohol concentrations that we posit are linked with territory marking. Our study provides compelling genomic, microbiome and metabolomic links showing the dingo has distinct physiology from domestic breed dogs with a unique role in the ecosystem.

The first dental proteomic profile of Iron Age individuals (ca. 2000–1000 years B.P.), collected from the site of Long Long Rak rock shelter in northwest Thailand is described. A bias toward the preservation of the positively charged aromatic, and polar amino acids is observed. It is evident that the 212 proteins identified (2 peptide, FDR <1%) comprise a palimpsest of alterations that occurred both ante-mortem and post-mortem. Conservation of amino acids within the taphonomically resistant crystalline matrix enabled the identification of both X and Y chromosome linked amelogenin peptides. A novel multiple reaction monitoring method using the sex specific amelogenin protein isoforms is described and indicate the teeth are of male origin. Functional analysis shows an enrichment of pathways associated with metabolic disorders and shows a capacity for harboring these conditions prior to death. Stable isotope analysis using carbon isotopes highlights the strongly C 3 based (≈80%) diet of the Long Long Rak cemetery people, which probably comprised rice combined with protein from freshwater fish among other food items. The combination of proteomics and stable isotope analysis provides a complementary strategy for assessing the demography, diet, lifestyle, and possible diseases experienced by ancient populations.

We give direct experimental evidence for the observation of the full transverse self-modulation of a long, relativistic proton bunch propagating through a dense plasma. The bunch exits the plasma with a periodic density modulation resulting from radial wakefield effects. We show that the modulation is seeded by a relativistic ionization front created using an intense laser pulse copropagating with the proton bunch. The modulation extends over the length of the proton bunch following the seed point. By varying the plasma density over one order of magnitude, we show that the modulation frequency scales with the expected dependence on the plasma density, i.e., it is equal to the plasma frequency, as expected from theory. © 2019 authors. Published by the American Physical Society.

We measure the effects of transverse wakefields driven by a relativistic proton bunch in plasma with densities of 2.1×1014 and 7.7×1014 electrons/cm3. We show that these wakefields periodically defocus the proton bunch itself, consistently with the development of the seeded self-modulation process. We show that the defocusing increases both along the bunch and along the plasma by using time resolved and time-integrated measurements of the proton bunch transverse distribution. We evaluate the transverse wakefield amplitudes and show that they exceed their seed value (< 15 MV=m) and reach over 300 MV=m. All these results confirm the development of the seeded self-modulation process, a necessary condition for external injection of low energy and acceleration of electrons to multi-GeV energy levels.