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Enfermedad Hepática Inducida por Sustancias y Drogas , Citocromo P-450 CYP2D6 , Trazodona , Humanos , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Trazodona/efectos adversos , Citocromo P-450 CYP2D6/genética , Polimorfismo Genético , Femenino , Masculino , Antidepresivos de Segunda Generación/efectos adversos , Persona de Mediana EdadRESUMEN
A four-year-old Labrador Retriever was presented for intermittent tachycardia. The electrocardiogram showed sinus rhythm conducted with ventricular pre-excitation and short runs of orthodromic atrioventricular reciprocating tachycardia. Four months later, the rhythm degenerated into a symptomatic sustained tachycardia, suspected to be pre-excited atrial fibrillation, a potentially life-threatening rhythm in the presence of an accessory pathway with a short refractory period. Two days after initiating oral diltiazem, the dog deteriorated and represented with sustained orthodromic atrioventricular reciprocating tachycardia, which was terminated by a precordial chest thump. It proceeded to sinus rhythm with ventricular pre-excitation followed by an episode of pre-excited focal atrial tachycardia. A bolus of lidocaine IV successfully restored sinus rhythm and sotalol treatment was started. The dog clinically recovered but died spontaneously 24 h later. This is the first case report that describes spontaneous pre-excited focal atrial tachycardia.
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Antiarrítmicos , Enfermedades de los Perros , Electrocardiografía , Taquicardia Supraventricular , Perros , Animales , Enfermedades de los Perros/tratamiento farmacológico , Taquicardia Supraventricular/veterinaria , Taquicardia Supraventricular/tratamiento farmacológico , Electrocardiografía/veterinaria , Antiarrítmicos/uso terapéutico , Masculino , Sotalol/uso terapéutico , Resultado Fatal , Lidocaína/uso terapéuticoRESUMEN
BACKGROUND AND AIM: HbA1c, the traditional and current gold standard biomarker guiding diabetic management, has been scrutinized for low predictive value for patients with chronic kidney disease due to variables affecting erythrocyte number and turnover. Glycated albumin, the precursor to advanced glycation end products, reflects glycemic status over the preceding 2-3 week period and already outperforms HbA1c for glycemic monitoring. Our aim was to establish whether serum GA can be further used to predict mortality risk in dialysis patients with diabetes mellitus (DM) METHODS: We did systematic review of the literature in PubMed/Medline, Web of Science, Embase (Elsevier) and the Cochrane Central Register of Controlled Trials (Wiley) up to and including February 2020. RESULTS: This meta-analysis included 25,932 dialysis patients across 12 studies with maximum follow-up of 11 years. Higher GA levels were associated with the risk of all-cause mortality in dialysis patients with DM (HR 1.02, 95% CI 1.01 to 1.03, P < 0.001) irrespective of the type of dialysis, whereas higher GA was not associated with cardiovascular mortality (HR 1.03, 95% CI 0.99 to 1.06, P = 0.15) and cardiovascular events (both fatal and non-fatal) (HR 1.03, 95% CI 0.97 to 1.09, P = 0.31) in dialysis patients with DM. CONCLUSION: Serum glycated albumin predicts all-cause mortality risk in dialysis patients with DM. The endpoints of cardiovascular mortality and cardiovascular events trended similarly, but did not reach significance at the current sample size.
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Diabetes Mellitus/mortalidad , Angiopatías Diabéticas/mortalidad , Diálisis Renal/mortalidad , Insuficiencia Renal Crónica , Albúmina Sérica/metabolismo , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Biomarcadores/sangre , Glucemia/análisis , Glucemia/metabolismo , Causas de Muerte , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/diagnóstico , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/mortalidad , Nefropatías Diabéticas/terapia , Femenino , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Productos Finales de Glicación Avanzada/análisis , Productos Finales de Glicación Avanzada/sangre , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Diálisis Renal/estadística & datos numéricos , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/terapia , Albúmina Sérica/análisis , Albúmina Sérica GlicadaRESUMEN
Micromorphology of conjugated polymers is expected to play a crucial role in both heat and charge transport properties. In this perspective, the details of the polymerization mechanism acquire a fundamental relevance, providing the link between the basic chemical reaction paths and the resulting molecular structure and arrangement. For PEDOT, the role played by the Brønsted bases (proton scavengers) and their impact on the distribution of polymer chain lengths are still a matter of debate. In the present work, we have systematically analyzed several reaction paths leading to PEDOT polymerization. By means of atomistic simulations, we identified the thermodynamically preferred reaction path, proving that tosylate anions rule proton scavenging. PEDOT chain length was computed to be â¼12-13 monomeric units. We could also demonstrate how the proton scavengers set at once the chain lengths and the sample crystallinity. Furthermore, we found that tosylate gives rise to a sharper multimodal distribution of chain length, a feature that supports hypotheses regarding the occurrence of a percolative transport regime mediated by tie chains bridging paracrystalline regions.
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Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Enfermedad Celíaca/inducido químicamente , Imidazoles/efectos adversos , Mucosa Intestinal/patología , Tetrazoles/efectos adversos , Anciano , Anciano de 80 o más Años , Diarrea/inducido químicamente , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
Schistosomiasis is a parasitic disease caused by Schistosoma species. Intestinal and hepatic schistosomiases are the most common forms of chronic disease. We describe a case of a 26-year old patient from Eritrea who was referred to our hospital with abdominal pain and diarrhea. The diagnosis of hepatosplenic schistosomiasis was made by liver biopsy and the patient was treated with praziquantel. Hepatic schistosomiasis is characterised by deposition of schistosomal eggs in the liver which results in a host cell immune response and leads to granuloma formation and neoangiogenesis. This is hallmarked by different grades of periportal fibrosis with portal hypertension leading to splenomegaly. Normal liver architecture is preserved and periportal fibrosis can be reversible if treated adequately and timely. With a recent native schistosomiasis cluster report from France and the expected influx to Europe of persons from regions endemic for schistosomiasis, increased awareness of this disease in healthcare practitioners is needed. We review the epidemiology, pathogenesis, clinical presentation and treatment of schistosomiasis.
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Antihelmínticos/uso terapéutico , Parasitosis Hepáticas/diagnóstico , Parasitosis Hepáticas/tratamiento farmacológico , Praziquantel/uso terapéutico , Esquistosomiasis/diagnóstico , Esquistosomiasis/tratamiento farmacológico , Esplenomegalia/parasitología , Adulto , Diagnóstico Diferencial , Humanos , MasculinoRESUMEN
BACKGROUND: Oligoclonal bands of IgG (OB) are proposed as an early prognostic factor of the disease. Growing attention is directed towards brain volume evaluation as a possible marker of the severity of MS. Previous studies found that MS patients lacking OB have less brain atrophy. AIM: to evaluate a possible relationship between OB and cerebral volume in a cohort of early MS patients. METHODS: Inclusion criteria were: diagnosis of relapsing-remitting MS; CSF analysis and MRI acquired simultaneously and within 12 months from clinical onset. A total of 15 healthy controls underwent MRI. RESULTS: In 20 MS patients, CSF analysis did not show OB synthesis (OB negative group). A control group of 25 MS patients in whom OB was detected was also randomly recruited (OB positive group). T test showed a significant difference in NWV between the OB positive and OB negative groups (P value = 0.01), and between the OB positive group and the healthy controls (P value = 0.001). No differences were detected between OB negative group and healthy controls. Multivariable linear regression showed a relationship between NWV and OB synthesis (P value = 0.02) controlling for age, gender, and EDSS. CONCLUSIONS: Our preliminary results suggest that OB positive patients show more atrophy of white matter since early phases of the disease, supporting the role of CSF analysis as a prognostic factor in MS.
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Encéfalo/patología , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/patología , Bandas Oligoclonales/líquido cefalorraquídeo , Sustancia Blanca/patología , Adulto , Atrofia/patología , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Pronóstico , Sustancia Blanca/diagnóstico por imagenRESUMEN
In recent years, melanoma treatment has radically changed with the emergence of targeted therapies and immunotherapies. Both have led to improved survival for patients with advanced or unresectable melanoma. Targeted therapies with BRAF inhibitors in the lead use the presence of activating driver mutations to inhibit tumour growth. Forty to 60% of melanomas harbour BRAF mutations, which makes them susceptible to treatment with BRAF and/or MEK inhibitors. In parallel, the development of immunotherapeutic agents has also expanded. These agents stimulate the endogenous immune system of the patient to eradicate cancer cells. Immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death 1 (PD-1) resulted in durable responses in a subset of patients. An important issue with immunotherapy lies in the identification of patients who will benefit from treatment. In this review, we will discuss these recent developments in melanoma therapy and highlight the role of the pathologist in both types of treatment.
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Inmunoterapia/métodos , Melanoma/terapia , Terapia Molecular Dirigida/métodos , Humanos , Inmunoterapia/tendencias , Terapia Molecular Dirigida/tendencias , Patología Molecular/métodos , Patología Molecular/tendenciasRESUMEN
Outgrowth heterogeneity of bacterial spore populations complicates both prediction and efficient control of spore outgrowth. In this study, the impact of mild preservation stresses on outgrowth of Bacillus cereus ATCC 14579 spores was quantified during the first stages of outgrowth. Heterogeneity in outgrowth of heat-treated (90°C for 10 min) and non-heat-treated germinated single spores to the maximum micro-colony stage of 256 cells was assessed by direct imaging on Anopore strips, placed on BHI plates at pH7 and pH5.5, without and with added NaCl or sorbic acid (HSA). At pH7 non-heated and heat-treated germinated spores required 6h to reach the maximum microcolony stage with limited heterogeneity, and these parameters were only slightly affected with both types of spores when incubated at pH7 with added NaCl. Notably, the most pronounced effects were observed during outgrowth of spores at pH5.5 without and with added NaCl or HSA. Non-heat-treated germinated spores showed again efficient outgrowth with limited heterogeneity reaching the maximum microcolony stage after 6h at pH5.5, which increased to 12h and 16 h with added NaCl and HSA, respectively. In contrast, heat-treated spores displayed a strong delay between initial germination and swelling and further outgrowth at pH5.5, resulting in large heterogeneity and low numbers of fastest growers reaching the maximum microcolony stage after 10, 12 and 24h, without and with added NaCl or HSA, respectively. This work shows that Anopore technology provides quantitative information on the impact of combined preservation stresses on outgrowth of single spores, showing that outgrowth of germinated heat-treated spores is significantly affected at pH5.5 with a large fraction of spores arrested in the early outgrowth stage, and with outgrowing cells showing large heterogeneity with only a small fraction committed to relatively fast outgrowth.
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Bacillus cereus/efectos de los fármacos , Bacillus cereus/crecimiento & desarrollo , Calor , Cloruro de Sodio/farmacología , Ácido Sórbico/farmacología , Concentración de Iones de Hidrógeno , Esporas Bacterianas/efectos de los fármacos , Esporas Bacterianas/crecimiento & desarrollo , Estrés FisiológicoRESUMEN
In this study, the impact of a range of organic acids and structurally similar alcohols with three to six carbon backbones and increasing lipophilic character, were tested on the germination behavior of B. cereus ATCC 14579 spores. This approach allowed substantiating whether the effectivity of the various compounds was largely dictated by membrane interference or a classic weak acid acidification effect. The octanol-water partition coefficient (log P(oct/water)) ranges from 0.25/0.33 to 2.03/1.96 for propanol/undissociated propionic acid and hexanol/undissociated hexanoic acid, respectively. Performance of germination assays at neutral (pH7) and acidic conditions (pH5.5) allowed for a comparative analysis of the action of dissociated versus undissociated acids, and the presumed pH-independent effect of the corresponding alcohols. Germination assays, based on both continuously measured optical density and time-based plating experiments, and microscopic observations demonstrated the correlation between the lipophilic character of the selected compounds and their inhibiting effect on spore germination. Real-time fluorescence based assays showed that membrane integrity in dormant spores was maintained in the presence of the tested inhibitors. Lowering the critical concentration of inhibitors by a one-step washing procedure resulted in the onset of nutrient-induced germination, indicating the reversible nature of the inhibition process. Furthermore, blocking of nutrient-induced germination in the presence of inhibitory concentrations of selected lipophilic acids and corresponding alcohols was by-passed upon addition of Ca-dipicolinic acid, pointing to loss of signaling capacity in germinant receptor-mediated germination activity. These findings show that lipophilicity is an important determinant for the ability of the selected acids and corresponding alcohols to accumulate in the spore inner membrane and their ability to act as a germination-inhibitor.
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Microbiología de Alimentos , Ácidos/metabolismo , Alcoholes/metabolismo , Bacillus cereus/efectos de los fármacos , Bacillus cereus/fisiología , Concentración de Iones de Hidrógeno , Ácidos Picolínicos/metabolismo , Esporas Bacterianas/efectos de los fármacos , Esporas Bacterianas/fisiologíaRESUMEN
Sorbic acid (SA) is widely used as a preservative, but the effect of SA on spore germination and outgrowth has gained limited attention up to now. Therefore, the effect of sorbic acid on germination of spores of Bacillus cereus strain ATCC 14579 was analyzed both at phenotype and transcriptome level. Spore germination and outgrowth were assessed at pH 5.5 without and with 0.75, 1.5 and 3.0 mM (final concentrations) undissociated sorbic acid (HSA). This resulted in distinct HSA concentration-dependent phenotypes, varying from reduced germination and outgrowth rates to complete blockage of germination at 3.0 mM HSA. The phenotypes reflecting different stages in the germination process could be confirmed using flow cytometry and could be recognized at transcriptome level by distinct expression profiles. In the absence and presence of 0.75 and 1.5 mM HSA, similar cellular ATP levels were found up to the initial stage of outgrowth, suggesting that HSA-induced inhibition of outgrowth is not caused by depletion of ATP. Transcriptome analysis revealed the presence of a limited number of transcripts in dormant spores, outgrowth related expression, and genes specifically associated with sorbic acid stress, including alterations in cell envelope and multidrug resistance. The potential role of these HSA-stress associated genes in spore outgrowth is discussed.
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Bacillus cereus/efectos de los fármacos , Bacillus cereus/fisiología , Microbiología de Alimentos , Ácido Sórbico/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Medios de Cultivo , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Contaminación de Alimentos/análisis , Contaminación de Alimentos/prevención & control , Perfilación de la Expresión Génica , Concentración de Iones de Hidrógeno , Análisis por Micromatrices , Fenotipo , Especificidad de la Especie , Esporas Bacterianas/genética , Esporas Bacterianas/crecimiento & desarrollo , Esporas Bacterianas/metabolismoRESUMEN
Amino acid- and inosine-induced germination of Bacillus cereus ATCC 14579 spores was reversibly inhibited in the presence of 3 mM undissociated sorbic acid. Exposure to high hydrostatic pressure, Ca-dipicolinic acid (DPA), and bryostatin, an activator of PrkC kinase, negated this inhibition, pointing to specific blockage of signal transduction in germinant receptor-mediated germination.
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Bacillus cereus/crecimiento & desarrollo , Bacillus cereus/metabolismo , Ácido Sórbico/metabolismo , Esporas Bacterianas/crecimiento & desarrollo , Esporas Bacterianas/metabolismo , Aminoácidos/metabolismo , Brioestatinas/metabolismo , Presión Hidrostática , Inosina/metabolismo , Redes y Vías Metabólicas , Ácidos Picolínicos/metabolismo , Transducción de SeñalRESUMEN
Variation within intron 19 of the CLEC16A (KIAA0350) gene region was recently found to be unequivocally associated with type 1 diabetes (T1D) in genome-wide association (GWA) studies in Northern European populations. A variant in intron 22 that is nearly independent of the intron 19 variant showed suggestive evidence of association with multiple sclerosis (MS). Here, we genotyped the rs725613 polymorphism, representative of the earlier reported associations with T1D within CLEC16A, in 1037 T1D cases, 1498 MS cases and 1706 matched controls, all from the founder, autoimmunity-prone Sardinian population. In these Sardinian samples, allele A of rs725613 is positively associated not only with T1D (odds ratio=1.15, P one-tail=5.1 x 10(-3)) but also, and with a comparable effect size, with MS (odds ratio=1.21, P one-tail 6.7 x 10(-5)). Taken together these data provide evidence of joint disease association in T1D and MS within CLEC16A and underline a shared disease pathway.
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Diabetes Mellitus Tipo 1/genética , Variación Genética , Estudio de Asociación del Genoma Completo , Lectinas Tipo C/genética , Proteínas de Transporte de Monosacáridos/genética , Esclerosis Múltiple/genética , Adulto , Edad de Inicio , Alelos , Estudios de Casos y Controles , Familia , Femenino , Humanos , Italia , Masculino , Oportunidad Relativa , Polimorfismo Genético , ProbabilidadRESUMEN
Several studies have indicated that multiple sclerosis (MS) is associated and linked to the major histocompatibility complex (MHC)/human leukocyte antigen (HLA) region of chromosome 6p21.3, but the exact location and nature of the primarily associated locus within the HLA complex is still controversial and largely presumptive. By linkage disequilibrium mapping, we have systematically investigated this chromosome region in the founder population of Sardinia to determine the relative associations of the various loci with MS. An overall 11.4 Mb region, which encompasses the whole HLA complex, was scanned with 19 microsatellite markers and with single nucleotide polymorphisms within 12 functional candidate genes and assessed for MS association using the extended transmission disequilibrium test (ETDT). A peak of association represented by the three adjacent DRB1, -DQA1 and -DQB1 loci was detected in the class II region. Two additional less significant areas of association were detected, respectively, in the centromeric side of the class II region at the DPB1 locus and, telomeric of the classically defined class I loci, at the D6S1683 microsatellite. Conditional ETDT analysis indicated that these regions of association could be independent of each other. Within the main peak of association, DRB1 and DQB1 contribute to the disease association independently of each other whereas DQA1 had no detectable primary genetic effects. We evaluated the haplotype distribution at the region showing the strongest association and found five DQB1-DRB1 haplotypes positively associated with MS in Sardinia. These consistently included all the haplotypes previously found associated with MS in the various human populations, thus supporting a primary effect of the products of these loci in MS. Overall these results are consistent with a multilocus model of the MHC encoded susceptibility to MS.
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Cromosomas Humanos Par 6/genética , Antígenos HLA-DP/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Esclerosis Múltiple/genética , Adolescente , Adulto , Anciano , Alelos , Niño , Femenino , Efecto Fundador , Variación Genética , Cadenas beta de HLA-DP , Cadenas beta de HLA-DQ , Cadenas HLA-DRB1 , Humanos , Italia , Desequilibrio de Ligamiento , Masculino , Repeticiones de Microsatélite , Persona de Mediana EdadRESUMEN
We investigated individual- and task-related differences in autonomic physiological responses induced by time limited figural and verbal inductive reasoning tasks. In a group of 52 participants, the percentage of correctly responded task items was evaluated together with nine different autonomic physiological response measures and respiration rate (RR). Weighted multidimensional scaling analyses of the physiological responses revealed three underlying dimensions, primarily characterized by RR, parasympathetic, and sympathetic activity. RR and sympathetic activity appeared to be relatively more important response dimensions for poor reasoners, whereas parasympathetic responsivity was relatively more important for good reasoners. These results suggest that poor reasoners showed higher levels of cognitive processing intensity than good reasoners. Furthermore, for the good reasoners, the dimension of sympathetic activity was relatively more important during the figural than during the verbal reasoning task, which was explained in terms of hemispheric lateralization in autonomic function.
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Sistema Nervioso Autónomo/fisiología , Cognición , Adulto , Toma de Decisiones , Femenino , Humanos , Lógica , Masculino , Procesos Mentales , Conducta VerbalRESUMEN
A minisatellite polymorphism located in the 3' flanking region of the interleukin-6 (IL-6) gene was analysed in 192 Sardinian simplex families with multiple sclerosis (MS). By applying a high-resolution sizing approach, 9 alleles were identified. None of these were associated with in globo susceptibility to MS as shown by transmission disequilibrium testing. Analysis of clinically different groups showed that the A5 allele was associated with a benign (P = 0.007) but not with a malignant (P = 0.45) course of disease. In particular, the frequency of the A5/A5 genotype was significantly higher in patients with benign MS (P = 0.002). In addition, carriage of any of the larger alleles (A6-->A9) was associated with accelerated onset of disease (P = 0.025). Our results suggest that allelic variations in the IL-6 gene may predispose to alterations in the course and initial onset of MS.
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Interleucina-6/genética , Repeticiones de Minisatélite , Esclerosis Múltiple/genética , Polimorfismo Genético , Adulto , Edad de Inicio , Alelos , Femenino , Genotipo , Humanos , Italia , Masculino , PronósticoRESUMEN
In a previous study it was found that infrequent deviant visual stimuli, in a series of standards, elicited event-related potentials (ERPs) with enhanced P2-N2s and P3 amplitudes, suggesting that these parameters reflect processes related to the orienting reaction (OR). In the present study a similar oddball series was presented against the background of a second class of stimuli. With respect to the latter stimuli, subjects had to perform either a very involved (hard) or an easy task. EEG was recorded to oddball (probe) stimuli from Oz, Pz, Cz, and Fz. Analysis of average ERPs revealed that, in the easy condition, deviant probes elicited both enhanced P2-N2s and enhanced P3s, relative to the standards. In contrast, in the hard condition P2-N2, but not P3, was enhanced by stimulus change. In addition, overall P3 amplitude to probes was smaller in the hard condition (sequence-independent load effect). Analysis of single-trial ERPs (SERPs) with orthogonal polynomial trend analysis largely replicated these effects. In addition, SERP analysis also revealed a sequence-independent load effect on P2, as well as a decreasing P3 to deviant stimuli in the Easy condition, which was observed at Cz and Fz, but not at Pz or Oz. The results are interpreted as suggesting that P2-N2 and P3 reflect different stages of the OR, one of automatic and one of capacity-limited processing.