Improved predictive diagnosis of diabetic macular edema based on hybrid models: An observational study.

Diabetic Macular Edema (DME) is the most common sight-threatening complication of type 2 diabetes. Optical Coherence Tomography (OCT) is the most useful imaging technique to diagnose, follow up, and evaluate treatments for DME. However, OCT exam and devices are expensive and unavailable in all clinics in low- and middle-income countries. Our primary goal was therefore to develop an alternative method to OCT for DME diagnosis by introducing spectral information derived from spontaneous electroretinogram (ERG) signals as a single input or combined with fundus that is much more widespread. Baseline ERGs were recorded in 233 patients and transformed into scalograms and spectrograms via Wavelet and Fourier transforms, respectively. Using transfer learning, distinct Convolutional Neural Networks (CNN) were trained as classifiers for DME using OCT, scalogram, spectrogram, and eye fundus images. Input data were randomly split into training and test sets with a proportion of 80 %-20 %, respectively. The top performers for each input type were selected, OpticNet-71 for OCT, DenseNet-201 for eye fundus, and non-evoked ERG-derived scalograms, to generate a combined model by assigning different weights for each of the selected models. Model validation was performed using a dataset alien to the training phase of the models. None of the models powered by mock ERG-derived input performed well. In contrast, hybrid models showed better results, in particular, the model powered by eye fundus combined with mock ERG-derived information with a 91 % AUC and 86 % F1-score, and the model powered by OCT and mock ERG-derived scalogram images with a 93 % AUC and 89 % F1-score. These data show that the spontaneous ERG-derived input adds predictive value to the fundus- and OCT-based models to diagnose DME, except for the sensitivity of the OCT model which remains the same. The inclusion of mock ERG signals, which have recently been shown to take only 5 min to record in daylight conditions, therefore represents a potential improvement over existing OCT-based models, as well as a reliable and cost-effective alternative when combined with the fundus, especially in underserved areas, to predict DME.

Presence of human papillomavirus in the buccal mucosa of blood donors.

OBJECTIVE: To determine the presence of human papillomavirus (HPV) in the oral mucosa of blood donors (BD) and risk factors associated with HPV and oral cancer. MATERIALS AND METHODS: Prospective cross-sectional study, population matched to BD from the National Cancer Institute, Mexico for HPV identification in oral cytological samples using the CLART® Human Papillomavirus 2 Kit (35 genotypes) and risk factors. RESULTS: Of 352 BD with signed informed consent, 285 were selected by simple randomization. The prevalence of oral HPV was 17.5% (95% CI 13-21.9%), the genotype was identified in 13 cases, with a total of 16 genotypes (10 high-risk), the most common being 16 and 84. Five cases had multiple infections, three with at least one high-risk type. Associations were found for marital status (OR 3.3) and educational level (OR-1.9). CONCLUSIONS: The percentage of HPV-positive cases in blood donors with no risk practices was similar to that found in Spanish-speaking population studies in which at least one risk practice was described. The presence of other genotypes with high oncogenic risk and multitype infection, described as a marker of persistence of HPV infection, is highlighted.

Genotypic spectrum underlying tetrahydrobiopterin metabolism defects: Experience in a single Mexican reference center.

Background: Pterin profiles or molecular analyses of hyperphenylalaninemia (HPA) caused by phenylalanine hydroxylase (PAH) deficiency or tetrahydrobiopterin deficiency (BH4D) are not always available in low- or middle-income countries, including Mexico, limiting information regarding the phenotypic and genotypic characteristics of patients exhibiting BH4D. Objective: To report the genotypes underlying BH4D and the clinical presentation in unrelated Mexican HPA pediatric patients with normal PAH genotypes who attended a single metabolic reference center in Mexico. Methods: Automated Sanger sequencing of the PTS, QDPR, and PCBD1 genes of 14 HPA patients was performed. Predicted effects on protein structure caused by missense variants were assessed by in silico protein modeling. Results and discussion: A high prevalence of BH4D was noted in our HPA cohort (9.8%, N = 14/142). Clinically relevant biallelic genotypes were identified in the PTS (N = 7/14 patients), QDPR (N = 6/14 patients), and PCBD1 (N = 1/14 patients) genes. Four novel QDPR variants [c.714dup or p.(Leu239Thrfs*44), c.106-1G>T or p.(?), c.214G>T or p.(Gly72*), and c.187_189dup or p.(Gln63dup)] were identified. In silico protein modeling of six missense variants of PTS [p.(Thr67Met), p.(Glu81Ala), and p.(Tyr113Cys)], QDPR [p.(Cys161Phe) and p.(Pro172Leu)], and PCBD1 [p.(Glu97Lys)] supports their pathogenicity. Progressive neurological symptoms (mainly intellectual and motor impairment and even death in three patients) were noted in all patients with biallelic QDPR genotypes and in 5/7 patients bearing biallelic PTS genotypes. The single homozygous PCBD1 p.(Glu97Lys) patient remains asymptomatic. Conclusion: A higher proportion of BH4D (9.8 vs. 1%-2% worldwide), attributable to a heterogeneous mutational spectrum and wide clinical presentation, was noted in our Mexican HPA cohort, with the PTS-related HPA disorder being the most frequent. Sequencing-based assays could be a reliable approach for diagnosing BH4D in our population.

Endogenous endophthalmitis during pregnancy: Case report. / Endoftalmitis endógena durante el embarazo: a propósito de un caso.

Endogenous endophthalmitis is a disease that potentially threatens vision. It is produced by the haematogenous spread of microorganisms from a septic focus. It is a rare condition that is related to debilitating diseases, immunosuppression states, and invasive procedures. Endogenous endophthalmitis during pregnancy is even rarer, and has become a challenge due to the safety and side effects of the local and systemic treatments. The case is presented of a pregnant woman with a history of complicated appendicitis, septic shock, and thrombocytopenia that presented endogenous endophthalmitis due to Candida albicans in the immediate post-operative period. This required the use of intravitreal and systemic antimycotics and vitrectomy. She made a significant anatomical and functional recovery, and without any maternal or foetal side effects.

Vitreous amyloidosis as primary manifestation of disease: case report. / Amiloidosis vítrea como manifestación primaria de enfermedad: reporte de caso.

A 35-year-old woman with progressive decrease of vision in both eyes and with no other associated symptoms, manifested as the only antecedent, the death of her brother due to amyloidosis. The visual acuity was counting fingers at 30 centimetres in the right eye and 20/70 in the left eye. In ophthalmoscopy of the right eye, a white, homogeneous vitreous, that was difficult to assess in detail, was observed, and in the left eye a whitish vitreous with band-like opacities in the cortical region. Vitrectomy was performed in the right eye, and a study with specific stains showed positive for amyloid material. A case is reported of amyloidosis diagnosed with specific stains in a vitreous sample for which the initial and only manifestation was the presence of vitreous opacities. The processing of these samples should be considered in patients with family history, early vitreous opacities, negative results of systemic biopsy, or atypical course of the disease.

Multiple lymphangiohemangiomas with thoracic and abdominal involvement: a case report. / Linfangiohemangiomas múltiples con afectación torácica y abdominal. Presentación de un caso.

We present a case of multiple lymphangiohemangiomas (hematolymphangiomas, hemangiolymphangiomas, or combined lymphatic venous malformation) with thoracic and abdominal involvement in an asymptomatic patient. We describe and illustrate the imaging findings in this disease, which are quite characteristic and can enable an accurate diagnosis. To our knowledge, there are no other reports of similar cases in the scientific literature.

Uterine contractility as a cause of amniotic band syndrome.

OBJECTIVE: The objective of this study was to determine whether puncturing the uterine wall and the amnion causes uterine contractions that result in fetal abnormalities. MATERIALS AND METHODS: An experimental study was performed using four groups of three female rabbits. Group A received a puncture of the amniotic membranes of one of the uteri on day 15 of gestation followed by group B on day 16, group C on day 17, and group D on day 18. The duration and force of contractions and fetal abnormalities were determined. RESULTS: There were immediate contractions after the puncture, which lasted 20 to 132 seconds with forces that ranged from 309 to 4,411 mg. All of the experimental fetuses exhibited anomalies of the head and extremities, exencephaly, cleft palates, and an absence of eye-lids. CONCLUSION: Injury to the uterine wall and the aniion can immediately cause uterine contractions, which are associated with different types of fetal abnormalities.

Occlusal characteristics of primary dentition in sudanese children in khartoum state / Características oclusais da dentição decídua em crianças Sudanesas do Estado de Khartoum

Background: Occlusal relationships in the primary dentition play an important role in the consequential final occlusion in permanent dentition. Therefore, good knowledge of occlusal relationships in children is essential for dental practitioners. Design: A descriptive, cross-sectional study done in randomly selected kindergartens in Khartoum State to determine the occlusal characteristics of primary dentition in a group of Sudanese children. Objective: To determine the occlusal characteristics feature of primary dentition in a group of Sudanese children. Methods: A sample of 381 children age 3-5 years old, randomly selected from kindergartens in Khartoum Stat. Clinical examination was done to all children fulfil the inclusion criteria in the teacher office and in natural day light. Prevalence of different types of terminal plane, types of primary canine relationship and spacing of the primary dentition were assessed. Results: Flush terminal plane was the most prevalent type of terminal plane (72.2%). Class I canine relationship was the most common type of primary canine relationships (95%). In the upper arch primate space and physiological spaces were present in 90.3% and 82.4% of the children, respectively. Nevertheless, the lower arch showed primate spaces in 70.1% and physiological spaces in 74.8% of the children. Conclusion: Large number of the examined children had flush terminal plane and spacing primary dentition that forecasts development of normal occlusion in their permanent dentition

Introdução: As relações oclusais na dentição decídua desempenham um papel importante na oclusão final, na dentição permanente. Portanto, um bom conhecimento das relações oclusais em crianças é essencial para os cirurgiões-dentistas. Foi realizado um estudo descritivo , transversal, em creches selecionadas aleatoriamente no estado de Khartoum (Sudão) para determinar as características oclusais de dentição decídua em um grupo de crianças sudanesas. Objetivo: Determinar as características oclusais de dentição decídua em um grupo de crianças sudanesas. Métodos: Uma amostra de 381 crianças com idade entre 3 e 5 anos foram selecionados aleatoriamente a partir creches no estado de Khartoum. O exame clínico foi feito em todas as crianças cumpriram os critérios de inclusão, na sala dos professores sob luz natural do dia. Foram avaliadas a prevalência dos diferentes tipos de plano terminal, tipos de relação canina e espaçamento da dentição decídua. Resultados: O plano terminal em topo foi o tipo mais prevalente de plano terminal (72,2%) . A relação canina de Classe I foi o tipo mais comum de relacionamentos nos caninos decíduos (95 %). Os espaços primatas e fisiológicas nos arcos superiores estavam presentes em 90,3% e 82,4 % das crianças , respectivamente. No entanto, os arcos inferiores mostraram espaços primatas em 70,1% e espaços fisiológicos em 74,8% das crianças. Conclusão: Grande número de crianças examinadas tinham plano terminal em topo e espaçamento dentição decídua, o que pode predizer um desenvolvimento da oclusão normal na sua dentição permanente.

Immunoexpression of matrix metalloproteinases and their inhibitors in different areas of oral squamous cell carcinoma.

BACKGROUND: Several studies have shown the participation of MMPs in oral squamous cell carcinoma, the most frequent malignant neoplasm of the oral cavity. The expression of some MMPs correlates with a more aggressive biological behaviour. The objective of this study was to determine which MMPs and TIMPs were expressed in both neoplastic and peritumoural stromal cells in different histopathology areas. METHODS: Patients who underwent primary tumour neck dissection for oral squamous cell carcinoma were included. Immunoexpression of MMP-1, -2, -3, -7, -9, -11, -13, and TIMP-1 and -2 in different areas of pathologic specimens (in situ carcinoma, primary tumour, invasive front, distant invasion carcinoma, and lymph node metastasis) was evaluated. Enzyme expression on mucosa adjacent to tumour served as control. RESULTS: Thirty cases were included. Only 6 MMPs and 1 TIMP were expressed in the studied areas. Statistically significant differences in the number of cases with positive MMPs or TIMP expression, in both neoplastic and peritumoural cells, between control and the rest of the areas were observed. MMP-2 expression was constant in the areas with a more aggressive biological behaviour. CONCLUSIONS: MMP-2 expression may represent a dynamic interaction between host and tumour that favours the establishment of neoplastic cells at distant sites.

[In-utero antiretroviral exposure and mitochondrial toxicity in a cohort of uninfected infants born to HIV-1-infected women]. / Exposición a antirretrovirales y toxicidad mitocondrial en una cohorte de niños no infectados hijos de madres VIH positivas.

INTRODUCTION: In this study, we attempt to find out the percentage of uninfected infants born to HIV-infected women and exposed in-utero and perinatally to Antiretroviral Treatment (ART) that show high lactate levels, or any other mitochondrial damage markers (such as hypertransaminasaemia or hyperamylasaemia), during the first three months of age. We shall also establish whether certain drugs used in-utero are associated with higher lactate, transaminase or amylase levels. METHODS: We analysed the available data from 623 uninfected infants born in the Spanish FIPSE cohort that were born in the period 2000-2005. The normal values for lactate, transaminases and amylase were set according to AIDS Clinical Groups Trials toxicity tables for infants. RESULTS: The percentages of children with high lactate levels at 0.5; 1.5 and 3 months of age were 48%, 51.4% and 43% among those infants with available data. Respectively, the percentages of children with high AST values were 13.2; 10.4 and 17.2%. The values for high ALT were 3.3%; 3.4% and 5%. The percentages for hyperamylasaemia were 0%; 0.6% and 2.6%. We found no significant difference among the drugs used in utero for the four analysed biochemical markers along the first three months of age. CONCLUSIONS: We have found a high proportion of hyperlactataemia among infants exposed in-utero to ART, as shown in other cohorts of similar characteristics. No morbidity or mortality was communicated to the cohort analysis group. No ART drug among those used in-utero was statistically associated with a higher proportion of high lactate levels in these infants.

Opportunistic infections and organ-specific diseases in HIV-1-infected children: a cohort study (1990-2006).

OBJECTIVES: Highly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV infection in children, but there are few studies in the literature about the incidence of clinical manifestations after HAART in this population, compared with adults. The aim of this study was to describe the influence of the widespread use of HAART on the development of opportunistic infections and organ-specific diseases in HIV-infected children. METHODS: An observational study of a cohort of 366 vertically HIV-infected children followed from 1990 to 2006 was carried out. According to the main antiretroviral protocol used, three calendar periods (CPs) were defined and compared: CP1 (1990-1996: no patients on HAART), CP2 (1997-1999: <60% on HAART) and CP3 (2000-2006: >60% on HAART). RESULTS: Children experienced a progressive increase in CD4 T cell count (P<0.05) and a decrease in HIV viral load from 1996 onwards (P<0.05). Similarly, rates of death, AIDS, opportunistic infections (bacteraemia, candidosis, cryptosporidiosis and bacterial pneumonia) and organ-specific diseases (wasting syndrome, thrombocytopenia, cardiomyopathy, lymphoid interstitial pneumonia and HIV-associated encephalopathy) were lower in CP2 and CP3 than in CP1. CONCLUSIONS: This study provides evidence of improved clinical outcomes in HIV-infected children over time and shows that mortality, AIDS, opportunistic infections and organ-specific diseases declined as HAART was progressively instituted in this population.

[Growth of uninfected infants exposed to antiretrovirals born to HIV-infected woman]. / Exposición a antirretrovirales y crecimiento en una cohorte de niños no infectados, hijos de madre con VIH positivo.

INTRODUCTION: Recent reports show that Antiretroviral Treatment (ART) during pregnancy does not affect somatic growth of children born to HIV-infected mothers, are reassuring. The aim of this study is to perform an anthropometric analysis of the uninfected children followed in the Spanish FIPSE cohort during their first 18 months of life, and to describe the possible risk factors during pregnancy that may influence low birth weight. METHODS: The FIPSE cohort includes 8 public hospitals in Madrid, and prospectively follows children born to HIV-infected women at these hospitals. We collected data on 601 uninfected children, following standardised protocols, during their first 2 years of life. A P value<0.05 was considered statistically significant. Data from the Pablo Orbegozo Foundation were used to compare the means of our population with the standard weight, longitude an occipitofrontal circumference (OFC) of the Spanish population during the first 18 months of life. RESULTS: The mean weight was 2766g (+/-590), and 2967g (+/-427) when premature neonates were excluded. The proportion of Intrauterine Growth Restriction among non- premature neonates was 19.8% (95% CI: 16.3-23.8). Children born to mothers that used illicit drugs weighed less: 2752g (+/-325) vs. 3002g (+/ 435), P<0.001, as did children born to mothers who smoked during pregnancy: 2842g (+/-363) vs. 3018g (+/-444), P>0.001. Maternal anaemia did not influence the low birth weight of the children when premature neonates were excluded. We found no statistically significant differences depending on the ART received during pregnancy. Children born to mothers who had CD4 > 500 cell /mm were heavier (2834g +/-503) than those whose mothers had CD4 of less than 200 cell/mm (2565g +/-702), P=0.008. These differences disappeared when premature neonates were excluded. Children born to mothers with undetectable viral load were heavier (2866g +/-532 vs. 2704g +/-588, P=0.005), but these differences also disappeared when the prematures were excluded from the analysis. Mean weight, length, and OFC of our population at birth (excluding premature neonates) were lower than the Spanish standards. (z for weight=-0.83; z for length =-1.02; z for OFC=-1.00), but these differences are not statistically significant and disappear at 18 months of age (z for weight=-0.08; z for height=-0.32; z for OFC=-0.31). The type of ART did not have any significant influence. DISCUSSION: There is a very significant difference between the weight of the children born to mothers addicted to illicit drugs and the rest of the children. Similarly, the weight of the children born to smoking mothers is significantly lower. There was no association between maternal anaemia and the type of ART. The children of our population have lower weights, length and OFC at birth, but this may due to the high number of scheduled caesarean births, practised at 38 weeks of pregnancy (54.5%). Our children catch-up with anthropometric measurements during the first and second year of life, and these are similar to Spanish standards at 18 months old.

[Birth defects in a cohort of uninfected children born to HIV-infected women]. / Malformaciones congénitas en una cohorte de niños no infectados, hijos de madres infectadas por el virus de la inmunodeficiencia humana.

INTRODUCTION: Mother-to-Child HIV transmission is now just 1% in western countries, due to prevention measures. Antiretroviral Treatment (ART) drugs do have adverse effects, anaemia and myelosupression caused by cidovudina being the most commonly observed effects. In the present study, we have analysed the proportion and characteristics of congenital malformations (CM) or birth defects (BD) in a cohort of uninfected children born to HIV-infected women. METHODS: A total of 623 uninfected children belonging to the FIPSE cohort were followed up according to standardised protocols. This cohort includes 8 public hospitals from Madrid and follows up HIV-infected pregnant women and their children. Children were classified according to prematurity, ethnic origin, birth weight, withdrawal syndrome, in-utero treatment. Birth defects were described and defined according to the EUROCAT, the European registry for BD. Mild errors of morphogenesis were excluded from the analysis. Categorical variables were compared with the X(2) or the Fisher test. RESULTS: A total of 78% (486) of the mothers were of Caucasian origin; 18.8% (117) used some illicit drug (heroine, cocaine or methadone) during gestation; 51 mothers (8.1%) received no ART, 10 (1.6%) received monotherapy and 469 (75.3%) received HAART. BD were seen in 52 children, with the most frequent being genitourinary and cardiological. Anaemia in the first trimester was an associated risk for BD (17.9% vs. 8.1%, P = 0,04). Similarly, mothers who used any illicit drug (plus methadone), had a slightly higher risk for BD in their offspring (13.8% vs. 7.6%, P = 0,04) There was no increased risk for BD significantly associated with any of the in-utero used antiretrovirals, although Nevirapine use in-utero showed a protective effect. Children born to mothers who received ART in the first trimester had the same rate of BD (7.4%) as those whose mothers started ART in the second trimester (8.8%), P = 0,67. CONCLUSIONS: The proportion of BD that we have observed seems higher than those shown in other European teratogenicity studies and also higher than those shown in cohorts with HIV and antiretroviral exposed infants. This may be due to the fact that our series show the results of an active surveillance system (that includes ultrasound), where BD classically appear in a higher proportion. Immunovirological characteristics of the mother did not influence the proportion of BD, but anaemia in the fist trimester and the use of illicit drugs (or methadone) did. No specific antiretroviral drug was associated with an increase in BD, although Nevirapine showed a possible protective effect in the statistical analysis. Mothers who started antiretrovirals in the first trimester do not have more BD in their offspring than mothers who started on antiretrovirals later on.

[Anaemia and neutropenia in a cohort of non-infected children of HIV-positive mothers]. / Anemia y neutropenia en una cohorte de niños no infectados hijos de madres positivas para el virus de la inmunodeficiencia humana.

INTRODUCTION: Mother-to-child HIV transmission is currently around 1% in western countries, due to prevention measures. Antiretroviral drugs do have adverse effects, anaemia and myelosupression caused by AZT being the most observed effects. In the present study, we analyse the prevalence of anaemia and neutropenia in an uninfected children cohort born to HIV-infected women. MATERIAL AND METHODS: We followed up 623 uninfected children belonging to the FIPSE cohort according to standardised protocols. This cohort groups 8 hospitals from Madrid and follows up HIV infected pregnant women and their children. Anaemia and neutropenia were defined according to the ACTG (AIDS Clinical Trails Group) toxicity tables. Children were classified according to prematurity, ethnic origin, birth weight, withdrawal syndrome, in-utero treatment and neonatal prophylaxis. Categorical variables were compared with the chi2 or the Fisher tests. RESULTS: Anaemia was observed in 188 (30.1%) children during follow-up and 161 (25.8%) had anaemia grade 2 or higher. Prematurity (p < 0.001), low birth weight (p = 0.005) and Highly Active Antiretroviral Treatment (HAART) with Protease Inhibitors (p = 0.016) were associated with higher percentages of anaemia in children. Nadir haemoglobin values were reached by 6 weeks of life and anaemia was transient and disappeared by six months of age. Neutropenia was present in 41.9% (261 children) and 22.7% of the children had moderate-severe neutropenia. Prematurity was again associated with neutropenia (p = 0.01) and low birth weigh was associated only with moderate-severe neutropenia (p = 0.023). African infants had a higher percentage of neutropenia than the rest of the children (50% vs. 44%), although the differences were not significant. The type of in-utero treatment did not appear to influence the neutropenia. Neutropenia was still present in 12.5% of infants at 18 months of age. The type of neonatal prophylaxis to prevent mother-to-child transmission (monotherapy, dual therapy or triple therapy) did not influence either cytopenia. CONCLUSION: In our series, the proportion of children with anaemia is high: 30.1% Prematurity, low birth weight and HAART with IP were associated with a higher proportion of anaemia, which was transient and had little clinical relevance. The proportion of children with neutropenia was higher (41.9%) and was associated with prematurity, low birth weight and African origin. The type of neonatal prophylaxis does not seem to influence the development of cytopenias. Persistence of neutropenia (without clinical significance) was observed in a small percentage of the children 12.5%, at 18 months of age.

Estimation of complex refractive index of polydisperse particulate systems from multiple-scattered ultraviolet-visible-near-infrared measurements.

A method to extract the complex refractive index of spherical particles from a polydisperse suspension at concentrations where multiple light-scattering effects are significant is presented. The optical constants are estimated from total diffuse reflectance and transmittance measurements and inverting the measurements using the radiative transfer equation (RTE) and the Mie theory for scattering by polydisperse spherical particles. The method is tested by applying it to three different polydisperse polystyrene suspensions and extracting the optical constants of polystyrene particles in the wavelength range of 450-1200 nm. The effect of particle size, concentration, and polydispersity on the estimated values of the optical constants is also discussed.