Impaired phase synchronization of motor-evoked potentials reflects the degree of motor dysfunction in the lesioned human brain.

The functional corticospinal integrity (CSI) can be indexed by motor-evoked potentials (MEP) following transcranial magnetic stimulation of the motor cortex. Glial brain tumors in motor-eloquent areas are frequently disturbing CSI resulting in different degrees of motor dysfunction. However, this is unreliably mirrored by MEP characteristics. In 59 consecutive patients with diffuse glial tumors and 21 healthy controls (CTRL), we investigated the conventional MEP features, that is, resting motor threshold (RMT), amplitudes and latencies. In addition, frequency-domain MEP features were analyzed to estimate the event-related spectral perturbation (ERSP), and the induced phase synchronization by intertrial coherence (ITC). The clinical motor status was captured including the Medical Research Council Scale (MRCS), the Grooved Pegboard Test (GPT), and the intake of antiepileptic drugs (AED). Motor function was classified according to MRCS and GPT as no motor deficit (NMD), fine motor deficits (FMD) and gross motor deficits (GMD). CSI was assessed by diffusion-tensor imaging (DTI). Motor competent subjects (CTRL and NMD) had similar ERSP and ITC values. The presence of a motor deficit (FMD and GMD) was associated with an impairment of high-frequency ITC (150-300 Hz). GMD and damage to the CSI demonstrated an additional reduction of high-frequency ERSP (150-300 Hz). GABAergic AED increased ERSP but not ITC. Notably, groups were indistinguishable based on conventional MEP features. Estimating MEP phase synchronization provides information about the corticospinal transmission after transcranial magnetic stimulation and reflects the degree of motor impairment that is not captured by conventional measures.

Brain State-dependent Gain Modulation of Corticospinal Output in the Active Motor System.

The communication through coherence hypothesis suggests that only coherently oscillating neuronal groups can interact effectively and predicts an intrinsic response modulation along the oscillatory rhythm. For the motor cortex (MC) at rest, the oscillatory cycle has been shown to determine the brain's responsiveness to external stimuli. For the active MC, however, the demonstration of such a phase-specific modulation of corticospinal excitability (CSE) along the rhythm cycle is still missing. Motor evoked potentials in response to transcranial magnetic stimulation (TMS) over the MC were used to probe the effect of cortical oscillations on CSE during several motor conditions. A brain-machine interface (BMI) with a robotic hand orthosis allowed investigating effects of cortical activity on CSE without the confounding effects of voluntary muscle activation. Only this BMI approach (and not active or passive hand opening alone) revealed a frequency- and phase-specific cortical modulation of CSE by sensorimotor beta-band activity that peaked once per oscillatory cycle and was independent of muscle activity. The active MC follows an intrinsic response modulation in accordance with the communication through coherence hypothesis. Furthermore, the BMI approach may facilitate and strengthen effective corticospinal communication in a therapeutic context, for example, when voluntary hand opening is no longer possible after stroke.

Waste soybean frying oil for the production, extraction, and characterization of cell-wall-associated lipases from Yarrowia lipolytica.

The lipolytic yeast Yarrowia lipolytica produces cell-wall-associated lipases, namely Lip7p and Lip8p, that could have interesting properties as catalyst either in free (released lipase fraction-RLF) or cell-associated (cell-bound lipase fraction-CBLF) forms. Herein, a mixture of waste soybean frying oil, yeast extract and bactopeptone was found to favor the enzyme production. Best parameters for lipase activation and release from the cell wall by means of acoustic wave treatment were defined as: 26 W/cm2 for 1 min for CBLF and 52 W/cm2 for 2 min for RLF. Optimal pH and temperature values for lipase activity together with storage conditions were similar for both the free enzyme and cell-associated one: pH 7.0; T = 37 °C; and > 70% residual activity for 60 days at 4, - 4 °C and for 15 days at 30 °C.

Recruitment of Additional Corticospinal Pathways in the Human Brain with State-Dependent Paired Associative Stimulation.

Standard brain stimulation protocols modify human motor cortex excitability by modulating the gain of the activated corticospinal pathways. However, the restoration of motor function following lesions of the corticospinal tract requires also the recruitment of additional neurons to increase the net corticospinal output. For this purpose, we investigated a novel protocol based on brain state-dependent paired associative stimulation.Motor imagery (MI)-related electroencephalography was recorded in healthy males and females for brain state-dependent control of both cortical and peripheral stimulation in a brain-machine interface environment. State-dependency was investigated with concurrent, delayed, and independent stimulation relative to the MI task. Specifically, sensorimotor event-related desynchronization (ERD) in the ß-band (16-22 Hz) triggered peripheral stimulation through passive hand opening by a robotic orthosis and transcranial magnetic stimulation to the respective cortical motor representation, either synchronously or subsequently. These MI-related paradigms were compared with paired cortical and peripheral input applied independent of the brain state. Cortical stimulation resulted in a significant increase in corticospinal excitability only when applied brain state-dependently and synchronously to peripheral input. These gains were resistant to a depotentiation task, revealed a nonlinear evolution of plasticity, and were mediated via the recruitment of additional corticospinal neurons rather than via synchronization of neuronal firing. Recruitment of additional corticospinal pathways may be achieved when cortical and peripheral inputs are applied concurrently, and during ß-ERD. These findings resemble a gating mechanism and are potentially important for developing closed-loop brain stimulation for the treatment of hand paralysis following lesions of the corticospinal tract.SIGNIFICANCE STATEMENT The activity state of the motor system influences the excitability of corticospinal pathways to external input. State-dependent interventions harness this property to increase the connectivity between motor cortex and muscles. These stimulation protocols modulate the gain of the activated pathways, but not the overall corticospinal recruitment. In this study, a brain-machine interface paired peripheral stimulation through passive hand opening with transcranial magnetic stimulation to the respective cortical motor representation during volitional ß-band desynchronization. Cortical stimulation resulted in the recruitment of additional corticospinal pathways, but only when applied brain state-dependently and synchronously to peripheral input. These effects resemble a gating mechanism and may be important for the restoration of motor function following lesions of the corticospinal tract.

Performance of Fetal Medicine Foundation Software for Pre-Eclampsia Prediction Upon Marker Customization: Cross-Sectional Study.

BACKGROUND: FMF2012 is an algorithm developed by the Fetal Medicine Foundation (FMF) to predict pre-eclampsia on the basis of maternal characteristics combined with biophysical and biochemical markers. Afro-Caribbean ethnicity is the second risk factor, in magnitude, found in populations tested by FMF, which was not confirmed in a Brazilian setting. OBJECTIVE: This study aimed to analyze the performance of pre-eclampsia prediction software by customization of maternal ethnicity. METHODS: This was a cross-sectional observational study, with secondary evaluation of data from FMF first trimester screening tests of singleton pregnancies. Risk scores were calculated from maternal characteristics and biophysical markers, and they were presented as the risk for early pre-eclampsia (PE34) and preterm pre-eclampsia (PE37). The following steps were followed: (1) identification of women characterized as black ethnicity; (2) calculation of early and preterm pre-eclampsia risk, reclassifying them as white, which generated a new score; (3) comparison of the proportions of women categorized as high risk between the original and new scores; (4) construction of the receiver operator characteristic curve; (5) calculation of the area under the curve, sensitivity, and false positive rate; and (6) comparison of the area under the curve, sensitivity, and false positive rate of the original with the new risk by chi-square test. RESULTS: A total of 1531 cases were included in the final sample, with 219 out of 1531 cases (14.30; 95% CI 12.5-16.0) and 182 out of 1531 cases (11.88%; 95% CI 10.3-13.5) classified as high risk for pre-eclampsia development, originally and after recalculating the new risk, respectively. The comparison of FMF2012 predictive model performance between the originally estimated risks and the estimated new risks showed that the difference was not significant for sensitivity and area under the curve, but it was significant for false positive rate. CONCLUSIONS: We conclude that black ethnicity classification of Brazilian pregnant women by the FMF2012 algorithm increases the false positive rate. Suppressing ethnicity effect did not improve the test sensitivity. By modifying demographic characteristics, it is possible to improve some performance aspects of clinical prediction tests.

Survey on the Adherence to the 2009 NASPGHAN-ESPGHAN Gastroesophageal Reflux Guidelines by Brazilian Paediatricians.

OBJECTIVE: The aim of the study was to evaluate the management of gastroesophageal reflux in children among Brazilian pediatricians and adherence to the 2009 North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN), and European Society of Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Guideline in Brazil. METHODS: An observational cross-sectional study was conducted, applying a standard questionnaire with 12 questions about gastroesophageal reflux (GER) and gastroesophageal reflux disease (GERD) management in infants, children, and adolescents to the pediatricians during the 37th Brazilian Pediatrics Congress in October, 2015. Adherence to the 2009 NASPGHAN-ESPGHAN Guideline was verified through analyses of interviewees' answers. Pediatricians' demographic and professional characteristics were screened. RESULTS: A total of 390 Brazilian pediatricians answered the questionnaire. None showed complete adherence to Guideline recommendations. GERD diagnosis by history alone was reported by 67%, irrespective of the child's age. The mean score for diagnostic adherence to the guidelines was 0.94 ±â€Š0.86 (range 0-4). Working in public health services (P = 0.026) was the only variable retained as a significant predictor of poor adherence for GER/GERD diagnosis after multivariate logistic regression analysis. No significant statistical differences were found between Brazilian regions on total score (P = 0.774). Proton pump inhibitors were prescribed by 28.4% of the pediatricians independent of child's age, and 59% use proton pump inhibitors to treat babies with unexplained crying and/or distressed behavior. CONCLUSIONS: 2009 NASPGHAN-ESPGHAN Guideline recommendations had poor adherence by Brazilian pediatricians. Studies evaluating the reasons for the poor adherence to NASPGHAN/ESPGHAN guidelines are urgently needed.

Blueberry Residue Encapsulation by Ionotropic Gelation.

In the processing of fruits such as blueberry (Vaccinium sp), that has high levels of phenolic acid, the food industry produces tons of organic waste that causes harm to the environment. Encapsulation is a technique used to take advantage of these wastes. Several methods are used to encapsulate substances, among them ionotropic gelation proves to be a simple, precise, efficient and economical method for obtaining particles with encapsulated bioactives. In this manner, the aim of this study was to test sodium alginate as wall material to encapsulate blueberry residue by ionotropic gelation. The microbeads were characterized by scanning electron microscopy (SEM), x-ray diffraction (XRD), total phenolic compounds, antioxidant capacity and in vitro dissolution. The results showed that the microbeads had surface invagination; retention of 67.01% of the phenolic compounds after encapsulation and 68.2%, phenolic release 120 min after in vitro dissolution. The results suggest that the tested matrix was suitable for encapsulation. The produced microbeads are promising for applications in food products, once the phenolic compounds present in the blueberry residues were maintained after encapsulation.

Brain-robot interface driven plasticity: Distributed modulation of corticospinal excitability.

Brain-robot interfaces (BRI) are studied as novel interventions to facilitate functional restoration in patients with severe and persistent motor deficits following stroke. They bridge the impaired connection in the sensorimotor loop by providing brain-state dependent proprioceptive feedback with orthotic devices attached to the hand or arm of the patients. The underlying neurophysiology of this BRI neuromodulation is still largely unknown. We investigated changes of corticospinal excitability with transcranial magnetic stimulation in thirteen right-handed healthy subjects who performed 40min of kinesthetic motor imagery receiving proprioceptive feedback with a robotic orthosis attached to the left hand contingent to event-related desynchronization of the right sensorimotor cortex in the ß-band (16-22Hz). Neural correlates of this BRI intervention were probed by acquiring the stimulus-response curve (SRC) of both motor evoked potential (MEP) peak-to-peak amplitudes and areas under the curve. In addition, a motor mapping was obtained. The specificity of the effects was studied by comparing two neighboring hand muscles, one BRI-trained and one control muscle. Robust changes of MEP amplitude but not MEP area occurred following the BRI intervention, but only in the BRI-trained muscle. The steep part of the SRC showed an MEP increase, while the plateau of the SRC showed an MEP decrease. MEP mapping revealed a distributed pattern with a decrease of excitability in the hand area of the primary motor cortex, which controlled the BRI, but an increase of excitability in the surrounding somatosensory and premotor cortex. In conclusion, the BRI intervention induced a complex pattern of modulated corticospinal excitability, which may boost subsequent motor learning during physiotherapy.

Chlorhexidine-loaded hydroxyapatite microspheres as an antimicrobial delivery system and its effect on in vivo osteo-conductive properties.

Hydroxyapatite (HA) has been investigated as a delivery system for antimicrobial and antibacterial agents to simultaneously stimulate bone regeneration and prevent infection. Despite evidence supporting the bactericidal efficiency of these HA carriers, few studies have focused on the effect of this association on bone regeneration. In this work, we evaluated the physico-chemical properties of hydroxyapatite microspheres loaded with chlorhexidine (CHX) at two different concentrations, 0.9 and 9.1 µgCHX/cm2 HA, and characterized their effects on in vitro osteoblast viability and bone regeneration. Ultraviolet-visible spectroscopy, scanning and transmission electron microscopy associated with energy-dispersive X-ray spectroscopy and electron energy loss spectroscopy were used to characterize the association of CHX and HA nanoparticles. The high CHX loading dose induced formation of organic CHX plate-like aggregates on the HA surface, whereas a Langmuir film was formed at the low CHX surface concentration. Quantitative evaluation of murine osteoblast viability parameters, including adhesion, mitochondrial activity and membrane integrity of cells exposed to HA/CHX extracts, revealed a cytotoxic effect for both loading concentrations. Histomorphological analysis upon implantation into the dorsal connective tissues and calvaria of rats for 7 and 42 days showed that the high CHX concentration induced the infiltration of inflammatory cells, resulting in retarded bone growth. Despite a strong decrease in in vitro cell viability, the low CHX loading dose did not impair the biocompatibility and osteoconductivity of HA during bone repair. These results indicate that high antimicrobial doses may activate a strong local inflammatory response and disrupt the long-term osteoconductive properties of CHX-HA delivery systems.

Oxidative stability and sensory evaluation of microencapsulated flaxseed oil.

Cold pressed flaxseed oil was microencapsulated by spray drying using an emulsion containing modified starch. The fatty acid composition, moisture, water activity, wettability, water holding capacity, water solubility, crystallinity, and particle size distribution of the microcapsules were determined. The stability of the microcapsules and the crude oil were assessed. An acceptance test was used for the sensory evaluation of a powdered supplement containing the microcapsules. The fatty acid composition was not significantly affected by the microencapsulation. The moisture, water activity, wettability, water solubility and crystallinity were appropriate for dry powders. The microcapsules had no cracks and showed better oxidative stability compared with the crude oil. Storage under vacuum prevented oxidation of the microcapsules. In sensory evaluation, all quality scores of the supplement containing microcapsules were mid-range or higher. The microencapsulation improved the oxidative stability of the oil and this procedure was satisfactorily applied in powdered food.

Study of trans-trans farnesol effect on hyphae formation by Yarrowia lipolytica.

Dimorphism is an ability of certain fungi related to its adaptation to the environment and provides a selective advantage under stress conditions and is associated to the development of human diseases. Hyphae inducing- and inhibitory-effect of farnesol on hyphae formation by the dimorphic yeast Yarrowia lipolytica was evaluated through digital image analysis. The agitation speed of the culture was the most effective hyphae inducer in comparison to bovine calf serum and N-acetylglucosamine. In low agitation system, bovine calf serum was more effective for hyphae formation inducing 57 % of hyphae transition. Farnesol inhibited hyphae formation even in low concentration (300 µM) and this effect increased with increasing concentrations. In the presence of N-acetylglucosamine, this effect was more evident in comparison to the presence of bovine calf serum, which might have protected the cells from farnesol. Digital image analysis was an important tool to evaluate this phenomenon.

Trichoderma longibrachiatum as a biostimulant of micropropagated banana seedlings under acclimatization.

The use of growth-promoting microorganisms with biostimulant characteristics is an important biological asset for the acclimatization of micropropagated seedlings. The present study aimed to evaluate the efficacy of the application of Trichoderma spp. on the promotion of the growth of micropropagated banana seedlings during acclimatization. The experiment was performed in an 8 × 6 completely randomized design using the following treatments: water, seedlings fertilized with controlled-release fertilizer, commercial biological inputs (A: T. asperellum, B/C: T. harzianum), and LPPC299 and LPPC300 strains. Plant height, pseudostem diameter, number of leaves, total leaf area, root length, fresh and dry mass of the plant, and accumulation of sodium, macronutrients, and micronutrients were evaluated 60 days after inoculation. Strains LPPC299 and LPPC300 were subjected to molecular identification by DNA sequencing of the ITS/5.8S locus. In vitro detection of growth promotion-related mechanisms and mycelial growth of biostimulants were performed using scanning electron microscopy. LPPC299 and LPPC300 had a greater similarity to T. longibrachiatum. LPPC299 was able to promote greater pseudostem diameter, number of leaves, and total leaf area in banana seedlings. T. asperellum (A) favored seedling performance in terms of fresh and dry mass of the plants. The strains were able to produce siderophores, indoleacetic acid, and catalase in vitro. Seedlings inoculated with the strains accumulated Mn, S (LPPC300), and Mg (LPPC299). LPPC299 from the banana rhizosphere was efficient in promoting performance in banana seedlings, showing its potential as a biostimulant for this crop.

Repetitive Transcranial Magnetic Stimulation for Tinnitus Treatment in Vestibular Schwannoma: A Pilot Study.

Background: Vestibular schwannomas (VS) are brain tumors affecting the vestibulocochlear nerve. Thus, VS patients suffer from tinnitus (TN). While the pathophysiology is mainly unclear, there is an increasing interest in repetitive transcranial magnetic stimulation (rTMS) for TN treatment. However, the results have been divergent. In addition to the methodological aspects, the heterogeneity of the patients might affect the outcome. Yet, there is no study evaluating rTMS exclusively in VS-associated tinnitus. Thus, the present pilot study evaluates low-frequency rTMS to the right dorsolateral pre-frontal cortex (DLPFC) in a VS-associated tinnitus. Methods: This prospective pilot study enrolled nine patients with a monoaural VS-associated tinnitus ipsilateral to the tumor. Patients were treated with a 10-day rTMS regime (1 Hz, 100% RMT, 1,200 pulses, right DLPFC). The primary endpoint of the study was the reduction of TN distress (according to the Tinnitus Handicap Inventory, THI). The secondary endpoint was a reduction of TN intensity (according to the Tinnitus Matching Test, TMT) and the evaluation of factors predicting tinnitus outcome (i.e., hearing impairment, TN duration, type of tinnitus). Results: No complications or side effects occurred. There was one drop-out due to a non-responsiveness of the complaint. There was a significant acute effect of rTMS on the THI and TMT. However, there was no significant long-term effect after 4 weeks. While the THI failed to detect any clinically relevant acute effect of rTMS in 56% of the patients, TMT revealed a reduction of TN intensity for more than 20 in 89% and for more than 50 in 56% of the patients. Notably, the acute effect of rTMS was influenced by the TN type and duration. In general, patients with a tonal TN and shorter TN duration showed a better response to the rTMS therapy. Conclusion: The present pilot study is the first one to exclusively evaluate the effect of low-frequency rTMS to the right DLPFC in a VS-associated tinnitus. Our results prove the feasibility and the efficacy of rTMS in this patient cohort. There is a significant acute but a limited long-term effect. In addition, there is evidence that patients with a tonal tinnitus and shorter tinnitus duration might have the strongest benefit. A larger, randomized controlled study is necessary to prove these initial findings.

Interhemispheric differences in time-frequency representation of motor evoked potentials in brain tumor patients.

OBJECTIVE: Conventional time-series parameters are unreliable descriptors of motor-evoked potentials (MEPs) in brain tumor patients. Frequency domain analysis is suggested to provide additional information about the status of the cortico-spinal motor system. Aim of the present study was to describe the time-frequency representation of MEPs and its relation to the motor performance. METHODS: This study enrolled 17 consecutive brain tumor patients with impaired dexterity. After brain mapping of the affected (AH) and non-affected (NAH) hemisphere, TMS was applied to the hotspots of the abductor pollicis brevis muscles (APB). Using a Morlet wavelet approach, event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) of the MEPs were calculated and compared to the Grooved Pegboard Test (GPT). Additionally, inter- and intra-subject reliability was assessed by the intraclass correlation coefficient (ICC). RESULTS: MEPs were projecting to a frequency band between 30 and 400 Hz with a local maximum between 100 and 150 Hz. There was a significant ERSP and ITC reduction of the AH in comparison to the NAH. In contrast, no interhemispheric differences were depicted in the conventional time-series analysis. ERSP and ITC values correlated significantly with GPT results (r = 0.35 and r = 0.50). Time-frequency MEP description had good inter-and intra-subject reliability (ICC = 0.63). CONCLUSIONS: Brain tumors affect corticospinal transmission resulting in a reduction of temporal and spectral MEP synchronization correlating with the dexterity performance. SIGNIFICANCE: Time-frequency representation of MEPs provide additional information beyond conventional time-domain features.

Clinical and Radiological Profiles of COVID-19 Patients with Neurological Symptomatology: A Comparative Study.

Patients with COVID-19 can require radiological examination, with chest CT being more frequent than neuro-imaging. The objective is to identify epidemiological, clinical and radiological factors considered as predictors of neurological involvement in patients with COVID-19 assessed by neuroimaging and to describe the neuroimaging findings. This retrospective study was performed with 232 consecutive confirmed COVID-19 patients, from two radiological units, which were divided into two groups: (1) those who underwent a brain CT/MRI scan (n = 35) versus (2) those who did not undergo the brain CT/MRI scan, but underwent only chest CT (n = 197). There was a statistically significant difference with associations regarding the COVID-19 brain scan group for: admission to ICU, greater severity of lung injuries, the use of a mechanical ventilator and sepsis. Statistical tendency was found for chronic renal failure and systemic arterial hypertension. Forty-percent of COVID-19 patients from the brain scan group were abnormal on brain CT and/or brain MRI (22.9% of the cases with bleeding or microbleeding, 8.6% with restricted diffusion lesions). One ischemic stroke case was associated with irregularity at the M1 segment of the right middle cerebral artery. There was a case of left facial nerve palsy with enhancement of the left geniculate ganglia. An analysis of the olfactory bulbs was possible in 12 brain MRIs and 100% had enhancement and/or microbleeding. In conclusion, a more severe COVID-19 disease from ICU, a more severe form of lung disease, the use of mechanical ventilator and sepsis were associated to the COVID-19 patients with neurological involvement who had undergone brain scans. Microvascular phenomenon was a frequent finding in the brain and olfactory bulbs evaluated by neuroimaging.

Dissecting the transcriptional networks underlying breast cancer: NR4A1 reduces the migration of normal and breast cancer cell lines.

INTRODUCTION: Breast cancer currently accounts for more than one-quarter of all female cancers and, despite the great progress in treatment observed in the past few years, the need for identification of new gene targets that can be used for diagnosis, prognosis and therapy is evident. A previous study identified the transcription factor NR4A1 as a gene upregulated in primary breast cancer compared with normal tissue by microarray analysis and sequencing technologies. The purpose of the study was to identify the role of NR4A1 in normal mammary epithelial and breast cancer cell biology. METHODS: NR4A1 expression in breast tumours was assessed by semiquantitative and real-time PCR using RNA from normal and tumour samples or breast cancer cell lines. Immunohistochemistry on tissue microarrays was performed to check NR4A1 protein expression in breast tumours. MCF-10A and 226L normal mammary epithelial cells as well as the tumour lines PMC42, ZR-75-1 and MDA-MB-231 were transduced with full-length NR4A1, and the ability of NR4A1-overexpressing cells to migrate was tested using scratch wound or transwell migration assays. Proliferation was measured using the MTT and BrdU assays, while apoptosis was determined by the Annexin V assay. The ability of the cells to adhere to extracellular matrix was tested by adhesion assays and integrin cell surface expression was measured by flow cytometry. Activation of the FAK as well as ERK1/2 and PI3K pathways was checked by western blotting. RESULTS: Breast tissue microarray analysis showed NR4A1 expression in primary tumours, which was reduced in higher grade and metastatic tumours. Ectopic expression of NR4A1 in MCF-10A, 226L, PMC42 and ZR-75-1 cells led to reduced ability of the cells to migrate, while no differences were observed in their proliferation and apoptotic index. NR4A1 expression altered the ability of the MCF-10A cells to adhere to the extracellular matrix and affected cell surface expression of integrins. CONCLUSIONS: NR4A1 acts as an antimigratory factor in two normal mammary epithelial and two breast cancer cell lines tested. It is therefore possible that NR4A1 acts as an antimigratory factor in breast tumours, and further studies should be conducted to understand the mechanisms involved.

Detecting poststroke cortical motor maps with biphasic single- and monophasic paired-pulse TMS.

BACKGROUND: Residual corticospinal connections are the precondition for poststroke motor recovery and necessary for targeted interventions. In severely affected patients, standard transcranial magnetic stimulation (TMS) may lead to false negative findings. OBJECTIVE: Detecting the cortical representation of paralyzed forearm muscles by applying different stimulation techniques and maps beyond the hotspot. METHODS: In seventeen chronic stroke patients with severe motor deficits, navigated biphasic single (SP) and monophasic paired-pulse (PP) TMS was applied at 100% stimulator output to an extended cortical area in the ipsilesional hemisphere, while recording surface EMG of the extensor carpi radialis muscle. RESULTS: In eleven patients, residual connectivity to the paralyzed forearm was detected with either mapping technique (five SP and PP, four PP only, two SP only). In five patients, connections originated from non-primary motor areas. CONCLUSION: These results could be instrumental for identifying candidates and stimulation targets for novel neuromodulation interventions in the context of neurorehabilitation.

Evaluation of uterine cervical cancer in pregnancy: A cross-sectional study.

OBJECTIVE: Evaluate the prevalence and the regression rate of cytological alteration in pregnant patients below the recommended age by the Brazilian Guidelines for the Screening of Uterine Cervical Cancer Guideline in the prenatal service of Maternidade Escola da Universidade Federal do Rio de Janeiro. STUDY DESIGN: We included the cytopathological exams of all pregnant patients that attended on the outpatient from January 2010 to May 2016. For the identification of the pregnant women, the Management and Integrated System and the Uterine Cervical Cancer Information System of the institution were used. We performed X2 test. The level of significance was 0.05. RESULTS: The study totaled 5825 cytopathological exams, of which 1822 were from pregnant patients ≤ 24 years of age. Only 4.06 % (74/1822) of altered results were found (p < 0.05). The most frequent change was low-grade squamous intraepithelial lesion with a prevalence of 1.92 % (35/1822) whereas high-grade squamous intraepithelial lesion had 0.16 % (3/1822). The regression rate in pregnant patients ≤24 years of age was 34,32 %. CONCLUSION: There was a low prevalence of cytological abnormalities in pregnant patients ≤ 24 years, low frequency of high-grade squamous intraepithelial lesion among the altered cytologies and a high spontaneous regression rate, therefore screening is not recommended before the age determined by the Brazilian Guideline.

Doxycycline containing hydroxyapatite ceramic microspheres as a bone-targeting drug delivery system.

Drug delivery technology is a promising way to enhance the therapeutic efficacy of drugs. The purpose of this study is to evaluate the physical and chemical properties of hydroxyapatite ceramic microspheres loaded with doxycycline (HADOX), their effects on in vitro osteoblast viability, and their antimicrobial activity, and to determine the effects of DOX on the healing of rat sockets after tooth extraction. The internal microsphere porosity was sensitive to the treatment used to adsorb DOX onto microsphere surface; HA microspheres without DOX presented 26% of pores, whereas HADOX0.15 microspheres presented 52.0%. An initial drug release of 49.15 µg/ml was observed in the first 24 hr. The minimal inhibitory concentration (MIC) tested against Enterococcus faecalis demonstrated that bacterial growth was inhibited for up to 7 days. Results of cell viability and cell proliferation did not indicate statistical differences in the metabolic activity of HADOX samples relative to HA without DOX microspheres (p > .05). After 1 week, a discreet inflammation reaction was observed in the control group, and after 6 weeks, newly-formed bone was observed in the HADOX0.15 (p < .05). The HADOX did not interfere in the bone repair and controlled the early inflammatory response. HADOX could be a promising biomaterial to promote bone repair in infected sites.

Production of bioactive films of carboxymethyl cellulose enriched with green coffee oil and its residues.

Carboxymethyl cellulose (CMC)-based films were developed by incorporating green coffee oil (GCO) obtained by cold pressing and hydroalcoholic extracts of its residues. The effect of cake (CE) and sediment extracts (SE) in different proportions (20-40%) and GCO on chemical, morphological, physical, mechanical, optical, and antioxidant properties of the films was investigated. Eight fatty acids and four major phenolic compounds were identified by High-Resolution Direct-Infusion Mass Spectrometry in GCO and residue extracts. FTIR indicated interactions among CMC, phenolic compounds, and fatty acids. Films enriched with residue extracts presented heterogeneous microstructure. The tensile strength of the films decreased from 58 to 3 MPa with the extracts concentration, while elongation increased from 28 to 156% (p < 0.05). The water vapor permeability (averaging 3.94 × 10-8 g mm/cm2 h Pa) was not significantly affected by the extracts and GCO. The surface color was influenced by the type and concentration of extracts (p < 0.05), the film with SE40% had remarkable UV-vis barrier properties. The incorporation of GCO residue extracts imparted high antioxidant capacity to the CMC-based films, especially with CE40% (643.8 µmol Trolox eq./g dried film; 51.3 mg GAE/g dried film). General observations indicated the potential of these films, mainly the ones containing CE, like active packaging material for food applications.