Isolation and characterization of polymorphic microsatellite loci for the three Iberian vipers, Vipera aspis, V. Latastei and V. seoanei by Illumina MiSeq sequencing.

BACKGROUND: European vipers (genus Vipera) are a well-studied taxonomic group, but the low resolution of nuclear sanger-sequenced regions has precluded thorough studies at systematic, ecological, evolutionary and conservation levels. In this study, we developed novel microsatellite markers for the three Iberian vipers, Vipera aspis, V. latastei and V. seoanei, and assessed their polymorphism in north-central Iberian populations. METHODS AND RESULTS: Genomic libraries were developed for each species using an Illumina Miseq sequencing approach. From the 70 primer pairs initially tested, 48 amplified reliably and were polymorphic within species. Cross-species transferability was achieved for 31 microsatellites loci in the three target species and four additional loci that were transferable to one species only. The 48 loci amplified in average seven alleles, and detected average expected and observed heterozygosities of 0.7 and 0.55, in the three genotyped populations/species (26 V. aspis, 20 V. latastei and 10 V. seoanei). CONCLUSIONS: Our study provides a selection of 48 polymorphic microsatellite markers that will contribute significantly to current knowledge on genetic diversity, gene flow, population structure, demographic dynamics, systematics, reproduction and heritability in these species, and potentially in other congeneric taxa.

Local niches explain coexistence in environmentally-distinct contact zones between Western Mediterranean vipers.

Species' ecological niches are frequently analysed to gain insights into how anthropogenic changes affect biodiversity. Coping with these changes often involves shifts in niche expression, which can disrupt local biotic interactions. Secondary contact zones, where competition and ecological segregation commonly occur, are ideal for studying the ecological factors influencing species' niches. In this study, we investigated the effect of climate and landscape factors on the ecological niches of two viper species, Vipera aspis and Vipera latastei, across three contact zones in northern Iberia, characterized by varying levels of landscape alteration. Using niche overlap tests, ecological niche models and spatial analyses we observed local variation in the expression of the species' niches across the three contact zones, resulting from the different abiotic and biotic conditions of each area. Rather than spatial niche segregation, we observed high niche overlap, suggesting niche convergence. A pattern of asymmetrical niche variation was identified in all contact zones, driven by species' climatic tolerances and the environmental conditions of each area. V. aspis generally exhibited a wider niche, except in the southernmost zone where the pure Mediterranean climate favored V. latastei. Human-induced landscape changes intensified niche asymmetry, by favoring the most generalist V. aspis over the specialist V. latastei, increasing habitat overlap, and likely competition. This study presents a comprehensive analysis of niche expression at range margins, anticipating a heightened impact of landscape changes in V. latastei. The methodological framework implemented here, and our findings, hold significant relevance for biodiversity management and conservation in human-impacted areas.

Phylogeographic and Paleoclimatic Modelling Tools Improve Our Understanding of the Biogeographic History of Hierophis viridiflavus (Colubridae).

Phylogeographic and paleoclimatic modelling studies have been combined to infer the role of Pleistocene climatic oscillations as drivers of the genetic structure and distribution of Mediterranean taxa. For the European whip snake, Hierophis viridiflavus, previous studies based on paleoclimatic modelling have depicted a low reliability in the pattern of past climatic suitability across the central Mediterranean Basin, which barely fits the species' genetic structure. In this study, we combined phylogeographic and paleoclimatic modelling tools to improve our understanding of the biogeographic history of H. viridiflavus, particularly extending the sampling and phylogeographic inferences to previously under-sampled regions. Phylogeographic analyses recovered two major clades that diverged at the beginning of the Pleistocene and had diversified in different ways by the late Pleistocene: the east clade (composed of three subclades) and the west clade (with no further structure). Paleoclimatic models highlighted the temperate character of H. viridiflavus, indicating range contractions during both the last inter-glacial and last glacial maximum periods. Range expansions from southern-located climatic refugia likely occurred in the Bølling-Allerød and Middle Holocene periods, which are supported by signals of demographic growth in the west clade and South-East-North subclade. Overall, this work improves our understanding of the historical biogeography of H. viridiflavus, providing further insights into the evolutionary processes that occurred in the Mediterranean Basin hotspot.

One Size Fits All-Venomics of the Iberian Adder (Vipera seoanei, Lataste 1878) Reveals Low Levels of Venom Variation across Its Distributional Range.

European vipers (genus Vipera) are medically important snakes displaying considerable venom variation, occurring at different levels in this group. The presence of intraspecific venom variation, however, remains understudied in several Vipera species. Vipera seoanei is a venomous snake endemic to the northern Iberian Peninsula and south-western France, presenting notable phenotypic variation and inhabiting several diverse habitats across its range. We analysed the venoms of 49 adult specimens of V. seoanei from 20 localities across the species' Iberian distribution. We used a pool of all individual venoms to generate a V. seoanei venom reference proteome, produced SDS-PAGE profiles of all venom samples, and visualised patterns of variation using NMDS. By applying linear regression, we then assessed presence and nature of venom variation between localities, and investigated the effect of 14 predictors (biological, eco-geographic, genetic) on its occurrence. The venom comprised at least 12 different toxin families, of which five (i.e., PLA2, svSP, DI, snaclec, svMP) accounted for about 75% of the whole proteome. The comparative analyses of the SDS-PAGE venom profiles showed them to be remarkably similar across the sampled localities, suggesting low geographic variability. The regression analyses suggested significant effects of biological and habitat predictors on the little variation we detected across the analysed V. seoanei venoms. Other factors were also significantly associated with the presence/absence of individual bands in the SDS-PAGE profiles. The low levels of venom variability we detected within V. seoanei might be the result of a recent population expansion, or of processes other than directional positive selection.

Optimization of Inhalation Technique Knowledge in the Pharmacies of Matosinhos Municipality, Portugal: An Intervention Project.

INTRODUCTION: The therapeutic approach to the most common respiratory diseases, asthma and chronic obstructive pulmonary disease (COPD), involves the use of inhalation devices. Its use is essential, but incorrect use is frequent, and learning and reviewing the technique is necessary for the adequate management of these diseases. OBJECTIVE: This study aims to increase the knowledge of health professionals from pharmacies in the municipality of Matosinhos, Portugal, about the correct inhalation technique. METHODS: The project developed from May 2022 to June 2023 was based on a training session for pharmacy professionals that took place after professionals completed a questionnaire and after evaluating each participant's inhalation technique by the authors using a checklist. Both were reapplied three months after the first evaluation. RESULTS: Fifteen pharmacies in Matosinhos, Portugal, were invited, of which eight agreed to participate, with a total of 16 health professionals (30.8% of professionals in these pharmacies). We found that professionals questioned and taught users more times about the inhalation technique and that a greater number of professionals considered they knew how to correctly perform the inhalation technique in the second assessment. It was also possible to verify statistically significant differences (p<0.001) between the mean of correct steps in the inhalation technique between the first and second assessments. There was also an improvement in the qualitative analysis of errors in the inhalation technique. In the first assessment, the inhalation devices with the lowest percentage of correct steps were Forspiro® and Respimat®. In the second evaluation, the Diskus® and Ellipta® devices obtained 100% correct steps, with the K-haler® being the device with the lowest percentage. CONCLUSIONS: This study confirms the effectiveness of continuous training for health professionals and the importance of multidisciplinary cooperation in teaching inhalation techniques. Other studies are needed to complement these results, particularly with representative samples of the general population, or assessing the impact of this intervention in patients with respiratory diseases.

Canine idiopathic orbital inflammation: A case series of four affected dogs (five orbits).

PURPOSE: In humans, idiopathic orbital inflammation (IOI) is a diagnosis attributed to benign, inflammatory orbital conditions without identifiable local or systemic cause. We describe the clinical signs, imaging and histopathological findings, management and outcome of four dogs diagnosed with IOI. METHODS: Multicentric retrospective study. RESULTS: A total of four dogs (five orbits) of three different breeds (three cases were English Springer Spaniels [ESS] or ESS-cross) and ages ranging from 3 to 12 years were included. Initial presenting signs were unilateral and included exophthalmos, enophthalmos, globe deviation, thickening and protrusion of the third eyelid and conjunctival hyperemia. Computed tomography and magnetic resonance imaging identified heterogeneous space-occupying, contrast-enhancing orbital lesions in all cases. Sparing of the retrobulbar space was detected in four of five orbits. Histopathology revealed mixed inflammatory infiltrates of lymphocytes, plasma cells, and histiocytes. Immunohistochemistry was performed in two cases highlighting the presence of histiocytes and lymphocytes, predominantly T cells. Resolution of clinical signs was achieved in two cases managed with oral immunosuppressant medication (corticosteroids alone or combined with cyclosporine or azathioprine), one went into spontaneous remission, one resolved with topical corticosteroids, and one underwent exenteration. Recurrence occurred in two cases within 15 months of initial diagnosis and required further immunosuppressant medication. One case developed signs in the contralateral orbit within 8 months of presentation. CONCLUSIONS: IOI is an uncommon condition in dogs. Its diagnosis relies on the combination of advanced imaging and histology. As in humans, it appears that spontaneous remission and recurrence may occur requiring long-term immunosuppressant medication.

Susceptibility of Sea Bream (Sparus aurata) to AIP56, an AB-Type Toxin Secreted by Photobacterium damselae subsp. piscicida.

Photobacterium damselae subsp. piscicida (Phdp) is a Gram-negative bacterium that infects a large number of marine fish species in Europe, Asia, and America, both in aquacultures and in the natural environment. Among the affected hosts are economically important cultured fish, such as sea bream (Sparus aurata), sea bass (Dicentrarchus labrax), yellowtail (Seriola quinqueradiata), and cobia (Rachycentron canadum). The best characterized virulence factor of Phdp is the Apoptosis-Inducing Protein of 56 kDa (AIP56), a secreted AB-type toxin that has been shown to induce apoptosis of sea bass phagocytes during infection. AIP56 has an A subunit that displays metalloprotease activity against NF-kB p65 and a B subunit that mediates binding and internalization of the A subunit in susceptible cells. Despite the fact that the aip56 gene is highly prevalent in Phdp isolates from different fish species, the toxicity of AIP56 has only been studied in sea bass. In the present study, the toxicity of AIP56 for sea bream was evaluated. Ex vivo assays showed that sea bream phagocytes are resistant to AIP56 cytotoxicity and that resistance was associated with an inefficient internalization of the toxin by those cells. Accordingly, in vivo intoxication assays revealed that sea bream is much more resistant to AIP56-induced lethality than sea bass. These findings, showing that the effect of AIP56 is different in sea bass and sea bream, set the basis for future studies to characterize the effects of AIP56 and to fully elucidate its virulence role in different Phdp susceptible hosts.

IL-31 and IL-8 in Cutaneous T-Cell Lymphoma: Looking for Their Role in Itch.

The itch associated with cutaneous T-cell lymphoma (CTCL), including Mycosis Fungoides (MF) and Sézary syndrome (SS), is often severe and poorly responsive to treatment with antihistamines. Recent studies have highlighted the possible role of interleukins in nonhistaminergic itch. We investigated the role of IL-31 and IL-8 in CTCL, concerning disease severity and associated itch. Serum samples of 27 patients with CTCL (17 MF and 10 SS) and 29 controls (blood donors) were analyzed for interleukin- (IL-) 31 and IL-8; correlations with disease and itch severity were evaluated. IL-31 serum levels were higher in CTCL patients than in controls and higher in SS than in MF. Also, serum IL-31 levels were higher in patients with advanced disease compared to those with early disease, and they correlated positively with lactate dehydrogenase and beta 2-microglobulin levels, as well as with the Sézary cell count. Itch affected 67% of CTCL patients (MF: 47%; SS: 100%). Serum IL-31 levels were higher in itching patients than in controls and in patients without itching. There was no association between serum IL-8 and disease severity, nor with itching. Serum IL-8 levels correlated positively with peripheral blood leukocyte and neutrophil counts in CTCL patients. Our study suggests a role for IL-31 in CTCL-associated itch, especially in advanced disease and SS, offering a rational target for new therapeutic approaches. Increased serum IL-8 observed in some patients may be related to concomitant infections, and its role in exacerbating itch by recruiting neutrophils and promoting the release of neutrophil proteases deserves further investigation.

αIIbß3 variants in ten families with autosomal dominant macrothrombocytopenia: Expanding the mutational and clinical spectrum.

BACKGROUND: Rare pathogenic variants in either the ITGA2B or ITGB3 genes have been linked to autosomal dominant macrothrombocytopenia associated with abnormal platelet production and function, deserving the designation of Glanzmann Thrombasthenia-Like Syndrome (GTLS) or ITGA2B/ITGB3-related thrombocytopenia. OBJECTIVES: To describe a series of patients with familial macrothrombocytopenia and decreased expression of αIIbß3 integrin due to defects in the ITGA2B or ITGB3 genes. METHODS: We reviewed the clinical and laboratory records of 10 Portuguese families with GTLS (33 patients and 11 unaffected relatives), including the functional and genetic defects. RESULTS: Patients had absent to moderate bleeding, macrothrombocytopenia, low αIIbß3 expression, impaired platelet aggregation/ATP release to physiological agonists and low expression of activation-induced binding sites on αIIbß3 (PAC-1) and receptor-induced binding sites on its ligand (bound fibrinogen), upon stimulation with TRAP-6 and ADP. Evidence for constitutive αIIbß3 activation, occurred in 2 out of 9 patients from 8 families studied, but also in 2 out of 12 healthy controls. We identified 7 missense variants: 3 in ITGA2B (5 families), and 4 in ITGB3 (5 families). Three variants (αIIb: p.Arg1026Trp and p.Arg1026Gln and ß3: p.Asp749His) were previously reported. The remaining (αIIb: p.Gly1007Val and ß3: p.Thr746Pro, p.His748Pro and p.Arg760Cys) are new, expanding the αIIbß3 defects associated with GTLS. The integration of the clinical and laboratory data allowed the identification of two GTLS subgroups, with distinct disease severity. CONCLUSIONS: Previously reported ITGA2B and ITGB3 variants related to thrombocytopenia were clustered in a confined region of the membrane-proximal cytoplasmic domains, the inner membrane clasp. For the first time, variants are reported at the outer membrane clasp, at the transmembrane domain of αIIb, and at the membrane distal cytoplasmic domains of ß3. This is the largest single-center series of inherited macrothrombocytopenia associated with αIIbß3 variants published to date.

Thermal melanism explains macroevolutionary variation of dorsal pigmentation in Eurasian vipers.

Colouration may endorse thermoregulatory and antipredatory functions in snakes. The thermal melanism hypothesis predicts that dark-coloured individuals are ecologically favoured in cool climates. However, the loss of aposematic and cryptic colourations may imply high predation for melanistic snakes. Here, we used the monophyletic group of Eurasian vipers (subfamily Viperinae) to test whether an increase in the extent of dark area inside the characteristic zigzag dorsal pattern is associated to colder environments. We measured two colouration traits in zigzag-patterned individuals (number of dorsal marks and weighted pigmentation index) and used a phylogenetic comparative approach to explore macroevolutionary patterns of dorsal pigmentation and test whether its extent is associated to ecogeographic characteristics of lineages' ranges. Phylogenetically-naïve and phylogenetically-informed analyses yielded a significant association between the degree of pigmentation of the zigzag pattern and environmental variables such as solar radiation, elevation and latitude. The degree of pigmentation of the zigzag pattern is highlighted as an adaptive trait that matches range attributes mirroring cold environments irrespective of the phylogeny. These results constitute the first large-scale evidence supporting the thermal melanism hypothesis in snakes, opening new avenues of inquiry for the mechanisms that shape the evolution of colour phenotypes.

Interferon lambda rs368234815 ΔG/ΔG is associated with higher CD4+:CD8+ T-cell ratio in treated HIV-1 infection.

BACKGROUND: The objectives of this study were to investigate the relationships between polymorphisms at the interferon lambda (IFNL) locus and CD4+:CD8+ ratio normalisation in people living with HIV (PLWH) on effective antiretroviral therapy (ART); and to examine whether these polymorphisms influence the composition of T lymphocyte compartments in long-term treated HIV-1 infection. METHODS: A cross-sectional study in PLWH enrolled into the Mater Immunology study. We performed IFNL genotyping on stored samples and evaluated the association of IFNL single-nucleotide polymorphisms (rs368234815 and rs12979860) with CD4+:CD8+ ratio normalization (> 1) and expanded CD4+ and CD8+ T-cell subsets; CD45RO+CD62L+ (central-memory), CD45RO+ CD62L-(effector-memory) and CD45RO-CD62L+ (naïve), using logistic and linear regression models, respectively. RESULTS: 190 ambulatory PLWH recruited to the main study, 143 were included in the analysis (38 had no stored DNA and 9 no T-lymphocyte subpopulation). Of 143 included, the median age (IQR) was 45(39-48) years, 64% were male and 66% were of Caucasian ethnicity. Heterosexual-contact (36%), injecting drug-use (33%) and men who have sex with men (24%) were the most presented HIV-transmission risk groups. The majority of subjects (90.2%) were on ART with 79% of the cohort having an undetectable HIV-RNA (< 40 copies/ml) and the time since ART initiation was 7.5 (3.7-10.4) year. rs368234815 and rs12979860 displayed similar allelic frequencies, with minor alleles ΔG and T representing 39% and 42%, respectively, of circulating alleles. rs368234815 ΔG/ΔG minor homozygotes were significantly associated with increased odds for attaining a normalised CD4+:CD8+ ratio compared to rs368234815 T/T major homozygotes in PLWH virologically suppressed on effective ART (OR = 3.11; 95% CI [1.01:9.56]). rs368234815 ΔG/ΔG homozygosity was also significantly associated with lower levels of CD4+ effector memory T-cells (regression coefficient: - 7.1%, p = 0.04) and CD8+ naïve T-cell subsets were significantly higher in HIV-1 mono-infected PLWH with rs368234815 ΔG/ΔG (regression coefficient: + 7.2%, p = 0.04). CONCLUSIONS: In virally-suppressed, long-term ART-treated PLWH, rs368234815 ΔG/ΔG homozygotes were more likely to have attained normalisation of their CD4+:CD8+ ratio, displayed lower CD4+ effector memory and higher naive CD8+ T-cells. Further studies are needed to replicate our findings in other, larger and more diverse cohorts and to determine the impact of IFNL genetic-variation on CD4+:CD8+ ratio normalisation and clinical outcomes in PLWH.

Upregulated Wnt-11 and miR-21 Expression Trigger Epithelial Mesenchymal Transition in Aggressive Prostate Cancer Cells.

: Prostate cancer (PCa) is the second-leading cause of cancer-related death among men. microRNAs have been identified as having potential roles in tumorigenesis. An oncomir, miR-21, is commonly highly upregulated in many cancers, including PCa, and showed correlation with the Wnt-signaling axis to increase invasion. Wnt-11 is a developmentally regulated gene and has been found to be upregulated in PCa, but its mechanism is unknown. The present study aimed to investigate the roles of miR-21 and Wnt-11 in PCa in vivo and in vitro. First, different Gleason score PCa tissue samples were used; both miR-21 and Wnt-11 expressions correlate with high Gleason scores in PCa patient tissues. This data then was confirmed with formalin-fixed paraffin cell blocks using PCa cell lines LNCaP and PC3. Cell survival and colony formation studies proved that miR-21 involves in cells' behaviors, as well as the epithelial-mesenchymal transition. Consistent with the previous data, silencing miR-21 led to significant inhibition of cellular invasiveness. Overall, these results suggest that miR-21 plays a significant role related to Wnt-11 in the pathophysiology of PCa.

Budd-Chiari Syndrome and Acute Liver Failure: An Uncommon Presentation of Acute Myeloid Leukaemia.

Acute liver failure (ALF) is a rare entity, particularly in the context of Budd-Chiari syndrome (BCS). BCS is an uncommon disorder with multiple risk factors, most commonly myeloproliferative disorders. In BCS, active search and exclusion of underlying malignancy is mandatory, particularly in the context of ALF, as it may contraindicate liver transplantation (LT). We present the case of a healthy 29-year-old male, without known risk factors for liver disease, who presented to the emergency department with abdominal pain, ascites, and jaundice. BCS with consequent severe acute liver injury with rapid progression to ALF was diagnosed. The patient was listed for LT. The study of peripheral blood finally revealed myeloid blasts, and flow cytometry showed a population of blast cells with abnormal immunophenotypic profile (CD33+ and myeloperoxidase, MPO+). The bone marrow biopsy showed morphological and immunophenotypic aspects of acute myeloid leukaemia (AML) FAB M1. This diagnosis was considered a formal contraindication to LT, so the patient was delisted. ALF contraindicated rescue chemotherapy and AML contraindicated LT. The patient died 48 h after ICU admission. The search for underlying neoplasia is mandatory in the context of BCS, moreover with associated ALF, as it may limit lifesaving treatments and interventions to supportive and palliative care.

A falência hepática aguda (FHA) é uma entidade rara, particularmente no contexto da Síndrome de Budd-Chiari (SBC). A SBC é uma doença incomum com múltiplos fatores de risco, principalmente as doenças mieloproliferativas. Na SBC, a procura ativa e exclusão de malignidade subjacente é obrigatória, particularmente no contexto de FHA, já que pode contraindicar o transplante hepático (TH). Apresentamos o caso de um homem de 29 anos saudável, sem fatores de risco conhecidos para doença hepática que se apresentou no serviço de urgência com dor abdominal, ascite e icterícia. A SBC associada a lesão hepática severa com rápida progressão para FHA foi diagnosticada e o doente colocado em lista para TH. O estudo do sangue periférico finalmente revelou a presença de blastos mieloides e a citometria de fluxo a presença de uma população de blastos com perfil imunofenotípico anormal (CD33 + e mieloperoxidase (MPO) +). A biópsia da medula óssea mostrou aspetos morfológicos e imunofenotípicos de leucemia mieloide aguda (LMA) FAB M1. Este diagnóstico foi considerado uma contraindicação formal para o TH, pelo que o doente foi retirado de lista. Pela FHA a quimioterapia de resgate estava também contraindicada. O doente faleceu 48 horas após a admissão na UCI. O despiste de neoplasia subjacente é obrigatório no contexto de SBC, ainda mais com FHA, pois pode limitar o tratamento lifesaving a cuidados de suporte e paliativos.

Outcome of phacoemulsification in 71 cats: A multicenter retrospective study (2006-2017).

PURPOSE: To assess outcome of phacoemulsification in cats. METHODS: Records of 71 cats (82 eyes) from five referral centers were reviewed. Groups were divided by cause of cataract (congenital/juvenile [n = 32], traumatic [n = 33], and secondary to uveitis [n = 6]), and group comparisons were performed for the most common complications: postoperative ocular hypertension (POH), uveitis, corneal ulceration, synechia/dyscoria, and posterior capsular opacity (PCO) in three different time periods: immediately postoperatively, at 1-90 days, and at >90 days. RESULTS: Median follow-up was 198 days (interquartile range 64-518 days). The overall visual success rate of the cats with a 12-month follow-up was 92.6% (25/27 eyes). POH occurred in 35/82 (42.6%) eyes. Immediately postoperatively, uveitis was the most common complication in 28/82 eyes (34.1%) followed by corneal ulceration in 22/82 eyes (26.8%). At 1-90 days, uveitis in 41/81 eyes (50.6%) remained the most common complication, followed by synechia/dyscoria in 21/81 eyes (25.9%), corneal ulceration in 16/81 eyes (19.7%), and PCO in 15/81 eyes (18.5%). At >90 days, PCO in 17/47 eyes (36.1%), followed by synechia/dyscoria in 16/47 eyes (34%), was the most common complications. The number of eyes with synechia/dyscoria in the trauma group was higher (13/33 [39.3%]) than in the congenital/juvenile group (5/31 [16.1%]) at 1-90 days (P = .039). No statistical difference was found for the other group comparisons. Three eyes in total were enucleated owing to endophthalmitis, post-traumatic ocular sarcoma, and secondary glaucoma. CONCLUSION: Uveitis in the short-term and PCO and synechia/dyscoria in the long-term were the most common complications following phacoemulsification in cats.

Comparison of Maternal and Fetal Outcomes in Parturients With and Without a Diagnosis of Gestational Diabetes.

OBJECTIVE: The present study aims to compare the maternal and fetal outcomes of parturients with and without a gestational diabetes diagnosis. METHODS: A case-control study including parturients with (cases) and without (control) a gestational diabetes diagnosis, who delivered at a teaching hospital in Southern Brazil, between May and August 2018. Primary and secondary data were used. Bivariate analysis and a backward conditional multivariate logistic regression were used to make comparisons between cases and controls, which were expressed by odds ratio (OR), with a 95% confidence interval (95%CI) and a statistical significance level of 5%. RESULTS: The cases (n = 47) were more likely to be 35 years old or older compared with the controls (n = 93) (p < 0.001). The cases had 2.56 times greater chance of being overweight (p = 0.014), and a 2.57 times greater chance of having a positive family history of diabetes mellitus (p = 0.01). There was no significant difference regarding weight gain, presence of a previous history of gestational diabetes, height, or delivery route. The mean weight at birth was significantly higher in the infants of mothers diagnosed with diabetes (p = 0.01). There was a 4.7 times greater chance of macrosomia (p < 0.001) and a 5.4 times greater chance of neonatal hypoglycemia (p = 0.01) in the infants of mothers with gestational diabetes. CONCLUSION: Therefore, maternal age, family history of type 2 diabetes, obesity and pregestational overweightness are important associated factors for a higher chance of developing gestational diabetes.

OBJETIVO: O presente estudo tem como objetivo comparar os desfechos maternos e fetais das parturientes com e sem diagnóstico de diabetes gestacional. MéTODOS: Estudo caso-controle, incluindo parturientes com (casos) e sem (controle) diagnóstico de diabetes gestacional, que tiveram parto em um hospital de ensino no Sul do Brasil, entre maio e agosto de 2018. Foram utilizados dados primários e secundários. Análise bivariada e regressão logística multivariada condicional retrógrada foram utilizadas para fazer comparações entre casos e controles, expressas por razão de probabilidades (RP), com intervalo de confiança de 95% (IC95%) e nível de significância estatística de 5%. RESULTADOS: Os casos (n = 47) tiveram maior chance de ter idade superior a 35 anos em comparação com os controles (n = 93) (p < 0,001), chance 2,56 vezes maior de estarem acima do peso (p = 0,014), e chance 2,57 vezes maior de terem história familiar positiva de diabetes mellitus (p = 0,01). Não houve diferença significativa relacionada ao ganho de peso, história pregressa de diabetes gestacional, estatura ou via de parto. O peso médio ao nascer foi significativamente maior nos lactentes de mães com diabetes gestacional (p = 0,01). Houve 4,7 vezes maior chance de macrossomia (p < 0,001), e 5,4 vezes maior chance de hipoglicemia neonatal (p = 0,01) em lactentes de mães com diabetes gestacional. CONCLUSãO: Portanto, idade materna, história familiar de diabetes tipo 2, obesidade e excesso de peso pré-gestacional são importantes fatores associados a uma maior chance de desenvolvimento de diabetes gestacional.

Comparison of maternal and fetal outcomes in parturients with and without a diagnosis of gestational diabetes / Comparação de desfechos maternos e fetais entre parturientes com e sem o diagnóstico de diabetes gestacional

Abstract Objective The present study aims to compare the maternal and fetal outcomes of parturients with and without a gestational diabetes diagnosis. Methods A case-control study including parturients with (cases) and without (control) a gestational diabetes diagnosis, who delivered at a teaching hospital in Southern Brazil, between May and August 2018. Primary and secondary data were used. Bivariate analysis and a backward conditionalmultivariate logistic regression were used to make comparisons between cases and controls, which were expressed by odds ratio (OR), with a 95% confidence interval (95%CI) and a statistical significance level of 5%. Results The cases (n=47) weremore likely to be 35 years old or older compared with the controls (n=93) (p<0.001). The cases had 2.56 times greater chance of being overweight (p=0.014), and a 2.57 times greater chance of having a positive family history of diabetes mellitus (p=0.01). There was no significant difference regarding weight gain, presence of a previous history of gestational diabetes, height, or delivery route. The mean weight at birth was significantly higher in the infants of mothers diagnosed with diabetes (p=0.01). There was a 4.7 times greater chance of macrosomia (p<0.001) and a 5.4 times greater chance of neonatal hypoglycemia (p=0.01) in the infants of mothers with gestational diabetes. Conclusion Therefore, maternal age, family history of type 2 diabetes, obesity and pregestational overweightness are important associated factors for a higher chance of developing gestational diabetes.

Resumo Objetivo O presente estudo tem como objetivo comparar os desfechos maternos e fetais das parturientes com e sem diagnóstico de diabetes gestacional. Métodos Estudo caso-controle, incluindo parturientes com (casos) e sem (controle) diagnóstico de diabetes gestacional, que tiveram parto em um hospital de ensino no Sul do Brasil, entre maio e agosto de 2018. Foram utilizados dados primários e secundários. Análise bivariada e regressão logística multivariada condicional retrógrada foram utilizadas para fazer comparações entre casos e controles, expressas por razão de probabilidades (RP), com intervalo de confiança de 95% (IC95%) e nível de significância estatística de 5%. Resultados Os casos (n=47) tiveram maior chance de ter idade superior a 35 anos em comparação com os controles (n=93) (p<0,001), chance 2,56 vezes maior de estarem acima do peso (p=0,014), e chance 2,57 vezes maior de terem história familiar positiva de diabetes mellitus (p=0,01). Não houve diferença significativa relacionada ao ganho de peso, história pregressa de diabetes gestacional, estatura ou via de parto. O peso médio ao nascer foi significativamente maior nos lactentes de mães com diabetes gestacional (p=0,01). Houve 4,7 vezes maior chance de macrossomia (p<0,001), e 5,4 vezes maior chance de hipoglicemia neonatal (p=0,01) em lactentes de mães com diabetes gestacional. Conclusão Portanto, idade materna, história familiar de diabetes tipo 2, obesidade e excesso de peso pré-gestacional são importantes fatores associados a uma maior chance de desenvolvimento de diabetes gestacional.

Conhecimento do Acadêmico de Medicina sobre Cuidados Paliativos / Knowledge of Medical Students about Palliative Care

RESUMO Introdução O envelhecimento da população mundial traz consigo o aumento de doenças crônicas, sem ser acompanhado de melhoria na qualidade de vida ou do enfrentamento das enfermidades. Nesse contexto, os cuidados paliativos se enquadram como um modelo interdisciplinar que visa garantir o cuidado integral ao ser humano. Em contrapartida, a busca incessante pela cura pode resultar em um sentimento de negação e derrota frente à finitude da vida. Durante o processo de graduação médica, é necessário abordar essa temática para que os futuros profissionais se sintam adequadamente preparados e seguros, proporcionando o melhor para seus pacientes. Objetivo Avaliar o conhecimento sobre cuidados paliativos dos acadêmicos do internato do curso de graduação em Medicina da Universidade do Sul de Santa Catarina (Unisul), campus Tubarão. Método Realizou-se um estudo transversal por meio de questionário autoaplicável com 39 questões, agrupadas em 12 questões sociodemográficas e 27 questões objetivas sobre cuidados paliativos. A coleta de dados ocorreu de março a junho de 2018. Foram utilizados os testes de qui-quadrado (X2), exato de Fisher, razão de verossimilhança, Anova e teste de Tukey. O nível de significância estatística adotado foi de 5%. Resultados Participaram do estudo 188 acadêmicos, 56,9% do sexo feminino, com faixa etária prevalente entre 21 e 25 anos. Caso fossem pacientes oncológicos, 3,2% (6) dos entrevistados prefeririam a decisão de tratamento tomada somente pelo médico, sendo que, destes, 83,3% (5) eram do sexo masculino (p = 0,04); 49,5% (93) dos entrevistados se declararam preparados para enfrentar o processo de morte e luto, sendo que, destes, 54,8% (51) eram do sexo masculino (p = 0,005); 80,3% (151) dos acadêmicos negaram ter adquirido habilidades para comunicar más notícias, sendo que, destes, 62,9% (95) eram do sexo feminino (p < 0,001). O décimo semestre do curso apresentou a melhor média de acertos em questões relacionadas à farmacologia do tratamento da dor. A maioria dos acadêmicos considerou importante incorporar conteúdos sobre cuidados paliativos ao currículo, porém 68,1% não tinham interesse em atuar nessa área. Conclusão O ensino sobre a temática de cuidados paliativos durante a graduação de Medicina da Unisul resultou em um conhecimento adequado dos acadêmicos do internato, porém se observa dificuldade frente ao processo de morte e insegurança na abordagem de comunicações e na atitude médica. É necessário aprimorar o ensino de competências e habilidades na área, enfatizando o cuidado universal centrado no paciente e não somente na cura de doenças, bem como mobilizar esforços a fim de incentivar a autoestima dos acadêmicos.

ABSTRACT Introduction The aging of the world's population brings with it the increase in chronic diseases, although without a concomitant improvement in quality of life or management of the diseases. In this context, palliative care constitutes an interdisciplinary care model aiming at the integral care of the human being. In contrast, the incessant search for a cure can result in a sense of denial and defeat when facing death. Approaching this subject is necessary during medical school, so that future professionals feel adequately prepared and secure, thus providing the best care for their patients. Purpose To evaluate the knowledge on palliative care of undergraduate medical students of Universidade do Sul de Santa Catarina (UNISUL), campus Tubarão. Method A cross-sectional study was carried out through the application of an anonymous, self-administered questionnaire containing 39 questions, divided into 12 sociodemographic questions and 27 objective questions about palliative care. Data collection was carried out from March to June 2018. The Chi-square test (X2), Fisher`s exact test, Likelihood ratio, Analysis of Variance (ANOVA) and Tukey's tests were used. The significance level was set at 5%. Results A total of 188 medical students, of which 56.9% were females, at the prevalent age range between 21 and 25 years old participated in the study. In the case of an oncological patient, 3.2% (6) of the interviewees would prefer that treatment decisions be made only by the physician, of which 83.3% (5) were males (p = 0.04); 49.5% (93) of the interviewees declared themselves prepared to face the process of death and grief, of which 54.8% (51) were males (p = 0.005); 80.3% (151) of the students denied having acquired skills to communicate bad news, of which 62.9% (95) were females (p <0.001). The students at the 10th semester of the Medical course showed a better average of right answers to questions about the pharmacology of pain management. Most students considered important the incorporation of palliative care content in the curriculum, but 68.1% of them had no interest in working in this area. Conclusion In conclusion, the teaching of the palliative care subject during UNISUL's medical course resulted in an adequate knowledge of internship students; however, there is some difficulty when facing the process of death and insecurity when approaching the communication and medical attitude. It is necessary to improve the teaching of capabilities and skills in the area, emphasizing universal care focused on the patient and not only on curing diseases, as well as mobilizing efforts to encourage the students' self-esteem.

Cataracts in Labrador Retriever and Jack Russell Terrier From the United Kingdom: A Two-Year Retrospective Study.

Cataracts are among the most common ocular diseases, and are a leading cause of vision loss in humans and dogs. Jack Russell Terriers (JRT) and Labrador Retrievers (LR) are among the most popular canine breeds in the United Kingdom, and also among the most affected by cataracts. This study aimed to analyze the clinical features and the surgical outcome of cataracts in JRT and LR in an ophthalmologic reference Veterinary Hospital in the United Kingdom. For that purpose, medical records from JRT and LR diagnosed with cataracts between January 2015 and December 2016 were retrospectively evaluated. Data related to identification, clinical history, preoperative features, and surgical outcomes were analyzed. Forty-four dogs (81 eyes), including 26 JRT and 18 LR, were enrolled in the study. Mean ages were 10.2 ± 3.2 years in JRT and 8.5 ± 3.7 years in LR. Twenty-eight (63.6%) were females and 16 (36.4%) were males. Most dogs (84.1%) presented with bilateral cataracts. Nuclear and cortical cataracts were the most prevalent type in both breeds (JRT: n = 30, 61.2%; LR: n = 16, 50.0%), although subcapsular cataracts were also frequent in LR (n = 10, 31.3%). Significant differences in cataract location within the lens were detected between the two breeds (P = .002). Senile in JRT (n = 7) and genetic in LR (n = 7) were the most common etiologies. Concomitant ocular lesions were more frequent in dogs presented with cataracts in advanced stages, and included lens (n = 18; JRT: n = 15; LR: n = 3) and retinal alterations (n = 8; JRT: n = 2; LR: n = 6), and glaucoma (n = 6; JRT: n = 5; LR: n = 1). Thirty-three animals (75.0%, 51 eyes) were submitted to phacoemulsification with intraocular lens placement. Of these, 28 eyes (54.9%; JRT: n = 21; LR: n = 7) were visual, 19 eyes (37.3%; JRT: n = 11; LR: n = 8) presented impaired vision and four eyes (7.8%; JRT: n = 0; LR: n = 4) were blind at last clinical record. Postoperative complications were detected in 11 eyes (21.6%), and were more frequent in dogs presented with cataracts in advanced stages. These results and the multifactorial nature of cataracts call for further studies to identify and characterize the variables in a broader assessment, including other breeds and influencing factors.

KIT D816V Positive Acute Mast Cell Leukemia Associated with Normal Karyotype Acute Myeloid Leukemia.

INTRODUCTION: Mast cell (MC) leukemia (MCL) is extremely rare. We present a case of MCL diagnosed concomitantly with acute myeloblastic leukemia (AML). CASE REPORT: A 41-year-old woman presented with asthenia, anorexia, fever, epigastralgia, and diarrhea. She had a maculopapular skin rash, hepatosplenomegaly, retroperitoneal adenopathies, pancytopenia, 6% blast cells (BC) and 20% MC in the peripheral blood, elevated lactate dehydrogenase, cholestasis, hypoalbuminemia, hypogammaglobulinemia, and increased serum tryptase (184 µg/L). The bone marrow (BM) smears showed 24% myeloblasts, 17% promyelocytes, and 16% abnormal toluidine blue positive MC, and flow cytometry revealed 12% myeloid BC, 34% aberrant promyelocytes, a maturation blockage at the myeloblast/promyelocyte level, and 16% abnormal CD2-CD25+ MC. The BM karyotype was normal, and the KIT D816V mutation was positive in BM cells. The diagnosis of MCL associated with AML was assumed. The patient received corticosteroids, disodium cromoglycate, cladribine, idarubicin and cytosine arabinoside, high-dose cytosine arabinoside, and hematopoietic stem cell transplantation (HSCT). The outcome was favorable, with complete hematological remission two years after diagnosis and one year after HSCT. CONCLUSIONS: This case emphasizes the need of an exhaustive laboratory evaluation for the concomitant diagnosis of MCL and AML, and the therapeutic options.

A pilot study on the usefulness of peripheral blood flow cytometry for the diagnosis of lower risk myelodysplastic syndromes: the "MDS thermometer".

BACKGROUND: Immunophenotypic analysis of the bone marrow (BM) cells has proven to be helpful in the diagnosis of Myelodysplastic Syndromes (MDS). However, the usefulness of flow cytometry (FCM) for the detection of myelodysplasia in the peripheral blood (PB) still needs to be investigated. The aim of this pilot study was to evaluate the value of FCM-based PB neutrophil and monocyte immunophenotyping for the diagnosis of lower risk MDS (LR-MDS). METHODS: We evaluated by 8-color FCM the expression of multiple cell surface molecules (CD10, CD11b, CD11c, CD13, CD14, CD15, CD16, CD34, CD45, CD56, CD64 and HLA-DR) in PB neutrophils and monocytes from a series of 14 adult LR-MDS patients versus 14 normal individuals. RESULTS: Peripheral blood neutrophils from patients with LR-MDS frequently had low forward scatter (FSC) and side scatter (SSC) values and low levels of CD11b, CD11c, CD10, CD16, CD13 and CD45 expression, in that order, as compared to normal neutrophils. In addition, patients with LR-MDS commonly display a higher fraction of CD14+CD56+ and a lower fraction of CD14+CD16+ monocytes in the PB. Based on these results, we proposed an immunophenotyping score based on which PB samples from patients with LR-MDS could be distinguished from normal PB samples with a sensitivity 93% and a specificity of 100%. In addition, we used this score to construct the MDS Thermometer, a screening tool for detection and monitoring of MDS in the PB in clinical practice. CONCLUSIONS: Peripheral blood neutrophil and monocyte immunophenotyping provide useful information for the diagnosis of LR-MDS, as a complement to cytomorphology. If validated by subsequent studies in larger series of MDS patients and extended to non-MDS patients with cytopenias, our findings may improve the diagnostic assessment and avoid invasive procedures in selected groups of MDS patients.