Prevalence of Fabry disease in patients with chronic kidney disease: A systematic review and meta-analysis.

Fabry disease (FD) is an X-linked lysosomal storage disease caused by pathogenic variants in the GLA gene. It has a wide range of clinical manifestations, typically related to the specific underlying GLA variant. One of the main features of FD is kidney involvement; therefore, several studies have addressed the prevalence of FD in all types of patients with chronic kidney disease. We performed a systematic review and meta-analysis of screening studies in chronic kidney disease patients, including those on dialysis, had undergone a kidney transplantation, and those who did not receive kidney replacement therapy, and assessed the prevalence of pathogenic variants in these cohorts. Fifty-five studies were included, involving a total of 84,062 individuals. Of these, 251 cases were positive for FD; a third of the reported GLA variants were of a benign phenotype (37.8%), followed by classical phenotype (31.7%), late onset (15.5%), and of uncertain significance (14.7%). The overall prevalence among dialysis patients was 0.10% (CI95%, 0.06-0.15), 0.28% (CI95%, 0.06-0.15) among patients with kidney transplantation, and 0.17% (CI95%, 0.11-0.39) among those without kidney replacement therapy. Although the overall prevalence of FD is low in patients with kidney involvement, screening, especially in patients who have not yet undergone kidney replacement therapy, is important, in order to provide timely and effective treatment interventions, including disease modifying therapies. The prevalence of kidney involvement in females with Fabry Disease is lower but this should not lead to inadequate follow up. Further research is also needed on the impact of genetic variants of uncertain significance to elucidate their role in Fabry disease.

StimuliApp: Psychophysical tests on mobile devices.

Psychophysical tests are commonly carried out using software applications running on desktop or laptop computers, but running the software on mobile handheld devices such as smartphones or tablets could have advantages in some situations. Here, we present StimuliApp, an open-source application in which the user can create psychophysical tests on the iPad and the iPhone by means of a system of menus. A wide number of templates for creating stimuli are available including patches, gradients, gratings, checkerboards, random-dots, texts, tones or auditory noise. Images, videos and audios stored in files could also be presented. The application was developed natively for iPadOS and iOS using the low-level interface Metal for accessing the graphics processing unit, which results in high timing performance.

Sensory adaptation for timing perception.

Recent sensory experience modifies subjective timing perception. For example, when visual events repeatedly lead auditory events, such as when the sound and video tracks of a movie are out of sync, subsequent vision-leads-audio presentations are reported as more simultaneous. This phenomenon could provide insights into the fundamental problem of how timing is represented in the brain, but the underlying mechanisms are poorly understood. Here, we show that the effect of recent experience on timing perception is not just subjective; recent sensory experience also modifies relative timing discrimination. This result indicates that recent sensory history alters the encoding of relative timing in sensory areas, excluding explanations of the subjective phenomenon based only on decision-level changes. The pattern of changes in timing discrimination suggests the existence of two sensory components, similar to those previously reported for visual spatial attributes: a lateral shift in the nonlinear transducer that maps relative timing into perceptual relative timing and an increase in transducer slope around the exposed timing. The existence of these components would suggest that previous explanations of how recent experience may change the sensory encoding of timing, such as changes in sensory latencies or simple implementations of neural population codes, cannot account for the effect of sensory adaptation on timing perception.

AguR, a Transmembrane Transcription Activator of the Putrescine Biosynthesis Operon in Lactococcus lactis, Acts in Response to the Agmatine Concentration.

Dairy industry fermentative processes mostly use Lactococcus lactis as a starter. However, some dairy L. lactis strains produce putrescine, a biogenic amine that raises food safety and spoilage concerns, via the agmatine deiminase (AGDI) pathway. The enzymatic activities responsible for putrescine biosynthesis in this bacterium are encoded by the AGDI gene cluster. The role of the catabolic genes aguB, aguD, aguA, and aguC has been studied, but knowledge regarding the role of aguR (the first gene in the cluster) remains limited. In the present work, aguR was found to be a very low level constitutively expressed gene that is essential for putrescine biosynthesis and is transcribed independently of the polycistronic mRNA encoding the catabolic genes (aguBDAC). In response to agmatine, AguR acts as a transcriptional activator of the aguB promoter (PaguB), which drives the transcription of the aguBDAC operon. Inverted sequences required for PaguB activity were identified by deletion analysis. Further work indicated that AguR is a transmembrane protein which might function as a one-component signal transduction system that senses the agmatine concentration of the medium and, accordingly, regulates the transcription of the aguBDAC operon through a C-terminal cytoplasmic DNA-binding domain typically found in LuxR-like proteins.

Implementation of the agmatine-controlled expression system for inducible gene expression in Lactococcus lactis.

BACKGROUND: Lactococcus lactis has been safely consumed in fermented foods for millennia. This Gram-positive bacterium has now become of industrial importance as an expression host for the overproduction of lipopolysaccharide-free recombinant proteins used as food ingredients, therapeutic proteins and biotechnological enzymes. RESULTS: This paper reports an agmatine-controlled expression (ACE) system for L. lactis, comprising the lactococcal agmatine-sensor/transcriptional activator AguR and its target promoter P(aguB). The usefulness and efficiency of this system was checked via the reporter gene gfp and by producing PEP (Myxococcus xanthus prolyl-endopeptidase), an enzyme of biomedical interest able to degrade the immunotoxic peptides produced during the gastrointestinal breakdown of gluten. CONCLUSION: The ACE system developed in this work was suitable for the efficient expression of the functional recombinant proteins GFP and PEP. The expression system was tightly regulated by the agmatine concentration and allowed high protein production without leakiness.

Putrescine production via the agmatine deiminase pathway increases the growth of Lactococcus lactis and causes the alkalinization of the culture medium.

Lactococcus lactis is the most important starter culture organism used in the dairy industry. Although L. lactis species have been awarded Qualified Presumption of Safety status by the European Food Safety Authority, and Generally Regarded as Safe status by the US Food and Drug Administration, some strains can produce the biogenic amine putrescine. One such strain is L. lactis subsp. cremoris CECT 8666 (formerly L. lactis subsp. cremoris GE2-14), which was isolated from Genestoso cheese. This strain catabolizes agmatine to putrescine via the agmatine deiminase (AGDI) pathway, which involves the production of ATP and two ammonium ions. The present work shows that the availability of agmatine and its metabolization to putrescine allows for greater bacterial growth (in a biphasic pattern) and causes the alkalinization of the culture medium in a dose-dependent manner. The construction of a mutant lacking the AGDI cluster (L. lactis CECT 8666 Δagdi) confirmed the latter's direct role in putrescine production, growth, and medium alkalinization. Alkalinization did not affect the putrescine production pattern and was not essential for increased bacterial growth.

Lactose-mediated carbon catabolite repression of putrescine production in dairy Lactococcus lactis is strain dependent.

Lactococcus lactis is the lactic acid bacterial (LAB) species most widely used as a primary starter in the dairy industry. However, several strains of L. lactis produce the biogenic amine putrescine via the agmatine deiminase (AGDI) pathway. We previously reported the putrescine biosynthesis pathway in L. lactis subsp. cremoris GE2-14 to be regulated by carbon catabolic repression (CCR) via glucose but not lactose (Linares et al., 2013). The present study shows that both these sugars repress putrescine biosynthesis in L. lactis subsp. lactis T3/33, a strain isolated from a Spanish artisanal cheese. Furthermore, we demonstrated that both glucose and lactose repressed the transcriptional activity of the aguBDAC catabolic genes of the AGDI route. Finally, a screening performed in putrescine-producing dairy L. lactis strains determined that putrescine biosynthesis was repressed by lactose in all the L. lactis subsp. lactis strains tested, but in only one L. lactis subsp. cremoris strain. Given the obvious importance of the lactose-repression in cheese putrescine accumulation, it is advisable to consider the diversity of L. lactis in this sense and characterize consequently the starter cultures to select the safest strains.

An agmatine-inducible system for the expression of recombinant proteins in Enterococcus faecalis.

BACKGROUND: Scientific interest in Enterococcus faecalis has increased greatly over recent decades. Some strains are involved in food fermentation and offer health benefits, whereas others are vancomycin-resistant and cause infections that are difficult to treat. The limited availability of vectors able to express cloned genes efficiently in E. faecalis has hindered biotechnological studies on the bacterium's regulatory and pathogenicity-related genes. The agmatine deiminase (AGDI) pathway of E. faecalis, involved in the conversion of agmatine into putrescine, is driven by a response inducer gene aguR. RESULTS: This study describes that the exposure to the induction factor (agmatine) results in the transcription of genes under the control of the aguB promoter, including the aguBDAC operon. A novel E. faecalis expression vector, named pAGEnt, combining the aguR inducer gene and the aguB promoter followed by a cloning site and a stop codon was constructed. pAGEnt was designed for the overexpression and purification of a protein fused to a 10-amino-acid His-tag at the C-terminus. The use of GFP as a reporter of gene expression in E. faecalis revealed that under induction with 60 mM agmatine, fluorescence reached 40 arbitrary units compared to 0 in uninduced cells. CONCLUSION: pAGEnt vector can be used for the overexpression of recombinant proteins under the induction of agmatine in E. faecalis, with a close correlation between agmatine concentration and fluorescence when GFP was used as reporter.

A synchronous surround increases the motion strength gain of motion.

Coherent motion detection is greatly enhanced by the synchronous presentation of a static surround (Linares, Motoyoshi, & Nishida, 2012). To further understand this contextual enhancement, here we measured the sensitivity to discriminate motion strength for several pedestal strengths with and without a surround. We found that the surround improved discrimination of low and medium motion strengths, but did not improve or even impaired discrimination of high motion strengths. We used motion strength discriminability to estimate the perceptual response function assuming additive noise and found that the surround increased the motion strength gain, rather than the response gain. Given that eye and body movements continuously introduce transients in the retinal image, it is possible that this strength gain occurs in natural vision.

The tyrosyl-tRNA synthetase like gene located in the tyramine biosynthesis cluster of Enterococcus durans is transcriptionally regulated by tyrosine concentration and extracellular pH.

BACKGROUND: The tyramine producer Enterococcus durans IPLA655 contains all the necessary genes for tyramine biosynthesis, grouped in the TDC cluster. This cluster includes tyrS, an aminoacyl-tRNA synthetase like gene. RESULTS: This work shows that tyrS was maximally transcribed in absence of tyrosine at acidic pH, showing a greater than 10-fold induction in mRNA levels over levels occurring in presence of tyrosine. Mapping of the tyrS transcriptional start site revealed an unusually long untranslated leader region of 322 bp, which displays the typical features of the T box transcriptional attenuation mechanism. The tyrosine concentration regulation of tyrS was found to be mediated by a transcription antitermination system, whereas the specific induction at acidic pH was regulated at transcription initiation level. CONCLUSIONS: The expression of the tyrS gene present in the TDC cluster of E. durans is transcriptionally regulated by tyrosine concentration and extracelular pH. The regulation is mediated by both an antitermination system and the promoter itself.

Surround facilitation for rapid motion perception.

Because we live in a dynamic environment with moving eyes and body, our retinas are often stimulated by new scenes that appear suddenly and are only briefly available. How the visual system successfully extracts information from such challenging stimulation is not yet understood. For some stimuli, like photos of natural scenes, we are accurate in detecting objects like animals or faces even when the stimulus is presented for a short time. For other stimuli, like noisy motion, previous studies have shown accurate perception only when the stimulus is presented for a long time--often longer than the typical available time of a stimulus in natural viewing. Here we show, however, that a transient surround can accelerate the perception of motion. We found that for briefly displayed random-dots, the signal necessary to detect motion is reduced from 19% to 8% when a task-irrelevant surround is presented in synchrony with the random-dots, while no improvement occurs when the surround is sustainedly presented, or when it is transiently, but asynchronously, presented. We also found that motion sensitivity increases steadily with duration when no surround is presented, confirming previous findings, but duration has little effect on sensitivity when a synchronous surround is presented. Further results indicate that the facilitation by a synchronous surround is related to relative-motion processing. Our findings suggest that spatial interactions might assist rapid perception of motion.

Biogenic amines in dairy products.

Biogenic amines (BA) are organic, basic, nitrogenous compounds with biological activity, mainly formed by the decarboxylation of amino acids. BA are present in a wide range of foods, including dairy products, and can accumulate in high concentrations. In some cheeses more than 1000 mg of BA have been detected per kilogram of cheese. The consumption of food containing large amounts of these amines can have toxicological consequences. Although there is no specific legislation regarding the BA content in dairy products, it is generally assumed that they should not be allowed to accumulate. Greater knowledge of the factors involved in the synthesis and accumulation of BA should lead to a reduction in their incidence in foods. This article focuses on the factors that affect BA production, in particular environmental conditions, the microorganisms that produce them, the genetic organization and regulation of the biosynthetic pathways involved, and the available methods for detecting the presence of BA or BA-producing microorganisms in dairy products.

Genome sequences of Lactococcus lactis MG1363 (revised) and NZ9000 and comparative physiological studies.

Lactococcus lactis NZ9000 and its parent MG1363 are the most commonly used lactic acid bacteria for expression and physiological studies. We noted unexpected but significant differences in the growth behaviors of both strains. We sequenced the entire genomes of the original NZ9000 and MG1363 strains using an ultradeep sequencing strategy. The analysis of the L. lactis NZ9000 genome yielded 79 differences, mostly point mutations, with the annotated genome sequence of L. lactis MG1363. Resequencing of the MG1363 strain revealed that 73 out of the 79 differences were due to errors in the published sequence. Comparative transcriptomic studies revealed several differences in the regulation of genes involved in sugar fermentation, which can be explained by two specific mutations in a region of the ptcC promoter with a key role in the regulation of cellobiose and glucose uptake.

Frequency of conjunctival epithelial dysplasia in patients with pterygium.

PURPOSE: To determine the frequency of ocular squamous surface neoplasia associated with pterygium in an ophthalmology reference center in Central Mexico. METHODS: We reviewed histopathological reports and slides of all patients who underwent pterygium surgery from 2014 to 2016 at the Instituto Mexicano de Oftalmologia in Queretaro (Mexico). RESULTS: We studied 177 biopsy samples; 66% were from women, and the median age was 52 years. We found ocular squamous surface neoplasias in 11.29% (n=20) of the samples. One biopsy sample revealed a poorly differentiated keratinizing and infiltrating carcinoma. CONCLUSIONS: The prevalence of ocular squamous surface neoplasia in our region appears to be high. Countrywide studies are necessary to determine the true prevalence of ocular squamous surface neoplasia in Mexico and to examine related risk factors.

Where is the moving object now? Judgments of instantaneous position show poor temporal precision (SD = 70 ms).

Humans can precisely judge relative location between two objects moving with the same speed and direction, as numerous studies have shown. However, the precision for localizing a single moving object relative to stationary references remains a neglected topic. Here, subjects reported the perceived location of a moving object at the time of a cue. The variability of the reported positions increased steeply with the speed of the object, such that the distribution of responses corresponds to the distance that the object traveled in 70 ms. This surprisingly large temporal imprecision depends little on the characteristics of the trajectory of the moving object or of the cue that indicates when to judge the position. We propose that the imprecision reflects a difficulty in identifying which position of the moving object occurs at the same time as the cue. This high-level process may involve the same low temporal resolution binding mechanism that, in other situations, pairs simultaneous features such as color and motion.

Decoupling sensory from decisional choice biases in perceptual decision making.

The contribution of sensory and decisional processes to perceptual decision making is still unclear, even in simple perceptual tasks. When decision makers need to select an action from a set of balanced alternatives, any tendency to choose one alternative more often-choice bias-is consistent with a bias in the sensory evidence, but also with a preference to select that alternative independently of the sensory evidence. To decouple sensory from decisional biases, here we asked humans to perform a simple perceptual discrimination task with two symmetric alternatives under two different task instructions. The instructions varied the response mapping between perception and the category of the alternatives. We found that from 32 participants, 30 exhibited sensory biases and 15 decisional biases. The decisional biases were consistent with a criterion change in a simple signal detection theory model. Perceptual decision making, thus, even in simple scenarios, is affected by sensory and decisional choice biases.

Elevada prevalencia de malformaciones anorrectales en recién nacidos a gran altitud / High prevalence of anorectal malformations in high-altitude newborns

Introducción. Las malformaciones anorrectales son un grupo de anomalías congénitas de etiología multifactorial, en las que intervienen diversos factores genéticos y ambientales. Los habitantes de regiones de gran altitud están expuestos a hipoxia hipobárica crónica, lo que se ha asociado a una mayor prevalencia de varias anomalías congénitas. Objetivo. El objetivo del estudio es investigar la prevalencia al nacimiento de malformaciones anorrectales en La Paz, Bolivia. Material y métodos. Se realizó un estudio transversal. Los casos fueron recolectados en el Hospital de la Mujer ubicado en La Paz, Bolivia, a una altitud promedio de 3600 metros sobre el nivel del mar. Resultados. De 56206 nacidos vivos registrados durante el periodo de estudio, 30 recién nacidos presentaban malformaciones anorrectales, lo que arrojaba una prevalencia de 5,34 por 10000 nacidos vivos. Esta prevalencia era superior a la prevalencia de 3 por 10000 nacidos vivos registrada anteriormente en la literatura. Conclusiones. Nuestro estudio muestra que la prevalencia de malformaciones anorrectales es mayor en la población de altura de La Paz, Bolivia, en comparación con la prevalencia previamente reportada en la literatura. Se necesitan más investigaciones para identificar los factores genéticos y ambientales subyacentes que contribuyen a esta mayor prevalencia, además de mejorar el diagnóstico y los sistemas de vigilancia.

Introduction. Anorectal matformations are a group of congenital anomalies that have a multifactorial etiology, involving various genetic and environmental factors. Inhabitants living at high-altitude regions are exposed to chronic hypobaric hypoxia, which has been associated with a higher prevalence of congenital anomalies. Objective. It was aimed to investígate the prevalence of anorectal malformations in newborns from La Paz, Bolivia. Material and methods. We conducted a cross-sectional study. Newborns data were collected at the Hospital de la Mujer located in La Paz, Bolivia, at an average altitude of 3600 masl. Results. Out of 56,206 live births were registered during the study period. 30 newborns had anorectal malformations, resulting in a prevalence of 5.34 per 10,000 live births. This prevalence was higher than the previously reported in the literature, 3 per 10,000 live births. Conclusions. Our study depicts the prevalence of anorectal malformations is higher in the population of La Paz-Bolivia living at high-altitude, this when compared to previously reported prevalence in the literature. Further research is needed to identify the underlying genetic and environmental factors that contribute to this increased prevalence, as well as to improve diagnosis and monitoring systems.

The biogenic amines putrescine and cadaverine show in vitro cytotoxicity at concentrations that can be found in foods.

Putrescine and cadaverine are among the most common biogenic amines (BA) in foods, but it is advisable that their accumulation be avoided. Present knowledge about their toxicity is, however, limited; further research is needed if qualitative and quantitative risk assessments for foods are to be conducted. The present work describes a real-time analysis of the cytotoxicity of putrescine and cadaverine on intestinal cell cultures. Both BA were cytotoxic at concentrations found in BA-rich foods, although the cytotoxicity threshold for cadaverine was twice that of putrescine. Their mode of cytotoxic action was similar, with both BA causing cell necrosis; they did not induce apoptosis. The present results may help in establishing legal limits for both putrescine and cadaverine in food.

Validation of motion perception of briefly displayed images using a tablet.

Motion perception of briefly displayed images has been reported to be abnormal in clinical populations afflicted with schizophrenia, major depression, autism, Alzheimer's disease and epilepsy. These abnormalities have been measured using CRT monitors connected to a computer. Given that the use of this experimental set-up in clinical environments can be difficult, we tested whether motion perception of briefly displayed images could also be measured using a tablet. For 13 participants, we found similar estimates of motion discrimination on a tablet and a CRT. This validates a tablet to measure motion perception of briefly displayed images.

Defectos del tubo neural en recien nacidos en el hospital de la mujer / Neural tube defects in newborns in women's hospital

OBJETIVO: Conocer la prevalencia al nacimiento de los defectos del tubo neural en recién nacidos del Hospital de la Mujer, La Paz, Bolivia, período comprendido entre el año 2008 - 2017. DISEÑO METODOLÓGICO: Observacional, descriptivo, de corte transversal, retrospectivo. LUGAR: Hospital de la Mujer, a 3650 m.s.n.m. La Paz, Bolivia. MÉTODOS: Se examinaron los expedientes clínicos de todos los recién nacidos del Hospital de la Mujer, en período ya establecido. Para la detección de anomalías congénitas, se utilizaron libros de registro de nacimientos. Se ingresaron los datos a una base Excel, se procedió al análisis de los mismos a través del uso de la estadística descriptiva. RESULTADOS: Se recurrió a registros de 58120 expedientes de recién nacidos, se presentaron 1269 casos con Anomalías Congénitas (2.2%) con una prevalencia al Nacimiento (PN) de 21.83/10.000 RN (22.57/10.000 RN vivos). De dichos 1269 casos, 69 (5.44%) correspondieron a Defectos del Tubo Neural (DTN), con una PN de 11.87/10.000 RN (12.27/10.000 RN vivos), 59.42% DTN asociados al sexo masculino. El tipo de DTN más frecuente evidenciado fue Mielomeningocele (52.17%), y los DTN mortinatos representan el 17.39%. CONCLUSIONS: La llamativa diferencia encontrada, (en relación a la predilección por el sexo masculino), podría sugerir la presencia de una carga genética cuantitativamente mayor (propia de la población estudiada) en la etiología de los DTN en nuestro medio, ya que cuando las condiciones multifactoriales como los DTN afectan al sexo menos frecuentemente descrito, se puede asumir un peso mayor de los factores genéticos en relación a factores ambientales, siguiendo conceptos de heredabilidad y la teoría del umbral para este modo de herencia, sin embargo, somos conscientes que se requiere un tamaño de muestra mayor para arribar a conclusiones más certeras, dichos factores se adicionan al subregistro y posibles sesgos de registro evidenciados durante la realización del estudio.

OBJECTIVE: To know the prevalence at birth of neural tube defects in newborns at Hospital de La Mujer, La Paz, Bolivia, 3650 m.a.s.l, period between 2008 - 2017. PLACE: Women's Hospital, La Paz, Bolivia. METHODS: Observational, descriptive, cross-sectional, retrospective. The clinical records of all newborns were examined, in an already established period. For the detection of congenital anomalies, birth registration books were used. The data were entered into an Excel database, and analyzed through the use of descriptive statistics. RESULTS: 58120 newborn records were examined, 1269 cases with Congenital Anomalies (2.2%) with a prevalence at Birth (PB) of 21.83/10.000 RN (22.57/10.000 RN alive) were presented. Of these 1269 cases, 69 (5,44%) corresponded to Neural Tube Defects (NTD), with a PB of 11.87/10,000 RN (12.27/10,000 RN alive), 59.42% DTN associated with the male sex. The most frequent type of NTD evidenced was Myelomeningocele (52.17%), and stillborn DTNs represented 17.39%. CONCLUSIONS: The distinctive difference found (predilection of NTD for the male sex), could suggest the presence of a quantitatively greater genetic load (typical of the population studied) in the etiology of NTDs in our environment, since when multifactorial conditions affect the less frequently described sex, a greater weight of genetic factors can be assumed compared to environmental factors, following concepts of heritability and the threshold theory for this mode of inheritance; however, we are aware that a larger sample size is needed to arrive at more accurate conclusions, these factors are added to the underreporting and possible recording biases evidenced during the study.