The vigabatrin-associated brain abnormalities on MRI and their differential diagnosis.

Vigabatrin is an anti-epileptic drug that inhibits the enzyme γ-aminobutyric acid (GABA)-transaminase. The anticonvulsant effect of vigabatrin involves increasing GABA levels and attenuating glutamate-glutamine cycling. Vigabatrin indications include infantile spasms and refractory focal seizures. Despite having a significant role in paediatric epileptology, vigabatrin has adverse effects, such as retinal toxicity, in up to 30% of patients after 1 year of use and brain abnormalities on magnetic resonance imaging (MRI). The percentage of patients with brain abnormalities on MRI varies between 22-32% of children using vigabatrin to treat infantile spasms. Risk factors for presenting these imaging abnormalities are cryptogenic infantile spasms, age <12 months old, high dosage, and possible concomitant hormonal therapy. Clinically, these abnormalities are usually asymptomatic. Histopathological analysis reveals white matter vacuolation and intramyelinic oedema. The typical findings of vigabatrin-associated brain abnormalities on MRI are bilateral and have a symmetrical hyperintense signal on T2-weighted imaging, with diffusion restriction, that often compromise the globi pallidi, thalami, subthalamic nuclei, cerebral peduncles, midbrain, dorsal brainstem, including the medial longitudinal fasciculi, and dentate nuclei of the cerebellum. In this article, the authors intend to review the clinical manifestations, histopathological features, imaging aspects, and differential diagnosis of vigabatrin-associated brain abnormalities on MRI.

Development of Ti-Al-V alloys for usage as single-axis knee prostheses: evaluation of mechanical, corrosion, and tribocorrosion behaviors.

Single-axis knee prosthesis is an artificial biomechanical device that provides motion to amputees without the need for assistance appliances. Besides it is mainly composed of metallic materials, the current commercial materials did not group adequate properties for long-term usage or accessible cost. This study produced and characterized Ti-(10 -x)Al-xV (x = 0, 2, and 4 wt.%) alloys for potential use as single-axis knee prostheses. The samples exhibited a gradual decrease in the density values, with proper chemical mixing of the alloying elements on the micro-scale. The phase composition exhibited a primary α phase with a minor α' + ß phase for the Ti-8Al-2V and Ti-6Al-4V samples. Due to their different atomic radius compared to Ti, the addition of alloying elements changed the cell parameters. Their selected mechanical properties (Young's modulus, Vickers microhardness, and damping factor) performed better values than the CP-Ti grade 4. The samples also exhibited good corrosion properties against the simulated marine solution. The tribocorrosion resistance of the samples was better than the reference material, with the wear tracks composed of some tribolayers and grooves resulting from adhesive and abrasive wear. The Ti-10Al alloy displayed the best properties and estimated low cost to be used as single-axis knee prostheses.

Histological evidence of superficial inflammation is associated with lower recurrence of equine sarcoids following surgical removal: A follow-up study of 106 tumours in 64 horses.

Although the equine sarcoid is the most common skin neoplasm in domesticated horses, histopathological characteristics have not previously been evaluated for association with recurrence. The aim of this retrospective cohort study was to investigate clinical and histopathological features of excised equine sarcoids and to evaluate their association with recurrence at the original surgical site and at new sites. Clinical records and excisional biopsies from 106 equine sarcoids from 64 horses referred to Leahurst Equine Hospital, University of Liverpool, between March 2010 and February 2015 were retrieved. Biopsies were re-evaluated histologically. Clinical data were obtained from hospital records, and owner-reported follow-up data were obtained by telephone questionnaire. Associations between clinical and histopathological features of sarcoids and their recurrence at the surgical site were determined using uni- and multivariable mixed effects logistic regression. Recurrence of sarcoids at the surgical site occurred in 30 horses (46.9%). Sarcoids developed at a distant site in 21 horses (32.8%). In the final mixed effects logistic regression model, only superficial inflammation was associated with reduced odds of recurrence at the surgical site (adjusted odds ratio, 0.32; 95% confidence intervals, 0.10-0.96; P = 0.04). This suggests that the inflammatory process may play a role in protecting horses against the recurrence of sarcoids.

Prevalencia de infección por Chlamydia trachomatis y relación con el perfil de conductas sexuales en adolescentes y mujeres jóvenes de la Provincia de Osorno, Chile / Prevalence of Chlamydia trachomatis infection and relationship with the profile of sexual behaviors in adolescents and young women in the Province of Osorno, Chile

INTRODUCCIÓN: La infección por Chlamydia trachomatis es la ITS bacteriana más frecuente del mundo. En el cervix se presenta mayormente de forma asintomática y afecta especialmente a mujeres jóvenes y adolescentes. Puede producir daño permanente en el tracto reproductor femenino, se asocia a parto prematuro, infecciones neonatales transmitidas vía vertical y mayor riesgo de adquirir otras ITS como VIH Y VPH. Por estos motivos se han establecido estrategias de tamizaje para detectar y tratar precozmente la infección asintomática por C. trachomatis en diferentes países. En nuestro país no contamos con un programa nacional de tamizaje. OBJETIVO: Determinar la prevalencia de infección asintomática por Chlamydia trachomatis en mujeres entre 12 y 21 años de la Provincia de Osorno, Región de Los Lagos, Chile. PACIENTES Y MÉTODOS: Se desarrolló un estudio de diseño transversal con una cohorte única de mujeres adolescentes y jóvenes consultantes en el Policlínico de Alto Riesgo Obstétrico y de Ginecología Infantil y Adolescente, del Hospital Base de Osorno, entre enero de 2019 y enero 2020. Se determinó el estado de infección asintomática mediante RPC en tiempo real para C. trachomatis. Se realizó una encuesta a fin de determinar características demográficas, hábitos y conductas sexuales de las pacientes estudiadas. RESULTADOS: Fueron reclutadas 124 mujeres entre 12 a 21 años de edad, de las cuales, 36 (29,3%) se encontraban embarazadas al momento del estudio. La prevalencia de infección asintomática por C. trachomatis fue de 14/124 (11,3%). En las mujeres gestantes se encontraron 6/36 (16,7%) casos positivos de infección por C. trachomatis y 8/88 (9,1%) en las no gestantes. Existe una mayor frecuencia de infección asintomática a menor edad de inicio de actividad sexual (33,3% en aquellas que inician entre 11-12 años vs. 16,2% en las que inician entre 1314 años, 7,4% entre 15-16 y 8% entre 17-21 años; p < 0,05). Esta tendencia no fue observada al comparar el estado de infección con el tiempo de vida sexual activa. Sólo 15,7% de las pacientes utilizó preservativo en todas sus relaciones sexuales. DISCUSIÓN: La infección asintomática por C. trachomatis es frecuente en las mujeres adolescentes y jóvenes sexualmente activas. Las pacientes con inicio más temprano de la actividad sexual coital (bajo 13 años de edad) podrían estar en mayor riesgo. Se requiere con urgencia establecer la frecuencia nacional de infección para desarrollar una estrategia sanitaria para su pesquisa y manejo oportuno en nuestro país.

BACKGROUND: Chlamydia trachomatis infection is the world most common bacterial STI. At uterine cervix it presents mostly asymptomatically and especially affects young women and adolescents. It can cause permanent damage to the female reproductive tract and is associated with premature birth, connatal infections and increased risk of acquiring other STIs such as HIV and HPV. For these reasons, other countries have established screening strategies to detect and treat asymptomatic C. trachomatis infection. Our country don't have a national screening program. AIM: To determine the prevalence of C. trachomatis asymptomatic infection in adolescent and young women in Osorno province, Los Lagos Region, Chile. METHODS: A crosssectional study was performed in adolescent and young women who consult at Hospital Base Osorno in the MaternoFetal and PediatricAdolescent Gynecology ambulatory clinics, between January 2019 and January 2020. The status of asymptomatic infection was determined by PCR for C. trachomatis. A survey was carried out to determine the demographic characteristics, habits and sexual behaviors. RESULTS: 124 women between 12 and 21 years of age were recruited, of which 36 (29,3%) were pregnant at the time of the study. The prevalence of asymptomatic infection by C. trachomatis was 11.3.%. In pregnant women, there were 6/36 (16.7%) positive cases for C. trachomatis and 8/88 (9.1%) in nonpregnant women. We found a higher frequency of asymptomatic infection at younger age of first sexual intercourse (33% in adolescents at 11-12 years old vs. 16.2% at 13-14, 7.4% at 15-16 and 8% at 17-21; p<0.05). Only 15.7% of the patients utilized condoms in all their intercourses. DISCUSSION: Asymptomatic C. trachomatis infection is common in adolescent and young women, with a higher risk in those who onset sexual activity at an early age (less than 13 years old). It is urgently required to determine the national frequency of asymptomatic C. trachomatis infection to develop a national strategy for screening and timely treatment.

Vertical transmission and pathological findings in the mother, the placenta and the offspring, during first and last thirds of gestation in a mouse model of congenital toxoplasmosis.

We performed a study of congenital toxoplasmosis of the first and third gestation periods in mice, and determined its effects on the embryos/fetuses, the placentae and the maternal organs. We infected pregnant BALB/c mice by i.v. injection of 2.5--10.0 × 106 tachyzoites of the ME49 T. gondii strain and euthanized them 72 h later. The tissues were analyzed by histopathology, immunohistochemistry and parasite-specific qPCR. Infections with the lowest dose induced remarkably different changes in the two thirds: a) all doses diminished the number of products/litter, the lowest dose only by 14%; but most embryos still visible were degenerated in the case of the first period, while the fetuses of the last third were perfectly preserved; b) the transmission rate in the first third was relatively high, but with a very low parasite burden; c) with the lowest dose, strong vascular changes (congestion, thrombosis and hemorrhage) predominated in the placentas of the first period, while they were absent in the last third; d) necrosis caused by T. gondii to maternal organs was much stronger during the last gestation period than in the first. Our results suggest that the vascular alterations at the placenta of the first third of pregnancy prevent embryo from large parasite burden, but provoke its death by starvation. In the last gestation period, there was poor control of parasite dissemination to the placenta and the fetus, but there was greater capacity of the product to defend itself from T. gondii.

Nanotechnology-Driven Cell-Based Therapies in Regenerative Medicine.

The administration of cells as therapeutic agents has emerged as a novel approach to complement the use of small molecule drugs and other biologics for the treatment of numerous conditions. Although the use of cells for structural and/or functional tissue repair and regeneration provides new avenues to address increasingly complex disease processes, it also faces numerous challenges related to efficacy, safety, and translational potential. Recent advances in nanotechnology-driven cell therapies have the potential to overcome many of these issues through precise modulation of cellular behavior. Here, we describe several approaches that illustrate the use of different nanotechnologies for the optimization of cell therapies and discuss some of the obstacles that need to be overcome to allow for the widespread implementation of nanotechnology-based cell therapies in regenerative medicine.

Impacto de la pandemia COVID-19 en las consultas de urgencias otorrinolaringológicas en el Hospital Guillermo Grant Benavente de Concepción / Impact of the COVID-19 pandemic on emergency ENT consultations at Guillermo Grant Benavente Hospital, Concepcion

Resumen Introducción: La pandemia COVID-19 ha afectado significativamente el uso de los sistemas de salud en todo el mundo y se han reducido las consultas de urgencia por patologías no relacionadas con el virus SARS-CoV-2. Objetivo: Analizar el impacto de la pandemia COVID-19 en las consultas de urgencia otorrinolaringológicas atendidas en el servicio de urgencia de un centro de alta complejidad. Material y Método: Se realizó un estudio retrospectivo en que se analizaron las consultas de urgencia otorrinolaringológicas atendidas entre el 3 de marzo y 31 de diciembre de 2020. Se comparó con los datos obtenidos el año 2019 para determinar los cambios epidemiológicos de la pandemia en curso. Resultados: Se evidenció una notoria disminución en las atenciones de urgencia otorrinolaringológicas desde el inicio de la pandemia COVID-19 (-23,3%). El mayor descenso se observó en el periodo de cuarentena o restricción total de movilidad (-59%). No hubo diferencias significativas entre los antecedentes sociodemográficos, tipo de patología otorrinolaringológica, número de cirugías de urgencias y admisiones hospitalarias en comparación con el periodo anterior. Conclusión: La pandemia COVID-19 ha generado una disminución de las consultas de urgencia otorrinolaringológicas agudizándose en el periodo de restricción total de movilidad impuesta por el gobierno. Si bien no se evidenciaron cambios en el patrón de atenciones predominante con respecto al periodo prepandemia, se estima un aumento de las patologías descompensadas o complicadas a mediano-largo plazo. Se requieren estudios prospectivos para determinar el verdadero impacto de la pandemia en curso.

Abstract Introduction: The COVID-19 pandemic has significantly affected the use of health systems around the world, and emergency consultations for diseases not related to the SARS-CoV-2 virus, have been reduced. Aim: To analyze the impact of the COVID-19 pandemic on emergency otolaryngology consultations attended in the emergency department of a highly complex center. Material and Method: A retrospective study was carried out in which the emergency otolaryngology consultations attended between March 3 and December 31, 2020. These data were analyzed and compared with the data obtained in 2019, to determine the epidemiological changes of the ongoing pandemic. Results: There was a noticeable decrease in ENT emergency care since the beginning of the COVID-19 pandemic (-23.3%). The greatest decrease is recorded in the period of quarantine or total mobility restriction (-59%). There were no significant differences between sociodemographic history, type of ENT pathology, number of emergency surgeries and hospital admissions compared to the previous period. Conclusion: The COVID-19 pandemic has generated a decrease in ENT emergency consultations, exacerbating the period of total mobility restriction imposed by the government. Although no changes were evidenced in the predominant care pattern with respect to the pre-pandemic period, an increase in decompensated or complicated pathologies is estimated in the medium-long term. Prospective studies are required to determine the true impact of the ongoing pandemic.

Umbilical Cord-derived Mesenchymal Stem Cells modulate TNF and soluble TNF Receptor 2 (sTNFR2) in COVID-19 ARDS patients.

OBJECTIVE: We aimed at explaining the mechanism of therapeutic effect of Umbilical Cord Mesenchymal Stem Cells (UC-MSC) in subjects with COVID-19 Acute Respiratory Distress Syndrome (ARDS). Patients with COVID-19 ARDS present with a hyperinflammatory response characterized by high levels of circulating pro-inflammatory mediators, including tumor necrosis factor α and ß (TNFα and TNFß). Inflammatory functions of these TNFs can be inhibited by soluble TNF Receptor 2 (sTNFR2). In patients with COVID-19 ARDS, UC-MSC appear to impart a robust anti-inflammatory effect, and treatment is associated with remarkable clinical improvements. We investigated the levels of TNFα, TNFß and sTNFR2 in blood plasma samples collected from subjects with COVID-19 ARDS enrolled in our trial of UC-MSC treatment. PATIENTS AND METHODS: We analyzed plasma samples from subjects with COVID-19 ARDS (n=24) enrolled in a Phase 1/2a randomized controlled trial of UC-MSC treatment. Plasma samples were obtained at Day 0 (baseline, before UC-MSC or control infusion), and Day 6 post infusion. Plasma concentrations of sTNFR2, TNFα, and TNFß were evaluated using a quantitative multiplex protein array. RESULTS: Our data indicate that at Day 6 after infusion, UC-MSC recipients develop significantly increased levels of plasma sTNFR2 and significantly decreased levels of TNFα and TNFß, compared to controls. CONCLUSIONS: These observations suggest that sTNFR2 plays a mechanistic role in mediating UC-MSC effect on TNFα and TNFß plasma levels, determining a decrease in inflammation in COVID-19 ARDS.

[Debate on the return to face-to-face classes in Pandemic]. / Debate sobre el retorno a clases presenciales en Pandemia.

The implications of closing educational establishments during the COVID-19 pandemic and the dis cussion about the opening of them, invite and require us to consider, from different positions and responsibilities, the changes that we must make as a society at the educational level. In this article, a group of health professionals collects information and reflects on the repercussions of returning or not to school activities, in terms of physical and emotional health and academic education. Based on what is known to be protective factors and possible threats to return, it is possible to conclude that each local reality must make its own informed decision, with the participation of all its members, seeking the common good, which favors students, protects teachers, and privileges the role of the educational system in socio-emotional learning. School is a space for containing the emotions and adaptation needs that students and their families have experienced in these uncertain times. We all have a level of responsibility in building a new civilization around these issues that link education, physical and mental health, social collaboration, and individual responsibility. Differences in people's living conditions and unequal opportunities have become more visible than before (others are still hidden) and create an opportunity for changes that we must face together.

Intervertebral disc and endplate cells response to IL-1ß inflammatory cell priming and identification of molecular targets of tissue degeneration.

Inflammation represents an important factor leading to metabolic imbalance within the intervertebral disc (IVD), conducive to degenerative changes. Therefore, a thorough knowledge of the IVD and endplate (EP) cell behaviour in such pathological environments is essential when designing regenerative therapeutic strategies. The present study aimed at assessing the molecular response of the IVD constitutive nucleus pulposus (NPCs)-, annulus fibrosus (AFCs)- and endplate (EPCs)-derived cells to interleukin (IL)-1ß treatment, through large-scale, high-throughput microarray and protein analysis, identifying the differentially expressed genes and released proteins. Overall, the inflammatory stimulus downregulated stemness genes while upregulating pro-inflammatory, pro-angiogenic and catabolic genes, including matrix metalloproteases, which were not balanced by a concomitant upregulation of their inhibitors. Upregulation of anti-inflammatory and anabolic tumour necrosis factor inducible gene 6 protein (TNFAIP6), of IL-1 receptor antagonist (IL-1Ra) (at gene and protein levels) and of trophic insulin-like growth factor 1 (IGF1) was also observed in all cell types; IGF1 particularly in AFCs. An overall inhibitory effect of tumour necrosis factor alpha (TNFα) signal was observed in all cell types; however, EPCs showed the strongest anti-inflammatory behaviour. AFCs and EPCs shared the ability to limit the activation of the signalling mediated by specific chemokines. AFCs showed a slightly senescent attitude, with a downregulation of genes related to DNA repair or pro-mitosis. Results allowed for the identification of specific molecular targets in IVD and EP cells that respond to an inflammatory environment. Such targets can be either silenced (when pathological targets) or stimulated to counteract the inflammation.

Umbilical Cord-derived Mesenchymal Stem Cells for COVID-19 Patients with Acute Respiratory Distress Syndrome (ARDS).

The coronavirus SARS-CoV-2 is cause of a global pandemic of a pneumonia-like disease termed Coronavirus Disease 2019 (COVID-19). COVID-19 presents a high mortality rate, estimated at 3.4%. More than 1 out of 4 hospitalized COVID-19 patients require admission to an Intensive Care Unit (ICU) for respiratory support, and a large proportion of these ICU-COVID-19 patients, between 17% and 46%, have died. In these patients COVID-19 infection causes an inflammatory response in the lungs that can progress to inflammation with cytokine storm, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), thromboembolic events, disseminated intravascular coagulation, organ failure, and death. Mesenchymal Stem Cells (MSCs) are potent immunomodulatory cells that recognize sites of injury, limit effector T cell reactions, and positively modulate regulatory cell populations. MSCs also stimulate local tissue regeneration via paracrine effects inducing angiogenic, anti-fibrotic and remodeling responses. MSCs can be derived in large number from the Umbilical Cord (UC). UC-MSCs, utilized in the allogeneic setting, have demonstrated safety and efficacy in clinical trials for a number of disease conditions including inflammatory and immune-based diseases. UC-MSCs have been shown to inhibit inflammation and fibrosis in the lungs and have been utilized to treat patients with severe COVID-19 in pilot, uncontrolled clinical trials, that reported promising results. UC-MSCs processed at our facility have been authorized by the FDA for clinical trials in patients with an Alzheimer's Disease, and in patients with Type 1 Diabetes (T1D). We hypothesize that UC-MSC will also exert beneficial therapeutic effects in COVID-19 patients with cytokine storm and ARDS. We propose an early phase controlled, randomized clinical trial in COVID-19 patients with ALI/ARDS. Subjects in the treatment group will be treated with two doses of UC-MSC (l00 × 106 cells). The first dose will be infused within 24 hours following study enrollment. A second dose will be administered 72 ± 6 hours after the first infusion. Subject in the control group will receive infusion of vehicle (DPBS supplemented with 1% HSA and 70 U/kg unfractionated Heparin, delivered IV) following the same timeline. Subjects will be evaluated daily during the first 6 days, then at 14, 28, 60, and 90 days following enrollment (see Schedule of Assessment for time window details). Safety will be determined by adverse events (AEs) and serious adverse events (SAEs) during the follow-up period. Efficacy will be defined by clinical outcomes, as well as a variety of pulmonary, biochemical and immunological tests. Success of the current study will provide a framework for larger controlled, randomized clinical trials and a means of accelerating a possible solution for this urgent but unmet medical need. The proposed early phase clinical trial will be performed at the University of Miami (UM), in the facilities of the Diabetes Research Institute (DRI), UHealth Intensive Care Unit (ICU) and the Clinical Translational Research Site (CTRS) at the University of Miami Miller School of Medicine and at the Jackson Memorial Hospital (JMH).

Brain MR Imaging of Patients with Perinatal Chikungunya Virus Infection.

Since 2005, it has been known that mother-to-child transmission of the chikungunya virus is possible. Transmission generally occurs in the perinatal period. In the present study, we describe the brain lesions seen on MR imaging of 6 cases of perinatal chikungunya infection. Patients who underwent brain MR imaging in the acute phase presented with areas of restricted diffusion in the white matter, suggesting a perivascular distribution, whereas those in the subacute/late phase showed cystic lesions, also with a perivascular distribution, with or without brain atrophy. One patient also presented with scattered hemorrhages in the frontal and parietal lobes. Important differential diagnoses include rotavirus, Parechovirus, herpes simplex infection, and hypoxic-ischemic encephalopathy, depending on the disease phase.

Sinonasal melanoma: a systematic review of the prognostic factors.

The objective was to evaluate the available published data on sinonasal melanoma and analyse its clinical features, treatment modalities, and prognostic factors. An electronic search was undertaken in March 2018 in multiple databases. Eligibility criteria included publications with sufficient clinical, histological, and immunohistochemical information to confirm the diagnosis. Seventy-three publications (439 cases) were included. The lesion was more prevalent in females than in males. There was a higher prevalence in the seventh and eighth decades of life. The lesions mainly presented as epistaxis and commonly involved the nasal cavity. Age (>67.6 years; P=0.0012), primary location (middle turbinate; P=0.0112), disease stage (advanced disease stage; P=0.0026), treatment (radiotherapy; P=0.0111), recurrence (recurrence presented; P=0.0137), and distant metastasis (distant metastasis presented; P=0.0011) were independently associated with a lower survival rate. Recurrence was significantly correlated with age (>67.6 years; P=0.0021), sex (males tended to present a higher recurrence rate than females; P=0.0051), disease stage (stages III and IV presented a higher recurrence rate than stages I and II; P=0.0331), and histological type (amelanotic lesions presented a higher index of recurrence than melanotic lesions; P=0.0095). In conclusion, sinonasal melanoma is a neoplasm with a poor prognosis, presenting a 30.69% possibility of survival after 5 years.

New Insights Into Pheochromocytoma Surveillance of Young Patients With VHL Missense Mutations.

CONTEXT: Von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by germline mutations in the VHL gene. Guidelines recommend pheochromocytoma (PHEO) biochemical screening should start at age 5 years. OBJECTIVE: Genotype-phenotype correlations in VHL, focusing on PHEO penetrance in children, were studied. DESIGN: We retrospectively evaluated 31 individuals (median age at diagnosis was 26 years) with diagnosed VHL disease. RESULTS: PHEO was diagnosed in six children with VHL. A large PHEO (5 cm) was detected in a 4-year-old boy with p.Gly114Ser mutation. PHEO penetrance was 55% starting at age 4 years. VHL missense mutations were identified in 11 of 22 families (50%), frameshift mutations in four (18.2%), stop codon in three (13.6%), splicing site in two (9.1%), and large gene deletion in two (9.1%). The codon 167 (n = 10) was a hotspot for VHL mutations and was significantly associated with PHEO (90% vs. 38%; P = 0.007). PHEOs and pancreatic neuroendocrine tumors (PNETs) were strongly associated with VHL missense mutations compared with other mutations (89.5% vs. 0% and 73.7% vs. 16.7%; P = 0.0001 and 0.002, respectively). In contrast, pancreatic cysts (91.7% vs. 26.3%; P = 0.0001), renal cysts (66.7% vs. 26.3%; P = 0.027), and central nervous system hemangioblastomas (91.7% vs. 47.3%; P = 0.012) were more frequent in VHL with nonmissense mutations. CONCLUSION: VHL missense mutations were highly associated with PHEO and PNETs. Our data support that in children with VHL harboring missense mutations, biochemical screening for PHEO should be initiated at diagnosis.

Microstructure and selected mechanical properties of aged Ti-15Zr-based alloys for biomedical applications.

In this study, Ti-15Zr-xMo (5, 10, 15, and 20 wt%) alloys were submitted to solution and aging treatments and their effects evaluated in terms of phase composition and selected mechanical properties (Vickers microhardness and Young's modulus) for use as biomedical implants. The solution treatment was performed at 1123 K for 2 h, while aging treatments were carried out at 698 K for 4, 8, and 12 h, followed by water quenching. Phase composition and microstructure were dependent of the heat treatments, with Ti-15Zr-5Mo (α +â€¯ß type) and Ti-15Zr-10Mo (metastable ß type) alloys exhibiting intense α phase precipitation. The α-phase precipitates were related to α″ → α and ß → α phase decompositions. The Ti-15Zr-10Mo alloy exhibited an intermediary isothermal ω-phase precipitation after aging for 4 h. Vickers microhardness and Young's modulus values changed gradually with the amount of α phase. Aged Ti-15Zr-15Mo and Ti-15Zr-20Mo alloys presented better combinations of hardness and Young's modulus than CP-Ti and Ti-64 ELI for biomedical applications.

What do anti-Toxoplasma gondii IgA and IgG subclasses in human saliva indicate?

Diagnostic tests for toxoplasmosis are based on serological techniques due to their high sensitivity. Some IgG subclasses are related to clinical outcome in the congenital form. In this work, we determined the levels of IgG, IgA, IgG1, IgG2, IgG3 and IgG4 anti-Toxoplasma gondii antibodies in paired saliva and serum samples from 91 women by indirect ELISA using a crude extract of the RH strain. The levels of IgA, IgG2, IgG3 and IgG4 antibodies and, to a lesser extent, IgG1 did not correlate between saliva and serum, that is, most cases that were positive for one Ig class in a sample were negative or very low in the other, and vice versa. We also observed that most samples of saliva that were positive for one IgG subclass were also positive for at least 2 of the other 3; this contrasted with findings in serum, wherein each person was positive almost exclusively for one subclass, as demonstrated before by us and other researchers. Although these findings are disappointing for the use in diagnosis, the richer response in saliva might indicate local exposure to T. gondii antigens without systemic infection; thus, saliva might be reflecting a local (protective?) response against this protozoan.

Plasma levels of innate immune mediators are associated with liver fibrosis in low parasite burden Schistosoma mansoni-infected individuals.

In the murine model, it was demonstrated that pro-inflammatory cytokines and chemokines are essential to the formation and modulation of Schistosoma-induced granulomatous inflammation. However, the relationship of these immune mediators and disease severity is hard to be established in naturally infected individuals. The current study evaluates the association between plasma concentrations of MIF, sTNF-R1, CCL3, CCL7 and CCL24 and schistosomiasis morbidity in Schistosoma mansoni-infected patients with a low parasite burden. For this propose, 97 S. mansoni-infected individuals were subjected to abdominal ultrasound analysis and clinical examination. Among them, 88 had plasma concentration of immune mediators estimated by ELISA assay. Multivariate linear regression models were used to evaluate the relationship between the plasma concentration of immune mediators and the variables investigated. Although most individuals presented low parasite burden, over 30% of them showed signs of fibrosis defined by ultrasound measurements and 2 patients had a severe form of schistosomiasis. No association between parasite burden and the plasma levels of chemokine/cytokines or disease severity was observed. There was a positive association between plasma concentration of CCL4, sTNF-R1, CCL3 and MIF with gall bladder thickness and/or with portal vein thickness that are liver fibrosis markers. In contrast, no association was found between CCL7 plasma concentrations with any of the schistosomiasis morbidity parameters evaluated. The data showed that CCL24, sTNFR1, MIF and CCL3 can be detected in plasma of S. mansoni-infected individuals and their concentration would be used as prognostic makers of Schistosoma-induced liver fibrosis, even in individuals with low parasite burden.

A pilot study of neuropsychological functions, APOE and amyloid imaging in patients with gliomas.

Brain tumor patients treated with radiotherapy (RT) often develop cognitive dysfunction, and recent studies suggest that the APOE ε-4 allele may influence cognitive outcome. The ε-4 allele is known to promote beta (ß) amyloid deposition in the cortex, and preliminary evidence suggests that RT may be associated with this process. However, it is unknown whether ß-amyloid accumulation contributes to treatment neurotoxicity. In this pilot study, we assessed neuropsychological functions and ß-amyloid retention using 18F-florbetaben (FBB) PET in a subset of brain tumor patients who participated in our study of APOE polymorphisms and cognitive functions. Twenty glioma patients treated with conformal RT ± chemotherapy participated in the study: 6 were APOE ε-4 carriers and 14 were non-ε-4 carriers. Patients completed a neuropsychological re-evaluation (mean time interval = 5 years, SD = 0.83) and brain MRI and FBB PET scans. Wilcoxon signed-rank test comparisons between prior and current neuropsychological assessments showed a significant decline in attention (Brief Test of Attention, p = 0.018), and a near significant decline in verbal learning (Hopkins Verbal learning Test-Learning, p = 0.07). Comparisons by APOE status showed significant differences over time in attention/working memory (WAIS-III digits forward, p = 0.028 and digits backward, p = 0.032), with a decline among APOE ε-4 carriers. There were no significant differences in any of the FBB PET analyses between APOE ε-4 carriers and non-ε-4 carriers. The findings suggest that glioma patients may experience worsening in attention and executive functions several years after treatment, and that the APOE ε-4 allele may modulate cognitive decline, but independent of increased ß-amyloid deposition.