Autoimmune encephalitis in a tertiary hospital in the Philippines.

BACKGROUND: Autoimmune encephalitis (AE) is an emerging disorder in adults and children. Due to its potentially reversible nature, prompt recognition and intervention are of utmost importance. OBJECTIVE: To describe the clinical and paraclinical features, as well as treatment outcomes of patients with AE admitted in a Philippine tertiary hospital. METHODS: Retrospective case series of patients with definite AE. RESULTS: Eighteen (18) patients were included (12 adults, 6 children), majority of whom had anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. The median age of onset was 32 (IQR: 10.8) years old and 13 (IQR: 4.8) years old in the adult and pediatric population, respectively. In both age groups, most presented with psychiatric symptoms and normal imaging findings. Cerebrospinal fluid (CSF) pleocytosis was detected in 8/12 (66.7%) adults and 2/6 (33.3%) children, while CSF protein elevation was only seen in 6/12 (50%) adults. Most patients presented with seizures, and the most frequent electroencephalography (EEG) abnormality detected was slow activity (70.5%). A high proportion of patients received high dose steroids, alone (35.3%) or in combination with intravenous immunoglobulin (IVIG, 52.9%). Overall, 66.7% had improved outcomes, mostly seen in the pediatric population. CONCLUSION: This study highlighted the broad clinical phenotype, as well as the similarities and differences of AE manifestations in adults and children. It demonstrated the limited but supportive role of laboratory investigations in the diagnosis of AE. It also underscored the importance of early intervention in AE and highlighted factors influencing treatment practices and discharge outcomes in the local setting.

Factors and issues on treatment adherence among Filipino patients with epilepsy and their caregivers

@#<p style="text-align: justify;"><strong>BACKGROUND:</strong> Non-adherence to treatment in epilepsy is considered as a worldwide problem ranging from 30-50% of patients. Despite its striking magnitude, only a few studies tried to explain the factors affecting it. Moreover, a standard method to measure adherence to treatment among patients is still lacking. An in-depth analysis on adherence to treatment of patients with epilepsy, taking into factor their values, beliefs, and culture, is deemed necessary.</p><p style="text-align: justify;"><strong>OBJECTIVES:</strong> The purpose of this qualitative study is to investigate the contributory factors and issues on treatment adherence faced by Filipino patients with epilepsy and their caregivers. This study also aimed to serve as a catalyst to further stimulate local researches on treatment adherence in epilepsy.</p><p style="text-align: justify;"><strong>METHODS:?</strong>Four focus group discussions were conducted with patients and caregivers who voluntarily agreed to participate and share their experiences on dealing with epilepsy. A total of 39 participants were included. The focus group discussions, facilitated by skilled moderators, were composed of an ice breaker and a discussion on the experiences and issues faced by the participants. The discussions were transcribed and analyzed using thematic coding.</p><p style="text-align: justify;"><strong>RESULTS:</strong> Three main content categories were identified from the focus group discussions, namely, 1) accepting a life with epilepsy, 2) dealing with the disease, and 3) ensuring freedom from seizure attacks, which were further sub-categorized. From these, a number of factors affecting treatment adherence were identified and a conceptual framework was developed by the investigators.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> This study was able to demonstrate that conducting a focus group discussion was an effective means of eliciting the experiences and issues in patients and their caregivers. Several factors affecting treatment adherence such as patient-doctor relationship, financial resources, government support, adverse medication effects, religious belief, trigger avoidance, frequent reminders, and safety precautions were elucidated in this study.</p>

O'Brien Actinic Granuloma: A Case Report and Brief Review of Literature.

O'Brien first described the actinic granuloma in 1975, as an infrequent granulomatous disorder occurring in sun-exposed skin, with a slow but often self-limited course. Ever since its initial description, the actinic physiopathogenic hypothesis has been debated by many authors. We report a 60-year-old female rural worker that presented with a 14 × 7 cm annular lesion with erythematous elevated borders and an atrophic center on the right calf. The lesion was evolving for 2 years, and histopathology confirmed actinic granuloma. She started acitretin with halting of disease progression after 6 months of therapy. Our case can also be associated to actinic damage, despite its unusual location, therefore highlighting the role of solar elastosis in the development of O'Brien actinic granuloma.

Delivery, breast feeding and child rearing in women with epilepsy

The occurrence of seizures during delivery is very low and convulsive status epilepticus is rare. Seizure freedom for at least 9 months prior to pregnancy is associated with a high likelihood of remaining seizure-free during pregnancy. Mode of delivery during pregnancy is most often based on obstetrical indications. Recent evidence shows good maternal and fetal outcome for pregnancy in women with epilepsy. Breastfeeding is encouraged for most mothers with epilepsy and is generally safe. There is a large knowledge gap on studies looking into the child rearing knowledge and practice of mothers with epilepsy.

Bioactive starch-based scaffolds and human adipose stem cells are a good combination for bone tissue engineering.

Silicon is known to have an influence on calcium phosphate deposition and on the differentiation of bone precursor cells. This study explores the effect of the incorporation of silanol (Si-OH) groups into polymeric scaffolds on the osteogenic differentiation of human adipose stem cells (hASC) cultured under dynamic and static conditions. A blend of corn starch with polycaprolactone (30/70 wt.%, SPCL) was used to produce three-dimensional fibre meshes scaffolds by the wet-spinning technique, and a calcium silicate solution was used as a non-solvent to develop an in situ functionalization with Si-OH groups. In vitro assessment, using hASC, of functionalized and non-functionalized scaffolds was evaluated in either α-MEM or osteogenic medium under static and dynamic conditions (provided by a flow perfusion bioreactor). The functionalized materials, SPCL-Si, exhibit the capacity to sustain cell proliferation and induce their differentiation into the osteogenic lineage. The formation of mineralization nodules was observed in cells cultured on the SPCL-Si materials. Culturing under dynamic conditions using a flow perfusion bioreactor was shown to enhance the hASC proliferation and differentiation and a better distribution of cells within the material. The present work demonstrates the potential of these functionalized materials for future applications in bone tissue engineering. Additionally, these results highlight the simplicity, economic and reliable production process of those materials.

HIV type 1 genetic diversity in newly diagnosed Cuban patients.

Knowledge of the genetic diversity of HIV-1 constitutes a fundamental premise in the epidemiological surveillance. In the present study, the HIV-1 genetic variability from 142 Cuban patients who were diagnosed with HIV-1 infection during 2009 and 2010 was determined. HIV-1 subtypes were determined by partial RT-PCR and sequencing of the HIV-1 pol gene. The phylogenetic analysis showed that 47 (33.1 %) samples were subtypes B and 95 (66.9 %) were non-B subtypes, where G, H, and C subtypes, as well as the recombinant forms CRF19_cpx, CRF18_cpx, and CRFs BG, were included. The circulation of CRF05_DF was detected for the first time in Cuba. The analyses of recombinants showed the presence of recombinant CRF18_cpx/CRF19_cpx. The study confirms the high genetic diversity of HIV-1 and the circulation of new genetic variants in the studied population, which indicates the importance of maintaining constant epidemiological surveillance in Cuba.

Diferencias transculturales en la manifestación del bullying en estudiantes de escuela secundaria / Diferenças trans-culturais na manifestação do bullying nos estudantes da escola secundária / Bullying transcultural differences in high-school students

Con un diseño de grupos apareados por edad y grado escolar, comparamos los resultados de dos investigaciones sobre bullying, realizadas en Colombia y Costa Rica. El propósito fue identificar los comportamientos de los agresores y agresoras para configurar su perfil, y explorar la variable género en este fenómeno. Utilizamos el “Cuestionario Paredes, Lega Vernon para Deteccion del Bullying” en 824 estudiantes de 6o a 8o. El resultado de un MANOVA de dos vías mostró diferencias significativas en las categorías género y país, y una relación significativa en la interacción género y país.

Com um desenho de grupos juntados por idade e grau escolar, comparamos os resultados de duas investigações sobre “bullying”, realizadas em Colômbia e Costa Rica. O propósito foi identificar os comportamentos dos agressores e agressoras para configurar seu perfil, e explorar a variable género neste fenómeno.Utilizamos o “Cuestionario Paredes, Lega Vernon para Deteccion do Bullying” em 824 estudantes de 6ou a 8ou. O resultado de um MANOVA de duas vias mostrou diferenças significativas nas categorias género e país, e uma relação significativa na interacção género e país.

A matched group design by age and grade level compared the results of two previous single experiments done in two different countries, Colombia and Costa Rica, on the phenomenon of bullying. The purpose was to identify the aggresor’s behavior to make and compare their profile and the explore the variable of gender in this issue. The study consisted of 824 male and female participants, ages of 12 to 16, grades 6th to 8th, anonimously answered the Paredes, Lega, Vernon Questionary for Bullying Detection. The results of a two-way MANOVA showed that there were main effects in gender and country, and a significant gender and country interaction.

Novel hydroxyapatite/carboxymethylchitosan composite scaffolds prepared through an innovative "autocatalytic" electroless coprecipitation route.

A developmental composite scaffold for bone tissue engineering applications composed of hydroxyapatite (HA) and carboxymethylchitosan (CMC) was obtained using a coprecipitation method, which is based on the "autocatalytic" electroless deposition route. The results revealed that the pores of the scaffold were regular, interconnected, and possess a size in the range of 20-500 microm. Furthermore, the Fourier transform infra-red spectrum of the composite scaffolds exhibited all the characteristic peaks of apatite, and the appearance of typical bands from CMC, thus showing that coprecipitation of both organic and inorganic phases was effective. The X-ray diffraction pattern of composite scaffolds demonstrated that calcium-phosphates consisted of crystalline HA. From microcomputed tomography analysis, it was possible to determine that composite scaffolds possess a 58.9% +/- 6% of porosity. The 2D morphometric analysis demonstrated that on average the scaffolds consisted of 24% HA and 76% CMC. The mechanical properties were assessed using compressive tests, both in dry and wet states. Additionally, in vitro tests were carried out to evaluate the water-uptake capability, weight loss, and bioactive behavior of the composite scaffolds. The novel hydroxyapatite/carboxymethylchitosan composite scaffolds showed promise whenever degradability and bioactivity are simultaneously desired, as in the case of bone tissue-engineering scaffolding applications.

Surface controlled biomimetic coating of polycaprolactone nanofiber meshes to be used as bone extracellular matrix analogues.

The aim of this work was to develop novel electrospun nanofiber meshes coated with a biomimetic calcium phosphate (BCP) layer that mimics the extracellular microenvironment found in the human bone structure. Poly (epsilon-caprolactone) (PCL) was selected because of its well-known medical applications, its biodegradability, biocompatibility and its susceptibility to partial hydrolysis by a straightforward alkaline treatment. The deposition of a calcium phosphate layer, similar to the inorganic phase of bone, on PCL nanofiber meshes was achieved by means of a surface modification. This initial surface modification was followed by treatment with solutions containing calcium and phosphate ions. The process was finished by a posterior immersion in a simulated body fluid (SBF) with nearly 1.5 x the inorganic concentration of the human blood plasma ions. After some optimization work, the best conditions were chosen to perform the biological assays. The influence of the bone-like BCP layer on the viability and adhesion, as well as on the proliferation of human osteoblast-like cells, was assessed. It was shown that PCL nanofiber meshes coated with a BCP layer support and enhance the proliferation of osteoblasts for long culture periods. The attractive properties of the coated structures produced in the present work demonstrated that those materials have potential to be used for applications in bone tissue engineering. This is the first time that nanofiber meshes could be coated with a biomimetic bone-like calcium phosphate layer produced in a way that the original mesh architecture can be fully maintained.

Estudio exploratorio sobre el fenómeno del "Bullying" en la ciudad de Cali, Colombia / Estudo exploratório sobre o fenômeno do "Bullying na cidade de Cali (Colômbia) / An exploratory study on the phenomenon of "bullying" in the city of Cali, Colombia

Este es el primer estudio sobre el fenómeno del hostigamiento entre pares o “bullying” que se realiza en la ciudad de Cali, Colombia. Se efectuaron 2.542 encuestas a estudiantes de sexto, séptimo y octavo grados de catorce colegios de la ciudad, con el fin de identificar la presencia del problema y –en caso de existir– de establecer las formas específicas de manifestación, teniendo en cuenta edad, género y estrato socioeconómico. Los resultados demostraron la presencia de “bullying” en el 24.7% de los encuestados y encuestadas, expresado en comportamientos de intimidación o agresión verbal, física y psicológica en estudiantes de ambos géneros de todos los estratos socioeconómicos. Se estableció que la forma de agresión demayor frecuencia es la verbal y que ésta sucede también en presencia de otroscompañeros, compañeras, profesoras y profesores en el aula de clase.

Este é o primeiro estudo sobre o fenômeno da perseguição entre pares ou “bullying” que si apresenta na cidade de Cali, Colômbia. Dois mil e quinhentos e quarenta e dois questionários foram aplicados a estudantes de sexto, sétimo e oitavo graus em quatorze escolas secundárias da cidade. O propósito consistiu em identificar a existência do problema e, em caso positivo, estabelecer as maneiras específicas de manifestação, levando em conta a idade, o gênero e a camada sócio-econômica. Os resultados demonstraram a presença do bullying no 24,7% dos interrogados e das interrogadas, expressado em comportamentos de intimidação ou agressão verbal, física e psicológica em estudantes de ambos sexos em todas as camadas sócio-econômicas. Estabeleceuse também que a agressão verbal tem a freqüência maior e que isto apresentase na presença de outros colegas de aula (de ambos sexos), professores e professoras na sala de aula.

This is the first study on the phenomenon of peer aggression or “bullying” in the city of Cali, Colombia. A survey of 2,542 students of 6th, 7th and 8th grade in 14 middle- and high-schools in the city was carried out with the purpose of identifying the presence or absence of this problem, and in case it existed, of establishing the specific forms of its manifestation, discriminating by age, gender and SES. Results showed that bullying occurs in 24.7% of all students in the survey, expressed as verbal, physical or psychological aggression or intimidation in both genders and all SES’s. It was also found that the most frequent form of aggression is verbal, and that this form also happens in the presence of peers and teachers in classrooms.

Growth of a bonelike apatite on chitosan microparticles after a calcium silicate treatment.

Bioactive chitosan microparticles can be prepared successfully by treating them with a calcium silicate solution and then subsequently soaking them in simulated body fluid (SBF). Such a combination enables the development of bioactive microparticles that can be used for several applications in the medical field, including injectable biomaterial systems and tissue engineering carrier systems. Chitosan microparticles, 0.6microm in average size, were soaked either for 12h in fresh calcium silicate solution (condition I) or for 1h in calcium silicate solution that had been aged for 24h before use (condition II). Afterwards, they were dried in air at 60 degrees C for 24h. The samples were then soaked in SBF for 1, 3 and 7 days. After the condition I calcium silicate treatment and the subsequent soaking in SBF, the microparticles formed a dense apatite layer after only 7 days of immersion, which is believed to be due to the formation of silanol (Si-OH) groups effective for apatite formation. For condition II, the microparticles successfully formed an apatite layer on their surfaces in SBF within only 1 day of immersion.

Functionalization of different polymers with sulfonic groups as a way to coat them with a biomimetic apatite layer.

Covalent coupling of sulfonic group (-SO 3H) was attempted on different polymers to evaluate efficacy of this functional group in inducing nucleation of apatite in body environment, and thereupon to design a simple biomimetic process for preparing bonelike apatite-polymer composites. Substrates of polyethylene terephthalate (PET), polycaprolactam (Nylon 6), high molecular weight polyethylene (HMWPE) and ethylene-vinyl alcohol co-polymer (EVOH) were subjected to sulfonation by being soaked in sulfuric acid (H2SO4) or chlorosulfonic acid (ClSO 3H) with different concentrations. In order to incorporate calcium ions, the sulfonated substrates were soaked in saturated solution of calcium hydroxide (Ca(OH)2). The treated substrates were soaked in a simulated body fluid (SBF). Fourier transformed infrared spectroscopy, thin-film X-ray diffraction, and scanning electron microscopy showed that the sulfonation and subsequent Ca(OH)2 treatments allowed formation of -SO3H groups binding Ca2+ ions on the surface of HMWPE and EVOH, but not on PET and Nylon 6. The HMWPE and EVOH could thus form bonelike apatite layer on their surfaces in SBF within 7 d. These results indicate that the -SO3H groups are effective for inducing apatite nucleation, and thereby that surface sulfonation of polymers are effective pre-treatment method for preparing biomimetic apatite on their surfaces.

Alkaline treatments to render starch-based biodegradable polymers self-mineralizable.

The present research aims to develop a new route for surface functionalization of biodegradable polymers. The method is based on a wet chemistry modification, resulting in etching and/or hydrolysis in order to increase the amount of polar groups, such as hydroxyl (--OH) and carboxylic (--COOH) groups on the surface of the polymer. The polymer used as substrate was a corn starch-ethylene vinyl alcohol biodegradable blend (SEVA-C). For that purpose it was used in two different types of activation: (a) calcium hydroxide solution [Ca(OH)(2)] and (b) sodium hydroxide solution (NaOH). These treatments lead to the formation carboxylic acid-rich SEVA-C surfaces. Then, the samples were soaked in simulated body fluid (SBF) for different time periods of time until 7 days. After 1 day in SBF, the surface of SEVA-C was fully covered with spherulite particles. As the soaking time increased, the particles increased and coalesced, leading to the formation of a dense and uniform layer. Furthermore, thin-film X-ray diffraction confirms that the layer formed on the surface of the polymer was an apatite-like layer. These results suggest that this rather simple treatment is a good method for surface functionalization and subsequent mineral nucleation and growth on biodegradable polymeric surfaces to be used for bone-related applications.

In vitro bioactivity of starch thermoplastic/hydroxyapatite composite biomaterials: an in situ study using atomic force microscopy.

The in vitro bioactivity of a composite composed by a biodegradable starch-based polymeric matrix and hydroxyapatite fillers was investigated, in situ, as a function of immersion time in a simulated body fluid (SBF) using atomic force microscopy (AFM). The surface roughness of the composite started to increase after the initial 8h because of both the degradation of the polymer matrix and the nucleation of calcium phosphate. After 24h of immersion the surface of the composite was fully covered with calcium phosphate nuclei with diameters around 126 nm. As the immersion time increased, the nuclei increased both in number and size, and coalesced leading to the formation of a dense and uniform calcium phosphate layer on the surface of the composite only after 126 h of SBF immersion. The results of in situ AFM observation agreed with those of standard in vitro bioactivity tests in combination with scanning electron microscopy observations. Thin-film X-ray diffraction demonstrated that the ratio of apatite to the polymer matrix was higher within the surface layer (40 microm deep from the surface) than that in the bulk after the immersion for 7 days. The water-uptake capability of the polymer contributes to the nucleation and growth of the calcium phosphate layer. These results suggest the great potential of the composite for a range of temporary applications in which bone-bonding ability is a desired property.

An innovative auto-catalytic deposition route to produce calcium-phosphate coatings on polymeric biomaterials.

The aim of this research is to develop a new methodology to obtain bioactive coatings on bioinert and biodegradable polymers that are not intrinsically bioactive. In this study three types of materials were used as substrates: (i) high molecular weight polyethylene (HMWPE) and two different types of starch based blends (ii) starch/ethylene vinyl alcohol blends, SEVA-C and (iii) starch/cellulose acetate blends, SCA. Two types of baths were originally proposed and studied to produce novel auto-catalytic calcium-phosphate (Ca-P) coatings. Then, the coated surfaces were analyzed by scanning electron microscopy and energy dispersive spectroscopy (SEM/EDS), as produced, and after different immersion periods in SBF. The evolution of Ca and P concentrations was determined by induced-coupled plasma emission (ICP) spectroscopy. The crystalline phases present on the films formed on the different material surfaces, after a certain soaking time, were identified by thin-film X-ray diffraction (TF-XRD). The obtained results indicated that it was possible to coat the materials surfaces with a Ca-P layer with only 60 min of immersion in both types of auto-catalytic solutions. Furthermore, it was possible to observe the clear bioactive nature of the Ca-P coatings after different immersion periods in a simulated body fluid (SBF). The results from TF-XRD confirmed the presence of partially amorphous Ca-P films with clearly noticeable hydroxylapatite peaks. These new methodologies allow for the production of an adherent bioactive film on the polymeric surfaces prior to implantation, which may allow for the development of bone-bonding, bioabsorbable implants and fixation devices.

In situ study of partially crystallized Bioglass and hydroxylapatite in vitro bioactivity using atomic force microscopy.

The present work investigates, in situ, the in vitro bioactivity of partially crystallized 45S5 Bioglass (BG) as a function of immersion time in a simulated body fluid (SBF) using atomic force microscopy (AFM). The results obtained for the crystallized BG were compared to those of hydroxyapatite c- and a-faces. The calcium phosphate layer grows on the crystallized 45S5 B by multiple two-dimensional nucleation and fusion of these two-dimensional islands, which is essentially the same mode as for the hydroxyapatite c-face. The surface of the crystallized 45S5 BG was almost fully covered with a dense and compact calcium phosphate layer after 24 h. The calcium phosphate formation on the crystallized BG arises from a low surface energy of the surface layer and/or an effect of the layer to lower the resistance when the growth units of calcium phosphate incorporate into the growing island. These results indicate that the crystallized 45S5 BG is suitable to be used as a filler for polymeric matrix bioactive composites, as it maintains a high bioactivity associated with a stiffer behavior (as compared to standard BG).

Novel starch thermoplastic/Bioglass composites: mechanical properties, degradation behavior and in-vitro bioactivity.

The present research aims to evaluate the possibility of creating new degradable, stiff and highly bioactive composites based on a biodegradable thermoplastic starch-based polymeric blend and a Bioglass filler. Such combination should allow for the development of bioactive and degradable composites with a great potential for a range of temporary applications. A blend of starch with ethylene-vinyl alcohol copolymer (SEVA-C) was reinforced with a 45S5 Bioglass powder presenting a granulometric distribution between 38 and 53 microm. Composites with 10 and 40 wt % of 45S5 Bioglass were compounded by twin-screw extrusion (TSE) and subsequently injection molded under optimized conditions. The mechanical properties of the composites were evaluated by tensile testing, and their bioactivity assessed by immersion in a simulated body fluid (SBF) for different periods of time. The biodegradability of these composites was also monitored after several immersion periods in an isotonic saline solution. The tensile tests results obtained indicated that SEVA-C/Bioglass composites present a slightly higher stiffness and strength (a modulus of 3.8 GPa and UTS of 38.6 MPa) than previously developed SEVA-C/Hydroxylapatite (HA) composites. The bioactivity of SEVA-C composites becomes relevant for 45S5 amounts of only 10 wt %. This was observed by scanning electron microscopy (SEM) and confirmed for immersion periods up to 30 days by both thin-film X-ray diffraction (TF-XRD) (where HA typical peaks are clearly observed) and induced coupled plasma emission (ICP) spectroscopy used to follow the elemental composition of the SBF as function of time. Additionally, it was observed that the composites are biodegradable being the results correlated with the correspondent materials composition.

Evidence for TeV Emission from GRB 970417a.

Milagrito, a detector sensitive to very high energy gamma rays, monitored the northern sky from 1997 February through 1998 May. With a large field of view and a high duty cycle, this instrument was well suited to perform a search for TeV gamma-ray bursts (GRBs). We report on a search made for TeV counterparts to GRBs observed by BATSE. BATSE detected 54 GRBs within the field of view of Milagrito during this period. An excess of events coincident in time and space with one of these bursts, GRB 970417a, was observed by Milagrito. The excess has a chance probability of 2.8x10-5 of being a fluctuation of the background. The probability for observing an excess at least this large from any of the 54 bursts is 1.5x10-3. No significant correlations were detected from the other bursts.

TeV Observations of Markarian 501 with the Milagrito Water Cerenkov Detector.

The Milagrito water Cerenkov detector near Los Alamos, New Mexico, was operated as a sky monitor at energies of a few TeV between 1997 February and 1998 May, including the period of the strong, long-lasting 1997 flare of Markarian 501. Milagrito served as a test run for the full Milagro detector. An event excess with a significance of 3.7 sigma from Markarian 501 was observed, in agreement with expectations.

Colitis ulcerativa y enfermedad de Crohn del colon

Se revisan los aspectos sobresalientes de la colitis ulcerativa idiopática (CUI) y de la enfermedad de Crohn del colon, así como también las publicaciones sobre el tema en el país desde 1944. Con base en la recopilación de la experiencia con 39 enfermos seguidos por el autor desde 1951, y en la revision de las literaturas ancional y mundial, se resaltan las manifestaciones clínicas, los factores predisponentes, la patología y el diagnóstico diferencial de ambas entidades. De igual manera se brinda una orientación práctica en el tratamiento, seguimiento y pronóstico en nuestro medio de pacientes con estas dos patologías.