Search

This research was aimed at providing an accurate low-dose benzene exposure assessment method, prospectively suitable to exposure limit values in the low ppb range, such as in the present-day chemical, petrochemical, foundry and pharmaceutical industry. The project addresses the need for a robust and fully validated method of personal exposure measurements considering that the Occupational Exposure Limit Value for benzene will be significantly lowered in the next few years. Diffusive sampling offers a reliable alternative to pumped sampling methods, intrinsic safety in potentially explosive atmospheres, lightness and ease of use. The tested diffusive sampler is radiello® with the RAD145 adsorption substrate. This configuration is packed with graphitised charcoal suitable for thermal desorption and analysis by HRGC-FID or HRGC-MS.The experiments have been conducted following the ISO 23320 standard in the range from 0.005 to 0.1 ppm (16 to 320 µg/m3), yielding a full validation of the sampling and analytical method. The sampler performances have fulfilled all requisites of the ISO 23320 standard, in particular: bias due to the selection of a non-ideal sorbent is lower than 10 % (no significant back diffusion of benzene due to concentration change in the atmosphere); bias due to storage of samples for up to 2 months is lower than 10 %; nominal uptake rate for benzene on RAD145 is 32.3 mL/min; expanded uncertainty of the sampling and analytical method is 22.1 % in the concentration range from 80 to 320 µg/m³. The sampling and analytical method is therefore fit-for-purpose for the personal exposure measurements aimed at testing compliance with lowered occupational exposure limit values for benzene. The method is also fit for short duration exposure monitoring related to specific tasks, and other volatile organic compounds, usually found in the same workplaces, such as aliphatic and aromatic hydrocarbons and some oxygenated compounds, have been also studied. In particular, n-hexane and isopropyl benzene (also known as cumene), whose classification is currently under revision, can be efficiently monitored by this technique.

Background: Subjects with mutations in the Ataxia-Telangiectasia mutated (ATM) gene encoding for ATM kinase have a greater predisposition to develop atherosclerosis, but the mechanism behind this phenomenon is not yet understood. NADPH oxidase type 2 may play a role in this process, leading to endothelial dysfunction and an increased susceptibility to thrombosis. The purpose of this study was to assess the redox state in individuals with ATM mutations and determine its impact on endothelial function. Methods: In this cross-sectional study, twenty-seven children with ataxia telangiectasia (AT) (13 males and 14 females, mean age 15.1 ± 7.6 years) were compared with 27 controls (13 males and 14 females, mean age 14.6 ± 8.4 years) matched for age and gender. Additionally, 29 AT parents with heterozygous mutation of ATM (h-ATM) gene, and 29 age- and gender-matched controls were included. Endothelial function was evaluated through brachial flow-mediated dilation (FMD) and the assessment of nitric oxide (NO) bioavailability. Oxidative stress was evaluated by measuring serum activity of soluble NOX2-dp (sNOX2-dp), hydrogen peroxide (H2O2) production, and hydrogen breakdown activity (HBA). Thrombus formation was assessed through the Total Thrombus Formation Analysis System (T-TAS). Results: AT children and parents with heterozygous ATM mutations exhibited significantly lower FMD, HBA, and NO bioavailability as compared to age and gender matched controls. AT children and ATM carrier of heterozygous ATM mutations had significantly higher concentrations of sNOX2-dp and H2O2 as compared to controls. Compared to the respective controls, AT children and their parents, who carried heterozygous ATM mutation, showed an accelerated thrombus growth as revealed by reduced occlusion time. Multivariable linear regression analysis revealed that sNOX2 (standardized coefficient β: −0.296; SE: 0.044; p = 0.002) and NO bioavailability (standardized coefficient β: 0.224; SE: 0.065; p = 0.02) emerged as the only independent predictive variables associated with FMD (R2: 0.44). Conclusions: This study demonstrates that individuals with ATM mutations experience endothelial dysfunction, increased oxidative stress, and elevated thrombus formation. These factors collectively contribute to the heightened susceptibility of these individuals to develop atherosclerosis.

Background: The bleeding risk of patients with atrial fibrillation (AF) changes over time. Most studies thus far evaluated only the baseline bleeding risk with discordant results. The impact of incident thrombocytopenia during direct oral anticoagulant (DOAC) therapy and its relation to bleeding has not been previously investigated. Objectives: To investigate the incidence rate of thrombocytopenia and major bleeding (MB) risk in AF patients on DOACs. Methods: Prospective ongoing ATHEROsclerosis in Atrial Fibrillation study including patients with nonvalvular AF on DOACs. Incident thrombocytopenia was defined as a platelet count

Up to 90 % of death from solid tumors are caused by metastases. By 2040, breast cancer (BC) is predicted to increase to over 3 million new cases. Additionally, with the personalization and intensification of BC follow-up, many patients will relapse with oligometastatic disease (OMD). Over the past decades, advances in treatment planning, image guidance, target position reproducibility, and online tracking, along with a compelling radiobiological rationale, have led to the implementation of Stereotactic Body Radiation Therapy (SBRT). This has become a valid ablative treatment option for OMD patients.However, there are still concerns about which patients benefit the most from ablative treatment. In this review, we will analyze the literature regarding SBRT for OMD in BC patients. We aim to present the current data on its effectiveness and define the optimal tailored scenarios for SBRT outcomes.

Searching for positive selection signals across genomes has identified functional genetic variants responding to environmental change. In Native Americans of Mexico, we used the fixation index (Fst) and population branch statistic (PBS) to identify SNPs suggesting positive selection. The 103 most differentiated SNPs were tested for associations with metabolic traits, the most significant association was FADS2/rs174616 with body mass index (BMI). This variant lies within a linkage disequilibrium (LD) block independent of previously reported FADS selection signals and has not been clearly associated with metabolic phenotypes. We tested this variant in two independent cohorts with cardiometabolic data. In the Genetics of Atherosclerotic Disease (GEA) cohort, the derived allele (T) was associated with increased BMI, lower LDL-C levels and a decreased risk of subclinical atherosclerosis in women. Significant gene-diet interactions affected lipid, apolipoprotein and adiponectin levels with differences according to sex, involving mainly total and complex dietary carbohydrate%. In the Genotype-related Effects of PUFA trial, the derived allele was associated with lower Δ-6 desaturase activity and erythrocyte membrane dihomo-gamma-linolenic acid (DGLA) levels, and with increased Δ-5 desaturase activity and eicosapentaenoic acid levels. This variant interacted with dietary carbohydrate% affecting Δ-6 desaturase activity. Notably, the relationship of DGLA and other erythrocyte membrane LC-PUFA indices with HOMA-IR differed according to rs174616 genotype, which has implications regarding how these indices should be interpreted. In conclusion, this observational study identified rs174616 as a signal suggesting selection in an independent linkage disequilibrium block, was associated with cardiometabolic and erythrocyte measurements of LC-PUFA in two independent Mexican cohorts and showed significant gene-diet interactions.

Delivering piglets is one of the most energy-demanding activities sows undergo in their lifetime. Sows can have myometrial contractions from 2 to 12 h before the first piglet is expelled as well as a nest-building behavior. Thus, when the first piglet is delivered, the female has already used part of her energy supply. When the sow gets exhausted due to lack of energy, the farrowing process can be interrupted, causing damage to the viability and vitality of the piglets. In the present study, we evaluated the effects of feeding sows an energy supplement at the onset of farrowing on farrowing kinetics and piglet vitality. The energy supplement consisted of a blend of carbohydrates and glycerol which provides 439 kJ of metabolizable energy per kg of metabolic weight. A total of 180 sows were used. At the onset of farrowing, sows were assigned to one of the following treatments: sows that were not supplied energy at the onset of farrowing, serving as controls (CON, n = 85); sows fed the energy supplement at the onset of farrowing (ESP, n = 95). Farrowing kinetics, blood glucose concentration, and piglet vitality were recorded for each sow. Blood glucose concentration was assessed by puncturing the auricular vein and using a portable glucometer at four different time points: after the birth of the 1st piglet (T0), and at 20 (T20), 40 (T40), 80 (T80), and 180 (T180) min after the birth of the 1st piglet. The vitality of the 1st, 6th, 12th, 17th, and 20th piglet born was evaluated using the Apgar score. Piglet birth weight and average colostrum intake were measured. The farrowing duration was 20 min shorter (P 0.05). In conclusion, feeding a blend of carbohydrates and glycerol as an energy supplement for farrowing sows improved farrowing kinetics and piglet vitality score.

Metastatic breast cancer (BC) remains an incurable disease. Besides endocrine and targeted agents, chemotherapy is still a relevant therapeutic option for this disease. Recently, antibody-drug conjugates (ADCs) have shown to overcome the lack of tumor specificity and systemic toxicity typically associated with traditional chemotherapies, thus improving the therapeutic index. To effectively exploit this technological breakthrough, identification of optimal target antigens (Ags) is of utmost importance. To make the ideal target, differential expression of target Ags between healthy and cancer tissues, as well as specific mechanisms of ADC internalization after Ag-antibody interaction are required.Therefore, several in silico strategies to identify and characterize new promising candidate Ags have been developed. If initial in vitro and in vivo positive data are documented, thus providing a biological rationale for further Ag investigation, early phase clinical trials are designed. In BC, these strategies have already led to the development of effective ADCs, namely trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), primarily targeting HER2 and TROP-2. However, promising new Ags are currently under investigation, with encouraging results especially coming from targeting HER3, FRα, Tissue Factor, LIV-1, ROR1-2, and B7–H4.In this review, we describe the landscape of emergent and future potential targets (i.e., other than HER2 and TROP-2) investigated in BC for ADC development. Predominant target expression, function, preclinical rationale, potential clinical implication, as well as preliminary clinical trial results are provided.

Summary: The host-microbiome associations occurring on the skin of vertebrates significantly influence hosts’ health. However, the factors mediating their interactions remain largely unknown. Herein, we used integrated technical and ecological frameworks to investigate the skin metabolites sustaining a beneficial symbiosis between tree frogs and bacteria. We characterize macrocyclic acylcarnitines as the major metabolites secreted by the frogs’ skin and trace their origin to an enzymatic unbalance of carnitine palmitoyltransferases. We found that these compounds colocalize with bacteria on the skin surface and are mostly represented by members of the Pseudomonas community. We showed that Pseudomonas sp. MPFS isolated from frogs’ skin can exploit acylcarnitines as its sole carbon and nitrogen source, and this metabolic capability is widespread in Pseudomonas. We summarize frogs’ multiple mechanisms to filter environmental bacteria and highlight that acylcarnitines likely evolved for another function but were co-opted to provide nutritional benefits to the symbionts.

Coffee, the most globally prevalent beverage, entails environmental and economic consequences due to the high content of toxic compounds in leftover from brewing. Waste-to-energy technologies propose recovering energy from solid or liquid wastes via various treatment methods. This study investigates the environmental performance of the spent coffee ground application in pellet production as a valuable bio-product by life cycle assessment. System boundaries comprise four stages: (1) spent coffee ground collection; (2) pellet production; (3) thermal energy generation; and (4) waste disposal. The LCA model is interpreted by ReCipe 2016 in both midpoint and endpoint levels per 1 MJ of thermal energy as functional unit. Alternative waste-to-energy approaches into transesterification, pyrolysis, and direct combustion of spent coffee ground are also assessed. The impact assessment shows that the pelletizing process significantly contributes to all impact categories except ozone formation and terrestrial ecotoxicity, which is influenced primarily by the transportation process in the spent coffee ground collection stage. The spent coffee ground pellet can lead to climate change mitigation, and reduction in freshwater eutrophication and use of resources due to credits from ash disposed to landfill.Biodiesel is the worst potential option among alternative scenarios, while pellet production and bio-oil demonstrate the most favorable environmental profiles for all impact categories. Damage assessment indicates that pellet production and alternative scenarios mainly influence human health.

A 77-year-old Caucasian man, a former surveyor in a chemical company, underwent a chest X-ray (CXR) as a follow-up exam for a melanoma of the back, surgically removed.CXR showed interstitial thickening in both lower lobes; then, a high-resolution computed tomography of the chest (HRCT) was performed to further investigate these findings, revealing multiple small, calcified nodules with branching appearance at both lung bases.Clinical examination and exposure history were negative, except for a decrease in diffusing capacity for carbon monoxide resulting from pulmonary function tests.Surgical lung biopsy was performed; histology revealed numerous nodules and branching tubules of bone tissue, some of which with marrow elements.After multidisciplinary discussion of the case, a diagnosis of idiopathic diffuse pulmonary ossification (DPO) was considered.Clinical status of the patient was stable over time, despite the increase in extent of calcifications.DPO is an uncommon condition that should be considered in different clinical-radiological settings; multidisciplinary discussion is essential for the final diagnosis.

Diffuse panbronchiolitis (DPB) is a rare disease characterized by bronchiolitis and chronic sinusitis. Being largely restricted to East Asia, its actual incidence in Caucasian patients is probably underestimated. DPB has been described in association with thymic neoplasms, mainly arising as a consequence of immune dysregulation. We present a rare case of DPB diagnosed in a 69-year-old Caucasian man who had undergone surgery for stage 2A thymoma a year before. The patient came to our hospital complaining of exertional dyspnea and productive cough, with a persistent lung consolidation described at chest X-rays. High resolution computed tomography (CT) showed diffuse centrilobular micronodules and solid nodules, tree-in-bud opacities, peripheral consolidations and cylindrical bronchiectasis. Sinus disease was also demonstrated by CT. Analysis of bronchoalveolar lavage showed marked granulocyte inflammation and allowed the isolation of Haemophilus Influenzae. Consequently, the diagnosis of DPB was reached by integrating clinical, and radiological data. Long-term therapy with azithromycin was prescribed, and was found to be effective in controlling symptoms and reducing radiological abnormalities at 6-month clinical and CT follow-up. Confidence with the radiological presentation and clinical significance of DPB is necessary, since the condition is responsive and reversible to long-term macrolide treatment, the effect of which is mainly attributed to an anti-inflammatory, and immunoregulatory action.

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. Objectives: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. Methods: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. Results: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. Conclusions: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.

Progesterone (P4) plays a key role in pregnancy establishment and maintenance; during early pregnancy, P4 stimulates the production and release of uterine secretions necessary for conceptus growth prior to implantation; therefore, exogenous P4 supplementation may improve embryo development. This study evaluated the effects of supplementation during early pregnancy with long-acting injectable progesterone or altrenogest on embryonic characteristics of sows and gilts. Thus, a total of 32 sows and 16 gilts were used. On day 6 of pregnancy sows and gilts were allocated to one of the following groups: non-supplemented; supplemented with 20 mg of altrenogest, orally, from days 6 to 12 of pregnancy; supplemented with 2.15 mg/kg of long-acting injectable progesterone on day 6 of pregnancy. Animals were killed on day 28 of pregnancy, and ovulation rate, embryo survival, embryo weight, crown-to-rump length, uterine glandular epithelium and endometrial vascularization were assessed. Treatments had no effect on pregnancy rate, embryo survival or endometrial vascular density (P > 0.05). Non-supplemented gilts presented larger and heavier embryos compared to gilts from supplemented groups (P < 0.05). Sows in the altrenogest group presented larger and heavier embryos compared to non-supplemented sows and sows supplemented with long-acting injectable progesterone. In conclusion, supplementation of sows and gilts with progestagen from day 6 of pregnancy can be used as a means to improve embryo survival without deleterious effects.

The use of additives such as ractopamine (Rac) in pregnant sows during early-mid pregnancy is an alternative to increase foetal and progeny growth and development. However, Rac supplementation in finishing pigs can lead to behavioural and physiological changes similar to the typical stress responses. The objective of this study was to evaluate the effects of dietary supplementation with Rac in pregnant sows from day 25 to 50 of gestation (pre-hyperplastic stage) on piglet’s vitality, blood parameters, number, diameter and perimeter of muscle fibres in semitendinosus muscle and developmental characteristics of piglets at birth to weaning. Forty-one hybrid sows were divided into three dietary treatments: (1) control diet without Rac (control), (2) addition of 10 mg/kg of Rac (Rac10) and (3) addition of 20 mg/kg of Rac (Rac20). Higher numbers of low-vitality piglets (P

The use of altrenogest (ALT) supplementation for oestrous synchronization improves subsequent reproductive performance of gilts and sows. However, the causes of this improvement in reproductive performance after ALT treatment are not fully/clearly understood. The objective of this study was to evaluate the effects of ALT supplementation for oestrous synchronization in gilts on the endometrial glands and embryonic development characteristics at 28 days of pregnancy. Pregnant gilts were divided into two experimental treatments: Control (did not receive ALT; n = 9 gilts) and ALT (ALT feeding at 20 mg/day for 18 days; n = 9 gilts). At 28 days of pregnancy, six gilts from each treatment were slaughtered, and reproductive tracts were immediately evaluated. There was no statistical difference (P > 0.05) between treatments regarding ovulation rate, number of embryos, number of vital embryos and number of non-vital embryos. Embryo weight, length and embryonic vesicle weight were lower in ALT treatment compared with Control (P < 0.01), and it was lower in the cervical uterine region compared with apex uterine region, respectively (P < 0.05). Higher values of gland duct area, gland duct perimeter, percentage of the glandular area and total endometrial area were observed in ALT treatment compared with Control (P < 0.05). The use of ALT during 18 days for oestrous synchronization in gilts increased the gland duct area, perimeter and total endometrial area but did not increase the embryo number and embryo size at day 28 of pregnancy.

The farrowing process is one of the most energy-demanding activities for the modern hyperprolific sow. This study evaluated the effects of supply of energy on the expected date of farrowing on the farrowing kinetics and piglets’ performance during the first 24 h after birth. A total of 80 sows were used. The sows and their respective litters were considered as the experimental unit. On the expected day of farrowing, the sows were allocated to one of the following groups: sows that did not have access to feed from farrowing induction until the end of the farrowing process (CON, n = 40); sows fed 500 g of energetic supplement, which consisted of 250 g of the basal lactation diet plus 250 g of cane sugar, 18 h after farrowing induction (SUP, n = 40). The farrowing duration, farrowing assistance, birth interval, number of total born, stillborn and mummified piglets were recorded for each sow. Piglets were weighed individually at birth and 24 h later. The interval from birth to first suckle was evaluated individually for each piglet in 16 randomly selected litters (eight litters per treatment group). Blood glucose concentrations of six sows were measured shortly after expulsion of the first piglet. Farrowing duration, farrowing assistance and stillborn rate tended to be greater (P = 0.06, P = 0.09 and P = 0.07, respectively) in sows from the CON group compared to sows from the SUP group. However, there was no difference (P > 0.05) between the groups for birth interval. Colostrum intake was greater (P < 0.05) for piglets from the SUP group compared to piglets from the CON group. Additionally, BW gain of the piglets suckling the SUP group was greater (P < 0.05) than those suckling the CON group at 24 h after birth. The blood glucose concentrations during the expulsive stage of farrowing were greater (P < 0.05) in the SUP group than for sows from the CON group. In conclusion, supplying modern hyperprolific sows energy on the expected day of farrowing is a valuable nutritional intervention to improve the farrowing kinetics and piglets’ performance in early life.

Background: Bromelia laciniosa Mart. ex Schult. & Schult.f. is a Bromeliaceae plant species from the Brazilian Caatinga, popularly used for the treatment of childhood colic, diarrhea, fever, jaundice, dandruff and hepatitis. The objective of this work was to evaluate the chemical composition and antimicrobial activity of the species B. laciniosa. Method: In this study, we evaluated the antimicrobial activity of ethanolic extract from the leaves of B. laciniosa by microdilution MIC method, and provided a comprehensive panel of B. laciniosa’s metabolite composition through mass spectrometry (MS) coupled to gas chromatography (GC–MS) and liquid chromatography (LC-MS). Results: B. laciniosa ethanolic extract inhibited Staphylococcus aureus growth at the lowest concentration tested. The GC–MS analysis revealed 45 non-polar metabolites, including campesterol, palmitic acid, oleic acid and α-tocopherol. Isolation and structural elucidation by NMR experiments supported the identification of cirsilineol (1), and the mixture of steroids β-sitosterol (2) and stigmasterol (3). The LC-MS metabolite profiling was assisted by Global Natural Product Social Molecular Networking (GNPS) and led to the putative annotation of 22 metabolites, consisting of phenylpropanoids, C- and O-glycosyl-flavonoids and fatty acids. In total, 39 chemical constituents are being described for the first time in B. laciniosa. Conclusions: The results show the diversity of secondary metabolites in the species B. laciniosa as well as antibacterial activity against S. aureus.

Paralelo à pandemia de COVID-19, Brasil continuou a enfrentar doenças tropicais como a Dengue. Mas, segundo os Boletins Epidemiológicos, os casos de Dengue no Brasil em 2020 foram subnotificados. O objetivo deste estudo é identificar a frequência de coinfecções por SARS-CoV-2 e DENV e avaliar a gravidade das coinfecções em relação às monoinfecções. Amostras de plasma de 143 pacientes COVID-19 de 2020, 15 doadores saudáveis e 15 pacientes com infecção por DENV de 2013 foram avaliados. Ensaios imunoenzimáticos utilizando testes comerciais foram realizados: Anti-SARS-CoV-2 IgA e IgG (Euroimmun), proteína NS1 do DENV (Platelia), anti-DENV IgM e IgG (Euroimmun). Dentre os doadores saudáveis foi detectado 75% de IgG anti-DENV; dentre os COVID-19, 75,9% IgA anti SARS-CoV-2, 66,7% IgG anti SARS-CoV-2, 80% IgG anti-DENV e por fim, IgM anti-DENV em 6 (4%) casos; dentre os casos confirmados de Dengue, IgA anti SARS-CoV-2 foi detectado em 1 caso (8,3%), IgG anti-SARS-CoV-2 em nenhum caso, NS1 de DENV em 41,7% e IgM anti-DENV em 33,3%. De acordo com o desfecho clínico, a presença ou não de sinais/sintomas no momento da coleta da amostras, os pacients COVID-19 foram reagrupados em brandos/moderados, graves, óbitos e aqueles já recuperados dos sinais/sintomas. Os 6 casos de COVID-19/Dengue também foram avaliados separadamente. Observamos que idosos são maioria em COVID-19 graves e óbitos; mulheres são maioria dos COVID-19 recuperados; tosse é mais frequente em COVID-19; cefaléia, mialgia/artralgia e vômito são mais frequentes na Dengue; pacientes COVID-19/Dengue foram aqueles com alterações vasculares. As DO IgA anti-SARS-CoV-2 foram mais elevadas nos COVID-19 graves, óbitos e COVID-19/Dengue comparados aos doadores saudáveis e pacientes Dengue; as DO IgG anti-SARS-CoV-2 foram mais elevadas nos COVID-19 comparados aos doadores saudáveis e pacientes Dengue; as DO IgA e IgG anti SARS-CoV-2 foram maiores nos COVID-19 óbitos comparado aos recuperados; COVID-19 recuperados ainda mantém níveis de detecção de IgA e IgG anti-SARS-CoV-2 detectáveis. Há diferenças clínicas, demográficas e de detecção de anticorpos anti-SARS-CoV-2 entre pacientes COVID-19 de acordo com o desfecho clínico e dias da doença. Até o momento, 6% de casos de COVID-19 com sugestiva infecção recente por DENV foram identificados. Os casos de coinfecção SARS-CoV-2/DENV estão sendo confirmados por RT-PCR DENV e esperamos a partir desses resultados, tirar mais conclusões.

A esquistossomose continua sendo um problema de saúde pública em muitas partes do mundo. Os pacientes portadores da forma hepatoesplênica da esquistossomose mansoni, podem evoluir com hipertensão porta não cirrótica e descompensar com sangramento digestivo ou ascite. O objetivo desse trabalho é relatar o primeiro tratamento com Transjugular Intrahepatic Portosystemic Shunt (TIPS) de paciente acompanhado no Ambulatório de Esquistossomose, Departamento de Moléstias Infecciosas e Parasitárias, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC/FMUSP), portador de esquistossomose mansoni hepatoesplênica, ascite refratária e trombose de veia porta, realizado pelo Serviço de Radiologia Vascular e Intervencionista (InRad/ FMUSP). Optou-se pelo cateterismo da veia hepática média e confecção de comunicação desta com o ramo esquerdo da veia porta. Dilatou-se o trajeto parenquimatoso com balão de angioplastia, posicionando stent revestido Viatorr (10 por 80 mm). Calibrou-se o shunt com balão, 9 mm de diâmetro, resultando gradiente portossistêmico final de 8 mmHg. O paciente evoluiu internado por sete dias sem deterioração das funções hepática ou renal, ou sinais de encefalopatia hepática, além de perviedade do TIPS e normalização do fluxo portal hepatopetal, ao ultrassom doppler abdominal. No seguimento ambulatorial reduziram-se progressivamente as doses de diuréticos. Após um mês, o paciente perdeu 22 kg, regrediu ascite, edemas e o USG Doppler abdominal resultou em TIPS pérvio com fluxo normal. O TIPS é uma medida pouco invasiva e duradoura, evitando acessos frequentes ao sistema de saúde e pode representar uma ferramenta para o tratamento da ascite refratária resultante da hipertensão porta esquistossomótica.

Summary: Angiotensin II (AngII) is a peptide hormone that affects the cardiovascular system, not only through typical effects on the vasculature, kidneys, and heart, but also through less understood roles mediated by the brain and the immune system. Here, we address the hard-wired neural connections within the autonomic nervous system that modulate splenic immunity. Chronic AngII infusion triggers burst firing of the vagus nerve celiac efferent, an effect correlated with noradrenergic activation in the spleen and T cell egress. Bioelectronic stimulation of the celiac vagus nerve, in the absence of other challenges and independently from afferent signals to the brain, evokes the noradrenergic splenic pathway to promote release of a growth factor mediating neuroimmune crosstalk, placental growth factor (PlGF), and egress of CD8 effector T cells. Our findings also indicate that the neuroimmune interface mediated by PlGF and necessary for transducing the neural signal into an effective immune response is dependent on α-adrenergic receptor signaling.

Aim: We explored the physical activity (PA) level and the variation in glycaemic control in children with type 1 diabetes (T1D) before and during the lockdown. Then, we proposed an online training program supported by sport-science specialists. Methods: Parents of children with T1D (

There is a growing body of knowledge about children as moral agents and their capacity and interest to participate in healthcare and research discussions/decisions that affect them. Although this has led to some research and practice improvements that have better-recognized children’s voices, this trend has not been globally embraced, especially within Sub-Saharan Africa. Objective: This study examines and analyzes the rights of children to participate in healthcare and research discussions and decisions within the normative discourse of child protection laws in Nigeria. Method: We conducted a normative documentary analysis based on five of the principal Nigerian child protection legislative documents enacted from 1999 to 2019. Results: Findings demonstrated that Nigerian legislation acknowledges the participation rights of children in healthcare and research. However, the normative document also emphasized children’s obligation to the given privileges in the form of respect to parents/guardians, superiors, and elders. Conclusion: Norms regulating the rights of children are in existence in Nigeria. Nevertheless, legal guidance to ethical practice in healthcare have been generalized and has not upheld the idea of dignity and liberty of children. We recommend that Nigeria should reconsider the code of ethical practices in the fields of health and research to give children the participatory authority that could provide active involvement and compliance.

Monocyte chemoattractant protein-1 (MCP-1)-induced monocyte chemotaxis is a major event in inflammatory disease. Our prior studies have demonstrated that MCP-1-dependent chemotaxis requires release of arachidonic acid (AA) by activated cytosolic phospholipase A2 (cPLA2). Here we investigated the involvement of AA metabolites in chemotaxis. Neither cyclooxygenase nor lipoxygenase pathways were required, whereas pharmacologic inhibitors of both the cytochrome-P450 (CYP) and the soluble epoxide hydrolase (sEH) pathways blocked monocyte chemotaxis to MCP-1. To verify specificity, we demonstrated that the CYP and sEH products epoxyeiscosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs), respectively, restored chemotaxis in the presence of the inhibitors, indicating that sEH-derived products are essential for MCP-1-driven chemotaxis. Importantly, DHETs also rescued chemotaxis in cPLA2-deficient monocytes and monocytes with blocked Erk1/2 activity, because Erk controls cPLA2 activation. The in vitro findings regarding the involvement of CYP/sEH pathways were further validated in vivo using two complementary approaches measuring MCP-1-dependent chemotaxis in mice. These observations reveal the importance of sEH in MCP-1-regulated monocyte chemotaxis and may explain the observed therapeutic value of sEH inhibitors in treatment of inflammatory diseases, cardiovascular diseases, pain, and even carcinogenesis. Their effectiveness, often attributed to increasing EET levels, is probably influenced by the impairment of DHET formation and inhibition of chemotaxis.

We examined the effects of three high-fat diets (HFD), differing in the percentage of total calories from saturated fat (SF) (6%, 12%, and 24%) but identical in total fat (40%), on body composition, macrophage behavior, inflammation, and metabolic dysfunction in mice. Diets were administered for 16 weeks. Body composition and metabolism [glucose, insulin, triglycerides, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), total cholesterol (TC)] were examined monthly. Adipose tissue (AT) expression of marker genes for M1 and M2 macrophages and inflammatory mediators [Toll-like receptor (TLR)-2, TLR-4, MCP-1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, suppressor of cytokine signaling (SOCS)1, IFN-γ] was measured along with activation of nuclear factor kappa-B (NFκB), c-Jun N-terminal kinase (JNK), and p38- mitogen-activated protein kinase (MAPK). AT macrophage infiltration was examined using immunohistochemistry. Circulating MCP-1, IL-6, adiponectin, and leptin were also measured. SF content, independent of total fat, can profoundly affect adiposity, macrophage behavior, inflammation, and metabolic dysfunction. In general, the 12%-SF diet, most closely mimicking the standard American diet, led to the greatest adiposity, macrophage infiltration, and insulin resistance (IR), whereas the 6%-SF and 24%-SF diets produced lower levels of these variables, with the 24%-SF diet resulting in the least degree of IR and the highest TC/HDL-C ratio. Macrophage behavior, inflammation, and IR following HFD are heavily influenced by dietary SF content; however, these responses are not necessarily proportional to the SF percentage.

When making decisions, people sometimes deviate from normative standards. While such deviations may appear to be alarmingly common, examining individual differences may reveal a more nuanced picture. Specifically, the personality factor of need for cognition (i.e., the extent to which people engage in and enjoy effortful cognitive activities; Cacioppo & Petty, 1982) may moderate decision makers’ susceptibility to bias, as could personality factors associated with being a leader. As part of a large-scale assessment of high-level leaders, participants completed a battery of decision-making competence and personality scales. Leaders who scored higher on need for cognition performed better on two of four components of a decision-making competence measure: framing and honoring sunk costs. In addition, the leader sample performed better than published controls. Thus, both individual differences in need for cognition and leadership experience moderate susceptibility to decision biases. Implications for broader theories of individual differences and bias are discussed.

Background and Aims: The SARS-CoV-2 pandemic has overwhelmed the treatment capacity of the health care systems during the highest viral diffusion rate. Patients reaching the emergency department had to be either hospitalized (inpatients) or discharged (outpatients). Still, the decision was taken based on the individual assessment of the actual clinical condition, without specific biomarkers to predict future improvement or deterioration, and discharged patients often returned to the hospital for aggravation of their condition. Here, we have developed a new combined approach of omics to identify factors that could distinguish coronavirus disease 19 (COVID-19) inpatients from outpatients. Methods: Saliva and blood samples were collected over the course of two observational cohort studies. By using machine learning approaches, we compared salivary metabolome of 50 COVID-19 patients with that of 270 healthy individuals having previously been exposed or not to SARS-CoV-2. We then correlated the salivary metabolites that allowed separating COVID-19 inpatients from outpatients with serum biomarkers and salivary microbiota taxa differentially represented in the two groups of patients. Results: We identified nine salivary metabolites that allowed assessing the need of hospitalization. When combined with serum biomarkers, just two salivary metabolites (myo-inositol and 2-pyrrolidineacetic acid) and one serum protein, chitinase 3-like-1 (CHI3L1), were sufficient to separate inpatients from outpatients completely and correlated with modulated microbiota taxa. In particular, we found Corynebacterium 1 to be overrepresented in inpatients, whereas Actinomycetaceae F0332, Candidatus Saccharimonas, and Haemophilus were all underrepresented in the hospitalized population. Conclusion: This is a proof of concept that a combined omic analysis can be used to stratify patients independently from COVID-19.

White cord syndrome is a rare condition involving sudden neurological deterioration following a decompressive cervical spinal surgery and characterized by the appearance of hyperintensity on T2-weighted magnetic resonance imaging. We present a report of a pediatric male patient who presented with the condition. This case shows that white cord syndrome can also be present in pediatric patients. We provide a brief review of the literature highlighting the main radiologic findings.

Background: The aim of this study is to illustrate the historical role of the International Commission on Occupational Health (ICOH) congresses as an arena where national and international occupational medicine can dialogue and as the first example of scientific transferability of the research and prevention results that have had such an impact on global public health. Methods: We used the ICOH Heritage Repository, in which ICOH congress proceedings (from the first congress in Milan in 1906 to the last congress, held in Dublin in 2018), are organised in an orderly way, updated and easily accessible according to open access logic. Results: We describe studies by three physicians who submitted significant scientific work to ICOH congresses, one on the battle against ancylostomiasis (Volante, 1906), the second (Quarelli, 1928) on carbon disulphide poisoning, and the third (Viola, 1969) on the carcinogenicity of vinyl chloride monomer. Priority is given to Italian cases, on account of the authors’ obvious familiarity with the issues. Conclusion: The visibility offered in ICOH conferences and their published proceedings has boosted the international spread of their findings, contributing to the scientific transferability of the research results and influencing the development of policies and prevention interventions that have had a great impact on global public health.

Introduction: Anterior cervical discectomy and fusion (ACDF) is a common procedure to address cervical spine pathology. The most common grafts used are titanium, polyetheretherketone (PEEK), or structural allograft. Comparison of fusion rate is difficult due to non-standardized methods of assessment. We stratified studies by method of fusion assessment and performed a systematic review of fusion rates for titanium, PEEK, and allograft. Research question: Which of the common implants used in ACDF has the highest reported rate of fusion? Materials and methods: An experienced librarian performed a five-database systematic search for published articles between 01/01/1990 and 08/07/2021. Studies performed in adults with at least 1 year of radiographic follow up were included. The primary outcome was the rate of fusion. Fusion criteria were stratified into 6 classes based upon best practices. Results: 34 studies met inclusion criteria. 10 studies involving 924 patients with 1094 cervical levels, used tier 1 fusion criteria and 6 studies (309 patients and 367 levels) used tier 2 fusion criteria. Forty seven percent of the studies used class 3–6 fusion criteria and were not included in the analysis. Fusion rates did differ between titanium (avg. 87.3%, range 84%–100%), PEEK (avg. 92.8%, range 62%–100%), and structural allograft (avg. 94.67%, range 82%–100%). Discussion and conclusion: After stratifying studies by fusion criteria, significant heterogeneity in study design and fusion assessment prohibited the performance of a meta-analysis. Fusion rate did not differ by graft type. Important surgical goals aside from fusion rate, such as degree of deformity correction, could not be assessed. Future studies with standardized high-quality methods of assessing fusion, are required.

The multicomponent syntheses of 2,4-di-aryl-quinolines and analogous polycyclic derivatives as anti-tuberculosis agents were described. They were prepared via Beyer and Friedländer methods under microwave irradiation in short reaction times and good yields. Several homogeneous and heterogeneous acid catalysts were compared for preparing 2,4-di-arylquinolines and among them trifluoroacetic acid (TFA) reached the higher yields. Two derivatives exhibited activity against Mycobacterium tuberculosis H37Rv (Mtb), underwent additional testing and were considered lead compounds. The synthesis of a series of polycyclic analogous led to six new active compounds and a Quantitative Structure Activity Relationship study (QSAR) study was established. Keywords: Substituted quinolines, DARQ, Microwave-assisted synthesis, Catalysis, Mycobacterium tuberculosis, QSAR

Nox2 is responsible for artery dysfunction via production of reactive oxidant species. RNA viruses may activate Nox2, but it is unknown if this occurs in coronavirus 2019(Covid-19). Nox2 activation by soluble Nox2-derived peptide(sNox2-dp) was measured in patients hospitalized for Covid-19 (n = 182) and controls (n = 91). sNox2-dp values were higher in Covid-19 patients versus controls and in severe versus non severe Covid-19. Patients with thrombotic events(n = 35,19%) had higher sNox2-dp than thrombotic event-free ones. A logistic regression analysis showed that sNox2 and coronary heart disease predicted thrombotic events. Oxidative stress by Nox2 activation is associated severe disease and thrombotic events in Covid-19 patients.

Our coalition of public health experts, doctors, and scientists worldwide want to draw attention to the need for high-quality evaluation protocols of the potential beneficial effect of hydroxychloroquine (HCQ) as a post-exposure drug for exposed people. In the absence of an approved, recognized effective pre or post-exposure prophylactic drug or vaccine for COVID-19, nor of any approved and validated therapeutic drug, coupled with social and political pressure raised by publicity both regarding the potential beneficial effect of hydroxychloroquine (HCQ) as well as potential risks from HCQ, we urge the immediate proper clinical trials. Specifically, we mean using HCQ for post-exposure of people with close contact with patients with positive COVID19 rtPCR, including home and medical caregivers. We have reviewed the mechanisms of antiviral effect of HCQ, the risk-benefit ratio taking into consideration the PK/PD of HCQ and the thresholds of efficacy. We have studied its use as an antimalarial, an antiviral, and an immunomodulating drug and concluded that the use of HCQ at doses matching that of the standard treatment of Systemic Lupus erythematous, which has proven safety and efficacy in terms of HCQ blood and tissue concentration adapted to bodyweight (2,3), at 6 mg/kg/day 1 (loading dose) followed by 5 mg/kg/ day, with a maximum limit of 600 mg/day in all cases should swiftly be clinically evaluated as a post-exposure drug for exposed people. Keywords: COVID19, SARS-CoV2, Hydroxychloroquine, Chloroquine, Systemic lupus erythematosus, Immunomodulation, Coronavirus, malaria, antiviral

The aim of this article was to illustrate a case of primary septic arthritis of the manubriosternal joint, due to Staphylococcus aureus infection, in an immunocompetent 28-year-old male patient. The manubriosternal joint can be rarely involved in inflammatory processes, but pyarthrosis is even more unusual in an otherwise healthy adult. Although rare, pyarthrosis could be associated with significant morbidity and mortality, first of all because of spreading to mediastinal structures. Diagnosis is generally made thanks to imaging findings after clinical suspicion in a patient with anterior chest pain and swelling, fever, and raised inflammatory markers, especially when any risk factors are known. Management is generally aggressive because intravenous antibiotics and surgical debridement are necessary.

The feasibility of getting “D” shaped plasma configurations in FTU, with a possible X point close to the first wall, has been investigated with the aim of achieving an H-mode regime in this machine. This regime could allow both evaluating the thermal effects on the liquid lithium limiter due to the possible Edge Localized Modes and studying the L-H transition properties in low recycling conditions due to the presence of lithium.. An alternative design for the magnetic system in FTU has been also proposed, to realize an X-point inside the plasma chamber, close to the Liquid Lithium Limiter.Preliminary experiments with elongated configurations and limited ECRH additional heating power did not allowed approaching the L-H transition but they were used to develop a proper elongation control. This controller allowed guaranteeing the vertical stability in elongated configurations despite the reduced power available for the horizontal field coils in FTU. The elongation was stably keep over 1.2, while the lithium limiter was very close to the last close flux surface. Neither limiter damages nor plasma pollution were observed in these configurations.A possible alternative connection of the poloidal field coils in FTU is here proposed, with the aim of achieving a true X-point configuration with a magnetic single null well inside the plasma chamber and strike points on the lithium limiter. A preliminary assessment of this design allowed estimating the required power supply upgrade and showed its compatibility with the existing mechanical structure and cooling system, at least for plasmas with current up to 300 kA and flat-top duration up to 4s. Keywords: FTU, Liquid lithium limiter, L-H transition, X-point, Plasma elongation

Background: Highly active antiretroviral therapy (HAART) is complex and many factors contribute to a patient’s response to initial therapy including adherence, drug effectiveness, and tolerance. Close HAART follow-up is needed, particularly when there are concurrent therapies such as prophylactic antibiotics and medications for the treatment of comorbidities. Objective: To assess the effectiveness of pharmacist intervention in reducing drug related problems in HIV/AIDS outpatients (intervention group) and in improving clinical parameters in the intervention group compared to the control group. Methods: We conducted a prospective controlled intervention study with patients paired by gender and initial T CD4+ lymphocyte (CD4) count. HIV-infected patients of a public outpatient service were enrolled for the study by consecutive and convenience sampling. Patients selected for the study were divided into a control group and an intervention group. Both groups were followed for one year; however, only the intervention group received pharmaceutical care. The primary outcome was the drug related problem (DRP) analysis for the intervention group. Secondary outcomes were CD4 count and viral load evaluation for both groups. Results: There was a total of 143 patients enrolled in this study, with 53 (37.06%) patients in the control group and 90 (62.94%) patients in the intervention group. A total of 202 pharmacist interventions with 193 pharmacist-patient and 9 pharmacist-physician interventions were proposed. After one year of pharmaceutical care, a reduction of 38.43% between the initial and final DRP was found (p = 0.0001). The most common DRPs found were related to medication safety. The intervention group showed a mean increase of 84% for the CD4 count in comparison with that observed in the control group. The viral load was not significantly different between the final and initial mean values for both groups. Conclusion: Pharmacist appointments enabled identification, prevention, and solving of drug related problems, especially those related to drug safety. Also, pharmacist interventions improved adherence and increased HAART effectiveness as suggested by the higher elevation in the CD4 count seen in the intervention group in comparison with the control group.

Summary: Interleukin-17-producing γδ T (γδ17) cells play a central role in protective and pathogenic immune responses. However, the tissue-specific mechanisms that control the activation of these innate lymphocytes are not known. Here, we demonstrate that CD109, a glycosylphosphatidylinositol (GPI)-anchored protein highly expressed by keratinocytes, is an important regulator of skin homeostasis and γδ17 cell activation. Genetic deletion of CD109 results in spontaneous epidermal hyperplasia, aberrant accumulation of dermal-derived γδ17 cells, and enhanced susceptibility to psoriasiform inflammation. In this context, γδ17 activation requires interleukin (IL)-23 signals and is reversed by transient depletion of the skin microbiota. Mechanistically, CD109 restrains γδ17 cell activation in a cell-extrinsic manner by fortifying skin barrier integrity. Collectively, our data provide insight into the regulation of the skin IL-23/IL-17 immune axis and how homeostasis is maintained at this important barrier site. : Zhang et al. demonstrate that CD109 acts in a skin-specific and cell-extrinsic manner to regulate interleukin (IL)-17 production by cutaneous γδ T cells. Genetic loss of CD109 results in spontaneous skin inflammation and an enhanced susceptibility to psoriasiform inflammation, a phenotype that can be reversed with topical application of antibiotics. Keywords: skin, CD109, IL-17, gamma delta T cells, barrier tissue, immunity, microbiota, psoriasis

Objective: Tissue inhibitor of metalloproteinase 3 (TIMP3) is an extracellular matrix (ECM) bound protein, which has been shown to be downregulated in human subjects and experimental models with cardiometabolic disorders, including type 2 diabetes mellitus, hypertension and atherosclerosis. The aim of this study was to investigate the effects of TIMP3 on cardiac energy homeostasis during increased metabolic stress conditions. Methods: ApoE−/−TIMP3−/− and ApoE−/− mice on a C57BL/6 background were subjected to telemetric ECG analysis and experimental myocardial infarction as models of cardiac stress induction. We used Western blot, qRT-PCR, histology, metabolomics, RNA-sequencing and in vivo phenotypical analysis to investigate the molecular mechanisms of altered cardiac energy metabolism. Results: ApoE−/−TIMP3−/− revealed decreased lifespan. Telemetric ECG analysis showed increased arrhythmic episodes, and experimental myocardial infarction by left anterior descending artery (LAD) ligation resulted in increased peri-operative mortality together with increased scar formation, ventricular dilatation and a reduction of cardiac function after 4 weeks in the few survivors. Hearts of ApoE−/−TIMP3−/− exhibited accumulation of neutral lipids when fed a chow diet, which was exacerbated by a high fat, high cholesterol diet. Metabolomics analysis revealed an increase in circulating markers of oxidative stress with a reduction in long chain fatty acids. Using whole heart mRNA sequencing, we identified apelin as a putative modulator of these metabolic defects. Apelin is a regulator of fatty acid oxidation, and we found a reduction in the levels of enzymes involved in fatty acid oxidation in the left ventricle of ApoE−/−TIMP3−/− mice. Injection of apelin restored the hitherto identified metabolic defects of lipid oxidation. Conclusion: TIMP3 regulates lipid metabolism as well as oxidative stress response via apelin. These findings therefore suggest that TIMP3 maintains metabolic flexibility in the heart, particularly during episodes of increased cardiac stress.

Sette Fasce Tampone, realizzate secondo le indicazioni tecniche contenute nello Standard di condizionalità 5.2, in diversi ambiti e contesti climatici, sono state monitorate per un periodo biennale, al fine di quantificare la loro efficienza nella rimozione di azoto inorganico disciolto. Tale azoto è costituito per lo più da molecole di azoto nitrico che vengono veicolate principalmente tramite deflussi sub-superficiali da zone soggette a diverse pratiche colturali verso i corpi idrici superficiali adiacenti. Ad eccezione di due casi: i siti di Lodi e Metaponto, in tutti i sistemi monitorati è stata confermata la presenza di deflussi trasversali ai sistemi tampone, permanenti o temporanei, in grado di veicolare inquinanti e con portate variabili fra 919 e 8.590 m3/anno per 100 m lineari di FT. Le differenze di portata sono imputabili principalmente alla diversa superficie dei bacini agricoli afferenti ai sistemi tampone, che nei casi analizzati occupano superfici variabili fra il 3,6 ed il 33,3% del bacino agricolo. Sulla base dei bilanci di massa è emerso che dai campi coltivati giungono ai sistemi tampone percentuali variabili fra l’1,6 ed il 29,4% dell’azoto inorganico applicato. Ad eccezione dei sistemi in cui i maggiori deflussi non hanno alcuna interazione con la rizosfera (deflussi profondi) oppure non attraversano la Fascia Tampone, in tutti gli altri siti si registra un effetto di riduzione dell’azoto fra entrata ed uscita, con percentuali variabili fra il 33 ed il 62 %. Percentuali di abbattimento non elevate sono giustificate dallo scarso grado di maturazione dei siti monitorati, in molti casi recentemente convertiti a Fascia Tampone. Ancora una volta si conferma l’estrema eterogeneità delle risposte di questi sistemi ed il ruolo prioritario delle forzanti idrologiche nel determinarne l’efficacia. Seven buffer strips (BS) adjacent to fresh water bodies, realized according to the technical data contained in the Standard 5.2 of Cross-compliance, located in different areas and climate contexts, were monitored for a period of two years. It was done in order to quantify their effectiveness in removing dissolved inorganic nitrogen conveyed through sub- surface flow from field crops with different cultural practices. Except for two case studies (sites: Lodi and Metaponto) in all monitored systems has been confirmed an outflow, permanent or temporary, through the buffer systems, with flow rates ranging from 919 to 8590 m3y-1 every 100 meters of buffer stip. The differences in flow rate were mainly due to different sizes of agricultural basins related to buffer systems, which in the case studies ranging from 3.6 to 33.3%. Based on the mass balance, was found percentages of applied inorganic nitrogen, flowing from cultivated fields to the buffer systems, varied between 1.6 and 29.4%. In most of the sites was estimated nitrogen reduction between inlet and outlet of BS, with percentages ranging from 33 to 61.9%. The exceptions were the systems with groundwater that: or have no interaction with the rhizosphere (deep flow) or not crossing the buffer zone. Low percentages of removal shall be justified by the young stage of the monitored sites, being in many cases recently converted to buffer strip. This study confirms the extreme variability of these systems efficiency and the key role of hydrology drives its effectiveness.

This paper shows the results of the monitoring carried out in three farms of the project MO.NA.CO. in order to verify the effectiveness of the cross-compliance standard 1.1c which obliges the farmer to the ‘Maintenance of farm channel networks and field convexity’ in order to ensure its efficiency and functionality in draining water. It was also examined the competitiveness gap induced to the agricultural enterprise by the application of the standard, that is to say the additional costs borne by the beneficiary of the single payment determined by cleaning farm collector channels. Effectiveness was determined by evaluating the degradation of soil structure at the end of winter, on flat fields sown in autumn with winter wheat, in the two cases: a) Factual (channels along the field edges not clogged and no waterlogging present on the cultivated soil) b) Counterfactual (channels clogged and waterlogging present on the cultivated soil). The monitoring confirmed a positive effect of the adoption of this standard on predisposing soil to the ideal conditions for the maintenance of the structure. Despite the statistical evidence found, it must be said that the change in the surface roughness factor was so small as not to take any practical significance in order to affirm that the functional maintenance of collectors channels have been effective in reducing erosion. Overall, the soils were unstructured and crusted at the end of the observation period. Indexes Icli, NTU, and DS show a structural fragility from medium to high for soils of the three monitoring farms. This explains the lack of appreciable differences in the soil roughness parameter, especially in relation to heavy rains and long waterlogging periods in the cropping years of monitoring. The competitiveness gap induced by the application of this standard, amounted to 19.89±€ 6.35 ha-1 year-1. Atmospheric emission of CO2, was equal to 14.53±6.62 kg ha-1 year-1. It is considered important to point out that at the present Annex II: ‘Rules of cross-compliance’ of Regulation (EU) No. 1306/2013 includes a BCAA not taking into account the environmental threats determined by waterlogging in cultivated land to soil, crops and to atmosphere, due to the possible production of greenhouse gases. As regards the infringement criteria to the standard it is suggested the introduction of the verification of the presence of convexity on cultivated fields in the plain.

Within the MO.NA.CO. Project the environmental effectiveness of GAEC cross-compliance Standard 3.1 ‘Ploughing in good soil moisture conditions’ was evaluated, as well as the economic evaluation of the competitiveness gap for farmers which conform or do not conform to cross-compliance. The monitoring has been carried out at nine experimental farms with different pedoclimatic characteristics, where some indicators of soil structure degradation have been evaluated, such as bulk density, packing density and surface roughness of the seedbed, and the crop productive and qualitative parameters. In each monitoring farm two experimental plots have been set up: factual with soil tillage at proper water content (tilth), counterfactual with soil tillage at inadequate water content (no tilth). The monitoring did not exhibit univocal results for the different parameters, thus the effectiveness of the Standard 3.1 is ‘contrasting’ (class of merit B), and there was an evident practical problem to till the soil at optimum water content, even in controlled experimental condition. Bulk density was significantly lower in the factual treatment although in soils with very different textures (sandy-loam and clayey). Packing density (PD) showed a high susceptibility to compaction in soils with low PD and medium texture. The tortuosity index, indicating the roughness of the seedbed, was lower and generally significantly different in the factual treatment. Results showed that the ploughing done in excessive soil moisture conditions is more expensive due to the increased force of traction of the tractor, which causes an increase in slip of the tractor wheels, with a speed reduction and increase in the working times and fuel consumption. Moreover, the crop yield is also reduced considerably according to the cultivated species.

Within the Project MO.NA.CO was evaluated the Environmental effectiveness of GAEC cross-compliance standard 2.2 “Maintaining the level of soil organic matter through crop rotation” and economic evaluation of the competitiveness gap for farmers who support or not the cross-compliance regime. The monitoring was performed in nine experimental farms of the Council for Agricultural Research and Economics (CREA) distributed throughout Italy and with different soil and climatic conditions. Were also evaluated the soil organic matter and some yield parameters, in a cereal monocropping (treatment counterfactual) and a two-year rotation cereal-legume or forage (treatment factual). The two-years application of the standard “crop rotations” has produced contrasting results with regards to the storage of soil organic matter through crop rotation and these were not sufficient to demonstrate a statistically significant effect of treatment in any of the farms considered in monitoring, only in those farms subjected to more years of monitoring was recorded only a slight effect of the standard as a trend. The variations of organic matter in soils in response to changes in the culture technique or in the management of the soil may have long lag times and two years of time are not sufficient to demonstrate the dynamics of SOM associated with the treatment, also in consideration of the large inter annual variability recorded in different monitored sites.

Starting from the observation that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/ Apo-2L protein is expressed in both malignant and inflammatory cells in some highly vascularized soft tissue sarcomas, the angiogenic potential of TRAIL was investigated in a series of in vitro assays. Recombinant soluble TRAIL induced endothelial cell migration and vessel tube formation to a degree comparable to vascular endothelial growth factor (VEGF), one of the best-characterized angiogenic factors. However, the proangiogenic activity of TRAIL was not mediated by endogenous expression of VEGF. Although TRAIL potentiated VEGF-induced extracellular signal-regulated kinase (ERK) phosphorylation and endothelial cell proliferation, the combination of TRAIL + VEGF did not show additive effects with respect to VEGF alone in inducing vessel tube formation. Thus, although TRAIL has gained attention as a potential anticancer therapeutic for its ability to induce apoptosis in a variety of cancer cells, our present data suggest that TRAIL might also play an unexpected role in promoting angiogenesis, which might have therapeutic implications.

Microscopic blood smear examinations done in health centers of Angola demonstrated a large overdiagnosis of malaria cases with an average rate of errors as high as 85%. Overall 83% of patients who received Coartem ® had an inappropriate treatment. Overestimated malaria diagnosis was noticed even when specific symptoms were part of the clinical observation, antimalarial treatments being subsequently given. Then, malaria overdiagnosis has three main consequences, (i) the lack of data reliability is of great concern, impeding epidemiological records and evaluation of the actual influence of operations as scheduled by the National Malaria Control Programme; (ii) the large misuse of antimalarial drug can increase the selective pressure for resistant strain and can make a false consideration of drug resistant P. falciparum crisis; and (iii) the need of strengthening national health centers in term of human, with training in microscopy, and equipment resources to improve malaria diagnosis with a large scale use of rapid diagnostic tests associated with thick blood smears, backed up by a "quality control" developed by the national health authorities. Monitoring of malaria cases was done in three Angolan health centers of Alto Liro (Lobito town) and neighbor villages of Cambambi and Asseque (Benguéla Province) to evaluate the real burden of malaria. Carriers of Plasmodium among patients of newly-borne to 14 years old, with or without fever, were analyzed and compared to presumptive malaria cases diagnosed in these health centers. Presumptive malaria cases were diagnosed six times more than the positive thick blood smears done on the same children. In Alto Liro health center, the percentage of diagnosis error reached 98%, while in Cambambi and Asseque it was of 79% and 78% respectively. The percentage of confirmed malaria cases was significantly higher during the dry (20.2%) than the rainy (13.2%) season. These observations in three peripheral health centers confirmed what has already been noticed in other malaria endemic regions, and highlight the need for an accurate evaluation of the Malaria control programme implemented in Angola., (Copyright © 2017 Elsevier B.V. All rights reserved.)