Repeated toluene and cyclohexane inhalation produces differential effects on HPA and HPT axes in adolescent male rats.

Misused volatile solvents typically contain toluene (TOL) as the main psychoactive ingredient. Cyclohexane (CHX) can also be present and is considered a safer alternative. Solvent misuse often occurs at early stages of life, leading to permanent neurobehavioral impairment and growth retardation. However, a comprehensive examination of the effects of TOL and CHX on stress regulation and energy balance is lacking. Here, we compared the effect of a binge-pattern exposure to TOL or CHX (4,000 or 8,000 ppm) on body weight, food intake, the hypothalamus-pituitary-adrenal (HPA) and hypothalamus-pituitary-thyroid (HPT) axes in male adolescent Wistar rats. At 8,000 ppm, TOL decreased body weight gain without affecting food intake. In addition, TOL and CHX altered the HPA and HPT axes' function in a solvent- and concentration-dependent manner. The highest TOL concentration produced HPA axis hyperactivation in animals not subjected to stress, which was evidenced by increased corticotropin-releasing-factor (CRF) release from the median eminence (ME), elevated adrenocorticotropin hormone (ACTH) and corticosterone serum levels, and decreased CRF mRNA levels in the hypothalamic paraventricular nucleus (PVN). TOL (8,000 ppm) also increased triiodothyronine (T3) serum levels, decreased pro-thyrotropin-releasing-hormone (pro-TRH) mRNA transcription in the PVN, pro-TRH content in the ME, and serum thyroid stimulating hormone (TSH) levels. CHX did not affect the HPA axis. We propose that the increased HPT axis activity induced by TOL can be related to the impaired body weight gain associated with inhalant misuse. These findings may contribute to a better understanding of the effects of the misused solvents TOL and CHX.

The application of Near-Infrared Spatially Resolved Spectroscopy in scope of achieving continuous real-time quality monitoring and control of tablets with challenging dimensions.

In scope of achieving real-time release of tablets, quality attributes need to be monitored and controlled through Process Analytical Technology tools such as near-infrared spectroscopy (NIRS). The authors evaluated the suitability of NIR-Spatially Resolved Spectroscopy (NIR-SRS) for continuous real-time monitoring and control of content uniformity, hardness and homogeneity of tablets with challenging dimensions. A novel user-friendly research and development inspection unit was used as standalone equipment for the analysis of small oblong tablets with deep-cut break lines. A total of 66 tablets varying in hardness and Active Pharmaceutical Ingredient (API) content were inspected, with each tablet being analysed five times and measurements repeated on three different days. Partial Least Squares (PLS) models were developed to assess content uniformity and hardness, of which the former showed higher accuracy. The authors attempted to visualize tablet homogeneity through NIR-SRS spectra by regressing all spectra obtained during a single measurement using a content uniformity PLS model. The NIR-SRS probe demonstrated its potential towards real-time release testing through its ability to quickly monitor content uniformity, hardness and visualize homogeneity, even for tablets with challenging dimensions.

Experimental testing of a prototype cantilevered liquid-nitrogen-cooled silicon mirror.

This report presents testing of a prototype cantilevered liquid-nitrogen-cooled silicon mirror. This mirror was designed to be the first mirror for the new soft X-ray beamlines to be built as part of the Advanced Light Source Upgrade. Test activities focused on fracture, heat transfer, modal response and distortion, and indicated that the mirror functions as intended.

Fístula utero-yeyunal secundaria a migración de dispositivo intrauterino: reporte de un caso / Utero-jejunal fistula secondary to intrauterine device migration: a case report

RESUMEN El dispositivo intrauterino (DIU) es un método anticonceptivo muy popular, eficaz y seguro. Aunque posee complicaciones bien descritas como es la migración, la que puede ser a otros órganos dentro de la cavidad peritoneal. La fístula uteroyeyunal es un evento clínico poco frecuente, pero de gran repercusión si no es diagnosticada y tratada. Se presenta el caso de una paciente usuaria de DIU, el que migra a cavidad abdominal, con posterior formación de fístula uteroyeyunal.

ABSTRACT The intrauterine device is a popular, efficient and safe contraceptive. Although it has some well described complications, such as migration, which may be to the different organs inside of the peritoneal cavity. The uterus-jejunal fistula is a rare clinical event, but with great repercussion if it is not well assessed and treated properly. We present the clinical case of a patient with a migrated intrauterine device and a fistula uterus-jejunal formation.

[Beliefs, perceptions and experiences in sexuality of Chilean adolescents with HIV acquired by vertical transmission]. / Creencias, percepciones y experiencias en sexualidad de adolescentes chilenos con infección por VIH adquirida por transmisión vertical.

BACKGROUND: Since the incorporation of antiretroviral therapy (ART) HIV has become a chronic condition, improving survival and allowing children with the virus to come in better conditions to adolescence, where they are faced with a series of changes, among them, to sexual awakening. AIM: To explore the main beliefs, perceptions and experiences in sexuality of a group of adolescents with HIV infection acquired through vertical transmission. METHODS: A qualitative research was carried out with exploratory and descriptive scope. Semi-structured interviews were applied to 28 adolescents, under control in hospitals in Santiago and Valparaíso, with HIV infection. The analysis was carried out according to the Grounded Theory. RESULTS: There was a lack of sexual education and a vision that focuses on risks, such as sexually transmissible infections or teenage pregnancy. There are fears about the possibility of rejection by others and of transmitting the virus to the couple or the children and they are invaded by feelings of shame and anger. CONCLUSION: It is important to train health professionals who work with this group, because they are identified as a reliable source of information and education.

Creencias, percepciones y experiencias en sexualidad de adolescentes chilenos con infección por VIH adquirida por transmisión vertical / Beliefs, perceptions and experiences in sexuality of Chilean adolescents with HIV acquired by vertical transmission

Resumen Introducción: Desde la incorporación de la terapia anti-retroviral (TAR) la infección por VIH ha pasado a ser una condición crónica, mejorando la sobrevida y permitiendo que los niños que han sido infectados con el virus lleguen en mejores condiciones a la adolescencia, donde se ven enfrentados a una serie de cambios, entre ellos, al despertar sexual. Objetivo: Explorar las principales creencias, percepciones y experiencias en sexualidad de un grupo de adolescentes con infección por VIH adquirida por transmisión vertical. Pacientes y Métodos: Se realizó una investigación cualitativa con alcance exploratorio y descriptivo. Se aplicaron entrevistas semiestructuradas a 28 adolescentes, bajo control en hospitales de Santiago y Región de Valparaíso, con infección por VIH. El análisis se realizó de acuerdo a la Teoría Fundamentada. Resultados: Se observó falta de educación sexual y una visión que se centra en los riesgos, tales como contagio de infecciones de transmisión sexual o embarazo adolescente. Existen temores frente a la posibilidad de rechazo de los otros y a transmitir el virus a la pareja o a los hijos y los invaden sentimientos de vergüenza y rabia. Conclusión: Es importante capacitar a los profesionales de salud que trabajan con este grupo, pues son identificados como fuente confiable de información y educación.

Background: Since the incorporation of antiretroviral therapy (ART) HIV has become a chronic condition, improving survival and allowing children with the virus to come in better conditions to adolescence, where they are faced with a series of changes, among them, to sexual awakening. Aim: To explore the main beliefs, perceptions and experiences in sexuality of a group of adolescents with HIV infection acquired through vertical transmission. Methods: A qualitative research was carried out with exploratory and descriptive scope. Semi-structured interviews were applied to 28 adolescents, under control in hospitals in Santiago and Valparaíso, with HIV infection. The analysis was carried out according to the Grounded Theory. Results: There was a lack of sexual education and a vision that focuses on risks, such as sexually transmissible infections or teenage pregnancy. There are fears about the possibility of rejection by others and of transmitting the virus to the couple or the children and they are invaded by feelings of shame and anger. Conclusion: It is important to train health professionals who work with this group, because they are identified as a reliable source of information and education.

The Geographic Structure of Viruses in the Cuatro Ciénegas Basin, a Unique Oasis in Northern Mexico, Reveals a Highly Diverse Population on a Small Geographic Scale.

The Cuatro Ciénegas Basin (CCB) is located in the Chihuahuan desert in the Mexican state of Coahuila; it has been characterized as a site with high biological diversity despite its extreme oligotrophic conditions. It has the greatest number of endemic species in North America, containing abundant living microbialites (including stromatolites and microbial mats) and diverse microbial communities. With the hypothesis that this high biodiversity and the geographic structure should be reflected in the virome, the viral communities in 11 different locations of three drainage systems, Churince, La Becerra, and Pozas Rojas, and in the intestinal contents of 3 different fish species, were analyzed for both eukaryotic and prokaryotic RNA and DNA viruses using next-generation sequencing methods. Double-stranded DNA (dsDNA) virus families were the most abundant (72.5% of reads), followed by single-stranded DNA (ssDNA) viruses (2.9%) and ssRNA and dsRNA virus families (0.5%). Thirteen families had dsDNA genomes, five had ssDNA, three had dsRNA, and 16 had ssRNA. A highly diverse viral community was found, with an ample range of hosts and a strong geographical structure, with very even distributions and signals of endemicity in the phylogenetic trees from several different virus families. The majority of viruses found were bacteriophages but eukaryotic viruses were also frequent, and the large diversity of viruses related to algae were a surprise, since algae are not evident in the previously analyzed aquatic systems of this ecosystem. Animal viruses were also frequently found, showing the large diversity of aquatic animals in this oasis, where plants, protozoa, and archaea are rare.IMPORTANCE In this study, we tested whether the high biodiversity and geographic structure of CCB is reflected in its virome. CCB is an extraordinarily biodiverse oasis in the Chihuahuan desert, where a previous virome study suggested that viruses had followed the marine ancestry of the marine bacteria and, as a result of their long isolation, became endemic to the site. In this study, which includes a larger sequencing coverage and water samples from other sites within the valley, we confirmed the high virus biodiversity and uniqueness as well as the strong biogeographical diversification of the CCB. In addition, we also analyzed fish intestinal contents, finding that each fish species eats different prey and, as a result, presents different viral compositions even if they coexist in the same pond. These facts highlight the high and novel virus diversity of CCB and its "lost world" status.

Raw material variability of an active pharmaceutical ingredient and its relevance for processability in secondary continuous pharmaceutical manufacturing.

Active Pharmaceutical Ingredients (API) raw material variability is not always thoroughly considered during pharmaceutical process development, mainly due to low quantities of drug substance available. However, synthesis, crystallization routes and production sites evolve during product development and product life cycle leading to changes in physical material attributes which can potentially affect their processability. Recent literature highlights the need for a global approach to understand the link between material synthesis, material variability, process and product quality. The study described in this article aims at explaining the raw material variability of an API using extensive material characterization on a restricted number of representative batches using multivariate data analysis. It is part of a larger investigation trying to link the API drug substance manufacturing process, the resulting physical API raw material attributes and the drug product continuous manufacturing process. Eight API batches produced using different synthetic routes, crystallization, drying, delumping processes and processing equipment were characterized, extensively. Seventeen properties from seven characterization techniques were retained for further analysis using Principal Component Analysis (PCA). Three principal components (PCs) were sufficient to explain 92.9% of the API raw material variability. The first PC was related to crystal length, agglomerate size and fraction, flowability and electrostatic charging. The second PC was driven by the span of the particle size distribution and the agglomerates strength. The third PC was related to surface energy. Additionally, the PCA allowed to summarize the API batch-to-batch variability in only three PCs which can be used in future drug product development studies to quantitatively evaluate the impact of the API raw material variability upon the drug product process. The approach described in this article could be applied to any other compound which is prone to batch-to-batch variability.

Impaired hypothalamic cocaine- and amphetamine-regulated transcript expression in lateral hypothalamic area and paraventricular nuclei of dehydration-induced anorexic rats.

Negative energy balance promotes physiological adaptations that ensure the survival of animals. The hypothalamic-pituitary-thyroid axis regulates basal energy expenditure and its down-regulating adaptation to negative energy balance is well described: in fasting, the serum content of thyrotrophin (TSH) and thyroid hormones (TH) decreases, enhancing the survival odds of individuals. By contrast, dehydration-induced anorexic (DIA) rats present an impaired hypothalamic-pituitary-thyroid (HPT) axis adaptation despite their negative energy balance: increased circulating TSH levels. The implication of cocaine- and amphetamine-regulated transcript (CART), an anorexic peptide, in HPT axis function impairment and food-avoidance behaviour displayed by DIA animals is unknown. Because CART is co-expressed with the peptide that regulates the HPT axis in hypophysiotrophic paraventricular nucleus (PVN) neurones (TSH-releasing hormone), we analysed CART expression and possible implications with respect to high TSH levels of DIA animals. We examined whether changes in CART expression from the lateral hypothalamic area (LHA) and arcuate nucleus (ARC) could participate in food-avoidance of DIA rats. DIA and forced-food restricted (FFR) animals reduced their body weight and food intake. FFR rats had a down-regulation of their HPT axis (reduced serum TH and TSH content), whereas DIA animals had reduced TH but increased TSH levels. CART mRNA expression in the ARC decreased similarly between experimental groups and diminished in anterior, medial PVN and in LHA of FFR animals, whereas DIA animals showed unchanged levels. This impaired CART mRNA expression in the anterior PVN and LHA could be related to the aberrant feeding behaviour of DIA rats but not to their deregulated HPT axis function.

Prepuberal light phase feeding induces neuroendocrine alterations in adult rats.

Feeding patterns are important factors in obesity evolvement. Time-restricted feeding schedules (tRF) during resting phase change energy homeostasis regulation, disrupting the circadian release of metabolism-regulating hormones, such as leptin, insulin and corticosterone and promoting body weight gain. Thyroid (HPT) and adrenal (HPA) axes exhibit a circadian regulation and are involved in energy expenditure, thus studying their parameters in tRF paradigms will elucidate their role in energy homeostasis impairments under such conditions. As tRF in young animals is poorly studied, we subjected prepuberal rats to a tRF either in light (LPF) or in darkness phase (DPF) and analyzed HPT and HPA response when they reach adulthood, as well as their arcuate (ARC) and paraventricular (PVN) hypothalamic nuclei neurons' sensitivity to leptin in subsets of 10-week-old animals after fasting and with i.p. leptin treatment. LPF group showed high body weight and food intake, along with increased visceral fat pads, corticosterone, leptin and insulin serum levels, whereas circulating T4 decreased. HPA axis hyperactivity was demonstrated by their high PVN Crf mRNA expression; the blunted activity of HPT axis, by the decreased hypophysiotropic PVN Trh mRNA expression. Trh impaired expression to the positive energy balance in LPF, accounted for their ARC leptin resistance, evinced by an increased Npy and Socs3 mRNA expression. We concluded that the hyperphagia of prepuberal LPF animals could account for the HPA axis hyperactivity and for the HPT blocked function due to the altered ARC leptin signaling and impaired NPY regulation on PVN TRH neurons.

Artificial reproduction of magnetic fields produced by a natural geomagnetic storm increases systolic blood pressure in rats.

The incidence of geomagnetic storms may be associated with changes in circulatory physiology. The way in which the natural variations of the geomagnetic field due to solar activity affects the blood pressure are poorly understood and require further study in controlled experimental designs in animal models. In the present study, we tested whether the systolic arterial pressure (AP) in adult rats is affected by simulated magnetic fields resembling the natural changes of a geomagnetic storm. We exposed adult rats to a linear magnetic profile that simulates the average changes associated to some well-known geomagnetic storm phases: the sudden commencement and principal phase. Magnetic stimulus was provided by a coil inductor and regulated by a microcontroller. The experiments were conducted in the electromagnetically isolated environment of a semi-anechoic chamber. After exposure, AP was determined with a non-invasive method through the pulse on the rat's tail. Animals were used as their own control. Our results indicate that there was no statistically significant effect in AP when the artificial profile was applied, neither in the sudden commencement nor in the principal phases. However, during the experimental period, a natural geomagnetic storm occurred, and we did observe statistically significant AP increase during the sudden commencement phase. Furthermore, when this storm phase was artificially replicated with a non-linear profile, we noticed a 7 to 9 % increase of the rats' AP in relation to a reference value. We suggested that the changes in the geomagnetic field associated with a geomagnetic storm in its first day could produce a measurable and reproducible physiological response in AP.

High conductivity organic thin films for spintronics: the interface resistance bottleneck.

Highly electrochemically doped poly(2,5-bis(3-dodecyl-2-yl)-thieno[3,2-b]thiophene (pBTTT) thin films exhibiting remarkably high conductivities values reaching 3000-5000 Ω(-1) cm(-1) are investigated. Experimental evidence of delocalized transport properties of this material at the onset of metallicity makes it an ideal candidate for spin valve device integration. Nevertheless, the interface resistance between the polymer and metallic electrodes is orders of magnitudes larger than the expected spin resistance of the active channel. This prevents the collection of a spin current. This finding can explain the lack of success in making lateral organic spin valves reported in the literature, especially the related absence of spin signals in non-local spin valve and Hanle current measurements in organic thin films.

A simple approach for ultrasensitive detection of bisphenols by multiplexed surface-enhanced Raman scattering.

Bisphenol A (BPA) is well known for its use in plastic manufacture and thermal paper production despite its risk of health toxicity as an endocrine disruptor in humans. Since the publication of new legislation regarding the use of BPA, manufacturers have begun to replace BPA with other phenolic molecules such as bisphenol F (BPF) and bisphenol B (BPB), but there are no guarantees regarding the health safety of these compounds at this time. In this context, a very simple, cheap and fast surface-enhanced Raman scattering (SERS) method was developed for the sensitive detection of these molecules in spiked tap water solutions. Silver nanoparticles were used as SERS substrates. An original strategy was employed to circumvent the issue of the affinity of bisphenols for metallic surfaces and the silver nanoparticles surface was functionalized using pyridine in order to improve again the sensitivity of the detection. Semi-quantitative detections were performed in tap water solutions at a concentrations range from 0.25 to 20 µg L(-1) for BPA and BPB and from 5 to 100 µg L(-1) for BPF. Moreover, a feasibility study for performing a multiplex-SERS detection of these molecules was also performed before successfully implementing the developed SERS method on real samples.

Vibrational spectroscopy and microspectroscopy analyzing qualitatively and quantitatively pharmaceutical hot melt extrudates.

Since the last decade, more and more Active Pharmaceutical Ingredient (API) candidates have poor water solubility inducing low bioavailability. These molecules belong to the Biopharmaceutical Classification System (BCS) classes II and IV. Thanks to Hot-Melt Extrusion (HME), it is possible to incorporate these candidates in pharmaceutical solid forms. Indeed, HME increases the solubility and the bioavailability of these drugs by encompassing them in a polymeric carrier and by forming solid dispersions. Moreover, in 2004, the FDA's guidance initiative promoted the usefulness of Process Analytical Technology (PAT) tools when developing a manufacturing process. Indeed, the main objective when developing a new pharmaceutical process is the product quality throughout the production chain. The trend is to follow this parameter in real-time in order to react immediately when there is a bias. Vibrational spectroscopic techniques, NIR and Raman, are useful to analyze processes in-line. Moreover, off-line Raman microspectroscopy is more and more used when developing new pharmaceutical processes or when analyzing optimized ones by combining the advantages of Raman spectroscopy and imaging. It is an interesting tool for homogeneity and spatial distribution studies. This review treats about spectroscopic techniques analyzing a HME process, as well off-line as in-line, presenting their advantages and their complementarities.

Data processing of vibrational chemical imaging for pharmaceutical applications.

Vibrational spectroscopy (MIR, NIR and Raman) based hyperspectral imaging is one of the most powerful tools to analyze pharmaceutical preparation. Indeed, it combines the advantages of vibrational spectroscopy to imaging techniques and allows therefore the visualization of distribution of compounds or crystallization processes. However, these techniques provide a huge amount of data that must be processed to extract the relevant information. This review presents fundamental concepts of hyperspectral imaging, the basic theory of the most used chemometric tools used to pre-process, process and post-process the generated data. The last part of the present paper focuses on pharmaceutical applications of hyperspectral imaging and highlights the data processing approaches to enable the reader making the best choice among the different tools available.

Development of a quantitative approach using surface-enhanced Raman chemical imaging: first step for the determination of an impurity in a pharmaceutical model.

This publication reports, for the first time, the development of a quantitative approach using surface-enhanced Raman chemical imaging (SER-CI). A pharmaceutical model presented as tablets based on paracetamol, which is the most sold drug around the world, was used to develop this approach. 4-Aminophenol is the main impurity of paracetamol and is actively researched in pharmaceutical formulations because of its toxicity. As its concentration is generally very low (<0.1%, w/w), conventional Raman chemical imaging cannot be used. In this context, a SER-CI method was developed to quantify 4-aminophenol assessing a limit of quantification below its limit of specification of 1000 ppm. Citrate-reduced silver nanoparticles were used as SERS substrate and these nanoparticles were functionalized using 1-butanethiol. Different ways to cover the tablets surface by butanethiol-functionalized silver nanoparticles were tested and a homogeneity study of the silver nanoparticles covering was realized. This homogeneity study was performed in order to choose the best way to cover the surface of tablets by silver colloid. Afterwards, the optimization of the SER-CI approach was necessary and different spectral intensity normalizations were tested. Finally, a quantitative approach using SER-CI was developed enabling to quantify 4-aminophenol from 0.025% to 0.2% in paracetamol tablets. This quantitative approach was tested on two different series of tablets using different batches of silver nanoparticles.

Determination of 4-aminophenol in a pharmaceutical formulation using surface enhanced Raman scattering: from development to method validation.

A surface enhanced Raman scattering (SERS) method able to quantify 4-aminophenol in a pharmaceutical formulation based on acetaminophen, also called paracetamol, was developed and, for the first time, successfully validated. In this context, silver nanoparticles were synthesized according to the method described by Lee-Meisel and used as SERS substrate. The repeatability of the silver colloid synthesis was tested using different methods to characterize the size and the zeta potential of silver nanoparticles freshly synthesized. To optimize the SERS samples preparation, a design of experiments implicating concentrations of citrate-reduced silver nanoparticles and aggregating agent was performed in order to maximize the Raman signal enhancement. Finally, an approach based on tolerance intervals and accuracy profiles was applied in order to thoroughly validate the method in a range of concentrations comprised from 3 to 15 µg mL(-1) using normalized band intensities. The standard addition method was selected as method calibration. Therefore, measurements were carried out on 4-aminophenol spiked solutions of the pharmaceutical formulation. Despite the well-known stability and reproducibility problems of SERS, the validation was performed using two operators and five batches of nanoparticles, one for each validation day.

Thermally assisted quantum annealing of a 16-qubit problem.

Efforts to develop useful quantum computers have been blocked primarily by environmental noise. Quantum annealing is a scheme of quantum computation that is predicted to be more robust against noise, because despite the thermal environment mixing the system's state in the energy basis, the system partially retains coherence in the computational basis, and hence is able to establish well-defined eigenstates. Here we examine the environment's effect on quantum annealing using 16 qubits of a superconducting quantum processor. For a problem instance with an isolated small-gap anticrossing between the lowest two energy levels, we experimentally demonstrate that, even with annealing times eight orders of magnitude longer than the predicted single-qubit decoherence time, the probabilities of performing a successful computation are similar to those expected for a fully coherent system. Moreover, for the problem studied, we show that quantum annealing can take advantage of a thermal environment to achieve a speedup factor of up to 1,000 over a closed system.

Cuerpos extraños (CE) en el tracto digestivo / Foreign bodies in the digestive tract

Foreign bodies can be of organic or inorganic nature. Ten to 20 percent of the foreign bodies occurring in the digestive tract require an endoscopic procedure. Public health reports identify the pediatric population, no sex-based prevalence, as the one with the highest risk. In adults, these typically correspond to men swallowing fish bones or dental prostheses. The elderly mainly swallow dental prostheses and also they are individuals with clinical pathologies. The increased risk of suspicion is relevant for diagnostic in children, because 40 percent of them swallow the foreign body on absence of adults and seem asymptomatic. Progress of the symptoms and physical examination are the base for clinical diagnostic. The locations where the foreign bodies may impact the esophagus, stomach and small intestine, are know, as well as the associated pathologies. Sixty percent of the foreign bodies are radiopaque; simple X-ray in two views (AP and lateral) is the main tool for diagnosis. Forty percent of the foreign bodies are radiolucid; the most effective tool for identification is endoscopy. Therapy, whether observation and clinical surveillance, endoscopic or surgical extraction, will depend on the type, size and shape of the foreign body, its location, time since swallowed, toxicity, capability of producing electricity or causing mechanical damage, the quantity and if it was swallowed together with other foreign bodies (batteries/magnet), radiotransparency, and the patient’s age and associated pathologies. Complications are acute obstruction, perforation, fistula and digestive hemorrhage.

Los cuerpos extraños pueden ser de naturaleza orgánica o inorgánica. El 10 a 20 por ciento de los cuerpos extraños que ingresan al tracto digestivo requieren algún procedimiento endoscópico. Informes de salud pública definen a la población pediátrica, sin prevalencia de sexo, como la de mayor riesgo. En adultos clásicamente corresponden a hombres que ingieren espinas de pescado o prótesis dentarias. Los ancianos, ingieren prótesis dentarias y son individuos con alguna patología médica. El alto índice de sospecha es relevante en la determinación del diagnóstico en niños, ya que el 40 por ciento de ellos, los ingieren en ausencia de adultos y están asintomáticos. La evaluación de la sintomatología y el examen físico son la base para el diagnóstico clínico. Son conocidos los segmentos del tracto digestivo y las patologías asociadas al lugar en que normalmente se impactan los cuerpos extraños en el esófago, estómago e intestino delgado. El 60 por ciento de los cuerpos extraños son de tipo radiopaco; la radiografía simple en dos proyecciones (AP y lateral) es la principal herramienta diagnóstica. El 40 por ciento de los cuerpos extraños es radiolúcido; la herramienta más eficiente para su identificación es la endoscopia. La conducta terapéutica, sea esta la observación y control clínico, la extracción por endoscopia o la cirugía, dependerá del tipo de cuerpo extraño, de su tamaño, forma, localización, tiempo post-ingesta, toxicidad, capacidad para generar electricidad o daño mecánico, su número o co-ingesta con otros cuerpos extraños (pilas e imanes), radiotransparencia, y la edad del paciente y sus patologías asociadas. Sus complicaciones son la obstrucción aguda, la perforación, la fistulización y la hemorragia digestiva.

Critical review of near-infrared spectroscopic methods validations in pharmaceutical applications.

Based on the large number of publications reported over the past five years, near-infrared spectroscopy (NIRS) is more and more considered an attractive and promising analytical tool regarding Process Analytical Technology and Green Chemistry. From the reviewed literature, few of these publications present a thoroughly validated NIRS method even if some guidelines have been published by different groups and regulatory authorities. However, as any analytical method, the validation of NIRS method is a mandatory step at the end of the development in order to give enough guarantees that each of the future results during routine use will be close enough to the true value. Besides the introduction of PAT concepts in the revised document of the European Pharmacopoeia (2.2.40) dealing with near-infrared spectroscopy recently published in Pharmeuropa, it agrees very well with this mandatory step. Indeed, the latter suggests to use similar analytical performance characteristics than those required for any analytical procedure based on acceptance criteria consistent with the intended use of the method. In this context, this review gives a comprehensive and critical overview of the methodologies applied to assess the validity of quantitative NIRS methods used in pharmaceutical applications.