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To investigate the use of computerized cardiotocography (cCTG) parameters in Intrauterine Growth Restriction (IUGR) pregnancies for the prediction of 1) complication with preeclampsia; 2) placental histological abnormalities, and 3) neonatal outcomes. A single-center observational retrospective case-control study was performed by reviewing medical records, cCTG databases and pathological reports of women with singleton pregnancy and IUGR uncomplicated (controls) and complicated by preeclampsia (cases). Primary endpoint was the association between cCTG parameters and preeclampsia in IUGR. Secondary endpoints were the association between cCTG parameters and 1) placental abnormalities, and 2) neonatal outcomes. The one-way ANOVA test was used to compare cCTG parameters in cases and controls. t-test was applied to compare neonatal outcomes and placental abnormalities in both groups. The Spearman Test value Correlation coefficients between the cCTG parameters and neonatal outcome in the two groups. A p value < .05 was considered significant for all analyses. Among all cCTG parameters, a significant association with preeclampsia in IUGR was found for Fetal Heart Rate (FHR, p = .008), Delta (p = .018), Short Term Variability (STV, p = .021), Long Term Variability (LTV, p = .028), Acceleration Phase Rectified Slope (APRS, p = .018) and Deceleration Phase Rectified Slope (DPRS, p = .038). Of all placental histologic abnormalities, only vascular alterations at least moderate were significantly associated with increased FHR (p = .02). About neonatal outcomes, all cCTG parameters were significantly associated with birth weight, Apgar index at 1 and 5 min, pH and pCO2. FHR, LTI, Delta, Approximate Entropy (ApEn) and LF were significantly associated with pO2; LTI, Interval Index (II) and ApEn with base excess. Among controls, Delta, ApEn, Low Frequency (LF) and High Frequency (HF) were significantly associated with pCO2, while among cases, STV and Delta were significantly associated with pH; STV, LTI, Delta, ApEn, LF and HF with pCO2; STV, LTI, Delta and ApEn with pO2; HF with base excess; FHR and LF with lactates. cCTG parameters may be useful to detect complication with preeclampsia in IUGR pregnancies. Regarding placental status, cCTG parameters may detect overall circulation alterations, but not specific histological abnormalities. Lastly, all cCTG parameters may predict neonatal outcomes, helping to tailor the patients’ management.

Orientadores: Job Jesus Batista, Bernardino Figueiredo Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Geociencias Resumo: O depósito mineral poli metálico do Igarapé Bahia (Cu-Au-Ag-Mo) é hospedado por rochas metavulcânicas e metassedimentares de baixo grau do Grupo Igarapé Bahia na Província Mineral de Carajás, norte do Brasil. O Grupo Igarapé Bahia constitui-se principalmente de rochas vulcânicas básicas e piroclásticas, rochas sedimentares psamopelíticas e formações ferríferas, que exibem direção NNW e mergulhos de 70° ENE. Estas rochas são capeadas por um manto laterítico, o qual hospeda um considerável depósito de ouro na área. O presente trabalho exibe os resultados petrográficos e litogeoquímicos realizados nas rochas vulcânicas básicas do depósito do Igarapé Bahia, assim como os resultados petrográficos da mineralização primária sulfetada associada a estas rochas. Um total de 23 amostras de rochas tiveram seus elementos maiores e traços analisados por Fluorescência de Raio-X, Absorção Atômica e outros métodos analíticos, realizados na UNICAMP e na UNESP. Os teores de ETR foram determinados em 8 amostras de rochas pelo método ICP, na GEOSOL. Estas rochas foram também estudadas microscopicamente e a paragênese do minério foi determinada num total de 25 seções polidas. Os tipos litológicos são: metabasaltos,metadiabásios com intercrescimento granofírico, meta-andesitos a metadacitos, rochas ricas em magnetita, as quais hospedam lentes de sulfeto maciço, e rochas básicas intrusivas que cortam a sequência vulcanosedimentar. No geral, as rochas vulcânicas do Igarapé Bahia foram alteradas hidrotermalmente em condições compatíveis a da facies xisto verde.Todos os tipos litológicos, exceto as rochas básicas intrusivas contêm quantidades variáveis de clorita, carbonato, quartzo e epidoto. Os teores de elementos incompatíveis e ETR obtidos para estas rochas indicam que elas correspondem provavelmente a Tholeiítos Continentais, com relativo enriquecimento em Rb, Ba, K, La e Ce. Este enriquecimento pode ser devido à alteração hidrotermal ou à contaminação crustal. A mineralização primária sulfetada do depósito do Igarapé Bahia sofreu remobilização durante o evento hidrotermal, em condições da faices xisto verde e foi também afetada por evento cisalhante Abstract: The polymetallic Igarapé Bahia mineral deposit (Cu-Au-Ag-Mo) is hosted by the low-grade metavolcanic and metasedimentary roeles of the Igarapé Bahia Group in the Carajás Mineral Province, northern Brazil. The Igarapé Bahia Group consists mainly of basic volcanic and pyroclastic rocks, psamo-pelitic sedimentary rocks and iron formation, which follow a general NNW strike with a dip of 7(1 ENE. These rocks are overlain by a lateritic sequence which hosts the largest gold deposit in the area. The present study reports a petrographic and lithogeochemica1 investigation on the basic volcanic rocks of the Igarapé Bahia deposit, as well as petrographic results on the primary sulfide mineralization associated with these rocks. A total of 23 rock samples were analyzed for both major and trace elements by XRF, ASS and other analytical methods available at UNICAMP and UNESP. REE contents were determined on 8 selected rock samples by ICP method at GEOSOL. These rocks were also studied by conventional optical microscopy and the ore paragenesis were recognized in a total of 25 polished-thin section. Lithologica1 types are: metabasalts, metabasalts with granophyric intergrowths, meta-andesites to metadacites, country rocks with interlayerings of magnetiterich rocks, which host massive sulfide lenses, and intrusive basic rocks crosscutting the volcanic-sedimentary sequence. In general, the Igarapé Bahia volcanic rocks have been hydrotermally altered at greenschist facies conditions. All types, except the subvolcanic basic rocks contain variable amounts of chlorite, carbonate, quartz and epidote. The incompatible element and REE patterns obtained for these rocks resemble those of Continental Tholeiites probably, with relative enrichment for Rb, Ba, k, La and Ce. These enrichment may be due to the hydrothermal alteration or crostal contamination. The primary sulfide mineralization of the Igarapé Bahia deposit underwent local remobilization during hydrothermal alteration events at greenschist facies and was also affected by shearing within a more brittle regime Mestrado Mestre em Geociências

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.

ObjectiveSingle cases and small series of Guillain-Barré syndrome (GBS) have been reported during the SARS-CoV-2 outbreak worldwide. We evaluated incidence and clinical features of GBS in a cohort of patients from two regions of northern Italy with the highest number of patients with COVID-19.MethodsGBS cases diagnosed in 12 referral hospitals from Lombardy and Veneto in March and April 2020 were retrospectively collected. As a control population, GBS diagnosed in March and April 2019 in the same hospitals were considered.ResultsIncidence of GBS in March and April 2020 was 0.202/100 000/month (estimated rate 2.43/100 000/year) vs 0.077/100 000/month (estimated rate 0.93/100 000/year) in the same months of 2019 with a 2.6-fold increase. Estimated incidence of GBS in COVID-19-positive patients was 47.9/100 000 and in the COVID-19-positive hospitalised patients was 236/100 000. COVID-19-positive patients with GBS, when compared with COVID-19-negative subjects, showed lower MRC sum score (26.3±18.3 vs 41.4±14.8, p=0.006), higher frequency of demyelinating subtype (76.6% vs 35.3%, p=0.011), more frequent low blood pressure (50% vs 11.8%, p=0.017) and higher rate of admission to intensive care unit (66.6% vs 17.6%, p=0.002).ConclusionsThis study shows an increased incidence of GBS during the COVID-19 outbreak in northern Italy, supporting a pathogenic link. COVID-19-associated GBS is predominantly demyelinating and seems to be more severe than non-COVID-19 GBS, although it is likely that in some patients the systemic impairment due to COVID-19 might have contributed to the severity of the whole clinical picture.

Introduction The prognosis of malignant gliomas remains largely unsatisfactory for the intrinsic characteristics of the pathology and for the delayed diagnosis. Multimodal imaging based on PET and MRI may assess the dynamics of disease onset and progression allowing the validation of preclinical models of glioblastoma multiforme (GBM). The aim of this study was the characterization of a syngeneic rat model of GBM using combined in vivo imaging and immunohistochemistry. Methods Four groups of Fischer rats were implanted in a subcortical region with increasing concentration of rat glioma F98 cells and weekly monitored with Gd-MR, [ 18 F]FDG- and [ 18 F]FAZA-PET starting one week after surgery. Different targets were evaluated on post mortem brain specimens using immunohistochemistry: VEGF, GFAP, HIF-1α, Ki-67 and nestin. Results Imaging results indicated that tumor onset but not progression was related to the number of F98 cells. Hypoxic regions identified with [ 18 F]FAZA and high-glucose metabolism regions recognized with [ 18 F]FDG were located respectively in the core and in external areas of the tumor, with partial overlap and remodeling during disease progression. Histological and immunohistochemical analysis confirmed PET/MRI results and revealed that our model resumes biological characteristics of human GBM. IHC and PET studies showed that necrotic regions, defined on the basis of [ 18 F]FDG uptake reduction, may include hypoxic clusters of vital tumor tissue identified with [ 18 F]FAZA. This last information is particularly relevant for the identification of the target volume during image- guided radiotherapy . Conclusions In conclusion, the combined use of PET and MRI allows in vivo monitoring of the biological modification of F98 lesions during tumor progression.

The objective of this study was to develop new solid self-emulsifying pellets to deliver milk thistle extract (silymarin). These pellets were prepared via extrusion/spheronisation procedure, using a self-emulsifying system or SES (Akoline MCM®, Miglyol®, Tween 80®, soy lecithin and propylene glycol), microcrystalline cellulose and lactose monohydrate. To select the most suitable formulations for extrusion and spheronisation, an experimental design of experiences was adopted. The screening amongst formulations (13 different blends) was performed preparing pellets and evaluating extrusion profiles and quality of the spheronised extrudates. The pellets were characterised for size and shape, density, force required to crush them. Although more than one type of pellets demonstrated adequate morphological and technological characteristics, pellets prepared from formulation 7 revealed the best properties and were selected for further biopharmaceutical investigations, including in vitro dissolution and in vivo trials on rats to study serum and lymph levels after oral administration of the pellets. These preliminary technological and pharmacokinetic data demonstrated that extrusion/spheronisation is a viable technology to produce self-emulsifying pellets of good quality and able to improve in vivo oral bioavailability of main components of a phytotherapeutic extract of more than 100 times by enhancing the lymphatic route of absorption.

Humoral immune mechanisms may have a role in the neurological complications of celiac disease (CD). We assessed 71 CID patients for neurologic manifestations and presence of serum antibodies to neural antigens. Sixteen patients (22.5%) were found to have neurological deficits including headache, depression, entrapment syndromes, peripheral neuropathy, and epilepsy. Antibody reactivity to neural antigens was detected in 30/71 (42.2%) patients. There was no clear correlation between anti-neural reactivity and neurologic dysfunction. Follow-up of 62 patients did not reveal change in electrophysiology or antibodies, regardless of diet. However, in 2 patients with neuropathy, symptoms improved or worsened depending on the diet. (C) 2008 Elsevier B.V. All rights reserved.

Antibodies to gangliosides and Purkinje cells have been reported in patients with celiac disease (CD) with neuropathy and ataxia, respectively. Whether these antibodies are pathogenic is not clear. The response of neurological symptoms and antibody titers to a gluten-free diet is still controversial. The objective of our study was to assess whether neurological manifestations in CD patients correlate with antibody titers and a gluten-free diet.Thirty-five CD patients (9 males, 26 females, mean age 37.1 +/- 12.6 yrs) were followed prospectively. At initial evaluation, 23 were on a gluten-free diet, 12 were not. At recruitment and during follow-up, patients underwent neurological and electrophysiological evaluation. IgG, IgM, and IgA anti-ganglioside antibodies were assayed by ELISA; anti-neuronal antibodies were assessed by immunohistochemistry and Western blot. Four patients, all males, had electrophysiological evidence of neuropathy; three had been on a gluten-free diet for several months, and one was newly diagnosed. One had reduced tendon reflexes; another complained of distal paresthesias. With regard to anti -ganglioside antibodies, three patients had a moderate increase in antibodies without symptoms or signs of neuropathy. No patients had ataxia or cerebellar dysfunction, although in four patients reactivity to neuronal antigens was found. In 17 patients, an electrophysiological follow-up (mean duration of follow-up, 9 months) showed no changes. In conclusion, the preliminary results of this prospective study indicate that neuropathy, usually subclinical, may accompany CD. Antibody titers do not seem to correlate with neurological symptoms/signs or diet. Ongoing follow-up will help confirm these data and clarify the role, if any, of antibodies in neurological involvement in CD.

We report here clinical, electrophysiological, and molecular findings in a family affected with two inherited genetic diseases: limb girdle muscular dystrophy type 1B (LGMD1B) and hereditary neuropathy with liability to pressure palsies (HNPP). Members of the family carry a novel missense mutation in the LMNA gene and a nonsense mutation in the PMP22 gene. Interestingly, the double LMNA/PMP22 mutations carriers showed clinical features more severe than usually seen in HNPP, and electrophysiological findings suggesting an axonal loss in addition to a typical myelinopathy. This study provides further insights into the relevance of lamin A/C in muscle and nerve.

Chemotherapy has been used for treating chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with incosistent results. Chemotheraphy has been used for treating with inconsistent results. Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen, used to treat B-cell lymphoma and reported to be effective in some neuropathies with IgM autoreactivity. We saw a 72-year-old man with CIDP refractory to steroids, plasma exchange, IV Ig, and cyclosporin. He was unable to walk; severe impairment was present also at the upper limbs. Electrodiagnostic studies revealed slowing of motor and sensory conduction velocities, and prolonged distal motor latencies. Immunoelectrophoresis evidence an IgM/k monoclonal gammopathy. Antibodies to Myelin Associated Glycoprotein (MAG) and other peripheral nerve antigens were negative. Bone marrow biopsy documented a small lymphocytic B-cell lymphoma (CD20+). Treated with Rituximab (375 mg/m2 for 4 weeks), the patient presented at follow-up evaluations (3, 6 and 8 months later) a progressive improvement. Eventually, he was able to walk, and regained full strength at upper limbs. Consistently, electrophysiological studies improved. We suggest considering treatment with Rituximab in CIDP resistant to conventional therapy, at least in cases associated with IgM lymphoproliferative diseases.

The clinical and neurophysiologic data from 65 patients taking thalidomide were reviewed. Thalidomide sensory neurotoxicity was found to be cumulative dose dependent but occurs only when the total dose is relatively high (>20 g). The risk of developing sensory neuropathy is around 10% below this threshold but increases with higher doses.