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BACKGROUND: The Bayley scales are a widely reported tool for the evaluation of development in the first years of life. Studies comparing the second edition (BSID-II) and the third (B-III) report higher than expected scores using B-III, others assume that the BSID-II places higher demands on various populations. There are no reports in the Spanish-speaking population. OBJECTIVE: Compare scores and classification of both versions in children with a history of perinatal risk. MATERIALS AND METHODS: Descriptive cross-sectional study in 671 children from 0 to 42 months, with a history of perinatal risk. The BSID-II and B-III scales were used. Each participant was evaluated in a single session. Average scores of the B-III Cognitive Language Composite (CLC) for comparison with Mental Development Index (MDI). RESULTS: The mean CLC (B-III) was 14.04 points higher than the MDI, and Motor Composite (MC) (B-III) 17.87 points higher than the Psychomotor Developmental Index (PDI). Linear regressions to estimate MDI from B-III showed values of r2 = 0.55 and by age range with r2 from 0.52 to 0.84 and for PDI with r2 of 0.58 overall, and for the 7 ranges with r2 between 0.51 to 0.75. CONCLUSIONS: With the BSID-II, a greater presence of alterations is observed in both subscales. The BSID-II underestimates the child's development compared to the B-III. [ABSTRACT FROM AUTHOR]

This paper reflects on the urgency of adopting a more complex notion of the nature of scientific knowledge, and how it is constructed, that shifts its emphasis from the assumptions of objectivity, neutrality, and universality to an interpretation that conceives it as a socially-configured, partial, uncertain, and complex phenomenon. A more complex and questioning analysis of science will broaden the possibilities of allowing citizens greater participation in the production and communication of science and establishing a dialogue of knowledge that recognizes the validity of other epistemologies as alternatives to scientific knowledge. A science that is willing to listen more attentively with humility and respect can learn to live with uncertainty and to design strategies that allow it to face its risks and modify its course. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to discuss and highlight intercultural inductive methodologies with the aim of giving voice to lead actors in the social transformation processes. In this way, non-conventional methods such as childrenauthored photography, photovoice and living maps are some alternatives to decolonize traditional pedagogies in order to reach a cross-comprehension and to foster dialogue. The paper is largely based on two projects that come "from below", from the actors themselves, in close collaboration between indigenous educators, children and academics. We discuss how these projects have turned to such methodologies and analyze their possible value, not only as a research strategy but also as a useful tool for fostering new educational practices in order to make visible other ways of understanding the world. [ABSTRACT FROM AUTHOR]

BACKGROUND: Homemade fractions of metformin tablets to adjust paediatric doses are difficult to administer, unstable and yields variable doses. In this work, a liquid extemporaneous formulation of metformin, sweetened with 1% sucralose, is proposed. PURPOSE: To determine the pharmacokinetics of the new formulation compared to the fractionated tablet in healthy adult volunteers and to demonstrate that it remains unaltered. METHODS: Randomised, crossed and longitudinal clinical trial, in 12 healthy adult volunteers, 7 males and 5 females (n=12), 24.3 ± 1.8 years, with BMI = 24.9 ± 2.5. Eight blood samples were obtained in Whatman 903® cards at 0, 0.25, 0.5, 1, 2, 4, 8 and 12 hours after administration of 250 mg metformin. Extraction was made by direct precipitation with acetonitrile (ACN) and methanol. Detection was car- ried out by UPLC and tandem mass spectrometry. Mobile phase: 5 mM ammonium acetate and ACN (80:20; v/v), 0.25 mL/min, isocratically. Pharmacokinetics was determined using WinNonlin Pro 3.1 software and analysed by one-way ANOVA (p ≤ 0.05). RESULTS: The method was accurate, precise, selective and linear from 50 to 1000 ng/mL (r=0.9982). Samples were stable at 4°C for 17 hours and for 2 months at -80°C. The metformin formulation had a Cmax of 652 ng/mL and 550 ng/mL in the tablet. Tmax and ke were lower with the formulation (1.6 h vs. 1.8 h and 0.32 h-1 vs. 0.29 h-1). The AUC0-12 was virtually the same in both forms (F%=1.01). CONCLUSIONS: The liquid formulation of metformin showed similar pharmacokinetics to the split tablet, but it additionally allows a more precise dose adjustment, ease of administration and uniformity of content. [ABSTRACT FROM AUTHOR]

Background:Collagen-covered prostheses can be used as a non-circumferential segmental tracheal replacement. However, the applicability of these implants in young subjects has not yet been reported.Methods:In this experimental, longitudinal study, dogs aged 29–32 days underwent limited segmental tracheal replacement with a polyester prosthesis or were allocated to a control, untreated group. The dogs were evaluated clinically, endoscopically and tomographically for up to one year.Results:Although there was evidence of tracheal growth in the experimental group, tomographic measurements were significantly smaller in this group than in the control group throughout the observation period. At the end of the study, there was no evidence of implant rejection, stenosis or collapse. Normal respiratory epithelium had grown across the implanted membrane in the experimental group.Conclusion:The homologous collagen mersylene membrane allowed for limited structural tracheal growth and was functionally integrated into the segmented tracheal wall in growing dogs. [ABSTRACT FROM PUBLISHER]

As part of the development of a new series of antibacterial agents derived from coupling a β-lactamic precursor with a fluoroquinolone and named cephalones, the pharmacokinetics of one derivate: CQ-M-EPCA in rats after intravenous, intragastric and intraduodenal routes, was carried out. After the IV injection of 20 mg/kg or 40 mg/kg of this cephalone, plasma concentrations at the time zero (Cp0) were 3.1 and 11.26 μg/ml, respectively. Plasma concentrations decreased rapidly to almost disappear in both instances. Forty-five minutes later, a surge in concentrations, in the 40 mg/kg group, with a maximal plasma concentration (Cpmax) of 2.97 μg/ml was observed. An elimination half-life (T(1/2)el) of 2.36 ± 0.33 h. was calculated. The drug was undetected by the ninth hour. Intragastric administration of the drug resulted in Cpmax of 3.78 ± 0.26 μg/ml with a time to reach Cpmax (Tmax) of 25 min and T(1/2)el = 3.22 h. Same variables after intraduodenal administration were Cpmax 4.71 μg/ml; Tmax 1 h, and T(1/2)el 3.41 h. Outstandingly high bioavailabilities after intragastric and intraduodenal administration (169 and 246%, respectively), together with the shape of the concentration versus time profiles after IV administration suggest that the drug undergoes a complex redistribution phenomenon, while showing high tissue diffusion with an apparent volume of distribution of 3.33 l/kg. [Copyright &y& Elsevier]

Objective To determine the influence of radiotherapy on the outcome of artificial urinary sphincter implantation. Patients and methods A series of 72 men who had an artificial urinary sphincter inserted were reviewed retrospectively, analysing in detail the information from 15 patients with a past history of pelvic radiotherapy. Results In those who had undergone radiotherapy, the complication rate was higher, both for re‐operation (eight of 15) and infection (three); 11 of the 15 patients were continent after surgery, compared with 51 (89%) of the 57 in the unirradiated group. Conclusions An artificial sphincter can be inserted after pelvic radiotherapy reasonably successfully, but at the cost of a high complication and re‐operation rate. Patients with a previous history of radiotherapy should be informed of the higher risk of surgical revision associated with insertion of the prosthesis. [ABSTRACT FROM AUTHOR]

BACKGROUND: The evaluation and diagnosis of Autism Spectrum Disorder (ASD) has changed over the years. Complementing the diagnosis with the difficulties in the regulatory processes provides more information about the specific profile of each patient. OBJECTIVE: Establish criteria for the diagnosis of Regulatory Alterations in preschoolers with ASD and developmental delay using the Regulation and Socio-Emotional Scale (ERSE). METHODOLOGY: The ERSE was applied to 229 children aged 36 to 72 months, belonging to three groups: Normal Development, Developmental Delay without ASD and ASD. The scores, frequencies of alterations and the distribution of expected responses by indicators were compared. RESULTS AND DISCUSSION: Only the ERSE cognitive regulation scores showed differences between the ASD and Delay group and the Normal Development group. While in the type of regulation categories differences are observed between the three groups, the differences were more evident when the proportions of responses indicative of adequate regulation were compared, those indicative of hyporreactivity and hyperreactivity were greater in the Delay without Tea and much greater in ASD, with the profiles of altered emotional and cognitive regulation being more extreme in children with ASD. Combining overall scores with response type proportions offers greater diagnostic sensitivity and characterization possibilities. CONCLUSIONS: The results obtained suggest the importance of considering regulatory patterns as part of the diagnostic characterization of ASD. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the gut microbiota composition in children with autism spectrum disorder (ASD) compared to neurotypical (NT) children, with a focus on identifying potential differences in gut bacteria between these groups. The microbiota was analyzed through the massive sequencing of region V3–V4 of the 16S RNA gene, utilizing DNA extracted from stool samples of participants. Our findings revealed no significant differences in the dominant bacterial phyla (Firmicutes, Bacteroidota, Actinobacteria, Proteobacteria, Verrucomicrobiota) between the ASD and NT groups. However, at the genus level, notable disparities were observed in the abundance of Blautia, Prevotella, Clostridium XI, and Clostridium XVIII, all of which have been previously associated with ASD. Furthermore, a sex-based analysis unveiled additional discrepancies in gut microbiota composition. Specifically, three genera (Megamonas, Oscilibacter, Acidaminococcus) exhibited variations between male and female groups in both ASD and NT cohorts. Particularly noteworthy was the exclusive presence of Megamonas in females with ASD. Analysis of predicted metabolic pathways suggested an enrichment of pathways related to amine and polyamine degradation, as well as amino acid degradation in the ASD group. Conversely, pathways implicated in carbohydrate biosynthesis, degradation, and fermentation were found to be underrepresented. Despite the limitations of our study, including a relatively small sample size (30 ASD and 31 NT children) and the utilization of predicted metabolic pathways derived from 16S RNA gene analysis rather than metagenome sequencing, our findings contribute to the growing body of evidence suggesting a potential association between gut microbiota composition and ASD. Future research endeavors should focus on validating these findings with larger sample sizes and exploring the functional significance of these microbial differences in ASD. Additionally, there is a critical need for further investigations to elucidate sex differences in gut microbiota composition and their potential implications for ASD pathology and treatment. [ABSTRACT FROM AUTHOR]

The article discusses the highlights of the sixth Coloquio International de Narrativa Fantástica that was held in Lima, Peru from October 24-26, 2013 whose team was "Writings of the New World: The Fantastic and Narratives of the Future."

Mexico City (MC) young residents are exposed to high levels of fine particulate matter (PM 2.5 ), have high frontal concentrations of combustion-derived nanoparticles (CDNPs), accumulation of hyperphosphorylated aggregated α -synuclein ( α -Syn) and early Parkinson's disease (PD). Swallowed CDNPs have easy access to epithelium and submucosa, damaging gastrointestinal (GI) barrier integrity and accessing the enteric nervous system (ENS). This study is focused on the ENS, vagus nerves and GI barrier in young MC v clean air controls. Electron microscopy of epithelial, endothelial and neural cells and immunoreactivity of stomach and vagus to phosphorylated ɑ-synuclein Ser129 and Hyperphosphorylated-Tau (Htau) were evaluated and CDNPs measured in ENS. CDNPs were abundant in erythrocytes, unmyelinated submucosal, perivascular and intramuscular nerve fibers, ganglionic neurons and vagus nerves and associated with organelle pathology. ɑSyn and Htau were present in 25/27 MC gastric,15/26 vagus and 18/27 gastric and 2/26 vagus samples respectively. We strongly suggest CDNPs are penetrating and damaging the GI barrier and reaching preganglionic parasympathetic fibers and the vagus nerve. This work highlights the potential role of CDNPs in the neuroenteric hyperphosphorylated ɑ-Syn and tau pathology as seen in Parkinson and Alzheimer's diseases. Highly oxidative, ubiquitous CDNPs constitute a biologically plausible path into Parkinson's and Alzheimer's pathogenesis. [ABSTRACT FROM AUTHOR]

Background Delayed central conduction times in the auditory brainstem have been observed in Mexico City (MC) healthy children exposed to fine particulate matter (PM 2.5 ) and ozone (O 3 ) above the current United States Environmental Protection Agency (US-EPA) standards. MC children have α synuclein brainstem accumulation and medial superior olivary complex (MSO) dysmorphology. The present study used a dog model to investigate the potential effects of air pollution on the function and morphology of the auditory brainstem. Methodology Twenty-four dogs living in clean air v MC, average age 37.1 ± 26.3 months, underwent brainstem auditory evoked potential (BAEP) measurements. Eight dogs (4 MC, 4 Controls) were analysed for auditory brainstem morphology and histopathology. Results MC dogs showed ventral cochlear nuclei hypotrophy and MSO dysmorphology with a significant decrease in cell body size, decreased neuronal packing density with regions in the nucleus devoid of neurons and marked gliosis. MC dogs showed significant delayed BAEP absolute wave I, III and V latencies compared to controls. Conclusions MC dogs show auditory nuclei dysmorphology and BAEPs consistent with an alteration of the generator sites of the auditory brainstem response waveform. This study puts forward the usefulness of BAEPs to study auditory brainstem neurodegenerative changes associated with air pollution in dogs. Recognition of the role of non-invasive BAEPs in urban dogs is warranted to elucidate novel neurodegenerative pathways link to air pollution and a promising early diagnostic strategy for Alzheimer's Disease. [ABSTRACT FROM AUTHOR]

Phytochemicals (Pch) present in fruits, vegetables and other foods, are known to inhibit or induce drug metabolism and transport. An exhaustive search was performed in five databases covering from 2000 to 2021. Twenty-one compounds from plants were found to modulate CYP3A and/or P-gp activities and modified the pharmacokinetics and the therapeutic effect of 27 different drugs. Flavonols, flavanones, flavones, stilbenes, diferuloylmethanes, tannins, protoalkaloids, flavans, hyperforin and terpenes, reduce plasma concentration of cyclosporine, simvastatin, celiprolol, midazolam, saquinavir, buspirone, everolimus, nadolol, tamoxifen, alprazolam, verapamil, quazepam, digoxin, fexofenadine, theophylline, indinavir, clopidogrel. Anthocyanins, flavonols, flavones, flavanones, flavonoid glycosides, stilbenes, diferuloylmethanes, catechin, hyperforin, alkaloids, terpenes, tannins and protoalkaloids increase of plasma concentration of buspirone, losartan, diltiazem, felodipine, midazolam, cyclosporine, triazolam, verapamil, carbamazepine, diltiazem, aripiprazole, tamoxifen, doxorubicin, paclitaxel, nicardipine. Interactions between Pchs and drugs affect the gene expression and enzymatic activity of CYP3A and P-gp transporter, which has an impact on their bioavailability; such that co-administration of drugs with food, beverages and food supplements can cause a subtherapeutic effect or overdose. Therefore, it is important for the clinician to consider these interactions to obtain a better therapeutic effect. [ABSTRACT FROM AUTHOR]

Residency in cities with high air pollution is associated with neuroinflammation and neurodegeneration in healthy children, young adults, and dogs. Nonsteroidal anti-inflammatory drugs may offer neuroprotection. The authors measured the plasma concentrations of 3-nitrotyrosine and the cerebro-spinal-fluid concentrations of prostaglandin E2 metabolite and the oligomeric form of amyloid derived diffusible ligand; measured the mRNA expression of cyclooxygenase-2, interleukin 1β, CD14, and Aquaporin-4 in target brain areas; and evaluated brain MRI, cognition, and neuropathology in 8 dogs treated with a preferential cyclooxygenase-2 inhibitor (Nimesulide®) versus 7 untreated litter-matched Mexico City dogs. Nimesulide® significantly decreased nitrotyrosine in plasma (p < .0001), frontal gray IL1β (p = .03), and heart IL1β (p = .02). No effect was seen in mRNA COX2, amyloid, and PGE2 in CSF or the MRI white matter lesions. All exposed dogs exhibited olfactory bulb and frontal accumulation of Aβ42 in neurons and blood vessels and frontal vascular subcortical pathology. White matter hyperintense MRI frontal lesions were seen in 4/6 non-treated and 6/8 treated dogs. Nonsteroidal anti-inflammatory drugs may offer limited neuroprotection in the setting of severe air pollution exposures. The search for potentially beneficial drugs useful to ameliorate the brain effects of pollution represents an enormous clinical challenge. [ABSTRACT FROM PUBLISHER]

The route followed by drug after its administration is known as LADME. Such route refers to liberation, absorption, distribution, metabolism and excretion. It is important to know each part of the process because it has a close relation with efficacy and toxicity of drugs. According with the route of administration used and the pharmaceutical presentation selected by the clinician, the drugs can reach and maintain their therapeutic purposes, which are defined by LADME. Minimal studies on LADME have been done in children, although recently they have increased. The purpose of this paper is to analyze the LADME route followed by drugs in children. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To analyse the influence of age at diagnosis on tumour characteristics and cancer-specific survival in renal cell carcinoma (RCC). Methods: Data on age, tumour characteristics, and survival for 4774 patients from 12 European RCC databases were recorded. Patients were divided into four groups according to age at diagnosis: ≤40, >40 and <60, ≥60 and <80, and ≥80 yr. The following variables were analysed: TNM stage, Fuhrman grade, tumour size, symptoms at diagnosis, ECOG performance status (PS), and cancer-specific survival. The groups were compared for usual clinical and pathologic variables, and cancer-specific survival. Results: The four groups accounted for 288 (6%), 1839 (38.5%), 2499 (52.3%), and 148 cases (3.2%), respectively. Differences were found among groups for tumour stage, symptoms at diagnosis, ECOG PS, Fuhrman grade (p <0.001), tumour size, M stage, and histologic subtype (p: 0.02). Patients ≤40 yr were more likely to have papillary or chromophobe RCCs and less likely to have clear-cell RCCs. No significant difference was found among groups for N stage (p: 0.15). The 5-yr cancer-specific survival rates for the four age categories were 85%, 74%, 70%, and 69%, respectively. In multivariate analysis age category remained an independent prognostic parameter (p <0.001). Conclusions: Renal tumours diagnosed in younger age are characterized by lower tumour stages and grades as well as favourable histologic patterns compared with tumours in older patients. Basic research is required for explaining such a relationship between age, tumour aggressiveness, and therefore tumour biology. [Copyright &y& Elsevier]

Abstract: Rupture of posterior urethra is usually seen in major traumas with associated pelvic fractures. Clinical presentation classically associates blood at the uretral meatus and urinary retention. Urinary diversion should be achieved by suprapubic puncture and major associated traumatic injuries (abdominal, orthopaedic, and neurological lesions) must be treated prior to urological management. Retrograde uretrocystography is performed a few days later in order to localize and classify the urethral lesion. Treatment of posterior urethral ruptures has evolved over the years. Immediate open repair is no longer recommended. The supra-pubic catheter can be left in place until Resorption of the pelvic hematoma. Obliteration occurs in 100% of the cases and is treated by open surgery at 3 months. More and more patients are treated by early endoscopic realignment which has diminished by half the incidence of urethral strictures. Impotence and incontinence secondary to trauma or surgery occur in 20% and 10% of the patients respectively. Long term follow-up should be achieved in every patient. [Copyright &y& Elsevier]

The present study was undertaken to determine if differences exist in the pharmacokinetic parameters of oral ranitidine caused by gender and stage of the menstrual cycle. The study was performed in two steps, in the first a pharmacokinetic study was performed on 10 men (average age 35.5 yrs) and 10 women (average age 34.7 yrs) during the follicular phase, and in the second the pharmacokinetic study was performed only on the same women in their luteal phase. Subjects received a tablet dose of 300 mg ranitidine, and blood samples were drawn at several times after its ingestion. Plasma ranitidine concentration was determined by high performance liquid chromatography. Comparison of the pharmacokinetic parameters of women and men revealed statistically significant differences both in distribution volume (Vd) with values of 2.0 and 6.3 l/kg, Area Under Curve (AUC) with values of 7312.15 and 11471.94 ng/ml/h, and clearance (CLt) with values of 0.65 and 0.59 l/kg/h, respectively. Several pharmacokinetic parameters in women were different in the follicular compared to the luteal phase; for example, Vd was 2.0 and 5.6 l/kg, AUC was 7312.15 and 5195.83 ng/ml/h, and CLt was 0.65 and 0.97 l/kg/h, in the respective phases. Moreover, the maximum concentration (Cmax) was 1086 ng/ml in the follicular vs. 864 ng/ml in the luteal phase. The first study detected differences between men and women in several pharmacokinetic parameters, mainly those indicative of drug availability, for example, Vd, AUC, and CLt. Comparison of data obtained in the follicular phase with those obtained in the luteal phase revealed differences in most pharmacokinetic parameters, which is seemingly indicative of the characteristic physiological changes associated with the luteal phase that largely affect the kinetics and availability of drugs such as ranitidine. Although it has been postulated that hormonal fluctuation within the menstrual cycle phase is the primary cause of documented gender differences... [ABSTRACT FROM AUTHOR]

BACKGROUND: Autism Spectrum Disorder (ASD) affects a significant number of individuals worldwide. Recently, there has been a growing interest in the role of the gut microbiome in its etiology and clinical manifestations. It has been observed that the interaction between the microbiota and the gut-brain axis may play a crucial role in the development and expression of ASD. OBJECTIVE: To evaluate the presence of gut dysbiosis in children with ASD. MATERIALS AND METHODS: Thirty children diagnosed with ASD and 31 neurotypical (NT) children were recruited and evaluated. Fecal samples were obtained for analysis by massive sequencing of the 16S rRNA gene. Taxonomic analysis was performed with Mothur and Stamp, and functional analysis with PICRUSt2. RESULTS AND DISCUSSION: The predominant bacterial phyla in both groups were Firmicutes and Bacteroidota, with no significant differences between them. At the genus level, significant differences were found in the relative abundance of Blautia, Prevotella, Clostridium_XI and Clostridium_XVIII. A decrease in the abundance of the genus Blautia was observed in children with ASD; this genus has intestinal antiinflammatory properties. On the other hand, the increased abundance of Prevotella and Clostridium in children with ASD could contribute to intestinal inflammation and the release of proinflammatory cytokines. Differences in the composition of the microbiota were identified between males and females in both groups, being relevant the presence of Megamonas exclusively in females with ASD, a propionic acid producing genus related to behavioral changes and neuroinflammation. Functional analysis revealed alterations in the metabolism of short-chain fatty acids, polyamines and carbohydrate fermentation, crucial processes in the regulation of the gut-brain axis and previously associated with ASD. CONCLUSIONS: This study presents evidence of gut dysbiosis and alterations in microbiome metabolism in Mexican children with ASD, with significant implications for understanding and addressing this disorder. In addition, it highlights the importance of considering sex differences in gut microbiota when investigating ASD. [ABSTRACT FROM AUTHOR]

Dexmedetomidine is an imidazole derivative, with high affinity for α2 adrenergic receptors, used for sedation, analgesia and adjuvant anaesthesia. In this study, an analytical method for the quantification of dexmedetomidine in dried blood spots was developed, validated and applied. The drug was extracted from dried blood spot by liquid extraction; the separation was carried out by ultra high-resolution liquid chromatography in reverse phase coupled to tandem mass spectrometry method. An X Select cyano 5 μm HSS column (2.1 X 150 mm, Waters) and a mobile phase composed of 0.1% formic acid: acetonitrile [50:50 v/v], were used. The test was linear over the concentration range of 50 to 2000 pg/mL. The coefficients of variation for the intra and interday trials were less than 15%. The drug was stable under the conditions tested. The method was successfully applied for the quantification of 6 patients, aged 0 to 2 years, with classification ASA I, who underwent ambulatory surgeries, receiving a dose of 1 μg/Kg dexmedetomidine IV. The drug concentrations in the different sampling times were in the range of 76 to 868 pg/mL. [ABSTRACT FROM AUTHOR]

Millions of urban children are chronically exposed to high concentrations of air pollutants, i.e., fine particulate matter (PM 2.5 ) and ozone, associated with increased risk for Alzheimer's disease. Compared with children living with clear air those in Mexico City (MC) exhibit systemic, brain and intrathecal inflammation, low CSF Aβ 42, breakdown of the BBB, attention and short-term memory deficits, prefrontal white matter hyperintensities, damage to epithelial and endothelial barriers, tight junction and neural autoantibodies, and Alzheimer and Parkinson's hallmarks. The prefrontal white matter is a target of air pollution. We examined by light and electron microscopy the prefrontal white matter of MC dogs ( n : 15, age 3.17±0.74 years), children and teens ( n : 34, age: 12.64±4.2 years) versus controls. Major findings in MC residents included leaking capillaries and small arterioles with extravascular lipids and erythrocytes, lipofuscin in pericytes, smooth muscle and endothelial cells (EC), thickening of cerebrovascular basement membranes with small deposits of amyloid, patchy absence of the perivascular glial sheet, enlarged Virchow–Robin spaces and nanosize particles (20–48 nm) in EC, basement membranes, axons and dendrites. Tight junctions, a key component of the neurovascular unit (NVU) were abnormal in MC versus control dogs ( χ 2 <0.0001), and white matter perivascular damage was significantly worse in MC dogs ( p =0.002). The integrity of the NVU, an interactive network of vascular, glial and neuronal cells is compromised in MC young residents. Characterizing the early NVU damage and identifying biomarkers of neurovascular dysfunction may provide a fresh insight into Alzheimer pathogenesis and open opportunities for pediatric neuroprotection. [ABSTRACT FROM AUTHOR]

The article presents information on services offered by the National Institute of Pediatrics that helps ensure the safe and effective use of drugs at this institution. Therapeutic drug monitoring is one of the main activities of the pharmacology laboratory, which allows physicians to define the optimal treatment based on the selected therapeutic agents. Determining a patient's serum drug concentration allows physicians to use pharmacokinetic values to individualize drug dosages. Another service offered by the institute is drug information service. A clinical pharmacologist directs the drug information service, which supplies objective, specific, and current drug information and promotes rational drug use. The service may provide information on the treatment of poisonings caused by agents such as drugs, chemical substances, plants, venomous animals, and environmental pollutants.

Mexico City Metropolitan Area children and young adults exposed to high concentrations of air pollutants including fine and ultrafine particulate matter (PM) vs. clean air controls, exhibit myocardial inflammation and inflammasome activation with a differential right and left ventricular expression of key inflammatory genes and inflammasomes. We investigated the mRNA expression levels of the prion protein gene PRNP, which plays an important role in the protection against oxidative stress and metal toxicity, and the glucose regulated protein 78, a key protein in endoplasmic reticulum (ER) stress signaling, in ventricular autopsy samples from 30 children and young adults age 19.97 ± 6.8 years with a lifetime of low (n:4) vs. high (n:26) air pollution exposures. Light microscopy and transmission electron microscopy studies were carried out in human ventricles, and electron microscopy studies were also done in 5 young, highly exposed Mexico City dogs. There was significant left ventricular PRNP and bi-ventricular GRP78 mRNA up-regulation in Mexico City young urbanites vs. controls. PRNP up-regulation in the left ventricle was significantly different from the right, p < 0.0001, and there was a strong left ventricular PRNP and GRP78 correlation (p = 0.0005). Marked abnormalities in capillary endothelial cells, numerous nanosized particles in myocardial ER and in abnormal mitochondria characterized the highly exposed ventricles. Early and sustained cardiac ER stress could result in detrimental irreversible consequences in urban children, and while highly complex systems maintain myocardial homeostasis, failure to compensate for chronic myocardial inflammation, oxidative and ER stress, and particles damaging myocardial organelles may prime the development of pathophysiological cardiovascular states in young urbanites. Nanosized PM could play a key cardiac myocyte toxicity role. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Do mild analgesics affect the endocrine system of the human adult testis? SUMMARY ANSWER Mild analgesics induce multiple endocrine disturbances in the human adult testis in vitro. WHAT IS KNOWN ALREADY Mild analgesics have recently been incriminated as potential endocrine disruptors. Studies of the effects of these widely used molecules on the androgenic status of men are limited and somewhat contradictory. This prompted us to investigate whether these compounds could alter the adult human testicular function. We therefore assessed in parallel the effects of paracetamol, aspirin and indomethacin on organo-cultured adult human testis and on the NCI-H295R steroid-producing human cell line. STUDY DESIGN, SIZE, DURATION Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with 10−4 or 10−5 M paracetamol, aspirin or indomethacin for 24–48 h. The effect of 10−5 M ketoconazole, used as an anti-androgenic reference molecule, was also assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS Testes were obtained from prostate cancer patients, who had not received any hormone therapy. The protocol was approved by the local ethics committee of Rennes, France and informed consent was given by the donors. Only testes displaying spermatogenesis, as assessed by transillumination, were used in this study. Hormone levels in the culture media were determined by radioimmunoassay (testosterone, insulin-like factor 3), Enzyme-Linked Immunosorbent Assay (inhibin B) or Enzyme Immunosorbent Assay [prostaglandin (PG) D2, and PGE2]. Tissues were observed and cells counted using classical immunohistochemical methods. MAIN RESULTS AND THE ROLE OF CHANCE The three mild analgesics caused multiple endocrine disturbances in the adult human testis. This was particularly apparent in the interstitial compartment. Effective doses were in the same range as those measured in blood plasma following standard analgesic treatment. The production of testosterone and insulin-like factor 3 by Leydig cells was altered by exposure to all these drugs. Inhibin B production by Sertoli cells was marginally affected by aspirin only. Our experiments also revealed that mild analgesics display direct anti-PG activity, which varied depending on the drug used, the dose and the duration of exposure. Nevertheless, associations between the alteration of the PG and testosterone profiles were not systematically observed, suggesting that a combination of mechanisms of endocrine disruption is at play. LIMITATIONS, REASONS FOR CAUTION Our studies were performed in vitro. WIDER IMPLICATIONS OF THE FINDINGS We provide the first evidence that direct exposure to mild analgesics can result in multiple endocrine disturbances in the human adult testis. Caution, concerning the consumption of mild analgesics by men, should be strengthened, particularly in high-risk population subgroups such as elite athletes. STUDY FUNDING/COMPETING INTEREST(S) This work was funded by Inserm (Institut national de la santé et de la recherche médicale), EHESP (Ecole des Hautes Etudes en Santé Publique), Ministère de l'Enseignement Supérieur et de la Recherche, Région Bretagne and Agence Nationale de sécurité du médicament et des produits de santé (IMPACTESTIS, Project no. AAP-2012-037). The authors declare they have no competing interests, be it financial, personal or professional. [ABSTRACT FROM AUTHOR]

BACKGROUND Phthalic acid esters are widely used in the manufacture of plastics. Numerous studies have shown that these phthalates impair testicular testosterone production in the rat. However, the scarce and contradictory data concerning humans have cast doubt over whether these compounds are also anti-androgenic in man. We therefore investigated the direct effects of di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) on organo-cultured adult human testis and a human cell line. METHODS Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with DEHP or MEHP. The effects of ketoconazole, used as a reference molecule, were also assessed. RESULTS In both models, DEHP and MEHP significantly inhibited testosterone production. The effects of both phthalates appeared to be specific for steroidogenesis, as INSL3 production by Leydig cells was not altered. Furthermore, the phthalates of interest had no effect on inhibin B production by Sertoli cells or on germ cell apoptosis. As only a small fraction of the phthalates added was found in the testis explants, and as these compounds were found to be metabolized, we estimate that the anti-androgenic effects observed occurred at concentrations of phthalates that are of the same order of magnitude as exposures reported in the literature for men. CONCLUSIONS We provide the first evidence that DEHP and MEHP can inhibit testosterone production in the adult human testis. This is consistent with recent epidemiological findings of an inverse correlation between exposure to MEHP and testosterone concentrations. [ABSTRACT FROM PUBLISHER]

Abstract: In this study, we propose to evaluate the potential of Raman spectroscopy (RS) to assess renal tumours at surgery. Different classes of Raman renal spectra acquired during a clinical protocol are discriminated using support vector machines classifiers. The influence on the classification scores of various preprocessing steps generally involved in RS are also investigated and evaluated in the particular context of renal tumour characterization. Encouraging results show the interest of RS to evaluate kidney cancer and suggest the potential of this technique as a surgical assistance during partial nephrectomy. [Copyright &y& Elsevier]

The article evaluates the efficacy and safety of the α-blocker tamsulosin hydrochloride versus placebo for the management of patients with ureteral colic owing to distal ureteral stones. Results of the multicentric, randomized, double-blind trial showed higher mean stone diameters in the placebo than the tamsulosin group. The researchers observed no difference in expulsion delay distributions, and 43 patients in the placebo group and 61 in the tamsulosin group expelled their stones within 42 days.

Mexico City (MC) residents exposed to fine particulate matter and endotoxin exhibit inflammation of the olfactory bulb, substantia nigra, and vagus nerve. The goal of this study was to model these endpoints in mice and examine the neuroprotective effects of chocolate. Mice exposed to MC air received no treatment or oral dark chocolate and were compared to clean-air mice either untreated or treated intraperitoneally with endotoxin. Cyclooxygenase-2 (COX-2), interleukin 1 beta (IL-1β), and CD14 messenger RNA (mRNA) were quantified after 4, 8, and 16 months of exposure in target brain regions. After 16 months of exposure, the dorsal vagal complex (DVC) exhibited significant inflammation in endotoxin-treated and MC mice (COX-2 and IL-1β P < .001). Mexico City mice had olfactory bulb upregulation of CD14 (P = .002) and significant DVC imbalance in genes for antioxidant defenses, apoptosis, and neurodegeneration. These findings demonstrate sustained DVC inflammation in mice exposed to MC air, which is mitigated by chocolate administration. [ABSTRACT FROM PUBLISHER]

Abstract: Background: New optical techniques of spectroscopy have shown promising results in the evaluation of solid tumours. Objective: To evaluate the potential of Raman spectroscopy (RS) to assess renal tumours at surgery. Design, setting, and participants: Over a 5-mo period, Raman optical spectra were prospectively acquired on surgical renal specimens removed due to suspicion of cancer. Measurements: Raman measures were normalised to ensure comparison between spectra. A lower resolution signal was computed using a wavelet decomposition procedure to diminish the size of the signal and exploit the complete spectrum. A support vector machine (SVM) with a linear kernel and a sequential minimal optimisation solver was applied. A leave-one-out cross-validation technique was used to train and test the SVM. Results and limitations: There were 36 patients with 34 malignant tumours (27 clear-cell, 6 papillary, and 1 chromophobe) and 2 benign (1 oncocytoma and 1 metanephric cyst) tumours. A total of 241 analysable Raman spectra were obtained. The SVM was able to classify tumoural and normal tissue with an accuracy of 84% (sensitivity 82%, specificity 87%). High-grade and low-grade tumours were differentiated with a precision of 82% (sensitivity 84%, specificity 80%). Histologic subtype could be categorised with an accuracy of 93% (sensitivity 96%, specificity 87%). SVM could not be applied to classify benign and malignant tumours because of the restricted number of benign spectra. Conclusions: RS can accurately differentiate normal and tumoural renal tissue, low-grade and high-grade renal tumours, and histologic subtype of renal cell carcinoma. Larger prospective studies are needed to confirm these preliminary data. [Copyright &y& Elsevier]

Abstract: The aim of this work was to analyze the effect of carbamazepine (CBZ) on sleep patterns and on “head and body shakes” and to determine the role of serotonin (5-HT) in a model of kainic-induced seizures. Thirty male Wistar rats (280–300g) were used for polygraphic sleep recording. After a basal recording, the rats were allocated into three groups: kainic acid-treated animals (KA; 10mg/kg; n =10), carbamazepine-treated animals (CBZ; 30mg/kg; n =10) and animals injected with KA 30min after pretreatment with CBZ (CBZ+KA; n =10). Polygraphic recordings were performed for 10h for 3 days, with the exception of the CBZ group, which were observed for 1 day. In order to measure the head and body shakes that occurred over that time, a behavioral assessment was performed in two additional groups of KA (n =10) and CBZ+KA (n =10) animals. After 10h of behavioral assessment, the rats were sacrificed, and the levels of 5-HT and 5-hydroxy-indol-acetic acid (5-HIAA) were analyzed. We compared these findings with the results from a group of rats without pharmacological intervention (n =10). All of the recordings were performed from 08:00 to 18:00h. Data analysis: the electrographic parameters, head and body shake counting and monoamine concentrations were analyzed by an ANOVA test. Differences of *p ≤0.01 and **p ≤0.001 were considered statistically significant. Our results showed that CBZ exerted a protective effect on sleep pattern alterations induced by KA, which when administered alone caused a complete inhibition of sleep for the first 10h after administration. Although there was a reduction in the amount of sleep after the administration of KA in CBZ-pretreated animals, sleep inhibition was incomplete. In addition, CBZ decreased the frequency of head and body shakes by 60% as compared to KA. The 5-HT and 5-HIAA levels in the pons were increased in the KA and KA+CBZ groups. Our conclusion is that in addition to decreasing seizure intensity, CBZ facilitates the partial recovery of sleep. These results suggest that CBZ provides neuro-protective effects on sleep and against seizures. [Copyright &y& Elsevier]

Abstract: Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n: 55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic resonance imaging MRI. Seven healthy young dogs with similar exposure to Mexico City air pollution had brain MRI, measurement of mRNA abundance of two inflammatory genes cyclooxygenase-2, and interleukin 1 β in target brain areas, and histopathological evaluation of brain tissue. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks. Fifty-six percent of Mexico City children tested showed prefrontal white matter hyperintense lesions and similar lesions were observed in dogs (57%). Exposed dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow–Robin spaces, gliosis, and ultrafine particulate matter deposition. Based on the MRI findings, the prefrontal cortex was a target anatomical region in Mexico City children and its damage could have contributed to their cognitive dysfunction. The present work presents a groundbreaking, interdisciplinary methodology for addressing relationships between environmental pollution, structural brain alterations by MRI, and cognitive deficits/delays in healthy children. [Copyright &y& Elsevier]

Abstract: Objectives: Partial nephrectomy by laparoscopy offers patients conservative surgery and a mini-invasive approach; however, clamping of the renal pedicle and the induced warm ischaemia can damage the renal parenchyma. We present a technique of laparoscopic partial nephrectomy with haemostasis obtained by clamping of the renal parenchyma. Methods: The procedure was performed by an intraperitoneal or a retroperitoneal approach. After a working space is created by pneumodissection, Gerota''s fascia is incised and the kidney convexity is dissected. An endoscopic Satinsky clamp is inserted percutaneously through a 1-cm incision. The renal parenchyma is clamped and the tumour is excised in a bloodless field. The cut renal parenchyma is coated with biologic glue. Results: Five patients with elective indications were operated. Mean age was 67.8 yr and mean tumour diameter 3.06cm. One lesion was located at the upper pole and four at the lower pole. Mean preoperative serum creatinine level was 10.9mg/l. Postoperative serum creatinine level was unchanged. Mean operative time was 238min. There was no conversion. Mean blood loss was 250ml; no transfusions were necessary. The collecting duct system was repaired in one patient. No complication was noticed. Resection margins were tumour free in all cases. Final pathologic examination revealed clear cell carcinoma in three cases and angiomyolipoma and oncocytoma in one case each. Conclusion: Laparoscopic partial nephrectomy with clamping of the renal parenchyma can be performed in selected patients with peripherally placed tumours. The procedure avoids warm ischaemia of the normal parenchyma while allowing the surgeon to operate in an almost bloodless field. This initial experience in five patients should be validated in a larger series. [Copyright &y& Elsevier]

Abstract: Objective: To analyse through a large multicentre series, morbidity of nephron-sparing surgery (NSS) in relation to tumour size and surgical indication. Methods: The study included patients from eight international academic centres. Age, sex, TNM stage, tumour size, Fuhrman grade, Eastern Cooperative Oncology Group performance status (ECOG-PS), surgical margins, local and distant recurrences, and overall and cancer-specific survival rates were collected and analysed. Indication for elective or mandatory NSS, medical and surgical complication rates, mean blood loss, blood transfusion, and length of hospital stay were specifically recorded for the purpose of this study. Groups were compared for qualitative and quantitative variables by using χ2 (Fischer exact test) and Student t tests, respectively. Results: A total of 1048 NSS procedures were included in this study. Mean tumour size was 3.4±2.1cm. In 730 elective procedures mean operative time (p =0.002), mean blood loss (p =0.01), the need for blood transfusion (p =0.001), and urinary fistula rate (p =0.01) were significantly increased for tumours >4cm. However, these differences did not result in significantly increased medical (p =0.4), surgical complication rates (p =0.6), or length of hospital stay (p =0.9). Finally, in elective procedures for malignant tumours, positive surgical margins, local or distant recurrence rates, and cancer-specific survival were not significantly different in tumours ≤4cm and >4cm. Conclusion: Excellent cancer control and outcomes can be achieved with NSS in carefully selected patients with tumours >4cm. Expanding the size indication of elective NSS results in an increased but acceptable morbidity. [Copyright &y& Elsevier]

Discusses the method to classify and diagnose cell bladder carcinomas. Incidence of various malignancies affecting the bladder tissue and its associated complication; Clinical features of the disease; Classification of nonurothelial tumor according to their epithelial and nonepithelial origin.

Résumé: Les lésions traumatiques de l''urètre sont peu fréquentes. La plupart des atteintes de l''urètre antérieur (urètre bulbaire) sont des lésions dues à un choc direct (chute à califourchon) qui sont traitées dans un premier temps par un drainage vésical par cathéter sus-pubien, avec traitement retardé quand s''ensuit une sténose urétrale. Les dysfonctions traumatiques de l''urètre postérieur sont dans la plupart des cas liées à une fracture du bassin, et sont souvent associées à de multiples lésions à risque vital qui sont traitées en priorité. Leur prise en charge demeure un sujet extrêmement controversé : les traitements alternatifs consistent en un réalignement urétral précoce sous contrôle endoscopique, une réparation chirurgicale précoce, la pose d''un cathéter sus-pubien précédant une réparation chirurgicale différée. Nous décrivons ici la prise en charge des lésions de l''urètre ainsi que les différentes techniques opératoires en détail. [Copyright &y& Elsevier]

Objectives: To study the evolution of renal tumours treated in a single institution over a 2-decade period.Material and Methods: 729 patients surgically treated due to a renal tumour were included in this study. Age at diagnosis, gender, tumour size, TNM stage, percentage (%) of benign tumours, type of treatment, histologic subtype and mode of presentation were compared over 3 periods (1984–1992, 1993–1997, and 1998–2003).Results: During the period of the study, the median tumour size decreased from 7.5 to 6 cm while the rate of nephron-sparing surgery (NSS) increased from 1.6 to 19.6% and from 3.1 to 46.9% in all tumours and in tumours measuring less than 4 cm respectively. In this former group, the percentage of benign tumours increased from 6.3 to 15.2% while the percentage of radical nephrectomies decreased from 100% to 54.2%.Conclusion: We are treating today a great amount of small good prognosis renal tumors as well as an increasing percentage of benign tumours. In both cases, expanding the role of NSS will significantly reduce the rate of useless radical nephrectomies. [Copyright &y& Elsevier]

Introduction: Spinal cord compression (SCC) in metastatic prostate cancer is not rare occurring in 1 to 12% of patients. We have analysed patients treated for this condition in our institution assessing outcome and prognostic factors.Material and Methods: Retrospective analysis of the notes of 24 patients hospitalised with SCC due to metastatic prostate cancer from 1987 to 2001.Results: At presentation 3 patients were ambulant with mild neurological deficit, 12 patients were paraparetic and 9 patients were paraplegic. Diagnosis was established by emergency myelogram, CT-scan or MRI of the spine. 8 patients had received no hormone treatment prior to diagnosis of SCC. 19 patients presented dorsal or lumbar pain requiring opioid treatment on average 60 days before onset of neurological symptoms (range 10–840).All patients underwent steroid treatment; the 8 patients without prior hormone therapy were treated with bilateral orchidectomy, 1 out of these 8 patients had castration without other treatments; 12 patients underwent radiotherapy alone and 9 radiotherapy and laminectomy; 2 patients were in terminal conditions and receive only steroid treatment.Overall 15/24 patients were ambulant after treatment. 8 out of 9 patients treated by laminectomy and radiotherapy were ambulant after treatment versus 7 out of 12 patients treated by radiotherapy alone.17 patients died during follow-up with a median survival of 4 months (2 weeks to 49 months). 7 patients were alive at the last control with a mean follow-up of 10 months (range 4–40).Conclusion: Outlook in patients with spinal cord compression from metastatic prostate cancer is poor. Efforts must be concentrated on prevention of spinal cord compression. Patients with hormone resistant prostate cancer who develop persistent back pain should undergo imaging studies (bone scan, spine CT-scan or MNR) and prophylactic local radiotherapy to the spine if bony metastases are identified. [Copyright &y& Elsevier]

Objectives: To compare renal tumors with respect to initial clinical presentation and assess the prognostic value of a symptom based classification.Material and Methods: Based on symptoms at diagnosis, 388 renal tumors were stratified into three groups: (1) asymptomatic tumors; (2) tumors with local symptoms (3) tumors with systemic symptoms. The three groups were compared for usual clinical and pathological variables using χ2-tests and Anova regression, for qualitative and quantitative variables, respectively. Survival assessment was made with univariate and multivariate analysis using the Kaplan–Meier method and Cox regression analysis.Results: The three defined groups were significantly different for all analysed variables except for age, sex ratio and pathological subtype. In univariate analysis: ECOG performance status, symptom classification, tumour size, TNM stage and grade, adrenal, perinephric fat or vein invasion were significant prognostic factors (p<0.001). In multivariate analysis, symptom classification, TNM stage, Fuhrman grade and perinephric fat invasion remained independent prognostic factors (p<0.001).Conclusion: The proposed classification merits further validation through multi-institutional studies before integrating it in further prognosis algorithms. [Copyright &y& Elsevier]

Introduction: Studies have demonstrated the need for pain control during multiple transrectal prostate biopsies. Due to encountered published results on periprostatic nerve block, we prospectively evaluated the efficacy and safety of periprostatic local anaesthesia at the apex in comparison to intrarectal lidocaine gel.Methods: From January 2001 to January 2002 110 patients underwent prostate biopsy. Patients were randomized to receive 10 cc of either 2% lidocaine gel intrarectally (Group 1) or 10 cc of 1% lidocaine solution injected under ultrasound guidance for bilateral periprostatic nerve block at the apex (Group 2). Pain during biopsy was assessed using a 10-point linear visual analog pain scale and a 5-point digital visual pain scale (continous variables). Statistical analysis of pain scores was performed using the Student t-test.Results: 96 patients fitted the inclusion and presented no exclusion criteria. 43 patients composed group 1, and 53 patients group 2. The mean pain score was 2.76±1.69 and 1.73±1.26 for group 1 and 2, respectively for the 10-point linear visual analog pain scale (p=0.001). The mean pain score was 2.26±0.82 and 1.62±0.56 for groups 1 and 2, respectively for the 5-point digital visual pain scale (p<0.001). There was no difference in mean patient age (p=0.348), prostate size (p=0.899), serum PSA (p=0.932), and complications when comparing both groups. The number of biopsies per patient was significantly higher in group 2 (p=0.006), but pain scores in each scale were significantly less.Conclusions: Periprostatic nerve block at the apex is superior to intrarectal lidocaine gel for controlling pain during transrectal prostate biopsy, with no increased complications. This technique should be recommended for those patients without anal or rectal inflammatory diseases. [Copyright &y& Elsevier]