Expression profiling of extramedullary acute myeloid leukemia suggests involvement of epithelial-mesenchymal transition pathways.

Extramedullary (EM) colonization is a rare complication of acute myeloid leukemia (AML), occurring in about 10% of patients, but the processes underlying tissue invasion are not entirely characterized. Through the application of RNAseq technology, we examined the transcriptome profile of 13 AMLs, 9 of whom presented an EM localization. Our analysis revealed significant deregulation within the extracellular matrix (ECM)-receptor interaction and focal-adhesion pathways, specifically in the EM sites. The transcription factor TWIST1, which is known to impact on cancer invasion by dysregulating epithelial-mesenchymal-transition (EMT) processes, was significantly upregulated in EM-AML. To test the functional impact of TWIST1 overexpression, we treated OCI-AML3s with TWIST1-siRNA or metformin, a drug known to inhibit tumor progression in cancer models. After 48 h, we showed downregulation of TWIST1, and of the EMT-related genes FN1 and SNAI2. This was associated with significant impairment of migration and invasion processes by Boyden chamber assays. Our study shed light on the molecular mechanisms associated with EM tissue invasion in AML, and on the ability of metformin to interfere with key players of this process. TWIST1 may configure as candidate marker of EM-AML progression, and inhibition of EMT-pathways may represent an innovative therapeutic intervention to prevent or treat this complication.

Sewage Sludge Management at District Level: Reduction and Nutrients Recovery via Hydrothermal Carbonization.

In this study, two scenarios of a municipal wastewater treatment plant (WWTP) are presented, which include the integration of the hydrothermal carbonization (HTC) process into the sludge line as a post-treatment of the anaerobic digestion (AD) process. The objective of the simulation is to investigate the performances of AD + HTC treatment to reduce sludge production and improve nutrient and energy recovery. For this purpose, the scheme of an under-construction WWTP was considered, named Trento 3 (Trento, Italy) and with a treatment capacity of 300,000 PE. In the first scenario, the HTC process was fed with thickened sludge from the Trento 3 WWTP, while in the second scenario, dewatered sludge from other local WWTPs was also used as feedstock for the HTC process. Both scenarios allowed to obtain a considerable sludge reduction ranging from 70 to 75% with a notably increase in the biogas production up to 47%, due to the recycling of HTC liquor (HTCL) to the anaerobic digester. Considering nutrients recovery, all the phosphorus and nitrogen present in the HTCL could be used for struvite precipitation with an average yearly gain of 1 million euros. Moreover, the introduction of HTC in the Trento 3 WWTP could allow a reduction in the sludge management costs of up to 2 M€/year.

Non-thyroidal illness syndrome and SARS-CoV-2-associated multisystem inflammatory syndrome in children.

PURPOSE: COVID-19 disease may result in a severe multisystem inflammatory syndrome in children (MIS-C), which in turn may alter thyroid function (TF). We assessed TF in MIS-C, evaluating its impact on disease severity. METHODS: We retrospectively considered children admitted with MIS-C to a single pediatric hospital in Milan (November 2019-January 2021). Non-thyroidal illness syndrome (NTIS) was defined as any abnormality in TF tests (FT3, FT4, TSH) in the presence of critical illness and absence of a pre-existing hormonal abnormality. We devised a disease severity score by combining severity scores for each organ involved. Glucose and lipid profiles were also considered. A principal component analysis (PCA) was performed, to characterize the mutual association patterns between TF and disease severity. RESULTS: Of 26 (19 M/7F) patients, median age 10.7 (IQR 5.8-13.3) years, 23 (88.4%) presented with NTIS. A low FT3 level was noted in 15/23 (65.3%), while the other subjects had varying combinations of hormone abnormalities (8/23, 34.7%). Mutually correlated variables related to organ damage and inflammation were represented in the first dimension (PC1) of the PCA. FT3, FT4 and total cholesterol were positively correlated and characterized the second axis (PC2). The third axis (PC3) was characterized by the association of triglycerides, TyG index and HDL cholesterol. TF appeared to be related to lipemic and peripheral insulin resistance profiles. A possible association between catabolic components and severity score was also noted. CONCLUSIONS: A low FT3 level is common among MIS-C. TF may be useful to define the impact of MIS-C on children's health and help delineate long term follow-up management and prognosis.

Morfologia do pâncreas da paca (Cuniculus paca, Linnaeus, 1766) / Morphology of the pancreas of pacas (Cuniculus paca, Linnaeus, 1766)

Este trabalho se baseou na descrição morfológica da paca (Cuniculus paca), espécie selvagem pertencente à ordem dos roedores, típica de regiões tropicais, sendo o seu conhecimento anatômico detalhado muito importante para sua conservação, experimentação e comercialização, pois ainda são escassos na literatura os trabalhos sobre morfologia de espécies selvagens. Macroscopicamente, o pâncreas da paca é formado por lóbulos, organizados em ramificações difusas, e, microscopicamente, tal órgão possui uma camada de tecido conjuntivo frouxo, a partir da qual partem septos, que dividem a glândula em lóbulos, compostos de ácinos e ilhotas pancreáticas.(AU)

The present study aimed to describe the morphology of pacas (Cuniculus paca), a wild species belonging to the order Rodentia, found in tropical areas. The detailed anatomical knowledge of pacas is very important for conservation, experimental studies and commercialization because studies in literature about wild species are scarce. The pancreas of paca has lobes organized in diffuse branches at the macroscopic level and microscopically this organ has a loose connective tissue layer, originating septa that divide the gland into lobes composed of acini and pancreatic islets.(AU)

Serum biochemical profile of neonatal buffalo calves / Perfil bioquímico sérico de bezerros bubalinos no período neonatal

Serum blood samples from 50 Murrah buffalo calves were examined in this study. The animals were allocated into three groups according to the number of parturitions of their mothers: G1 (n= 15) calves from primiparous buffaloes, G2 (n= 19) calves from buffaloes with two to four parturitions, and G3 (n= 16) calves from buffaloes with five or more parturitions. Blood samples were taken at birth, before colostrum ingestion, at 24h, 48h, and 72h after birth, and at 7, 14, 21, and 30 days after birth for determination of levels of gammaglutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), creatine kinase, total protein, albumin, globulins (including immunoglobulin G), iron, total calcium, ionized calcium, phosphorus, sodium, and potassium. The age of the calves was found to influence all of the biochemical parameters, with the exception of ionized calcium and potassium in the calves in groups G1 and G3. The calving order was found to influence AST, GGT, total protein, albumin, and globulins, including IgG. The high serum ALP activity in the first two days after birth indicates that measurement of the levels of this enzyme may be used as an indirect method of assessing passive immunity transfer.(AU)

Amostras de sangue de 50 bezerros de búfalo Murrah foram examinados nesse estudo. Os animais foram distribuídos em três grupos de acordo com a paridade de suas genitoras: G1 (n=15) bezerros de búfalas primíparas, G2 (n=19) bezerros de búfalas com 2 a 4 gestações, e G3 (n=16) bezerros de búfalas com cinco ou mais gestações. Amostras de sangue foram colhidas ao nascimento, antes da ingestão de colostro e 24h, 48h, e 72h após o nascimento e 7, 14, 21 e 30 dias após nascimento para determinar níveis de gammaglutamil transferase (GGT), fosfatase alcalina (ALP), aspartato aminotrasferase (AST), creatina quinase, proteínas totais, albumina, globulina (inclusive imunoglobulina G), ferro, cálcio total, cálcio ionizado, fósforo, sódio e potássio. A idade dos bezerros influenciou todos os parâmetros bioquímicos, exceto cálcio ionizado e potássio nos bezerros dos grupos G1 e G3. A ordem de nascimento influenciou AST, GGT, proteínas totais, albumina e globulinas, inclusive IgG. Intensa atividade ALP no soro nos primeiros dois dias após nascimento indica que medidas dos níveis dessa enzima podem ser utilizados como método indireto de avaliar transferência passiva de imunidade.(AU)

Adverse Effects and Surgical Complications in Pediatric Patients Undergoing Vagal Nerve Stimulation for Drug-Resistant Epilepsy.

Vagal nerve stimulation (VNS) is an effective treatment for drug-resistant epilepsy that is not suitable for resective surgery, both in adults and in children. Few reports describe the adverse effects and complications of VNS. The aim of our study was to present a series of 33 pediatric patients who underwent VNS for drug-resistant epilepsy and to discuss the adverse effects and complications through a review of the literature.The adverse effects of VNS are usually transient and are dependent on stimulation of the vagus and its efferent fibers; surgical complications of the procedure may be challenging and patients sometimes require further surgery; generally these complications affect VNS efficacy; in addition, hardware complications also have to be taken into account.In our experience and according to the literature, adverse effects and surgical and hardware complications are uncommon and can usually be managed definitely. Careful selection of patients, particularly from a respiratory and cardiac point of view, has to be done before surgery to limit the incidence of some adverse effects.

Evaluation of the Implementation of Good Handling Practices in Food and Beverage Areas of Hotels.

Because of the major international-level events that have recently been held in Brazil, concerns about the sensory and hygienic-sanitary conditions of food have increased. The objective of this study was to evaluate the implementation of good handling practices in food and beverage areas of hotels, with and without outsourced professional intervention. We evaluated 19 food and beverage areas in hotels in Porto Alegre, Rio do Sul, Brazil, using a checklist that was developed by a municipal surveillance team based on existing laws for good handling practices. The evaluation was done by a skilled professional in the food safety area on two occasions, at the beginning of the study (January to May 2013) and at the end (July to November 2014), and the establishments were classified as good, regular, or poor. After the baseline evaluation, an action plan listing the noncompliance found at each location was given to those responsible for the establishments, and a period of 1 year 6 months was stipulated for improvements to be made. In the repeat evaluation, those responsible for the establishments were asked whether they had hired an outsourced professional to assist them in the improvements. The hotels showed improvement during the repeat evaluation, but a significant increase in the percentage of overall adequacy was seen only in the food and beverages areas of the 12 hotels that used the intervention of an outsourced professional. The better percentage of adequacy in establishments with outsourced professional intervention underlines the importance of an external and impartial view of routine activities in the implementation of good handling practices.

Lipid profiles of oil from trout (Oncorhynchus mykiss) heads, spines and viscera: trout by-products as a possible source of omega-3 lipids?

Lipid profiles of fish oil extracted from trout heads, spines and viscera using supercritical carbon dioxide and Randall extraction with hexane were measured. The amount of unsaturated fatty acids (as a percentage of total fatty acids) was within the range of 72.6-75.3% in all the substrates. A significant presence of the most important omega-3 fatty acids was detected. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content in oil from spines, heads and viscera resulted to be 8.7% and 7.3%, 7.9% and 6.3%, and 6.4% and 6.0%, respectively. A low (≈3%), but worth noting, presence of lipids with omega-1 polyunsaturated fatty chains was observed in all the oils. Finally, significant differences were noticed in the relative amounts of triacylglycerides (TAG), diacylglycerides (DAG) and free fatty acids (FFA). Whereas oil from heads and spines was essentially composed of TAG (≈98%), in viscera oil the molar distribution ratio became TAG:DAG:FFA=87:8:5.

X chromosome and suicide.

Suicide completion rates are significantly higher in males than females in most societies. Although gender differences in suicide rates have been partially explained by environmental and behavioral factors, it is possible that genetic factors, through differential expression between genders, may also help explain gender moderation of suicide risk. This study investigated X-linked genes in suicide completers using a two-step strategy. We first took advantage of the genetic structure of the French-Canadian population and genotyped 722 unrelated French-Canadian male subjects, of whom 333 were suicide completers and 389 were non-suicide controls, using a panel of 37 microsatellite markers spanning the entire X chromosome. Nine haplotype windows and several individual markers were associated with suicide. Significant results aggregated primarily in two regions, one in the long arm and another in the short arm of chromosome X, limited by markers DXS8051 and DXS8102, and DXS1001 and DXS8106, respectively. The second stage of the study investigated differential brain expression of genes mapping to associated regions in Brodmann areas 8/9, 11, 44 and 46, in an independent sample of suicide completers and controls. Six genes within these regions, Rho GTPase-activating protein 6, adaptor-related protein complex 1 sigma 2 subunit, glycoprotein M6B, ribosomal protein S6 kinase 90 kDa polypeptide 3, spermidine/spermine N(1)-acetyltransferase 1 and THO complex 2, were found to be differentially expressed in suicide completers.

Gene expression profiling of suicide completers.

Despite strong evidence for a role of biological factors in the etiology and pathology of suicide, the study of traditional neurotransmitter systems has been able to explain only a small proportion of the neurobiology of what is now recognized as a complex genetic trait. The use of microarrays to simultaneously examine the expression levels of thousands of gene transcripts has vastly expanded our capacity to detect the involvement of additional genes and pathways in suicidality, and has opened many new avenues for the discovery of the biological underpinnings of suicide completion. This review examines microarray studies which have been used to identify genes displaying altered expression in suicide completers, and highlights some of the important methodological considerations and metabolic pathways which have emerged from these analyses.

Phenotypic variability, neurological outcome and genetics background of 6-pyruvoyl-tetrahydropterin synthase deficiency.

This study aimed to investigate the clinical variability and factors implied in the outcome of 6-pyruvoyl-tetrahydropterin synthase deficiency (PTPSd). Biochemical and clinical phenotype, treatment variables, and 6-pyruvoyl-tetrahydropterin synthase (PTS) genotype, were explored retrospectively in 19 Italian patients (12 males and 7 females, aged 4 months to 33 years). According to the level of biogenic amines in cerebrospinal fluid (CSF) at the diagnosis, the patients were classified as mild (6) (normal level) or severe (13) (abnormal low level) form (MF and SF, respectively). Blood Phe ranged from 151 to 1053 micromol/l in MF (mean +/- SD: 698 +/- 403) and 342-2120 micromol/l in SF (mean +/- SD: 1175 +/- 517) (p = 0.063). Patients with MF showed a normal neurological development (a transient dystonia was detected in one), while all SF patients except one presented with severe neurological impairment and only four had a normal neurological development. The outcome of the SF was influenced by the precocity of the treatment. Serial CSF examinations revealed a decline of 5-hydroxyindolacetic acid in MFs and an incomplete restoration of neurotransmitters in SFs: neither obviously affected the prognosis. PTS gene analysis detected 17 different mutations (seven so far unreported) (only one affected allele was identified in three subjects). A good correlation was found between genotype and clinical and biochemical phenotype. The occurrence of brain neurotransmitter deficiency and its early correction (by the therapy) are the main prognostic factors in PTPSd.

How individuals with phenylketonuria experience their illness: an age-related qualitative study.

BACKGROUND: The aim of the study was to explore the illness experience of individuals affected by phenylketonuria (PKU) and its differences in different patient age groups. METHODS: A qualitative-interpretative methodology was used through in-depth interviews. Textual data were explored using the principles of grounded theory. RESULTS: Forty-seven patients participated in the study, aged from 10 to >25 years old. The results suggested the age-related PKU experience: (1) a paradox, either to feel normal but isolated from the social context, or to be different while participating in the convivial aspects of the social being; and (2) the need for education about the disease tailored to the individual and growing needs. Specific themes seem to characterize each age range. CONCLUSIONS: This study constitutes a first attempt at understanding PKU from a non-medical-biological perspective.

Bio-drying of grape marc and other biomass: a comparison.

The winery industry produces every year in the world about 270 millions of hectolitres of wine. A consequent amount of grape marc is then generated that has to be somehow treated and processed. For this reason a technique to treat grape marc (bio-drying) was studied and applied at the University of Trento. Grape marc, as is, is not suitable for direct combustion because of its high water content. By bio-drying the lower heating value has been increased up to the limit for a good combustion. This result allows a decentralized management of a grape marc drying differently from the conventional solutions.

Biomass as an energy source: thermodynamic constraints on the performance of the conversion process.

In the present work an equilibrium model (gas-solid), based on the minimization of the Gibbs energy, has been used in order to estimate the theoretical yield and the equilibrium composition of the reaction products (syngas and char) of biomass thermochemical conversion processes (pyrolysis and gasification). The data obtained from this model have also been used to calculate the heating value of the fuel gas, in order to evaluate the overall energy efficiency of the thermal conversion stage. The proposed model has been applied both to partial oxidation and steam gasification processes with varying air to biomass (ER) and steam to carbon (SC) ratio values and using different feedstocks; the obtained results have been compared with experimental data and with other model predictions obtaining a satisfactory agreement.

Treating phenylketonuria: a single centre experience.

Hyperphenylalaninaemia (HPA) is an inherited disorder that results in raised plasma phenylalanine levels with a range of severities, including phenylketonuria (PKU). Since the first attempts at treatment using a low-phenylalanine diet and after more than 50 years of research, considerable progress has been made so we are now at a stage where mental retardation caused by high plasma phenylalanine can be prevented. We must, however, be aware of the new challenges we face in managing PKU. These include: maintaining optimal growth by providing enough phenylalanine without jeopardizing the child's psychomotor development; providing an optimal nutritional status that ensures other essential nutrients, such as long chain polyunsaturated fatty acids, are not excluded from the diet; ensuring optimal compliance to the dietary intervention; and considering patients' quality of life. New strategies, such as tetrahydrobiopterin (BH4) supplementation, need to be evaluated with regard to safety, efficacy and expected outcomes in specific types of HPA.

Combined transcranial and endoscopic nasal resection for esthesioneuroblastoma. Technical note.

Esthesioneuroblastoma is a rare malignant neoplasm arising in the nasal cavity. Huge esthesioneuroblastomas, extending into the ethmoid roof and the cribriform plate, or invading the anterior cranial fossa, have traditionally been treated by craniofacial resection. Because of the invasiveness and potentially disfiguring results of a transfacial approach, a new technique has been proposed, combining endoscopic nasal and anterior craniotomy resection. We describe the case of a young male presenting with a large esthesioneuroblastoma involving the nasal cavity and the anterior cranial fossa, causing a huge skull base destruction. A combined transcranial and endoscopic nasal resection resulted in a macroscopically total removal of the tumor. The operative technique is reviewed in detail, along with the method used for the reconstruction of the anterior skull base defect.

Phenylketonuria: dietary and therapeutic challenges.

PKU subjects need special attention in the definition of optimal supplementation of nutrients, which may be insufficient in relation to the type of diet and may otherwise manifest symptoms of deficit. In particular, it is necessary to pay great attention to the long-chain polyunsaturated fatty acid (LC-PUFA) levels in relation to correct development of the central nervous system. On the basis of numerous beneficial effects currently known, a permanent supplementation with LC-PUFAs, in particular with docosahexaenoic acid, should be considered. Moreover, new formulas, Phe-free peptides, and 'modulated' amino acid preparations might help in preventing nutritional deficiencies and imbalances, with the ultimate aim of improving growth. New strategies--such as supply of tetrahydrobiopterin--need to be optimized in terms of targets, patients and expected outcomes.

Double blind placebo control trial of large neutral amino acids in treatment of PKU: effect on blood phenylalanine.

Large neutral amino acids (LNAA) have been used on a limited number of patients with phenylketonuria (PKU) with the purpose of decreasing the influx of phenylalanine (Phe) to the brain. In an open-label study using LNAA, a surprising decline of blood Phe concentration was found in patients with PKU in metabolic treatment centres in Russia, the Ukraine, and the United States. To validate the data obtained from this trial, a short-term double-blind placebo control study was done using LNAA in patients with PKU, with the participation of three additional metabolic centres--Milan, Padua and Rio de Janeiro. The results of the short trial showed significant lowering of blood Phe concentration by an average of 39% from baseline. The data from the double-blind placebo control are encouraging, establishing proof of principle of the role of orally administered LNAA in lowering blood Phe concentrations in patients with PKU. Long-term studies will be needed to validate the acceptability, efficacy and safety of such treatment.

Pharmacokinetics of orally administered tetrahydrobiopterin in patients with phenylalanine hydroxylase deficiency.

The oral loading test with tetrahydrobiopterin (BH(4)) is used to discriminate between variants of hyperphenylalaninaemia and to detect BH(4)-responsive patients. The outcome of the loading test depends on the genotype, dosage of BH(4), and BH(4) pharmacokinetics. A total of 71 patients with hyperphenylalaninaemia (mild to classic) were challenged with BH(4) (20 mg/kg) according to different protocols (1 x 20 mg or 2 x 20 mg) and blood BH(4) concentrations were measured in dried blood spots at different time points (T(0), T(2), T(4), T(8), T(12), T(24), T(32) and T(48 h)). Maximal BH(4) concentrations (median 22.69 nmol/g Hb) were measured 4 h after BH(4) administration in 63 out of 71 patients. Eight patients presented with maximal BH(4) concentrations approximately 44% higher at 8 h than at 4 h. After 24 h, BH(4) blood concentrations dropped to 11% of maximal values. This profile was similar using different protocols. The following pharmacokinetic parameters were calculated for BH(4) in blood: t (max) = 4 h, AUC (T(0-32)) = 370 nmol x h/g Hb, and t (1/2) for absorption (1.1 h), distribution (2.5 h), and elimination (46.0 h) phases. Maximal BH(4) blood concentrations were not significantly lower in non-responders and there was no correlation between blood concentrations and responsiveness. Of mild PKU patients, 97% responded to BH(4) administration, while one was found to be a non-responder. Only 10/19 patients (53%) with Phe concentrations of 600-1200 mumol/L responded to BH(4) administration, and of the patients with the severe classical phenotype (blood Phe > 1200 mumol/L) only 4 out of 17 patient responded. An additional 36 patients with mild hyperphenylalaninaemia (HPA) who underwent the combined loading test with Phe+BH(4) were all responders. Slow responders and non-responders were found in all groups of HPA.

Abdominal ultrasonography in inheredited diseases of carbohydrate metabolism.

PURPOSE: To determine the usefulness of abdominal sonography in inherited diseases of carbohydrate metabolism. MATERIALS AND METHODS: Thirty patients (age range, 4 months to 27 years) with glycogen storage diseases, galactosemia, disorders of fructose metabolism were studied with sonography. Echogenicity of the liver, sonographic dimensions of liver, kidneys and spleen were evaluated. Plasma blood parameters (ALT, AST, total cholesterol, triglycerides) were determined. RESULTS: Liver was enlarged in 21/22 patients (95.4%) with glycogen storage diseases, in both subjects with disorders of fructose metabolism, and in 2/6 patients (33.3%) with galactosemia. Hepatic echogenicity was increased in 20/22 patients (90.9%) with glycogen storage diseases, and in the subject with hereditary fructose intolerance. Patients with galactosemia did not show increased liver echogenicity. Both kidneys were enlarged in 8/17 patients (47.0%) with glycogen storage disease type I. Subjects with increased hepatic echogenicity exhibited higher plasma concentrations of any blood parameter than the others with normal echogenicity (p<0.05). CONCLUSIONS: Sonography can be useful in identification of inherited diseases of carbohydrate metabolism even if further examinations are necessary for an ultimate diagnosis.