Efficacy of continuous versus intermittent administration of nanoformulated benznidazole during the chronic phase of Trypanosoma cruzi Nicaragua infection in mice.

BACKGROUND: Benznidazole and nifurtimox are effective drugs used to treat Chagas' disease; however, their administration in patients in the chronic phase of the disease is still limited, mainly due to their limited efficacy in the later chronic stage of the disease and to the adverse effects related to these drugs. OBJECTIVES: To evaluate the effect of low doses of nanoformulated benznidazole using a chronic model of Trypanosoma cruzi Nicaragua infection in C57BL/6J mice. METHODS: Nanoformulations were administered in two different schemes: one daily dose for 30 days or one dose every 7 days, 13 times. RESULTS: Both treatment schemes showed promising outcomes, such as the elimination of parasitaemia, a reduction in the levels of T. cruzi-specific antibodies and a reduction in T. cruzi-specific IFN-γ-producing cells, as well as an improvement in electrocardiographic alterations and a reduction in inflammation and fibrosis in the heart compared with untreated T. cruzi-infected animals. These results were also compared with those from our previous work on benznidazole administration, which was shown to be effective in the same chronic model. CONCLUSIONS: In this experimental model, intermittently administered benznidazole nanoformulations were as effective as those administered continuously; however, the total dose administered in the intermittent scheme was lower, indicating a promising therapeutic approach to Chagas' disease.

Awareness on oral cancer among patients attending dental school clinics in Brazil.

BACKGROUND: Oral cancer is considered a public health problem worldwide. Dental schools may play an important role in educating patients about oral cancer. This study aimed at evaluating the knowledge of patients attending clinics at two dental schools in Brazil. MATERIAL AND METHODS: From March 2017 to April 2017, 251 patients who were attending clinics at two dental schools in Recife, Brazil, were included in the study. Patients were contacted in the waiting rooms of the clinic. Each participant completed a self-administered questionnaire, which consists of 21 questions, including socio-demographic and specific information on the disease. Data were analyzed using descriptive statistics, and a chi-square test (with a 5% significance level) was used to assess the correlation between the variables, education and family income and other variables. RESULTS: Most participants were women (64.9%) with a mean age of 42.72 years. Most participants were knowledgeable about oral cancer and identified tobacco use (48.6%), alcohol consumption (25.1%), and solar radiation (12%) as the primary risk factors for the disease. Only 36.7% of the participants reported having received counselling on oral cancer, of which 18.3% received the information from a dentist. All patients with an income higher than six minimum wages were aware about oral cancer (p = 0.001). CONCLUSIONS: These findings emphasize the importance of educational programs in dental schools as well providing integrated services for patients seeking care at school clinics, including population's awareness on oral cancer.

Component-resolved diagnosis and beyond: Multivariable regression models to predict severity of hazelnut allergy.

BACKGROUND: Component-resolved diagnosis (CRD) has revealed significant associations between IgE against individual allergens and severity of hazelnut allergy. Less attention has been given to combining them with clinical factors in predicting severity. AIM: To analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy. METHODS: Patients reporting hazelnut allergy (n = 423) from 12 European cities were tested for IgE against individual hazelnut allergens. Symptoms (reported and during Double-blind placebo-controlled food challenge [DBPCFC]) were categorized in mild, moderate, and severe. Multiple regression models to predict severity were generated from clinical factors and sensitization patterns (CRD- and extract-based). Odds ratios (ORs) and areas under receiver-operating characteristic (ROC) curves (AUCs) were used to evaluate their predictive value. RESULTS: Cor a 9 and 14 were positively (OR 10.5 and 10.1, respectively), and Cor a 1 negatively (OR 0.14) associated with severe symptoms during DBPCFC, with AUCs of 0.70-073. Combining Cor a 1 and 9 improved this to 0.76. A model using a combination of atopic dermatitis (risk), pollen allergy (protection), IgE against Cor a 14 (risk) and walnut (risk) increased the AUC to 0.91. At 92% sensitivity, the specificity was 76.3%, and the positive and negative predictive values 62.2% and 95.7%, respectively. For reported symptoms, associations and generated models proved to be almost identical but weaker. CONCLUSION: A model combining CRD with clinical background and extract-based serology is superior to CRD alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions.

Balanced secretion of anti-CEA × anti-CD3 diabody chains using the 2A self-cleaving peptide maximizes diabody assembly and tumor-specific cytotoxicity.

Adoptive transfer of genetically engineered human cells secreting bispecific T-cell engagers has shown encouraging therapeutic effects in preclinical models of cancer. However, reducing the toxicity and improving the effectiveness of this emerging immunotherapeutic strategy will be critical to its successful application. We have demonstrated that for gene-based bispecific antibody strategies, two-chain diabodies have a better safety profile than single-chain tandem scFvs (single-chain variable fragments), because their reduced tendency to form aggregates reduces the risk of inducing antigen-independent T-cell activation. Here, we demonstrate that the incorporation of a 2A self-processing peptide derived from foot-and-mouth disease virus conveying co-translational cleavage into a two-chain anti-CD3 × anti-CEA diabody gene enables near-equimolar expression of diabody chains 1 and 2, and thus increases the final amount of assembled diabody. This was found to maximize diabody-mediated T-cell activation and cytotoxicity against carcinoembryonic antigen-positive tumor cells.

Validation of Recipes for Double-Blind Placebo-Controlled Challenges With Milk, Egg White, and Hazelnut.

BACKGROUND: The double-blind, placebo-controlled food challenge (DBPCFC) is considered the definitive diagnostic test for food allergy. Nevertheless, validated recipes for masking the foods are scarce, have not been standardized, and differ between centers. Sensory evaluation techniques such as the triangle test are necessary to validate the recipes used for DBPCFC. METHODS: We developed 3 recipes for use in DBPCFC with milk, egg white, and hazelnut and used the triangle test to validate them in a 2-phase study in which 197 volunteers participated. In each phase, participants tried 3 samples (2 active-1 placebo or 2 placebo-1 active) and had to identify the odd one. In phase 1, the 3 samples were given simultaneously, whereas in phase 2, the 3 samples of foods that failed validation in phase 1 were given sequentially. A visual analog scale (VAS) ranging from 1 to 10 was used to evaluate how much participants liked the recipes. RESULTS: In phase 1, the egg white recipe was validated (n=89 volunteers, 38.9% found the odd sample, P=.16). Milk and hazelnut recipes were validated in phase 2 (for both foods, n=30 participants, 36.7% found the odd sample, P=.36). Median VAS scores for the 3 recipes ranged from 6.6 to 9.7. CONCLUSIONS: We used sensory testing to validate milk, egg white, and hazelnut recipes for use in DBPCFC. The validated recipes are easy to prepare in a clinical setting, provide the equivalent of 1 serving dose, and were liked by most participants.

Advancing allele group-specific amplification of the complete HLA-C gene--isolation of novel alleles from three allele groups (C*04, C*07 and C*08).

A variety of strategies have been designed for sequence-based HLA typing (SBT) and for the isolation of new human leucocyte antigen (HLA) alleles, but unambiguous characterization of complete genomic sequences remains a challenge. We recently reported a simple method for the group-specific amplification (GSA) and sequencing of a full-length C*04 genomic sequence in isolation from the accompanying allele. Here we build on this strategy and present homologous methods that enable the isolation of HLA-C alleles belonging to another two allele groups. Using this approach, which can be applied to sequence-based typing in some clinical settings, we have successfully characterized three novel HLA-C alleles (C*04:128, C*07:01:01:02, and C*08:62).

RECALMIN IV. Evolution in the activity of internal medicine units of the National Health System (2008-2021).

AIMS: This work aims to analyze the structure, activity, and outcomes of internal medicine units and departments (IMU) of the Spanish National Health System (SNHS) and to analyze the challenges for the specialty and propose policies for improvement. It also aims to compare the results from the 2021 RECALMIN survey with IMU surveys from previous years (2008, 2015, 2017, 2019). METHODS: This work is a cross-sectional, descriptive study of IMUs in acute care general hospitals of the SNHS that compares data from 2020 with previous studies. The study variables were collected through an ad hoc questionnaire. RESULTS: Between 2014 and 2020, hospital occupancy and discharges by IMU increased (annual mean of 4% and 3.8%, respectively), as did hospital cross-consultation and initial consultation rates (2.1% in both cases). E-consultations increased notably in 2020. Risk-adjusted mortality and length of hospital stay did not show significant changes from 2013-2020. Progress in the implementation of good practices and systematic care for complex chronic patients was limited. A consistent finding in RECALMIN surveys was the variability among IMUs in terms of resources and activity, though no statistically significant differences were found in regard to outcomes. CONCLUSIONS: There is considerable room for improvement in the operation of IMUs. The reduction in unjustified variability in clinical practice and inequities in health outcomes are a challenge for IMU managers and the Spanish Society of Internal Medicine.

[Usefulness of Clinical Risk Index for Babies based on birth weight in predicting hospital death and severe intraventicular hemorrhage in the SEN 1500 Spanish neonatal network]. / Análisis de la utilidad del Clinical Risk Index for Babies por estratos de peso como predictor de muerte hospitalaria y de hemorragia intraventricular grave en la Red Neonatal Española SEN 1500.

OBJECTIVE: To evaluate the usefulness of the Clinical Risk Index for Babies (CRIB) in predicting hospital mortality and severe intraventricular hemorrhage (IVH) in very low birth weight infants stratified by weight groups, in the Spanish neonatal network SEN 1500. PATIENTS AND METHODS: A prospective cohort study was made. Morbidity-mortality data and CRIB were collected in newborns weighing below 1500 g and admitted to 68 neonatal intensive care units between January 2002 and December 2006. Data were analyzed globally and stratified by weight groups (< 501 g, 500-750 g, 751-1000 g, 1001-1250 g, 1251-1500 g). Multivariate models were generated and ROC curves were plotted for estimating predictive values. RESULTS: A total of 10,608 patients were analyzed. The mean weight was 1116 g (SD 267), and gestational age 29.5 weeks (SD 2.9). Low birth weight for gestational age was 34.3% and the multiple birth rate 36%. Prenatal corticoids were given in 78.2%. Severe intraventricular hemorrhage was diagnosed in 8.5%. Gender, prenatal corticoids, birth weight, gestational age and CRIB proved significant for the outcomes. CRIB showed the highest predictive accuracy in all strata (P < 0.001) except in the 501-750 g group, where it was similar to gestational age. Body weight showed the lowest AUC in all groups, except in the 1251-1500 g group, where it was no different to gestational age. Gestational age and CRIB yielded greater AUC values than weight (P < 0.001) in all groups. No significant differences were found between CRIB and gestational age, except in the 751-1000 g group, where gestational age was greater (P = 0.029). CONCLUSIONS: The CRIB is the best predictor among newborns below 1500 g, except in the 501-750 g group, where CRIB is similar to gestational age. Body weight is the worst predictor, except in the group 1251-1500 g, where it is similar to gestational age. The accuracies of CRIB and gestational age in the prediction of IVH are similar, and both superior to body weight. This similarity persists in all the groups, except in the 751-1000 g interval, where gestational age is a better predictor.

Intranasal vaccination with poly(lactide-co-glycolide) microparticles containing a peptide T of Ole e 1 prevents mice against sensitization.

BACKGROUND: Biodegradable microparticles, in particular poly(lactide-co-glycolide) (PLGA), have been shown as potential delivery vehicles for intranasal (i.n.) vaccines in animal models. OBJECTIVES: To evaluate whether i.n. administration of PLGA microparticles containing a peptide with the major T cell epitope of Ole e 1, the main allergen of olive pollen, prevented mice from allergic sensitization to the whole protein. METHODS: Peptide-PLGA microparticles were prepared by a solvent evaporation double emulsion method. Microparticles in a size range of 0.8 mum were evaluated for peptide loading and in vitro antigen release. Stability and immunogenicity of the entrapped peptide were retained, as determined by dot blot and ELISA inhibition. BALB/c mice were intranasally treated with peptide-PLGA microparticles for 3 consecutive days, 1 week before sensitization/challenge to Ole e 1. Blood, lungs and spleen were collected and analysed for immune response. Biodistribution of microparticles was investigated using confocal microscopy. RESULTS: I.n. pretreatment of BALB/c mice with peptide-PLGA microparticles before sensitization to Ole e 1 led to a significant inhibition of serum allergen-specific IgE and IgG1 antibody levels, but a marked increase of specific IgG2a antibodies as compared with sham-pretreated mice. Moreover, IL-5 and IL-10 levels in spleen cell cultures were suppressed in peptide-PLGA pretreated mice. The airway histopathologic parameters associated with inflammation were significantly suppressed by the pretreatment. CONCLUSION: These results demonstrate that i.n. immunization with peptide T-PLGA microparticles is effective in preventing subsequent allergic sensitization to Ole e 1. Our data indicate that peptide-PLGA microparticles may be promising candidates for the design of nasal vaccines against allergic diseases in humans.

Olive pollen recombinant allergens: value in diagnosis and immunotherapy.

Olive pollen has a complex allergenic profile, from which more than 10 allergens have been identified and characterized. Some of these belong to well-known protein families and others cannot be included in reported biochemical types. Most of these allergens have been produced by recombinant technology, mainly in Escherichia coli or in Pichia pastoris, and they are good candidates for diagnostic and therapeutic purposes. Diagnosis and immunotherapy of allergy currently use extracts prepared from homogenates of natural sources, which only allow us to detect sensitivity to the complete source. These extracts can be successfully replaced by mixtures with controlled amounts of specific allergenic proteins obtained by recombinant technology in order to define the sensitization profile of individual patients. Recombinant Ole e 1 can be used as a marker for sensitization to Oleaceae. Recombinants Ole e 2 (profilin) and Ole e 3 (polcalcin) can serve as markers of polysensitivity. Finally, recombinant forms of Ole e 6, Ole e 10, and the carboxy-terminal and amino-terminal domains of Ole e 9 would help to detect sensitization to these minority allergens that could be overlooked in the complete olive pollen extract. These recombinant molecules can help provide an accurate diagnosis of sensitivity to individual allergens and, therefore, improve the design of more efficacious allergen-based immunotherapy strategies.

[Gastric pull-up reconstruction in hypopharyngeal and cervical oesophageal cancer]. / Reconstrucción con interposición gástrica en el cáncer de hipofaringe y esófago cervical.

OBJECTIVE: To determine the results of gastric pull-up reconstruction following pharyngo-laryngo-esophagectomy. METHODS: The clinical data of 12 patients who were treated with pharyngolaryngo/esophagectomy were analysed, from 1995 to 2000. All patients had advanced disease, and required a gastric pull-up reconstruction. Clinical swallowing function and morbidity were evaluated postoperatively and the survival group was studied using a Kaplan-Meier survival curve. RESULTS: Five cases of hypopharyngeal cancer and seven cases of cervical esophageal cancer were studied. In three cases a regional flap was used. A total of 16 cervical dissections were carried out. Only in 2 patients the nodes were free of metastasis. There were four hospital deaths. At discharge, 7 patients out of the 8 had a good swallowing. The most common complications were pulmonary (58%). The five years survival was 31%. CONCLUSION: Gastric pull up transposition must be used for reconstruction following pharyngolaryngoesophagectomy. Proper selection of patients may reduce considerably the morbidity and mortality of this surgical procedure.

Dental treatment in children with asthma - a review.

This article aims to explain the effects of long-term use of asthma medications. It will discuss the effects of asthma on the oral cavity, as well considerations for the dentist when treating asthmatic patients. It will also explain how to manage asthma in the dental setting and provide advice on maintaining oral health for asthmatic patients.

[Diagnostic value of head-shaking nystagmus in vestibular clinical evaluation]. / Utilidad del nistagmo de agitación cefálica en la exploración vestibular clínica básica.

OBJECTIVES: To determine the sensitivity and specificity of the head-shaking nystagmus test (HSN), the nystagmus elicited in response to a vigorous rotation of the head in the horizontal plane, in the study of patients with peripheral unilateral vestibular disease. PATIENTS AND METHODS: Retrospectively, we analyze the relationships between the HSN and the rest of the videonystagmographic tests on eighty-three patients with peripheral unilateral vestibular disease. RESULTS: Twenty-three patients showed a positive head-shaking nystagmus; twenty-one of them had unilateral caloric hypofunction and only two had a symmetric caloric test, but both of them showed some type of vestibular dysfunction on other videonystagmographic test. In our series, the HSN sensitivity for the existence of peripheral vestibular disease was 48.8%, while the specificity was 95% in relation to the caloric test, reaching 100% when the gold standard was the presence of any abnormal videonystagmographic test. CONCLUSION: HSN is a simple test that can be useful to identify patients having unilateral vestibular hypofunction.

Distribution of neurokinin B in rat spinal cord and peripheral tissues: comparison with neurokinin A and substance P and effects of neonatal capsaicin treatment.

In the present study, highly specific radioimmunoassays were developed and used to measure neurokinin B, neurokinin A and substance P in the rat spinal cord and various peripheral tissues. The results are as follows. (1) Neurokinin B and neurokinin A were distributed all along the rostrocaudal axis of the spinal cord, as is substance P, and were more concentrated in the dorsal than in the ventral region. (2) Substance P was more abundant in the central and peripheral nervous tissues than neurokinin A, while in certain peripheral organs, neurokinin A was more abundant than substance P. In the spinal cord, neurokinin B concentrations were lower than those of the other two tachykinins. (3) In contrast to neurokinin A and substance P, neurokinin B was not detected in any of the peripheral tissues examined. (4) Capsaicin treatment reduced by half neurokinin A and substance P concentrations in the dorsal region of the spinal cord, the dorsal root ganglia and the sciatic nerve, but was without effect on neurokinin B concentrations in the spinal cord. Neurokinin A, like substance P, may therefore have an important function in the transmission of sensory information, particularly in nociceptive transmission from the periphery to the spinal cord and in peripheral neurogenic inflammation. In contrast, since neurokinin B was not found in the sensory neurons, it is not likely to have these functions, but may perhaps control them.

Inhibition of neurogenic inflammation in the meninges by a non-peptide NK1 receptor antagonist, RP 67580.

RP 67580, a non-peptide NK1 receptor antagonist, inhibited in a stereoselective and dose-dependent manner plasma extravasation caused in the dura mater by intravenous injection of capsaicin in guinea-pigs and of exogenous substance P in rats (ED50 = 35 and 2.5 micrograms/kg i.v., respectively). In the two species, RP 67580 appeared to be more effective in the dura mater than in the peripheral organs. These results indicate that selective NK1 receptor antagonists could be potentially effective for the treatment of migraine headache.

[Quantitative spectral evaluation of vocal hypofunction]. / Evaluación espectral cuantitativa de la hipofunción vocal.

The purpose of this study was to explore the interaction between voice asthenicity and the acoustic prediction of vocal hypofunction. One hundred and seven phonatory samples of Reinke's edema were categorized by listeners using GRBAS scale. Seven frequency and time domain parameters were used to predict perceptual severity of asthenicity. Logistic regresion analysis showed that a useful measure for the prediction of asthenicity was the loss of harmonic components in the middle and upper portion of the spectrum. A spectral classification of vocal hypofunction is proposed.

[Paranasal sinus osteomas. Revision of 14 cases]. / Osteomas de senos paranasales: revisión de 14 casos.

OBJECTIVE: To present our experience in the management of paranasal sinus osteomas. MATERIAL AND METHODS: We review 14 patients with frontoethmoidal osteomas removed in our hospital between 1988-2001. The initial symptoms, site and size of the lesions, surgical approaches and short and long term complications were assesed. RESULTS: The most common symptom in our series was headache (57%); most of the tumors were located in frontal (35%) and frontoethmoidal (35%) regions with a mean size of 4.2 cm (maximum diameter) at the time of surgery. All symptomatic osteomas were resected by classic external surgical approaches but two cases were removed by endonasal surgery. DISCUSSION: Although osteomas are benign tumors, they may enlarge progressively and produce complications. Their resection is not free of risks, so there is some controversy about the management of asymptomatic patients. Endonasal surgery reduces the morbidity of the treatment but the location and size of the lesions do not allow to employ this technique in all cases.

[Cerebellopontine angle and internal auditory canal lipomas: report of four cases and review of the literature]. / Lipomas de angulo pontocerebeloso y conducto auditivo interno: serie de 4 casos clínicos y revisión de la literatura.

AIM: Lipomas are exceptional tumors at the Cerebellopontine Angle (CPA) or the Internal Auditory Canal (IAC). We evaluate clinical, histological and radiological characteristics of the cases diagnosed in our Hospital and the results of conservative versus surgical treatment. MATERIAL AND METHODS: We report 4 cases of CPA and/or IAC and review 99 previously reported in the literature. RESULTS: Unilateral tinnitus was the most frequent symptom (100%). All lesions showed hyperintensity on T1 and hypo/isointensity on T2--weighted MNR images. Two patients underwent a retro-sigmoidal approach without complete tumoral resection and with additional neurological consequences. Another two cases were followed up by annual MNRs. During the follow-up period (4.2 years average), neither clinical nor radiological changes were detected. CONCLUSION: The surgical resection of CPA y/o IAC lipomas is associated to a significant morbidity due to the high vascularization and the dense adherence of these lesions to the surrounding tissues. The MNR is the suitable technique for differential diagnosis between lesions at this location.

[Complicated sinusitis and nasal endoscopic surgery]. / Sinusitis complicadas y cirugía endoscópica nasal.

BACKGROUND: Complicated sinusitis can result in a significant morbidity if not appropriately managed. Traditionally, surgical cases were treated by external approaches. Now a days, the introduction of endoscopic sinus surgery allows such complications to be endoscopically approached. AIM: This study was designed to evaluate our results in complicated sinusitis treated by endoscopic sinus surgery. METHODS: The study reviewed 18 patients with evidence of sinusitis complications treated with endoscopic sinus surgery between 1993 and March 2000. There were 12 orbital and 6 intracraneal complications. Six patients did need an additional surgical approach. RESULTS: Seventeen patients (94%) had a relief of their symptoms. One patient with a superior orbital fisura syndrome died a month later due to vascular and respiratory complications. Another patient with fronto-lateral sinusitis required frontal osteoplasty for persistent disease. Two patients had long-term neurological sequelae (seizure). None had ocular sequelae. There were no complications due to the surgery. CONCLUSION: The endoscopic sinus surgery is a safe procedure with a high success rate in the treatment of complicated sinusitis. At present, open approaches to the sinuses are rarely indicated.

[Genetic alterations in sinonasal adenocarcinoma in wood workers studies with comparative genomic hybridization]. / Alteraciones genéticas en adenocarcinomas nasosinusales de trabajadores de la madera mediante hibridación genómica comparativa.

Eleven wood-workers with sinonasal adenocarcinoma were analyzed by comparative genomic hybridization. This technique serves as a screening test for regions of copy number changes in tumor genomes. We have applied the technique to map DNA gains and losses in 9 cases of formalin-fixed, paraffin-embedded tumors and 2 cases of frozen tumors. Gains were found most frequently than losses. Whole arm chromosomic gains were detected in high frequencies at 8q, 7q, 12q and 18p and losses at 18q, 8p, 10q, 5q, 14q and 17p. The segment most frequently amplified was 18p11.1-q11 (45%), even though others like 7q21-22 (18%) were related with lower survival rates. This analysis allows us to know for the first time the chromosomic aberrations that occur and may play an important role in sinonasal adenocarcinoma. In the future, comparative genomic hybridization could be used in the woodworkers with long exposition to wood dust to detect initial genetic aberrations and obtain an early treatment and diagnosis of the disease.