Craniomaxillofacial morphology alterations in children, adolescents and adults with neurofibromatosis 1: A cone beam computed tomography analysis of a Brazilian sample.

BACKGROUND: Oral manifestations are common in neurofibromatosis 1 (NF1), and include jaws and teeth alterations. Our aim was to investigate the craniomaxillofacial morphology of Brazilian children, adolescents and adults with NF1 using cone beam computed tomography. MATERIAL AND METHODS: This study was conducted with 36 Brazilian individuals with NF1 with ages ranging from 4 to 75. The participants were submitted to anamnesis, extra and intraoral exam and cephalometric analysis using cone beam computed tomography. Height of the NF1 individuals was compared to the length of jaws and skull base. The results of the cephalometric measurements of the NF1 group were compared with a control group paired by age, gender and skin color. RESULTS: Individuals with NF1 had lower maxillary length (p<0.0001), lower mandibular length (p<0.0001), lower skull base length (p<0.0001). In children and adolescents, the mandible was more posteriorly positioned (p=0.01), when compared with the control group. There was no association between jaws and skull base length with the height of the individuals with NF1. CONCLUSIONS: Brazilian children, adolescents and adults with NF1 have short mandible, maxilla and skull base. Moreover, children and adolescents present mandibular retrusion.

Position Paper from the Portuguese Association of Hospital Pharmacists for biosimilar therapeutic antibodies.

WHAT IS KNOWN AND OBJECTIVE: Biopharmaceuticals are an important class of drugs for the treatment of autoimmune/inflammatory and oncologic diseases. With patent expiries, biotechnological manufacturers can now develop biosimilar drugs. Due to timeliness of introducing new and more complex biosimilars, the Portuguese Association of Hospital Pharmacists gathered to develop a common positioning on the use of biosimilar monoclonal antibodies. MAIN ISSUES: The European pathway to biosimilar approval was developed to improve affordability and access to biological therapies, but it remains a work in progress because unresolved issues remain. Due to the present reality of biosimilar monoclonal antibodies, hospital pharmacists must play an important role in ensuring the safe, effective and cost-effective use of biosimilars in health systems; and educating healthcare administrators, providers, legislators, policymakers, payors and patients about these products. WHAT IS NEW AND CONCLUSION: The conclusions presented in this work focused on the proposal for optimal biosimilar prescription criteria, the preparation of original biologics and biosimilars in the pharmacy, the management and selection of suppliers, extrapolation issues, the specific role of pharmacovigilance and risk management for the optimal use of biosimilar monoclonal antibodies.

Nanocrystalline cellulose applied simultaneously as the gate dielectric and the substrate in flexible field effect transistors.

Cotton-based nanocrystalline cellulose (NCC), also known as nanopaper, one of the major sources of renewable materials, is a promising substrate and component for producing low cost fully recyclable flexible paper electronic devices and systems due to its properties (lightweight, stiffness, non-toxicity, transparency, low thermal expansion, gas impermeability and improved mechanical properties).Here, we have demonstrated for the first time a thin transparent nanopaper-based field effect transistor (FET) where NCC is simultaneously used as the substrate and as the gate dielectric layer in an 'interstrate' structure, since the device is built on both sides of the NCC films; while the active channel layer is based on oxide amorphous semiconductors, the gate electrode is based on a transparent conductive oxide.Such hybrid FETs present excellent operating characteristics such as high channel saturation mobility (>7 cm(2) V (-1) s(-1)), drain-source current on/off modulation ratio higher than 10(5), enhancement n-type operation and subthreshold gate voltage swing of 2.11 V/decade. The NCC film FET characteristics have been measured in air ambient conditions and present good stability, after two weeks of being processed, without any type of encapsulation or passivation layer. The results obtained are comparable to ones produced for conventional cellulose paper, marking this out as a promising approach for attaining high-performance disposable electronics such as paper displays, smart labels, smart packaging, RFID (radio-frequency identification) and point-of-care systems for self-analysis in bioscience applications, among others.

Intracranial subdural haematoma following dural puncture accidental: clinical case. / Hematoma subdural intracraneal tras punción dural accidental: caso clínico.

Intracranial subdural hematoma is a rare, but potentially lethal complication of neuraxial procedures. Considering the high frequency of neuraxial techniques in the obstetric population, parturients are more susceptible to this fearful complication. The diagnosis is often masked and delayed because it shares similar clinical characteristics with posdural puncture headache, with headache being the most common symptom. This case report describes a timely diagnosis and successful management of an intracranial subdural hematoma, after unintentional dural puncture during labour epidural analgesia. Postpartum headache following epidural analgesia, remains a clinical challenge for the caring team, requiring a close follow-up and awareness for non-benign causes that require prompt management, avoiding devastating consequences.

Dilemmas in primary spinal glioblastoma management during pregnancy. / Dilemas en el manejo de glioblastoma espinal primario durante el embarazo.

Primary spinal glioblastoma (GBM) is a clinically rare entity with rapid progression and a dismal outcome despite aggressive treatment. In a pregnant woman, this malignancy is particularly dramatic because the potential benefits to the mother offered by standard GBM treatment must be balanced against the risks to the fetus. There is little guidance in the literature on how to manage pregnant patients with malignant neuraxial tumours and, to the authors' knowledge, no reports have been published so far regarding this specific neoplasm in such population. This case report describes the management of a pregnant patient with a previously undiagnosed and rapidly progressive intramedullary GBM submitted to an elective caesarean delivery to allow subsequent onset of oncological treatment. Dilemmas faced by anaesthetists are discussed in hope to provide guidance for future decisions and optimize outcomes.

Amifostine protects from the peripheral sensory neuropathy induced by oxaliplatin in mice.

Sensory neuropathy is a dose-limiting side effect of oxaliplatin-based cancer treatment. This study investigated the antinociceptive effect of amifostine and its potential neuroprotective mechanisms on the oxaliplatin-related peripheral sensory neuropathy in mice. Oxaliplatin (1 mg/kg) was injected intravenously in Swiss albino male mice twice a week (total of nine injections), while amifostine (1, 5, 25, 50, and 100 mg/kg) was administered subcutaneously 30 min before oxaliplatin. Mechanical and thermal nociceptive tests were performed once a week for 49 days. Additionally, c-Fos, nitrotyrosine, and activating transcription factor 3 (ATF3) immunoexpressions were assessed in the dorsal root ganglia. In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05). Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05). Moreover, amifostine protected against neuronal hyperactivation, nitrosative stress, and neuronal damage in the dorsal root ganglia, detected by the reduced expression of c-Fos, nitrotyrosine, and ATF3 (P<0.05 vs the oxaliplatin-treated group). In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.

Next generation flow for minimally-invasive blood characterization of MGUS and multiple myeloma at diagnosis based on circulating tumor plasma cells (CTPC).

Here, we investigated for the first time the frequency and number of circulating tumor plasma cells (CTPC) in peripheral blood (PB) of newly diagnosed patients with localized and systemic plasma cell neoplasms (PCN) using next-generation flow cytometry (NGF) and correlated our findings with the distinct diagnostic and prognostic categories of the disease. Overall, 508 samples from 264 newly diagnosed PCN patients, were studied. CTPC were detected in PB of all active multiple myeloma (MM; 100%), and smoldering MM (SMM) patients (100%), and in more than half (59%) monoclonal gammopathy of undetermined significance (MGUS) cases (p <0.0001); in contrast, CTPC were present in a small fraction of solitary plasmacytoma patients (18%). Higher numbers of CTPC in PB were associated with higher levels of BM infiltration and more adverse prognostic features, together with shorter time to progression from MGUS to MM (p <0.0001) and a shorter survival in MM patients with active disease requiring treatment (p ≤ 0.03). In summary, the presence of CTPC in PB as assessed by NGF at diagnosis, emerges as a hallmark of disseminated PCN, higher numbers of PB CTPC being strongly associated with a malignant disease behavior and a poorer outcome of both MGUS and MM.

Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma.

Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾107 cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.

A morphological and biochemical appraisal of the liver and renal effects of lamivudine on rat pregnancy.

No data exist on the perinatal safety of lamivudine alone, as it is used in combination with other antiretroviral agents. Until now, only preliminary data on the lamivudine-zidovudine combination have been available, thus we decided to examine the gross maternal and fetal effects of lamivudine administered alone during the entire period of rat pregnancy. Forty pregnant animals were assigned at random to four groups (C1 = control; E1 = 5 mg/kg; E2 = 15 mg/kg; E3 = 45 mg/kg) from day 0 up to the 20th day of gestation. These doses were divided into two daily administrations by gavage. Controls (n = 10) received distilled water in the same schedule. At term-pregnancy, the rats were deeply anesthetized and blood samples were collected for alanine and aspartate aminotransferases, creatinine and urea determinations. Fragments of maternal and fetal livers and kidneys were taken and processed for histopathological study. In all groups blood transaminases were within the normal limits, as were the levels of creatinine and urea, thus indicating that treatment with lamivudine during the entire gestation was essentially devoid of liver or kidney effects which could result in altered metabolic parameters. Morphological (light microscopy) studies revealed that no significant effects of the drug could be detected regarding either maternal or fetal organs of the E1 and E2 groups. However, the maternal hepatocytes in the E3 group showed heterochromatic nuclei. In addition, there was some fatty infiltration, congested sinusoids and portal dilatation. Maternal kidneys in the E3 group revealed vascular dilation around the convoluted tubules. It is concluded that only doses of lamivudine used during the entire gestation in doses well above the usual human doses could be considered to be potentially hepatotoxic for the pregnant rat.

A new class of large band gap quantum spin hall insulators: 2D fluorinated group-IV binary compounds.

We predict a new class of large band gap quantum spin Hall insulators, the fluorinated PbX (X = C, Si, Ge and Sn) compounds, that are mechanically stable two-dimensional materials. Based on first principles calculations we find that, while the PbX systems are not topological insulators, all fluorinated PbX (PbXF2) compounds are 2D topological insulators. The quantum spin Hall insulating phase was confirmed by the explicitly calculation of the Z2 invariant. In addition we performed a thorough investigation of the role played by the (i) fluorine saturation, (ii) crystal field, and (iii) spin-orbital coupling in PbXF2. By considering nanoribbon structures, we verify the appearance of a pair of topologically protected Dirac-like edge states connecting the conduction and valence bands. The insulating phase which is a result of the spin orbit interaction, reveals that this new class of two dimensional materials present exceptional nontrivial band gaps, reaching values up to 0.99 eV at the Γ point, and an indirect band gap of 0.77 eV. The topological phase is arisen without any external field, making this system promising for nanoscale applications, using topological properties.

Perfil hematológico e bioquímico sérico de capivaras (Hydrochoerus hydrochaeris) de vida livre nos biomas Mata Atlântica e Caatinga / Hematological and serum biochemical profile of free-living capybaras (Hydrochoerus hydrochaeris) in Atlantic Forest and Caatinga biomes

Devido à ausência de estudos sobre capivaras na região Nordeste do Brasil, o objetivo deste estudo foi avaliar a sanidade desses roedores de vida livre em três áreas dos biomas Mata Atlântica (2) e Caatinga (1) do estado de Pernambuco, por meio da determinação de parâmetros da hematologia e bioquímica sérica. De novembro de 2016 a dezembro de 2017, foram capturados 21 animais, dos quais foram coletadas amostras de sangue para avaliação hematológica (eritrograma, leucograma e plaquetometria) e bioquímica sérica (atividade enzimática, perfil proteico, energético e mineral). A maioria dos parâmetros esteve dentro dos valores de normalidade para a espécie, embora alguns apresentassem diferenças estatisticamente significativas de acordo com a área de estudo (hemoglobina, hematócrito, VCM, CHCM, eosinófilos, fosfatase alcalina, proteína total, albumina, ácido úrico, creatinina, lactato, sódio e magnésio) e o sexo dos animais (ácido úrico). Os parâmetros obtidos são apresentados como referência e atestam a sanidade e o bom estado nutricional de populações de capivaras nos biomas Mata Atlântica e Caatinga da região Nordeste do Brasil. As informações aportadas neste estudo pioneiro na região Nordeste contribuem para aumentar o conhecimento sobre a ecofisiologia e a conservação in situ de capivaras.(AU)

Due to the lack of studies about capybaras in the northeast region of Brazil, the objective of this study was to evaluate the health status of free-ranging capybaras in three areas of Atlantic Forest (2) and Caatinga (1) biomes in Pernambuco state, through the determination of hematological and serum biochemical parameters. From November 2016 to December 2017, 21 animals were captured and blood samples were collected for the hematological (erythrogram, leukogram and platelet counts) and serum biochemistry (enzymatic activity, protein, energy and mineral profile) evaluation. Hematological and serum biochemical parameters were within the normal range for the species, but some presented statistically significant variations according to the study area (hemoglobin, hematocrit, MCV, MCHC, eosinophils count, alkaline phosphatase, total proteins, albumin, uric acid, creatinine, lactate, sodium and magnesium) and sex of the animals (uric acid). The parameters obtained are presented as reference and attest to the health and good nutritional status of populations of capybaras in the Atlantic Forest and Caatinga biomes of northeastern Brazil. The information provided in this pioneering study in the northeast region contributes to increased knowledge about the ecophysiology and in situ conservation of capybaras.(AU)

Amifostine protects from the peripheral sensory neuropathy induced by oxaliplatin in mice

Sensory neuropathy is a dose-limiting side effect of oxaliplatin-based cancer treatment. This study investigated the antinociceptive effect of amifostine and its potential neuroprotective mechanisms on the oxaliplatin-related peripheral sensory neuropathy in mice. Oxaliplatin (1 mg/kg) was injected intravenously in Swiss albino male mice twice a week (total of nine injections), while amifostine (1, 5, 25, 50, and 100 mg/kg) was administered subcutaneously 30 min before oxaliplatin. Mechanical and thermal nociceptive tests were performed once a week for 49 days. Additionally, c-Fos, nitrotyrosine, and activating transcription factor 3 (ATF3) immunoexpressions were assessed in the dorsal root ganglia. In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05). Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05). Moreover, amifostine protected against neuronal hyperactivation, nitrosative stress, and neuronal damage in the dorsal root ganglia, detected by the reduced expression of c-Fos, nitrotyrosine, and ATF3 (P<0.05 vs the oxaliplatin-treated group). In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.

Absent tibiae--polydactyly--triphalangeal thumbs with fibular dimelia: variable expression of the Werner (McKusick 188770) syndrome?

We report on a family in which the autosomal dominant Werner syndrome (WS) (MIM# 188770) affects ten members in three generations. Besides the absent tibiae the propositus had duplication of the fibulae. Possible pathogenetic mechanism is discussed.

Vector densities that potentiate dengue outbreaks in a Brazilian city.

To identify the critical vector density that potentiates dengue outbreaks in an endemic site and to identify obstacles to anti-dengue activities, we correlated a series of dengue outbreaks in a Brazilian city with the intensity of its anti-vector source-reduction activities. The proportion of houses infested by vector mosquitoes correlated inversely with intensity of anti-mosquito interventions, and the vector population developed independently of rainfall. Local periods of drought promoted vector abundance in two ways: residents stored water in which vector mosquitoes could breed, and cholera outbreaks due to contaminated water diverted local health workers from routine anti-vector activities. One dengue outbreak became apparent to authorities more than two months after it commenced but would have been identified almost immediately had dengue-like disease in indicator hospitals been monitored. Active surveillance, therefore, offers a window of opportunity for promptly executed anti-dengue interventions. Source-reduction measures that suppress vector infestations to less than 1% of houses effectively avert outbreaks of dengue.

Presurgical ketoprofen, but not morphine, dipyrone, diclofenac or tenoxicam, preempts post-incisional mechanical allodynia in rats.

The treatment of pain before it initiates may prevent the persistent pain-induced changes in the central nervous system that amplify pain long after the initial stimulus. The effects of pre- or postoperative intraperitoneal administration of morphine (2 to 8 mg/kg), dipyrone (40 and 80 mg/kg), diclofenac (2 to 8 mg/kg), ketoprofen (10 and 20 mg/kg), and tenoxicam (10 and 20 mg/kg) were studied in a rat model of post-incisional pain. Groups of 5 to 8 male Wistar rats (140-160 g) were used to test each drug dose. An incision was made on the plantar surface of a hind paw and the changes in the withdrawal threshold to mechanical stimulation were evaluated with Von Frey filaments at 1, 2, 6 and 24 h after the surgery. Tenoxicam was given 12 or 6 h preoperatively, whereas the remaining drugs were given 2 h or 30 min preoperatively. Postoperative drugs were all given 5 min after surgery. No drug abolished allodynia when injected before or after surgery, but thresholds were significantly higher than in control during up to 2 h following ketoprofen, 6 h following diclofenac, and 24 h following morphine, dipyrone or tenoxicam when drugs were injected postoperatively. Significant differences between pre- and postoperative treatments were obtained only with ketoprofen administered 30 min before surgery. Preoperative (2 h) intraplantar, but not intrathecal, ketoprofen reduced the post-incisional pain for up to 24 h after surgery. It is concluded that stimuli generated in the inflamed tissue, rather than changes in the central nervous system are relevant for the persistence of pain in the model of post-incisional pain.

[Measles in rural workers: a methodological essay in social epidemiology]. / Sarampo em trabalhadores rurais: ensaio metodológico de epidemiologia social.

The study of a measles epidemic in the Ribeirão Preto region, in 1984, showed a high proportion of cases occurring among people above 15 years of age. This finding led to the identification of a particular characteristic of the disease's distribution in the area, i.e. the high incidence among rural workers (especially those restricted to collective lodgings when working in agricultural and industrial activities related to sugar cane plantations). A methodological exercise of synthesis between the descriptive phase of the traditional epidemiology and the was carried out. This procedure aimed at incorporating some aspects of the social process of the area with a view to explaining this particular distribution of measles as a result to that social process (i.e. the pattern of the occurrence of measles among rural workers is understood as a historically determined social event). Finally, the need to consider the appearance of specific diseases in different human groups according to the social process into which they are inserted in disenssed in such a way that their history and specificity are taken into account.

[Dengue in a urban locality of southeastern Brazil: epidemiological aspects]. / Dengue em localidade urbana da região sudeste do Brasil: aspectos epidemiológicos.

A dengue fever epidemic which occurred in Ribeirão Preto County, S. Paulo State, Brazil, during the period November, 1990 to March, 1991 has been analysed elsewhere. The general aspects of dengue epidemiology and control have been reviewed in this article. Emphasis is given to the analysis of some factors involved in the risk of dengue haemorrhagic fever and ecological aspects of the vector, as well as to the appropriateness of strategies for dengue eradication or control. Epidemiological characteristics of dengue, mainly those related to its occurrence in different geographical areas and periods of time are described. The Ribeirão Preto epidemic has thus, been set within the context of the spread of the disease at global level, in the Americas, and particularly in Brazil and S. Paulo State.

[Dengue epidemic in Ribeirão Preto, SP, Brazil: a preliminary note]. / Epidemia de dengue em Ribeirão Preto, SP, Brasil: nota prévia.

A preliminary note on an outbreak of dengue which occurred in the city of Ribeirão Preto, State of S. Paulo, Brazil, from November 1990 to March 1991, is given. One case of Level II Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS) and two deaths associated with dengue related shock are described. Clinicians and epidemiologists are alerted to the possibility of sporadic DHF/DSS cases during outbreaks of classical dengue in formerly free areas.

Delimitation of homogeneous regions in the UNIFESP/EPM healthcare center coverage area based on sociodemographic indicators.

CONTEXT: The drawing up of adequate Public Health action planning to address the true needs of the population would increase the chances of effectiveness and decrease unnecessary expenses. OBJECTIVE: To identify homogeneous regions in the UNIFESP/EPM healthcare center (HCC) coverage area based on sociodemographic indicators and to relate them to causes of deaths in 1995. DESIGN: Secondary data analysis. SETTING: HCC coverage area; primary care. SAMPLE: Sociodemographic indicators were obtained from special tabulations of the Demographic Census of 1991. MAIN MEASURES: Proportion of children and elderly in the population; family providers' education level (maximum: > 15 years, minimum: < 1 year) and income level (maximum: > 20 minimum wages, minimum: < 1 minimum wage); proportional mortality distribution RESULTS: The maximum income permitted the construction of four homogeneous regions, according to income ranking. Although the proportion of children and of elderly did not vary significantly among the regions, minimum income and education showed a statistically significant (p < 0.05) difference between the first region (least affluent) and the others. A clear trend of increasing maximum education was observed across the regions. Mortality also differed in the first region, with deaths generated by possibly preventable infections. CONCLUSION: The inequalities observed may contribute to primary health prevention.

[Hepatic changes in patients with nonspecific ulcerative colitis]. / Alterações hepáticas em pacientes portadores de retocolite ulcerativa inespecífica.

The presence of hepatic changes in ulcerative colitis ranges from 4.7% to 90% and the mechanisms are not clear. This study had the purpose to verify their frequency, observe the relation between clinical forms and hepatic lesions and identify the possible histological changes in the liver. We studied 21 patients with ulcerative colitis (Group 1, subdivided in Group 1A non-alcoholic and 1B alcoholic) and compared with 10 patients with irritable bowel syndrome (Group 2). The study involved clinical evaluation, ultrasonography liver function tests and needle biopsy of the liver, performed by laparoscopy, when necessary. Clinical alterations were present in three patients. The ultra-sonographic study was altered in 14.3% in Group 1A and in 57.1% in Group 1B. The albumin and cholinesterase levels were the most frequent abnormality in ulcerative colitis. In irritable bowel syndrome (Group 2), these exams were normal. Liver biopsy was performed in 15 patients and variable degrees of histologic changes were present in all.