CycleGAN-Based Image to Image Translation for Realistic Surgical Training Phantoms.

Training in surgery is essential for surgeons to develop skill and dexterity. Physical training phantoms provide excellent haptic feedback and tissue properties for stitching and operating with authentic instruments and are easily available. However, they lack realistic traits and fail to reflect the complex environment of a surgical scene. Generative Adversarial Networks can be used for image-to-image translation, addressing the lack of realism in physical phantoms, by mapping patterns from the intraoperative domain onto the video stream captured during training with these surgical simulators. This work aims to achieve a successful I2I translation, from intra-operatory mitral valve surgery images onto a surgical simulator, using the CycleGAN model. Different experiments are performed - comparing the Mean Square Error Loss with the Binary Cross Entropy Loss; validating the Fréchet Inception Distance as a training and image quality metric; and studying the impact of input variability on the model performance. Differences between MSE and BCE are modest, with MSE being marginally more robust. The FID score proves to be very useful in identifying the best training epochs for the CycleGAN I2I translation architecture. Carefully selecting the input images can have a great impact in the end results. Using less style variability and input images with good feature details and clearly defined characteristics enables the network to achieve better results.Clinical Relevance- This work further contributes for the domain of realistic surgical training, successfully generating fake intra operatory images from a surgical simulator of the cardiac mitral valve.

Impacted estuaries on the Brazilian Amazon coast near port regions influence histological and enzymatic changes in Sciades herzbergii (Ariidae, Bloch, 1794).

Enzymatic (glutathione S-transferase, GST and catalase, CAT) and histological biomarkers in S. herzbergii are important for the analysis of impacted estuaries in port regions of the Brazilian Amazon coast. Fish specimens were collected in two areas in the rainy and dry seasons: Porto Grande (potentially impacted region) and Ilha dos Caranguejos (less impacted region). Sediment samples were collected for chemical analysis. Morphometric, histological, and enzymatic biomarker analyzes were performed. The analysis of the sediments collected in the potentially impacted region showed levels of iron, aluminum and polycyclic aromatic hydrocarbons above the limits allowed by CONAMA legislation. Histological changes in the gills and liver, as well as GST and CAT activities, were high in fish collected at the port. Analyzes suggest that fish in the potentially impacted region are subject to pollutants that compromise their health.

[Family outbreak caused by the nematode Trichostrongylus colubriformis in a rural area of the province of Valdivia: a rare occurrence zoonoses]. / Brote familiar por el nematodo Trichostrongylus colubriformis en una zona rural de la provincia de Valdivia: una zoonosis de rara ocurrencia.

Trichostrongylosis is a rare occurrence zoonosis caused by intestinal nematodes, favored by the consumption of raw vegetables or water contaminated with infective larvae of Trichostrongylus spp. In 2015, a family outbreak of foodborne disease was registered in a rural zone of Valdivia, affecting to 51-year-old woman and her 56-year-old partner and her 12-year-old daughter. Only the adult woman, the index case, presented symptoms such as diarrhea, abdominal pain, asthenia, and nausea. The patients revealed Trichostrongylidae gen. sp. eggs in their stools, identifying Trichostrongylus colubriformis adults in two of them. They had a good response to treatment with albendazol. In Chile, 0.1 to 3.5% prevalence of infection has been reported, including a total of 93 cases recorded between the provinces of Concepción and Llanquihue.

Brote familiar por el nematodo Trichostrongylus colubriformis en una zona rural de la provincia de Valdivia: una zoonosis de rara ocurrencia / Family outbreak caused by the nematode Trichostrongylus colubriformis in a rural area of the province of Valdivia: a rare occurrence zoonoses

Resumen La trichostrongylosis es una zoonosis de rara ocurrencia causada por nematodos intestinales, favorecida por el consumo de vegetales crudos o agua contaminada con larvas infectantes de Trichostrongylus spp. En 2015, se registró un brote familiar transmitido por alimentos en una zona rural de Valdivia, afectando a una mujer de 51 años de edad y su pareja e hija de 56 y 12 años; respectivamente. Solo la mujer adulta, el caso índice, presentó síntomas como diarrea, dolor abdominal, astenia y náuseas. Los pacientes eliminaron huevos de Trichostrongylidae gen. sp. en sus deposiciones, identificándose en dos de ellos, adultos de Trichostrongylus colubriformis. Tuvieron una buena respuesta a albendazol. En Chile, se han registrado prevalencias de infección de 0,1 a 3,5%, incluyendo un total de 93 casos diagnosticados entre las provincias de Concepción y Llanquihue.

Abstract Trichostrongylosis is a rare occurrence zoonosis caused by intestinal nematodes, favored by the consumption of raw vegetables or water contaminated with infective larvae of Trichostrongylus spp. In 2015, a family outbreak of foodborne disease was registered in a rural zone of Valdivia, affecting to 51-year-old woman and her 56-year-old partner and her 12-year-old daughter. Only the adult woman, the index case, presented symptoms such as diarrhea, abdominal pain, asthenia, and nausea. The patients revealed Trichostrongylidae gen. sp. eggs in their stools, identifying Trichostrongylus colubriformis adults in two of them. They had a good response to treatment with albendazol. In Chile, 0.1 to 3.5% prevalence of infection has been reported, including a total of 93 cases recorded between the provinces of Concepción and Llanquihue.

Synthesis and characterization of pH sensitive hydrogel nanoparticles based on poly(N-isopropyl acrylamide-co-methacrylic acid).

In this work, pH-sensitive hydrogel nanoparticles based on N-isopropyl acrylamide (NIPAM) and methacrylic acid (MAA) at various molar ratios, were synthesized and characterized in terms of physicochemical and biological properties. FTIR and 1HNMR spectra confirmed the successful synthesis of the copolymer that formed nanoparticles. AFM images and FE-SEM micrographs showed that nanoparticles were spherical, but their round-shape was slightly compromised with MAA content; besides, the size of particles tends to decrease as MAA content increased. The hydrogels nanoparticles also exhibited an interesting pH-sensitivity, displaying changes in its particle size when changes in pH media occurred. Biological characterization results indicate that all the synthesized particles are non-cytotoxic to endothelial cells and hemocompatible, although an increase of MAA content leads to a slight increase in the hemolysis percentage. Therefore, the pH-sensitivity hydrogels may serve as a versatile platform as self-regulated drug delivery systems in response to environmental pH changes.

Mars Extant Life: What's Next? Conference Report.

On November 5-8, 2019, the "Mars Extant Life: What's Next?" conference was convened in Carlsbad, New Mexico. The conference gathered a community of actively publishing experts in disciplines related to habitability and astrobiology. Primary conclusions are as follows: A significant subset of conference attendees concluded that there is a realistic possibility that Mars hosts indigenous microbial life. A powerful theme that permeated the conference is that the key to the search for martian extant life lies in identifying and exploring refugia ("oases"), where conditions are either permanently or episodically significantly more hospitable than average. Based on our existing knowledge of Mars, conference participants highlighted four potential martian refugium (not listed in priority order): Caves, Deep Subsurface, Ices, and Salts. The conference group did not attempt to reach a consensus prioritization of these candidate environments, but instead felt that a defensible prioritization would require a future competitive process. Within the context of these candidate environments, we identified a variety of geological search strategies that could narrow the search space. Additionally, we summarized a number of measurement techniques that could be used to detect evidence of extant life (if present). Again, it was not within the scope of the conference to prioritize these measurement techniques-that is best left for the competitive process. We specifically note that the number and sensitivity of detection methods that could be implemented if samples were returned to Earth greatly exceed the methodologies that could be used at Mars. Finally, important lessons to guide extant life search processes can be derived both from experiments carried out in terrestrial laboratories and analog field sites and from theoretical modeling.

Current trends of strabismus surgery in a tertiary hospital. / Tendencias actuales de la cirugía de estrabismo en un hospital terciario.

OBJECTIVE: To analyze the strabismus surgeries and the outcomes during a year and a half in a tertiary hospital. MATERIAL AND METHODS: A retrospective study of patients who underwent strabismus surgery. The mean age, sex, diagnosis, diplopia, surgery, anesthesia, adjustable sutures, results, reoperations and follow up time from surgery were analyzed. A good outcome was considered when the final horizontal deviation was less than 10prism diopters (pd) and the vertical deviation less than 5pd without diplopia. RESULTS: A total of 153 cases were operated on, mean age: 43.14 ±25.58years (61.4%: women). 74.5% of patients were ≥18years (33.33% ≥60). Diplopia was present in 51% of patients. The most frequent deviation was horizontal: 83.6%. The most frequent diagnosis was cranial nerve palsies: 32% (VI nerve: 12.4%), restrictive strabismus: 7.2%, and the aged related distance esotropia: 6.5%. Adjustable sutures were used in 19.7% of cases and topical anesthesia in 65.4%. Good outcomes was present in 79.2% of cases at the end of follow-up. Reoperations were needed in 25.5%. Follow-up evolution time was 11.87 months ±6.5. The sex female (P=.012) and the oblique superior surgery (P=.017) were associated with bad outcome. CONCLUSION: The adult strabismus surgery was three times more frequent than the children strabismus surgery. The third of the adults that were operated on were ≥60 years. The cranial nerve palsies were the most frequent diagnosis. Adjustable sutures were rarely used. Good outcomes were obtained in most of the patients at the end of follow-up.

Reliability and validity of two software systems used to measure the pharyngeal airway space in three-dimensional analysis.

The aim of this study was to test the reliability and validity of two software systems used to measure the pharyngeal airway space three-dimensionally. A sample of 40 cone beam computed tomography images from adult patients was taken from a database. The cone beam computed tomography images were analysed by InVivoDental and Dolphin 3D software systems by two calibrated examiners. Three nasopharynx and oropharynx prototypes were used as a reference standard to validate the software systems. The volume, minimum area and minimum area localization were the measurements tested. Measurements were compared using a paired t-test; correlated using Pearson's correlation and linear regression. Bland-Altman analysis was also used. We found significant differences in the oropharynx volume (P=0.002) and nasopharynx minimum area localization (P=0.009). The Dolphin 3D software presented higher-volume values than the ones found in the prototype, while the InVivoDental software presented lower values. Strong (r>0.7; P>0.001) or very strong (r>0.9; P>0.001) correlations were observed between the software systems. Bland-Altman analysis found good agreement between prototypes and the software systems. The measurements obtained from the Dolphin 3D and InVivoDental software systems are both reliable, strongly correlated, but should not be assumed as equal. Dolphin 3D software overestimates the nasopharynx and oropharynx volumes, while the InVivoDental software underestimates them.

Communicating branches between the median and ulnar nerves: proposal for inclusion in terminologia anatomica / Ramos comunicantes entre los nervios mediano y ulnar: propuesta de inclusión en terminologia anatomica

The ulnar and median nerves are widely distributed, innervating the muscles of the forearm and hand. In the latter, it also registers the sensitivity of a significant part of the skin. A series of communicating branches (CB) is described on the path of these nerves, including: 1) the Martin-Gruber communicating branch, 2) the Marinacci communicating branch, 3) the Riché-Cannieu communicating branch and 4) the Berrettini communicating branch. The aim of this study was to establish a correct denomination of these CB, using Latin and eliminating the use of eponyms. The exploratory study included books on anatomy and scientific articles that detailed the anatomical aspects of these CB. To these were added the terms that these branches presented in the various anatomical lists and terminologies. Each term proposal was done in Latin, using the corresponding gender, number and case. The CB between the median and ulnar nerves are described in anatomy texts as well as a plethora of publications. The prevalence rates of the CB range between 1.7 and 94 %; however, their inclusion in the anatomical terminologies has been limited. Based on the description of these branches and the presence of some of them in the existing terminologies, a proposal was prepared in line with the indications of the Federative International Programme on Anatomical Terminologies (FIPAT): 1) Ramus comunicans cum nervo ulnari, 2) Ramus comunicans cum nervo mediano, 3) Ramus communicans cum ramo profundo nervi ulnaris y 4) Ramus communicans cum nervo digitali palmari communi. Considering that terminologies are dynamic linguistic corpora, it is important to analyze constantly the incorporation of new terms that are in harmony with the scientific findings. The incorporation of new structures must follow FIPAT guidelines and include the grammatical aspects of Latin.

Los nervios ulnar y mediano presentan una amplia distribución que permite inervar músculos del antebrazo y mano, en esta última, también registran la sensibilidad de un importante territorio cutáneo. En el recorrido de estos nervios se describen una serie de ramos comunicantes (RC), entre los cuales destacan: 1) Ramo comunicante de Martin-Gruber 2) Ramo comunicante de Marinacci 3) Ramo comunicante de Riché-Cannieu y 4) Ramo comunicante de Berretini. El propósito de este trabajo fue establecer una correcta denominación de estos RC, usando para ello el latín y eliminando el uso de epónimos. El estudio exploratorio incluyó libros de anatomía y artículos científicos que detallaran los aspectos anatómicos de estos RC. A lo anterior se sumaron los términos que estos ramos presentaron en las diversas nóminas y terminologías anatómicas. Cada propuesta de denominación se realizó en latín, utilizando el género, número y caso correspondiente. Los RC entre los nervios mediano y ulnar se encuentran descritos tanto en textos de anatomía como en un sinnúmero de publicaciones. Las tasas de prevalencia de los RC fluctúan entre 1,7 y 94 %; a pesar de ello; su inclusión en las terminologías anatómicas ha sido limitado. En base a la descripción de éstos ramos y la presencia de algunos de ellos en las terminologías existentes, se elaboró una propuesta alineada con las indicaciones del Programa Federativo Internacional de Terminología Anatómica (FIPAT): 1) Ramus comunicans cum nervo ulnari, 2) Ramus comunicans cum nervo mediano, 3) Ramus communicans cum ramo profundo nervi ulnaris y 4) Ramus communicans cum nervo digitali palmari communi. Considerando que las terminologías son cuerpos lingüísticos dinámicos, resulta importante analizar constantemente la incorporación de nuevos términos que se encuentren en sintonía con los hallazgos científicos. La incorporación de nuevas estructuras debe seguir los lineamientos de FIPAT y considerar los aspectos gramaticales del latín.

Coverage and Access for Americans with Cardiovascular Disease or Risk Factors After the ACA: a Quasi-experimental Study.

BACKGROUND: Atherosclerotic cardiovascular disease (CVD) is the leading cause of death in the USA. Many with CVD or cardiovascular risk factors (CVRFs) lacked insurance coverage and access to care before enactment of the Affordable Care Act (ACA). OBJECTIVE: To assess the effect of the ACA on insurance coverage, access to care, and racial/ethnic disparities among non-elderly adults with CVD or CVRFs. DESIGN: Quasi-experimental policy intervention. PARTICIPANTS: Nationally representative, non-institutionalized sample of 1,014,450 adults aged 18 to 64 years with CVD or at least 2 established CVRFs in the pre-ACA (2012-2013) and post-ACA (2015-2016) periods. INTERVENTION: Implementation of ACA provisions on 1 January 2014. MAIN MEASURES: Insurance coverage, having a check-up, having a personal physician, and not having to forgo a needed physician visit because of cost. KEY RESULTS: Following ACA implementation, insurance coverage increased by 6.9 percentage points (95% CI, 6.6 to 7.2), not having to forgo a physician visit increased by 3.6 percentage points (CI, 3.3 to 3.9), having a check-up increased by 2.1 percentage points (CI, 1.8 to 2.6), and having a personal physician increased by 1 percentage point (0.6 to 1.3); changes were approximately doubled for those with lower incomes (< $35,000/year). Changes in coverage varied substantially by state and all outcomes improved more in Medicaid expansion states. Although racial/ethnic minorities had greater improvements in some outcomes, approximately 13% black and 29% Hispanic adults continued to lack coverage and access to care post-ACA. CONCLUSION: The ACA increased coverage and access for adults with CVD or multiple CVRFs; substantial gaps remain, particularly for minorities and those in Medicaid non-expansion states.

Plasma cytokines as potential biomarkers of kidney damage in patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus is a heterogeneous chronic inflammatory autoimmune disorder characterized by an exacerbated expression of cytokines and chemokines in different tissues and organs. Renal involvement is a significant contributor to the morbidity and mortality of systemic lupus erythematosus, and its diagnosis is based on renal biopsy, an invasive procedure with a high risk of complications. Therefore, the development of alternative, non-invasive diagnostic tests for kidney disease in patients with systemic lupus erythematosus is a priority. AIM: To evaluate the plasma levels of a panel of cytokines and chemokines using multiplex xMAP technology in a cohort of Colombian patients with active and inactive systemic lupus erythematosus, and to evaluate their potential as biomarkers of renal involvement. RESULTS: Plasma from 40 systemic lupus erythematosus non-nephritis patients and 80 lupus nephritis patients with different levels of renal involvement were analyzed for 39 cytokines using Luminex xMAP technology. Lupus nephritis patients had significantly increased plasma eotaxin, TNF-α, interleukin-17-α, interleukin-10, and interleukin-15 as compared to the systemic lupus erythematosus non-nephritis group. Macrophage-derived chemokine, growth regulated oncogene alpha, and epidermal growth factor were significantly elevated in systemic lupus erythematosus non-nephritis patients when compared to lupus nephritis individuals. Plasma eotaxin levels allowed a discrimination between systemic lupus erythematosus non-nephritis and lupus nephritis patients, for which we performed a receiver operating characteristic curve to confirm. We observed a correlation of eotaxin levels with active nephritis (Systemic Lupus Erythematosus Disease Activity Index). Our data indicate that circulating cytokines and chemokines could be considered good predictors of renal involvement in individuals with systemic lupus erythematosus.

Novel consortium of Klebsiella variicola and Lactobacillus species enhances the functional potential of fermented dairy products by increasing the availability of branched-chain amino acids and the amount of distinctive volatiles.

AIMS: Identify novel bacterial taxa that could increase the availability of branched-chain amino acids and the amount of distinctive volatiles during skim milk fermentation. METHODS AND RESULTS: We recovered 344 bacterial isolates from stool samples of healthy and breastfed infants. Five were selected based on their ability to produce branched-chain amino acids. Three strains were identified as Escherichia coli, one as Klebsiella pneumoniae and other as Klebsiella variicola by molecular and biochemical methods. HPLC and solid-phase microextraction with GC-MS were used for the determination of free amino acids and volatile compounds respectively. The consortium formed by K. variicola and four Lactobacillus species showed the highest production of Leu and Ile in skim milk fermentation. In addition, the production of volatile compounds, such as acetoin, ethanol, 2-nonanone, and acetic, hexanoic and octanoic acids, increased in comparison to commercial yogurt, Emmental and Gouda cheese. Also, distinctive volatiles, such as 2,3-butanediol, 4-methyl-2- hexanone and octanol, were identified. CONCLUSION: The use of K. variicola in combination with probiotic Lactobacillus species enhances the availability of Leu and Ile and the amount of distinctive volatiles during skim milk fermentation. SIGNIFICANCE AND IMPACT OF THE STUDY: The identified consortium increases the functional potential of fermented dairy products.

Concomitant use of direct-acting antivirals and chemotherapy in hepatitis C virus-infected patients with cancer.

BACKGROUND: Antiviral therapy improves hepatic outcomes in hepatitis C virus (HCV)-infected cancer patients. However, such patients are not treated simultaneously with antivirals and chemotherapy, owing to overlapping toxicities with previous standard of care treatment of pegylated interferon and ribavirin. AIM: To examine the safety and clinically-significant drug-drug interactions observed in patients who received simultaneous treatment with direct-acting antivirals (DAAs) and chemotherapy. METHODS: Safety was determined by the presence of adverse events which were graded according to the division of AIDS Table (version 2.0). Adverse events were monitored throughout antiviral treatment and up to 3 months after its completion. Drug-drug interactions were assessed using current online databases. Sustained virological response (SVR) was defined as absence of serum HCV RNA 12 weeks after end of DAA treatment. Cirrhosis was diagnosed via imaging, biopsy or with the use of non-invasive fibrosis markers. RESULTS: Twenty-one patients received concomitant treatment with DAAs and chemotherapy between January 2013 and September 2016. Concomitant treatment was started either for virological (14; 67%) or oncologic (7; 33%) reasons. DAAs used were sofosbuvir, ledipasvir, simeprevir, daclatasvir ± ribavirin. The adverse events observed were mainly constitutional (12; 57%), hematological and gastrointestinal (7; 33% each). Physicians changed the DAA regimens in two patients (10%) in anticipation of drug-drug interactions with daclatasvir and dexamethasone. The overall SVR rate was 95% (20/21). CONCLUSIONS: Hepatitis C virus-targeted antiviral therapy can be used concomitantly with selected anti-neoplastic agents under close monitoring for drug-drug interactions. This therapeutic intervention may prevent delay in the administration of chemotherapy in HCV-infected cancer patients.

Initial use of combination treatment does not impact survival of 106 patients with haematologic malignancies and mucormycosis: a propensity score analysis.

In view of the poor outcomes associated with mucormycosis in patients with haematologic malignancies (HM) and haematopoietic cell transplant recipients, antifungal combinations are frequently used, yet the value of such strategy remains unclear. We reviewed the records of HM patients treated for mucormycosis from 1994 to 2014. The primary outcome was 6-week mortality after treatment initiation. Of the 106 patients identified, 44% received monotherapy and 56% received combination treatment as initial therapy. Six-week mortality was associated with disseminated mucormycosis (p 0.018), active malignancy (p <0.01), higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores (p <0.001), neutropenia (p 0.049), lymphopenia (p 0.0003) and intensive care unit (ICU) admission at diagnosis (p 0.0001). Survivors were more likely to have localized mucormycosis (p <0.01) and to receive hyperbaric oxygen therapy (p 0.02). There were no differences in mortality between monotherapy and combination treatment groups (43% vs. 41%; p 0.85). In multivariate analysis, lymphopenia (odds ratio (OR), 5.5; 95% confidence interval (CI), 1.9-15.9; p 0.002) and ICU admission at diagnosis (OR, 8.2; 95% CI, 2.3-29.2; p 0.001) were associated with increased mortality. Localized mucormycosis was associated with better outcome (OR, 0.06; 95% CI, 0.01-0.6; p 0.019). Initial combination treatment had no impact on mortality, even after propensity score adjustment (OR, 0.8; 95% CI, 0.3-2.4; p 0.69). A weighted mortality risk score was then calculated for each patient based on the factors independently associated with mortality and baseline APACHE II score. In the low-risk group (n = 49), 13% of monotherapy versus 15% of combination therapy patients died within 6 weeks (p >0.99). In the high-risk group (n = 57), 71% of monotherapy versus 61% of combination therapy patients died within 6 weeks (p 0.42). With the current status of mucormycosis diagnosis, there was no difference in mortality in HM patients, whether they received monotherapy or combination treatment as initial therapy. Earlier diagnosis and immune reconstitution are unmet needs to affect outcomes.

Previous Exposure to Anesthesia and Autism Spectrum Disorder (ASD): A Puerto Rican Population-Based Sibling Cohort Study.

BACKGROUND: Autism Spectrum Disorder (ASD) is characterized by impaired social interaction and communication, and by restricted and repetitive behavior, that begins usually before a child is three years old.(1) Researchers have shown that prevalence rates in the U.S. may be as high as 1 in 68.(52) A number of studies have examined the effects of early exposure to anesthesia on brain development and subsequent impairment in neurocognitive function; yet, little is known about the possible effects of anesthetic agents on social-behavioral functioning. The association between exposure to anesthesia either in uterus, during the first years of life, or later and development of Autistic Spectrum Disorder (ASD) or its severity was determined in a retrospective population based cohort study. OBJECTIVES: Identify if children who had previous exposure to anesthesia either in uterus, first years of life during their developing brain years, or later, are at risk of developing ASD and its severe form of the disease. METHODS: Data was obtained from structured interviews administered to a sample of 515 parents/guardians distributed in two groups: ASD = 262 children diagnosed with this condition and Non-ASD: 253 children (siblings of ASD group) without diagnosis (95% confidence interval) that freely decided to participate and agreed to a consent form. Variables studied include: demographics, diagnosis and severity of ASD, exposure to anesthesia, method of childbirth, and age of exposure Children less than 2 years of age were considered into have developing brain period. Data was analyzed using Chi-square or Fisher exact test. RESULTS: In contrast to non-ASD group, most of the children within ASD group were male, 76% (p=0.0001). With regards to methods of childbirth, 64% of the ASD population were vaginal delivery (VD; Non-anesthesia exposure group) and 36% cesarean delivery (CD) compared to non-autistic population with 71% VD and 29% CD, which demonstrates no statistical difference between both groups (p=0.1113). Out of the 36% of ASD population that underwent CD, 7% were performed using general anesthesia and 93% regional anesthesia, while the 29% of the CD of non-ASD, 5% were performed using general anesthesia and 95% regional anesthesia. This reveals no statistical significance (p=0.7569) with the development of ASD and the type of anesthesia used when comparing ASD with non-ASD patients. In view of severity of autism, in VD, 56% of ASD population had mild form of the disorder, 34% moderate, and 10% severe; while CD had a 54% mild form of the disorder, 33% moderate, and 13% severe. This shows no statistical association (p=0.8069) when comparing exposure to anesthesia in uterus to subsequent severe form of ASD. Of the 262 ASD patients, 99 had exposure to anesthetics before their diagnosis, while in Non-ASD population, 110 had exposure to anesthesia, demonstrating no statistically significant association between both groups (p=0.2091). Out of 99 ASD patients exposed to anesthesia prior to their diagnosis, 72 were exposed before age 2. When compared to the 110 Non-ASD patients exposed to anesthesia, 86 had exposure during this developing brain period, which indicates no statistically significant association (p=0.4207). In addition, most of the ASD children exposed to anesthesia during developing brain were diagnosed with mild degree of the disorder when compared to ASD children without any previous exposure to anesthesia (p=0.9700) during the same period. When the exposure occurred after age 2, ASD children developed mild form of the disorder as compared with ASD children without any previous exposure to anesthesia (p=0.1699) in that period. CONCLUSIONS: Children under early exposure to anesthesia in uterus, first 2 years of life, or later are not more likely to develop neither ASD nor severe form of the disorder.

Caspase-8 polymorphisms result in reduced Alemtuzumab-induced T-cell apoptosis and worse survival after transplantation.

Allo-SCT using unrelated donors is a curative treatment for patients with hematological disorders. The best donor is one matched for 10/10 HLA alleles, however studies have shown an additional survival benefit when considering other genetic factors. It has been shown that a six-nucleotide insertion/deletion polymorphism in the CASP8 gene promoter results in reduced susceptibility of T lymphocytes to undergo apoptosis. In 186 SCT recipients, we found a significantly better OS in those who received a transplant from a WT/WT donor compared with donors with a deletion (3 years: 52 vs 34%; P=0.03; multivariate analysis; RR 0.61; 95% CI 0.38-0.98, P=0.04). This was more marked when both the patient and the donor had a deletion (3 years OS: 62% compared with 36%, P=0.01). As the majority of these patients received Alemtuzumab during conditioning, we went on to analyze the in vitro effect of the polymorphism on Alemtuzumab-induced apoptosis. We showed statistically significantly higher percentages of apoptotic naïve CD4 (P<0.0005) and CD8 (P<0.0005) T cells in WT/WT donors in comparison with donors with a deletion. These data imply an unrecognized role for the CASP8 promoter polymorphism on survival following unrelated SCT particularly in the context of T-cell depletion with Alemtuzumab.