Computational pathology identifies a low B-cell content in the tumour microenvironment as a predictor of adverse outcome in patients with classic Hodgkin lymphoma treated with ABVD.

Aims: The prognostic impact of B lymphocytes surrounding Hodgkin and Reed Sternberg (HRS) cells in classic Hodgkin lymphoma (cHL) and pathogenic variants in genes associated with apoptosis regulation remains undefined.

Methods: We have quantified the proportion of B lymphocytes in tumour microenvironment (TME) in 220 diagnostic slides from 110 cHL patients applying computational pathology (CP) and sequenced cases using a targeted panel including 47 genes recurrently mutated in mature B-cell neoplasms. Kaplan-Meier estimators and multivariate Cox regression on overall survival (OS) and progression-free survival (PFS) were assessed following the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines.

Magnetic Resonance Imaging (MRI) of Spanish Sheep Cheese: A Study on the Relationships between Ripening Times, Geographical Origins, Textural Parameters, and MRI Parameters.

The evolution of structural changes and the textural features during the ripening process of four varieties of Spanish sheep cheese were studied using Magnetic Resonance Imaging (MRI). Specifically, longitudinal () and transverse () relaxation times and apparent diffusion coefficient maps were analyzed. Also, proton density was used to improve the description of the structure of the cheeses.

Pathogenic Variants Associated with Epigenetic Control and the NOTCH Pathway Are Frequent in Classic Hodgkin Lymphoma.

Classic Hodgkin lymphoma (cHL) constitutes a B-cell neoplasm derived from germinal center lymphocytes. Despite high cure rates (80-90%) obtained with the current multiagent protocols, a significant proportion of cHL patients experience recurrences, characterized by a lower sensitivity to second-line treatments. The genomic background of chemorefractory cHL is still poorly understood, limiting personalized treatment strategies based on molecular features.

Ipsilesional Hippocampal GABA Is Elevated and Correlates With Cognitive Impairment and Maladaptive Neurogenesis After Cortical Stroke in Mice.

Background: Cognitive dysfunction is a frequent stroke sequela, but its pathogenesis and treatment remain unresolved. Involvement of aberrant hippocampal neurogenesis and maladaptive circuitry remodeling has been proposed, but their mechanisms are unknown. Our aim was to evaluate potential underlying molecular/cellular events implicated.

New Cases and Mutations in Gene Causing Congenital Dyserythropoietic Anemia Type II.

Congenital dyserythropoietic anemia type II (CDA II) is an inherited autosomal recessive blood disorder which belongs to the wide group of ineffective erythropoiesis conditions. It is characterized by mild to severe normocytic anemia, jaundice, and splenomegaly owing to the hemolytic component. This often leads to liver iron overload and gallstones.

The Application of 3D Anatomy for Teaching Veterinary Clinical Neurology.

Neuroanatomy is always a challenging topic for veterinary students. It is widely accepted that understanding the anatomy of the central nervous system (CNS) is essential to explain many of the pathological processes that affect the brain. Although its study has varied over time to achieve this goal, in human and veterinary medicine it is difficult to find a teaching method that associates normal anatomy with pathological alterations of the brain.

Identification of prognostic factors in classic Hodgkin lymphoma by integrating whole slide imaging and next generation sequencing.

Digital pathology and genomics are increasingly used to improve our understanding of lymphoid neoplasms. Algorithms for quantifying cell populations in the lymph node and genetics can be integrated to identify new biomarkers with prognostic impact in classic Hodgkin lymphoma (cHL). In 16 cHL patients, we have performed whole slide imaging (WSI) analysis and quantification of CD30+, CD20+, CD3+ and MUM1+ cells in whole tissue slides, and Next Generation Sequencing (NGS) in formalin fixed paraffin-embedded (FFPE) tissue, using a widely used NSG panel (Oncomine® Focus Assay) to define genetic variants underlying tumor development.

The Need for Standardization in Next-Generation Sequencing Studies for Classic Hodgkin Lymphoma: A Systematic Review.

Classic Hodgkin lymphoma (cHL) constitutes a B cell-derived neoplasm defined by a scarce tumoral population, termed Hodgkin and Reed-Sternberg (HRS) cells, submerged into a histologically heterogeneous microenvironment. The paucity of HRS cells has historically hampered genetic studies, rendering the identification of the recurrent genetic lesions and molecular pathways deregulated in this lymphoma difficult. The advent of high-throughput sequencing methods such as next-generation sequencing (NGS) could sensibly optimize the identification of the mutational landscape of cHL.

Intraventricular hemorrhage induces inflammatory brain damage with blood-brain barrier dysfunction in immature rats.

Background: We aimed to characterize a preclinical model of intraventricular hemorrhage-induced brain damage (IVH-BD) in extremely low birth weight newborns (ELBWN), to identify potential therapeutic targets based on its pathophysiology.

Methods: IVH was induced in 1-day-old (P1) Wistar rats by left periventricular injection of clostridium collagenase (PVCC). At P6, P14, and P45 IVH-BD (area of damage, motor and cognitive deficits, Lactate/N-acetylaspartate ratio), white matter injury (WMI: ipsilateral hemisphere and corpus callosum atrophy, oligodendroglial population and myelin basic protein signal reduction), blood-brain barrier (BBB) dysfunction (occludin and Mfsd2a expression, Gadolinium leakage) and inflammation (TNFα, TLR4, NFkB, and MMP9 expression; immune cell infiltration), excitotoxicity (Glutamate/N-acetylaspartate), and oxidative stress (protein nitrosylation) were assessed.

Prognostic Role of the Expression of Latent-Membrane Protein 1 of Epstein-Barr Virus in Classical Hodgkin Lymphoma.

The prognostic impact of the presence of Epstein-Barr virus (EBV) in classical Hodgkin lymphoma (cHL) is controversial. Previous studies reported heterogeneous results, rendering difficult the clinical validation of EBV as a prognostic biomarker in this lymphoma. The objective of this study was to evaluate the survival impact of the expression of EBV Latent-Membrane Protein 1 (EBV-LMP1) in tumoral Hodgkin-Reed-Sternberg (HRS) cells of primary diagnostic samples of cHL.

Influence of metabolic syndrome on post-stroke outcome, angiogenesis and vascular function in old rats determined by dynamic contrast enhanced MRI.

Stroke affects primarily aged and co-morbid people, aspects not properly considered to date. Since angiogenesis/vasculogenesis are key processes for stroke recovery, we purposed to determine how different co-morbidities affect the outcome and angiogenesis/vasculogenesis, using a rodent model of metabolic syndrome, and by dynamic enhanced-contrast imaging (DCE-MRI) to assess its non-invasive potential to determine these processes. Twenty/twenty-two month-old corpulent (JCR:LA-Cp/Cp), a model of metabolic syndrome and lean rats were used.

Early detection of skeletal muscle bioenergetic deficit by magnetic resonance spectroscopy in cigarette smoke-exposed mice.

Skeletal muscle dysfunction is a common complication and an important prognostic factor in patients with chronic obstructive pulmonary disease (COPD). It is associated with intrinsic muscular abnormalities of the lower extremities, but it is not known whether there is an easy way to predict its presence. Using a mouse model of chronic cigarette smoke exposure, we tested the hypothesis that magnetic resonance spectroscopy allows us to detect muscle bioenergetic deficit in early stages of lung disease.

Lack of the aryl hydrocarbon receptor accelerates aging in mice.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, largely known for its role in xenobiotic metabolism and detoxification as well as its crucial role as a regulator of inflammation. Here, we have compared a cohort wild-type and AhR-null mice along aging to study the relationship between this receptor and age-associated inflammation, termed as "inflammaging," both at a systemic and the CNS level. Our results show that AhR deficiency is associated with a premature aged phenotype, characterized by early inflammaging, as shown by an increase in plasma cytokines levels.

Insights into real-time chemical processes in a calcium sensor protein-directed dynamic library.

Dynamic combinatorial chemistry (DCC) has proven its potential in drug discovery speeding the identification of modulators of biological targets. However, the exchange chemistries typically take place under specific reaction conditions, with limited tools capable of operating under physiological parameters. Here we report a catalyzed protein-directed DCC working at low temperatures that allows the calcium sensor NCS-1 to find the best ligands in situ.

Evaluation of E-beam irradiation and storage time in pork exudates using NMR metabolomics.

Seventy-two exudates from pork tenderloin samples, subjected to E-beam irradiation treatments, have been employed to monitor, through H NMR analysis, the effects of irradiation dose (0, 1, 2 and 6 kGy) and storage time (1, 6 and 12 days). As far as we know, this is the first study where meat exudate is employed to monitor the effects of irradiation dose and storage time. The H NMR spectra, obtained after ~ 2 min, allowed to determine the main components of the pork exudate.

Use of MRI as a predictive tool for physicochemical and rheologycal features during cured ham manufacturing.

Magnetic resonance imaging (MRI) was used to study the structural changes during dry-cured ham manufacturing. T, T and apparent diffusion coefficient (ADC) were determined. Dry cured hams were analysed at different steps of the manufacturing process (raw, salted, post salted, half-cured and cured).

Hypersensitivity to alemtuzumab. A safe and effective desensitization protocol: A case report.

We describe a successful desensitization to alemtuzumab in one patient diagnosed with T-cell prolymphocytic leukaemia. Alemtuzumab treatment was initiated during infusion number 18, the patient showed cutaneous eruption with a miliary pattern, despite premedication with corticosteroids and antihistamines. The eruption returned with successive alemtuzumab infusions (infusions 19, 20 and 21), remained present for longer and was more severe with each infusion.

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) produces edema due to BBB disruption induced by MMP-9 activation in rat hippocampus.

The recreational drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier (BBB) integrity in rats through an early P2X receptor-mediated event which induces MMP-9 activity. Increased BBB permeability often causes plasma proteins and water to access cerebral tissue leading to vasogenic edema formation. The current study was performed to examine the effect of a single neurotoxic dose of MDMA (12.

Mild and Short-Term Caloric Restriction Prevents Obesity-Induced Cardiomyopathy in Young Zucker Rats without Changing in Metabolites and Fatty Acids Cardiac Profile.

Caloric restriction (CR) ameliorates cardiac dysfunction associated with obesity. However, most of the studies have been performed under severe CR (30-65% caloric intake decrease) for several months or even years in aged animals. Here, we investigated whether mild (20% food intake reduction) and short-term (2-weeks) CR prevented the obese cardiomyopathy phenotype and improved the metabolic profile of young (14 weeks of age) genetically obese Zucker rats.

Follow-up monoclonal gammopathy of undetermined significance in kidney transplant.

Objective: The aim of this work was to review the incidence of monoclonal gammopathy of undetermined significance (MGUS) and complications in kidney transplant (KT) patients at the Puerta del Mar Hospital in Cádiz, Spain. This diagnosis was not considered to be a contraindication for transplantation.

Methods: To estimate the incidence of MGUS in KT patients we used the database of our hospital, which included 1,016 patients who received a KT from 1992 to 2012 with a median follow-up of 30 months.

2D ultrafast HMBC 1H,31P: obtaining mechanistic details on the Michaelis–Arbuzov reaction.

Ultrafast NMR spectroscopy (UF-NMR) can be used to monitor chemical reactions in real time and to provide insights into their mechanisms and the nature of the intermediates formed. Here, we have developed a 2D 1H,31P UF-HMBC method and the corresponding NMR experimental setup to enable the study of a Michaelis–Arbuzov reaction at two different temperatures, 25 and 70 °C. The specific reaction studied was between triethyl phosphite and benzyl bromide to produce diethylbenzyl phosphonate.

Discovering mechanistic insights by application of tandem ultrafast multidimensional NMR techniques.

Ultrafast multidimensional NMR acquisition techniques have shown promising capabilities in studies of dynamic systems in real time. The method's characteristics have permitted the focus to be on the mechanistic details of organic reactions. The tandem UF-TOCSY/HMBC sequence applied here combines both homonuclear and heteronuclear details and therefore provides complete information about the evolution of a dynamic reaction in real time.

Do chronic myeloid leukemia patients with late "warning" responses benefit from "watch and wait" or switching therapy to a second generation tyrosine kinase inhibitor?

In the latest recommendations for the management of chronic-phase chronic myeloid leukemia suboptimal responses have been reclassified as "warning responses." In contrast to previous recommendations current guidance advises close monitoring without changing therapy. We have identified 198 patients treated with first-line imatinib, with a warning response after 12 months of treatment (patients with a complete cytogenetic response but no major molecular response [MMR]).