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The aim of this article is to solve the system XA=Y, where A=(ai,j)∈Mn×m(S), Y∈Sm and X is an unknown vector of a size n, with S being an additively idempotent semiring. If the system has solutions, then we completely characterize its maximal one, and in the particular case where S is a generalized tropical semiring, a complete characterization of its solutions is provided as well as an explicit bound of the computational cost associated with its computation. Finally, we show how to apply this method to cryptanalyze two different key exchange protocols defined for a finite case and the tropical semiring, respectively.

We present an active attack that targets Ateniese et al.’s authenticated group key agreement, which, as a particular case, includes the well-known multiparty key exchange protocol CLIQUES that allows a group of users to build a common secret using some private values in a collaborative and distributed way, naturally extending the foundational key exchange introduced by Diffie and Hellman between two communicating parties that motivated the birth of public key cryptography. Ateniese et al.’s protocol adds some authentication information, allowing the parties to trust the exchanged information, but we show that it is possible to surpass this as well. The attack allows a malicious party to agree on a secret with the rest of the legal members of the group without their knowledge, so all the distributed information can be accessed using this secret. In addition, this is shown under a well-known cryptographic model that, in principle, requires absolute control of group communications, but, in fact, it only requires malicious control of the communications of a single arbitrary user and only for the duration of the key exchange. This means that after the attack, the malicious party does not have to take any other actions that could reveal a clue that an attack occurred and that the distributed information is being illegally accessed, contrary to a typical man-in-the-middle attack where the attacker has to continue the activity, meaning this could be detected at some point.

Background: SARS-CoV-2 genomic analysis has been key to the provision of valuable data to meet both epidemiological and clinical demands. High-throughput sequencing, generally Illumina-based, has been necessary to ensure the widest coverage in global variant tracking. However, a speedier response is needed for nosocomial outbreak analyses and rapid identification of patients infected by emerging VOCs. An alternative based on nanopore sequencing may be better suited to delivering a faster response when required; however, although there are several studies offering side-by-side comparisons of Illumina and nanopore sequencing, evaluations of the usefulness in the hospital routine of the faster availability of data provided by nanopore are still lacking. Results: We performed a prospective 10-week nanopore-based sequencing in MinION in a routine laboratory setting, including 83 specimens where a faster response time was necessary. The specimens analyzed corresponded to i) international travellers in which lineages were assigned to determine the proper management/special isolation of the patients; ii) nosocomial infections and health-care-worker infections, where SNP-based comparisons were required to rule in/out epidemiological relationships and tailor specific interventions iii) sentinel cases and breakthrough infections to timely report to the Public Health authorities. MinION-based sequencing was compared with the standard procedures, supported on Illumina sequencing; MinION accelerated the delivery of results (anticipating results 1-12 days) and reduced costs per sample by 28€ compared to Illumina, without reducing accuracy in SNP calling. Conclusions: Parallel integration of Illumina and nanopore sequencing strategies is a suitable solution to ensure both high-throughput and rapid response to cope with accelerating the surveillance demands of SARS-CoV-2 while also maintaining accuracy.

(1) Background: Infantile colic (IC) is a functional gastrointestinal disorder that affects around 20% of infants, and postpartum (PPD) depression is a common disorder that affects between 15 and 22% of mothers. In this study, our objective was to evaluate the relationship between the maternal psychological state in the first postpartum year and IC, with the aim of assessing the importance of feeding type in infants and maternal well-being. (2) Methods: A cross-sectional study was conducted in women in their first year postpartum. Demographic, medical, and obstetric data of the mothers and infants were collected, and the type of feeding was identified. The emotional status of the mother was evaluated using the Edinburgh Postnatal Depression Scale (EPDS), and the Infant Colic Severity Questionnaire (ICSQ) was used for IC diagnosis. (3) Results: A total of 528 women were analyzed, of which 170 (32%) were diagnosed with possible PPD. Two-thirds of the women without depression breastfed their babies on demand; therefore, we report that exclusive breastfeeding (EBF) appears to reduce the risk of possible PPD (p < 0.001; OR = 2.353). IC was present in 39% of babies, and around 70% of babies without colic were breastfed on demand. Infants who were not exclusively breastfed showed almost double the risk of developing colic (p = 0.016; OR = 1.577). There was a significant association between the EPDS and ICSQ scores (p < 0.001). More than half of the women with PPD had babies with colic. However, our results show that 75% of babies without colic had mothers who reported optimal postpartum emotional well-being (p < 0.001; OR = 2.105). (4) Conclusions: The results of this study suggest that postpartum maternal psychological well-being reduces the risk of IC. Therefore, we report that EBF on demand, together with a healthy emotional state in new mothers, may be a protective factor against colic in infants.

Worldwide, water is essential for maintaining an adequate agricultural production and fostering a sustainable ecosystem for humanity alongside diverse flora, fauna, and microbial life. However, the intensification of anthropogenic activities, the occurrence of climate variability, and the presence of environmental issues are still threatening the quantity and quality of fresh water. Therefore, integrated water management is critical for the sustainable development of a region. This Agrociencia Uruguay Special Issue on “Advances in Water in Agroscience” is designed to draw attention to new concepts, approaches, methodologies, and novel applications aiming to improve sustainable and integrated water resource management. This Special Issue contains fifteen publications sorted into the following macro fields: irrigation and water management, integrated catchment management, and water quality and environmental sustainability.

El principal objetivo de la citricultura en Uruguay es incrementar el rendimiento, la calidad, mejorar la sostenibilidad y la eficiencia de los recursos naturales. Actualmente no es posible concebir un sistema eficiente de producción de cítricos sin el uso de tecnologías de riego. El objetivo de este trabajo fue incorporar el concepto de productividad del agua al comparar diferentes sistemas de plantación enfocados en acelerar la producción. Para ello se instaló un experimento en mandarina Nadorcott con dos densidades de plantación (909 y 1220 pl. ha-1) y tres diseños de plantación: camellones cubiertos con tela plástica blanca; camellones descubiertos y plantación plana a nivel del suelo. Al final del período de evaluación, el volumen de los árboles plantados sobre los camellones cubiertos duplicó al de los plantados en plano (1 m3). Los árboles en el sistema en plano consistentemente produjeron menos frutos y con menor rendimiento que las plantas sobre los camellones. El diseño de plantación en camellón cubierto mostró el mejor desempeño. El contenido de agua del suelo se mantuvo más alto y la temperatura del suelo más baja en los camellones cubiertos. En general, los árboles plantados en camellones con o sin cubierta plástica permitieron una mejor productividad en el uso del agua y la temperatura más baja del suelo, creando mejores condiciones de crecimiento del árbol.

Rhabdoid meningiomas (RM) are a rare meningioma subtype with a heterogeneous clinical course which is more frequently associated with recurrence, even among tumors undergoing-complete surgical removal. Here, we retrospectively analyzed the clinical-histopathological and cytogenetic features of 29 tumors, from patients with recurrent (seven primary and 14 recurrent tumors) vs. non-recurrent RM (n = 8). Recurrent RM showed one (29%), two (29%) or three (42%) recurrences. BAP1 loss of expression was found in one third of all RM at diagnosis and increased to 100% in subsequent tumor recurrences. Despite both recurrent and non-recurrent RM shared chromosome 22 losses, non-recurrent tumors more frequently displayed extensive losses of chromosome 19p (62%) and/or 19q (50%), together with gains of chromosomes 20 and 21 (38%, respectively), whereas recurrent RM (at diagnosis) displayed more complex genotypic profiles with extensive losses of chromosomes 1p, 14q, 18p, 18q (67% each) and 21p (50%), together with focal gains at chromosome 17q22 (67%). Compared to paired primary tumors, recurrent RM samples revealed additional losses at chromosomes 16q and 19p (50% each), together with gains at chromosomes 1q and 17q in most recurrent tumors (67%, each). All deceased recurrent RM patients corresponded to women with chromosome 17q gains, although no statistical significant differences were found vs. the other RM patients.

Mechanosensitive ion channels comprise a broad group of proteins that sense mechanical extracellular and intracellular changes, translating them into cation influx to adapt and respond to these physical cues. All cells in the organism are mechanosensitive, and these physical cues have proven to have an important role in regulating proliferation, cell fate and differentiation, migration and cellular stress, among other processes. Indeed, the mechanical properties of the extracellular matrix in cancer change drastically due to high cell proliferation and modification of extracellular protein secretion, suggesting an important contribution to tumor cell regulation. In this review, we describe the physiological significance of mechanosensitive ion channels, emphasizing their role in cancer and immunity, and providing compelling proof of the importance of continuing to explore their potential as new therapeutic targets in cancer research.

Objectives The large number of infected patients requiring mechanical ventilation has led to the postponement of scheduled neurosurgical procedures during the first wave of the COVID-19 pandemic. The aims of this study were to investigate the factors that influence the decision to postpone scheduled neurosurgical procedures and to evaluate the effect of the restriction in scheduled surgery adopted to deal with the first outbreak of the COVID-19 pandemic in Spain on the outcome of patients awaiting surgery.Design This was an observational retrospective study.Settings A tertiary-level multicentre study of neurosurgery activity between 1 March and 30 June 2020.Participants A total of 680 patients awaiting any scheduled neurosurgical procedure were enrolled. 470 patients (69.1%) were awaiting surgery because of spine degenerative disease, 86 patients (12.6%) due to functional disorders, 58 patients (8.5%) due to brain or spine tumours, 25 patients (3.7%) due to cerebrospinal fluid (CSF) disorders and 17 patients (2.5%) due to cerebrovascular disease.Primary and secondary outcome measures The primary outcome was mortality due to any reason and any deterioration of the specific neurosurgical condition. Second, we analysed the rate of confirmed SARS-CoV-2 infection.Results More than one-quarter of patients experienced clinical or radiological deterioration. The rate of worsening was higher among patients with functional (39.5%) or CSF disorders (40%). Two patients died (0.4%) during the waiting period, both because of a concurrent disease. We performed a multivariate logistic regression analysis to determine independent covariates associated with maintaining the surgical indication. We found that community SARS-CoV-2 incidence (OR=1.011, p

Abstract Diagnosis and classification of gliomas mostly relies on histopathology and a few genetic markers. Here we interrogated microarray gene expression profiles (GEP) of 268 diffuse astrocytic gliomas—33 diffuse astrocytomas (DA), 52 anaplastic astrocytomas (AA) and 183 primary glioblastoma (GBM)—based on multivariate analysis, to identify discriminatory GEP that might support precise histopathological tumor stratification, particularly among inconclusive cases with II–III grade diagnosed, which have different prognosis and treatment strategies. Microarrays based GEP was analyzed on 155 diffuse astrocytic gliomas (discovery cohort) and validated in another 113 tumors (validation set) via sequential univariate analysis (pairwise comparison) for discriminatory gene selection, followed by nonnegative matrix factorization and canonical biplot for identification of discriminatory GEP among the distinct histological tumor subtypes. GEP data analysis identified a set of 27 genes capable of differentiating among distinct subtypes of gliomas that might support current histological classification. DA + AA showed similar molecular profiles with only a few discriminatory genes overexpressed (FSTL5 and SFRP2) and underexpressed (XIST, TOP2A and SHOX2) in DA vs AA and GBM. Compared to DA + AA, GBM displayed underexpression of ETNPPL, SH3GL2, GABRG2, SPX, DPP10, GABRB2 and CNTN3 and overexpression of CHI3L1, IGFBP3, COL1A1 and VEGFA, among other differentially expressed genes.

Rhabdoid meningiomas (RM) shows heterogeneous histological findings, and a wide variety of chromosomal copy number alterations (CNA) are associated with an unpredictable course of the disease. In this study, we analyzed a series of 305 RM samples from patients previously reported in the literature and 33 samples from 23 patients studied in our laboratory. Monosomy 22-involving the minimal but most common recurrent region loss of the 22q11.23 chromosomal region was the most observed chromosomal alteration, followed by losses of chromosomes 14, 1, 6, and 19, polysomies of chromosomes 17, 1q, and 20, and gains of 13q14.2, 10p13, and 21q21.2 chromosomal regions. Based on their CNA profile, RM could be classified into two genetic subgroups with distinct clinicopathologic features characterized by the presence of (1) chromosomal losses only and (2) combined losses and gains of several chromosomes. The latter displays a higher frequency of WHO grade 3 tumors and poorer clinical outcomes.

ABSTRACT The SARS-CoV-2 variant of concern (VOC) Delta (B.617.2 lineage) displaced the predominant VOC Alpha (B.1.1.7 lineage) in the United Kingdom. In Madrid, recent start of the decline of predominant VOC Alpha suggested an equivalent phenomenon. However, 11 different variants, none overrepresented in frequency, occupied progressively over a period of 7 weeks the niche previously dominated by VOC Alpha. Only after these 7 weeks, VOC Delta started to emerge. Viral competition due to the entry of VOC Delta is not the major force driving the start of VOC Alpha decline in Madrid. IMPORTANCE Our data indicate that the dynamics of SARS-CoV-2 VOCs turnover in our setting differ from those proposed for other countries. A systematic genomic analysis, updated on a weekly basis, of representative randomly selected samples of SARS-CoV-2 circulating variants allowed us to define a lapse of 7 weeks between the start of VOC Alpha decline and the final emergence of VOC Delta. During this period, VOC Alpha showed a sustained decline, while 11 VOCs, variants of interest (VOIs), and other identified variants, none overrepresented, occupied the niche left by VOC Alpha. Only after these 7 weeks, emergence of VOC Delta occurred, indicating that viral competition involving VOC Delta was not the exclusive direct driving force behind the starting of VOC Alpha decline.

Human WHO grade 1 meningiomas are generally considered benign tumors; despite this, they account for ≈50% of all recurrent meningiomas. Currently, limited data exist about the mutational profiles of grade 1 meningiomas and patient outcome. We investigated the genetic variants present in 32 WHO grade 1 meningiomas using whole exome sequencing, and correlated gene mutational profiles with tumor cytogenetics and patient outcome. Overall, WHO grade 1 meningiomas harbored numerous and heterogeneous genetic variants, which most frequently affected the NF2 (47%) gene and to a less extent the PNMA6A (22%), TIGD1 (16%), SMO (13%), PTEN (13%), CREG2 (9%), EEF1A1 (6%), POLR2A (6%), ARID1B (3%), and FAIM3 (3%) genes. Notably, non-synonymous genetic variants of SMO and POLR2A were restricted to diploid meningiomas, whereas NF2 mutations were only found among tumors that showed -22/22q─ (with or without a complex karyotype). Based on NF2 mutations and tumor cytogenetics, four genetic profiles were defined with an impact on patient recurrence-free survival (RFS). These included (1) two good-prognosis tumor subgroups—diploid meningiomas (n=9) and isolated -22/22q─ associated with NF2 mutation (n=7)—with RFS rates at 10 y of 100%; and (2) two subgroups of poor-prognosis meningiomas—isolated -22/22q─ without NF2 mutation (n=3) and tumors with complex karyotypes (n=11)—with a RFS rate at 10 y of 48% (p=0.003). Our results point out the existence of recurrent but heterogeneous mutational profiles in WHO grade 1 meningiomas which have an impact on patient outcome.

ABSTRACT Reverse transcription-PCRs (RT-PCRs) targeting SARS-CoV-2 variant of concern (VOC) mutations have been developed to simplify their tracking. We evaluated an assay targeting E484K/N501Y to identify B.1.351/P1. Whole-genome sequencing (WGS) confirmed only 72 (59.02%) of 122 consecutive RT-PCR P.1/B.1.351 candidates. Prescreening RT-PCRs must target a wider set of mutations, updated from WGS data from emerging variants.

Evapotranspiration (ET) is a key process in hydrological systems and, consequently, in agroecosystems. It can be measured or derived with a large variety of models at scales ranging from leaf to catchment. MODIS16A2 is a satellite ET product with 500 meters / 8-day spatio-temporal resolution worldwide. It is based on the Penman-Monteith equation and considers the effect of vegetation dynamics, albedo and land cover. This technical paper compares the ET estimated from MODIS16A2 against the ET estimated at different scales from three reference methods: (1) the INIA-GRAS Water Balance on a country-scale, (2) the SWAT model of the Santa Lucia basin on the catchment scale, and (3) the Eddy Covariance Flux located in Colonia on a farmer scale. The analysis shows similarities between MODIS16A2 and the reference methods depending on seasonality, geographic location and scale of ET estimation. The assumptions about vegetation cover, vegetation dynamics, meteorological forcing and soil characteristics of the reference methods compared with MODIS16A2 ones could explain some deviations in the ET estimations. The results of this work contribute with a first approximation towards the quantification of the uncertainty of MODIS16A2 in Uruguay.

Hematological malignancies comprise a plethora of different neoplasms, such as leukemia, lymphoma, and myeloma, plus a myriad of dysplasia, such as myelodysplastic syndromes or anemias. Despite all the advances in patient care and the development of new therapies, some of these malignancies remain incurable, mainly due to resistance and refractoriness to treatment. Therefore, there is an unmet clinical need to identify new biomarkers and potential therapeutic targets that play a role in treatment resistance and contribute to the poor outcomes of these tumors. RNA-binding proteins (RBPs) are a diverse class of proteins that interact with transcripts and noncoding RNAs and are involved in every step of the post-transcriptional processing of transcripts. Dysregulation of RBPs has been associated with the development of hematological malignancies, making them potential valuable biomarkers and potential therapeutic targets. Although a number of dysregulated RBPs have been identified in hematological malignancies, there is a critical need to understand the biology underlying their contribution to pathology, such as the spatiotemporal context and molecular mechanisms involved. In this review, we emphasize the importance of deciphering the regulatory mechanisms of RBPs to pinpoint novel therapeutic targets that could drive or contribute to hematological malignancy biology.

Background: Functional Fitness Training (FFT) is a new exercise modality prioritizing functional multi-joint movements executed at high intensity as a circuit. Objective: To examine the impacts of introducing rest intervals in a FFT workout compared to “rounds for time” (RFT) FFT. Materials and Methods: Participants were 25 resistance-trained adults who completed two FFT workouts 1 week apart. The study design was crossover such that in a given session half the participants completed the standard and the other half the adapted FFT (FFTadapted). The workouts consisted of the same exercises (circuit of four rounds of exercises), but one (FFTadapted) included preset rest intervals (three sets of 1 min after each completed round). Before and after the workouts, countermovement jump ability and blood lactate were measured. Heart rate (HR) and ratings of perceived exertion (RPE) were measured post-exercise. Results: For both the standard and adapted protocols, mean HR was 90% age-predicted maximum. Final RPE was also similar for both workouts (~15–15.5) and indicated a “hard” work intensity. Both FFTs took the same time to complete (~13 min). Furthermore, no significant differences were observed in jump ability between FFTs. In contrast, lactate (15.11 ± 3.64 vs. 13.48 ± 3.64 mmol·L−1, p < 0.05), measured 3 min post-exercise, was significantly lower in FFTadapted. Conclusions: In FFTadapted, there was a significant reduction in RPE and blood lactate concentrations after exercise, while there were no significant differences in either HR or jumping ability, compared to a FFT workout in RFT methodology.

This work considers the problem of forecasting the normal solar irradiance with high spatial and temporal resolution (5 minutes). The forecasting is based on a dataset registered during one year from the high resolution radiometric network at a operational solar power plan at Almeria, Spain. In particular, we show a technique for forecasting the irradiance in the next few minutes from the irradiance values obtained on the previous hour. Our proposal employs a type of recurrent neural network known as LSTM, which can learn complex patterns and that has proven its usability for forecasting temporal series. The results show a reasonable improvement with respect to other prediction methods typically employed in the studies of temporal series.

Meningiomas contain highly variable levels of infiltrating tissue macrophages (TiMa) and other immune cells. In this study we investigated the potential association between the number and immunophenotype of inflammatory and other immune cells infiltrating the tumor as evaluated by multiparameter flow cytometry, and the clinico-biological, cytogenetic and gene expression profile (GEP) of 75 meningioma patients. Overall, our results showed a close association between the amount and cellular composition of the inflammatory and other immune cell infiltrates and the cytogenetic profile of the tumors. Notably, tumors with isolated monosomy 22/del(22q) showed greater numbers of TiMa, NK cells and (recently)-activated CD69(+) lymphocytes versus meningiomas with diploid and complex karyotypes. In addition, in the former cytogenetic subgroup of meningiomas, tumor-infiltrating TiMa also showed a more activated and functionally mature phenotype, as reflected by a greater fraction of CD69(+), CD63(+), CD16(+) and CD33(+) cells. GEP at the mRNA level showed a unique GEP among meningiomas with an isolated monosomy 22/del(22q) versus all other cases, which consisted of increased expression of genes involved in inflammatory/immune response, associated with an M1 TiMa phenotype. Altogether, these results suggest that loss of expression of specific genes coded in chromosome 22 (e.g. MIF) is closely associated with an increased homing and potentially also anti-tumoral effect of TiMa, which could contribute to explain the better outcome of this specific good-prognosis cytogenetic subgroup of meningiomas.

Summary: Connexin43 (CX43), a protein that forms gap junction channels and hemichannels in astrocytes, is downregulated in high-grade gliomas. Its relevance for glioma therapy has been thoroughly explored; however, its positive effects on proliferation are counterbalanced by its effects on migration and invasion. Here, we show that a cell-penetrating peptide based on CX43 (TAT-Cx43266-283) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells (GSCs) derived from patients. Consequently, TAT-Cx43266-283 reduced GSC motility, as analyzed by time-lapse microscopy, and strongly reduced their invasive ability. Interestingly, we investigated the effects of TAT-Cx43266-283 on freshly removed surgical specimens as undissociated glioblastoma blocks, which revealed a dramatic reduction in the growth, migration, and survival of these cells. In conclusion, a region of CX43 (amino acids 266–283) exerts an important anti-tumor effect in patient-derived glioblastoma models that includes impairment of GSC migration and invasion. : In this article, Arantxa Tabernero and colleagues show that a short region of Connexin43 exerts an important anti-tumor effect in patient-derived glioblastoma models that includes the impairment of glioma stem cell migration and invasion. This peptide targets important proteins for glioblastoma, such as Src, FAK, and PTEN, highlighting its relevance for therapeutic development against this incurable disease. Keywords: glioma stem cell, connexin, Src, PTEN, FAK, migration, invasion

Objectives: Endoscopic evacuation of intracerebral hemorrhage (ICH) has been developed in order to reduce the tissue injury that conventional craniotomy could generate. Experimental studies are important to assess the effectiveness of the technique and its modifications. The objectives of this study are to develop in pig an experimental model of endoscopic evacuation of ICHs, to assess effectiveness of surgical evacuation, and to evaluate a new transparent sheath as complement to the endoscopy. Methods: Autologous blood was infused into the frontal lobe white matter in 16 pigs. In the problem group, endoscopic evacuation was performed with the aid of a new transparent sheath, which has outer and inner sheaths with blunt and closed finals. Pigs were sacrificed at 4 h, 24 h and 5 days. The volumes of hematoma and histopathological features were determined. Results: Residual volume of the problem group was significantly 70.09% lower than in control group, without significant differences in injected volumes, in percentage of subarachnoid hemorrhage, and in time interval from hematoma induction to pig´s death. The vital reaction after hemorrhage was similar in both groups. Conclusions: The experimental model developed is useful to assess endoscopic evacuation of ICHs. The endoscopy is an effective technique in the treatment of ICHs, without increasing the vital reaction secondary to hematoma. The new transparent sheath increases the visualization of surgical field and allows a continuous visual control since the beginning of the procedure. Its closed final prevents unwanted injury of the brain by the instruments used to remove the hematoma.

Se realizó un estudio prospectivo descriptivo de 58 pacientes con Enfermedad Trofoblástica Gestacional (ETG), que consultaron por primera vez al Hospital Universitario San Vicente de Paúl (HUSVP) durante 19 meses, comprendidos entre el 1o. de agosto de 1985 y el 28 de febrero de 1987, de tal manera que el 1o. de septiembre de 1987 tuvieron un seguimiento mínimo de seis meses. Ocho pacientes tuvieron un seguimiento menor. Se analizaron factores de riesgo de esta enfermedad, tales como: edad, grupo sanguíneo de la paciente, paridad, tipo de embarazo precedente, título inicial de HCG, duración de la enfermedad, altura uterina en relación con la amenorrea, enfermedades médicas asociadas (toxemia, hipertiroidismo) y presencia de quistes tecalutéinicos, con relación a los estados clínicos de la enfermedad.

Por ser este un informe preliminar, con un volumen pequeño de casos y un seguimiento muy corto, no estaba dentro de los objetivos analizar resultados en forma definitiva ni dar pautas de manejo, hasta tanto no se termine la investigación. Sin embargo, en este trabajo se recalca la importancia de esta patología en nuestro medio y la necesidad de un estudio sistematizado con los métodos actuales tanto de diagnóstico como de seguimiento y tratamiento con miras a obtener mejores resultados.