Assessing the Burden of Clostridium difficile Infection in Low- and Middle-Income Countries.

In contrast to the significant resources invested in the diagnosis and prevention of Clostridium difficile infection (CDI) in resource-rich settings, in resource-limited settings patients with community- and hospital-acquired diarrhea may not routinely be tested for CDI. Is CDI actually less frequent or severe in resource-limited settings, or might we be missing an important opportunity to prevent CDI-related morbidity and mortality (and to promote antibiotic stewardship) in these settings? Here, we review the literature to assess the overall burden of CDI in low- and middle-income countries.

[Obesity, metabolic syndrome and olfactory perception]. / Obesidad, síndrome metabólico y percepción olfativa.

Nowadays, it is well accepted that obesity and metabolic syndrome are diseases that constitute a global public health issue. In consequence, the interest in the study of the effects these pathologies produce in the central nervous system has greatly increased in the last decades. One of the most overlooked topics in the literature is the impact they exert in sensory systems, among which is olfaction. The olfactory system is related to a number of vital functions, like the activation of defense mechanisms, contribution to appetitive and digestive reflexes, recognition of conspecifics, and even has socio-sexual implications. It has been discovered that the olfactory system also plays a crucial role in food intake, the choice of foods, appetite and satiety mechanisms; therefore, it is involved in obesity development. Clinical studies have proven that obese patients exhibit hyposmia more frequently than aged-matched healthy controls. Olfactory alterations have also been found in obese rodents or in animals with similar features of human metabolic syndrome. The causes of this association are still being investigated. This work reviews the studies that have tried to understand this association from a preclinical and clinical approach as well as those biological mechanisms that could be involved. The evidences here presented suggest that obesity and metabolic syndrome affect the adequate function of olfactory sensory system.

TITLE: Obesidad, síndrome metabólico y percepción olfativa.En la actualidad, la obesidad y el síndrome metabólico son enfermedades que representan un grave problema global de salud pública. A consecuencia de ello, en las últimas décadas ha aumentado el interés por estudiar los efectos de estas patologías sobre el funcionamiento del sistema nervioso central. Uno de los aspectos más ignorados en la bibliografía ha sido el impacto que tienen sobre los sistemas sensoriales, entre los que se encuentra el olfato. El sistema olfativo se relaciona con distintas funciones vitales, como activar mecanismos de defensa, contribuir a la inducción de reflejos apetitivos y digestivos, y reconocer individuos de su misma especie, e incluso tiene implicaciones sociosexuales. Se sabe que, además, desempeña un papel importante en la ingesta de alimentos, en la decisión de lo que se va a consumir, en los mecanismos de apetito y saciedad y, por ende, está involucrado en el desarrollo de obesidad. Estudios clínicos han demostrado que pacientes con obesidad presentan hiposmia con mayor frecuencia en comparación con sujetos delgados de la misma edad. También se han encontrado alteraciones en el olfato de roedores que presentan obesidad o rasgos similares a los del síndrome metabólico del humano. Las causas por las cuales existe esta asociación apenas están comenzando a investigarse; en este trabajo se revisan los estudios que han intentado entenderla desde un enfoque clínico y preclínico, así como los mecanismos biológicos que hasta el momento se han explorado en la bibliografía.

[Anatomic spectrum between complete and partial atrioventricular septal defect. Two and three-dimensional echocardiography approach]. / Espectro anatómico entre el defecto de la tabicación atrioventricular completo y parcial. Evaluación con ecocardiografía bi y tridimensional.

INTRODUCTION: It has been postulated that there is a morphogenetic relation between the atrioventricular septal defect (AVSD) type A of Rastelli and the type of two separated orifices, this so called partial forms, existent between both types a spectrum of anatomical forms in which interchordal spaces determinate the ventricular septal defects (VSD) size to forms in which the VSD is closed by fusion of the left septal valves to the crest of ventricular septum. METHODS: We present five patients which illustrates the variability of the atrioventricular defect by means of two dimensional and three-dimensional echocardiography. In each case was made a transesophagic echocardiogram using three-dimensional reconstruction with an Echo-Scan system (4.0 TomTec Gmb version, Munich, Germany). RESULTS: It was observed the following spectrum of atrioventricular defect: one patient had a complete closure of the VSD by the insertion of the left septal valves to the interventricular septal crest. One patient has a partially closed VSD. The last 3 patients had a large VSD with a large shunt and high pulmonary pressure. In those patients in whom the VSD was completely or partially closed, the hemodynamic behavior depended of the interatrial shunt and the regurgitation of the atrioventricular valve. They didn't present pulmonary hypertension, what allowed them to be less symptomatic. CONCLUSIONS: The three-dimensional echocardiographic study of the spectrum of AVSD type A of Rastelli, defines accurately the valve components and septal structures, so we can understand the transition between complete and partial forms. This difference determines the clinical evolution of the patients.

Relevance of Alternative Routes of Kynurenic Acid Production in the Brain.

The catabolism of tryptophan has gained great importance in recent years due to the fact that the metabolites produced during this process, with neuroactive and redox properties, are involved in physiological and pathological events. One of these metabolites is kynurenic acid (KYNA), which is considered as a neuromodulator since it can interact with NMDA, nicotinic, and GPR35 receptors among others, modulating the release of neurotransmitters as glutamate, dopamine, and acetylcholine. Kynureninate production is attributed to kynurenine aminotransferases. However, in some physiological and pathological conditions, its high production cannot be explained just with kynurenine aminotransferases. This review focuses on the alternative mechanism whereby KYNA can be produced, either from D-amino acids or by means of other enzymes as D-amino acid oxidase or by the participation of free radicals. It is important to mention that an increase in KYNA levels in processes as brain development, aging, neurodegenerative diseases, and psychiatric disorders, which share common factors as oxidative stress, inflammation, immune response activation, and participation of gut microbiota that can also be related with the alternative routes of KYNA production, has been observed.

Low Serum Tryptophan Levels as an Indicator of Global Cognitive Performance in Nondemented Women over 50 Years of Age.

Aging is a physiological decline process. The number of older adults is growing around the world; therefore, the incidence of cognitive impairment, dementia, and other diseases related to aging increases. The main cellular factors that converge in the aging process are mitochondrial dysfunction, antioxidant impairment, inflammation, and immune response decline, among others. In this context, these cellular changes have an influence on the kynurenine pathway (KP), the main route of tryptophan (Trp) catabolism. KP metabolites have been involved in the aging process and neurodegenerative diseases. Although there are changes in the metabolite levels with age, at this time, there is no study that has evaluated cognitive decline as a consequence of Trp catabolism fluctuation in aging. The aim of this study was to evaluate the relation between the changes in Trp catabolism and cognitive impairment associated with age through KP metabolites level alterations in women over 50 years of age. Seventy-seven nondemented women over 50 years old were examined with a standardized cognitive screening evaluation in Spanish language (Neuropsi), Beck anxiety inventory (BAI), and the geriatric depression scale (GDS). Also, serum levels of Trp, kynurenine (Kyn), kynurenic acid (KYNA), and 3-hydroykynurenine (3-HK) and the glutathione ratio (GSH/GSSG) were measured. Results showed a negative correlation between age and Trp levels and a positive correlation between age and KYNA/Trp and 3-HK/Trp ratios. The level of cognitive impairment showed a significant positive association with age and with kynurenine pathway activation and a significant negative correlation with Trp levels. The GSH/GSSG ratio correlated positively with Trp levels and negatively with Kyn/Trp and 3-HK/Trp ratios. The depression score correlated negatively with Trp and positively with the 3-HK/Trp ratio. We concluded that KP activation increases with age and it is strongly associated with the level of cognition performance in nondemented women over 50 years of age.

Are executive functions related to emotional intelligence? A correlational study in schizophrenia and borderline personality disorder.

This research explored the relationship between executive functions (working memory and reasoning subtests of the Wechsler Adult Intelligence Scale, Trail Making and Stroop tests, fluency and planning tasks, and Wisconsin Card Sorting Test) and emotional intelligence measured by the Mayer-Salovey-Caruso Emotional Intelligence Test in patients with schizophrenia or borderline personality disorder compared to a control group. As expected, both clinical groups performed worse than the control group in executive functions and emotional intelligence, although the impairment was greater in the borderline personality disorder group. Executive functions significantly correlated with social functioning. Results are discussed in relation to the brain circuits that mediate executive functions and emotional intelligence and the findings obtained with other models of social cognition.

Assessing the optimal liquid volume to be sprayed on isolated olive trees according to their canopy volumes.

The application of pesticides to traditional and intensive olive orchards in Southern Spain has led to environmental problems. More specifically, the lack of an accurate, useful criterion to regulate the spray volume in relation to canopy characteristics has led to spray drift and runoff, which are threats to local ecosystems. The aim of this study was to determine the optimal relationship between canopy volume and the spray application volume, called specific spray volume, CV, through laboratory and field trials. In the laboratory trial, 6 specific spray volumes (0.05, 0.08, 0.10, 0.12, 0.15, and 0.20Lm(-3)) were tested in a specially designed structure containing small, live olive trees in order to simulate an intensive plantation system. The model aimed to evaluate the coverage of pesticide application on water sensitive paper (WSP) collectors. In the field trial, the three laboratory specific spray volumes that gave the best coverage values were tested on live, intensively managed trees, whose crown volume was manually measured. Food dye E-102 was used to determine the spray deposition on artificial targets (10×10cm absorbent paper pieces), and WSP was used to evaluate spray coverage. The spray penetration and deposit homogeneity inside the canopy were also evaluated. Weather conditions during the field trial were monitored with a weather station. The results of the laboratory trial showed that the three best specific spray volumes were 0.08, 0.10, and 0.12Lm(-3), resulting in mean coverage values of approximately 30%. The ANOVA of the field trial results showed that the 0.12Lm(-3) was the optimal specific spray volume for isolated olive trees. This specific spray volume gave the highest mean deposits, the best efficiency (as measured by the greatest normalized deposit), the most favourable penetration and homogeneity, and the highest coverage values.

Effects of physostigmine infusion on healthy volunteers deprived of rapid eye movement sleep.

Rapid eye movement sleep (REMS) deprivation is believed to alter the sensitivity of various neurotransmitter systems. In the present article, we studied 20 healthy volunteers divided into three groups. Group A attended the sleep laboratory for three nights: acclimatization, a baseline night, and one night of physostigmine infusion. Group B attended for eight nights; acclimatization, baseline, four nights of REMS deprivation, and two recovery nights. With the exception of the first recovery night, when group C volunteers were administered physostigmine, group C's schedule was identical to group B's. The infusions received by group A and C were composed of 1.0 mg of physostigmine, dissolved in 100 ml of saline solution. These were administered 5 min after sleep onset and thereafter every hour, except when the subjects were either awake or in REMS. All of the subjects receiving the cholinomimetic infusion were given a peripheral anticholinergic. Group A experienced a great number of awakenings with a decrease in REMS percentage. Group B recovery occurred over two nights, with an increase in the average length of REMS. Group C exhibited maximum REMS rebound on the first recovery night with an increased number of REMS episodes, as well as significant reductions in the first REMS latency. Our findings suggest that physostigmine alters REMS rebound following REMS deprivation.

The effect of total sleep deprivation on plasma melatonin and cortisol in healthy human volunteers.

Twelve healthy volunteers were included in this study. Baseline curves for melatonin and cortisol were obtained after one night of adaptation to laboratory conditions. From 10:00 p.m. to 6:00 a.m., blood samples were drawn every hour. On the third night, the subjects were kept awake at the sleep unit. Curves for the two hormones were then obtained after 36 h of total sleep deprivation (SD). The levels of these hormones were evaluated by calculating the area under the curve at each hour in both situations (basal and after sleep deprivation). It was found that the melatonin levels were increased after sleep deprivation, whereas the cortisol levels remained the same. These results suggest a mechanism by which a reset of abnormal rhythms can occur in depression.

Anxiolytics reverse the acceleration of ejaculation resulting from enforced intercopulatory intervals in rats.

The enforced interval of copulation (EIC) consists of the artificial prolongation of the interintromission interval, induces a reduction in the number of intromissions preceding ejaculation, and is accompanied by an anxiety like behavioral repertoire. The administration of the benzodiazepine anxiolytics diazepam, chlordiazepoxide, flurazepam, and flunitrazepam produced a dose-dependent inhibition of the EIC effect with a concomitant increase in mounting. These actions were blocked by the central benzodiazepine antagonist Ro 15-1788. The anxiogenic agent beta-carboline Zk 39106 had no effect. Treatment with pentobarbital also produced a blockade of the reduction in the number of intromissions during EIC, whereas muscimol and bicuculline lacked this effect. The serotonergic anxiolytic buspirone reversed the facilitatory action induced by EIC; however, two putative serotonergic antianxiety agents, 8-OH-DPAT and ipsapirone, did not modify or potentiate it, respectively. Finally, the nonanxiolytic serotonergic compounds 5-hydroxytryptophan and TFMPP drastically increased the number of mounts but did not antagonize the reduction of intromissions produced by EIC. These results suggest that an increase in the anxiety levels may be responsible for the excitatory action of EIC on sexual behavior.

Tetrodotoxin blockade of amygdala overlapping with poisoning impairs acquisition of conditioned taste aversion in rats.

The role of several forebrain structures in the association of the short-term gustatory memory (GSTM) of the conditioned stimulus (CS; 0.1% sodium saccharin) with the visceral unconditioned stimulus (US; 0.15 M LiCl, 2% b.wt.) in acquisition of conditioned taste aversion (CTA) was investigated. Experiment 1 examined the effects of bilateral reversible inactivation of amygdala (Amy), hippocampus (Hipp), gustatory cortex (GC), bed nucleus of stria terminalis (BNST), lateral hypothalamic area (LHA), ventral thalamus (VT) or LHA+VT, induced by intracerebral injection of tetrodotoxin (TTX; 10 ng/microliters per site) applied before i.p. injection of LiCl to rats anesthetized by pentobarbital (50 mg/kg) immediately after saccharin drinking. Amy blockade resulted in a complete disruption of learning, while the inactivation of the remaining areas examined produced mild or no impairments. The dose-related effects of TTX injection into Amy were investigated in Experiment 2. Doses of 3 and 1 ng TTX were as effective as the 10 ng dose used in Expt. 1. However, 0.3 ng or saline did not interfere with CTA acquisition. Analysis of the retrograde amnesic effect produced by transient amygdalectomy (Experiment 3), showed that TTX (10 ng) injected immediately or 1.5 h after LiCl application induced a marked learning disruption, whereas no amnesia was elicited at 6 and 24 h post-acquisition intervals. It is suggested that Amy plays an essential role in the associative phase of acquisition, but not in the consolidation of the permanent taste aversion engram.

Ipsilateral connections between the gustatory cortex, amygdala and parabrachial nucleus are necessary for acquisition and retrieval of conditioned taste aversion in rats.

Acquisition and retrieval of conditioned taste aversion (CTA) is implemented by the interaction of several brain structures. In order to clarify the role of 3 important gustatory and visceral relays, gustatory neocortex (GC), amygdala (AM) and parabrachial nucleus (PB), two experimental series were carried out. In Expt. 1 reversible unilateral lesions of the PB and AM or of AM and GC were induced by 10 ng of tetrodotoxin (TTX) either in the same hemisphere or in the opposite hemispheres during CTA acquisition. It was found that contralateral TTX injections into the above structures caused a complete blockade of CTA acquisition which was not affected by ipsilateral TTX administration. In Expt. 2, retrieval of CTA acquired during unilateral blockade of the PB or AM in one hemisphere has been examined during unilateral TTX blockade of GC alone, AM alone or during combined GC and AM inactivation either in the same or in the contralateral hemispheres. A clear CTA retrieval impairment was found only when structures in the opposite hemispheres were blocked. These results indicate a complete lateralization of CTA acquisition and retrieval processes and suggest that the long-term CTA engram can be formed in each hemisphere separately without participation of the contralateral hemisphere.

Differential involvement of gustatory insular cortex and amygdala in the acquisition and retrieval of conditioned taste aversion in rats.

Lesion studies of the role of the gustatory insular cortex (GC) and amygdala (Am) in conditioned taste aversion (CTA) are confounded by the irreversibility of the intervention. Functional ablation methods allow more specific influencing of different phases of CTA acquisition and retrieval. Bilateral tetrodotoxin (TTX) blockade of GC (10 ng) or Am (3 ng) before or after saccharin drinking in rats with chronically implanted intracerebral cannulae showed that GC is indispensable for the initial processing of the taste stimulus but not for the association of the gustatory trace with the symptoms of LiCl poisoning. Gustatory signals can by-pass the blocked Am, the inactivation of which, however, impairs the gustatory trace-poisoning association. TTX injection into both GC and Am impairs CTA retrieval more than isolated blockade of either of these structures. It is argued that GC and Am implement processing of gustatory and visceral signals, respectively, but that formation and consolidation of the CTA engram proceeds outside forebrain, probably at the level of the brainstem.

Dose- and time-dependent scopolamine-induced recovery of an inhibitory avoidance response after its extinction in rats.

The present investigation was aimed at elucidating the dose and time dependency of scopolamine-induced recovery of inhibitory avoidance after its extinction. Two experiments were conducted: in the first, we analyzed the effects of four doses (1, 2, 4, and 8 mg/kg) of the musacrinic receptor antagonist scopolamine, on the expression of this conditioned response once it had been extinguished. Independent groups of rats were trained in a one-trial, step-through inhibitory avoidance task and submitted to daily retention (extinction) tests. After extinction had occurred, animals were injected intraperitoneally 10 min before retention testing, either with saline or scopolamine. Results show that scopolamine produced a dose-dependent recovery of the avoidance response. The second experiment was carried out in the same animals, which were now tested for retention of inhibitory avoidance at 1, 2, 3, 6, and 9 months after completion of the first experiment. All rats received counterbalanced injections of saline or scopolamine 10 min before testing at each time interval. Reliable recovery of the avoidance response was observed at the 1-month interval with a clear dose dependency while, after the second month, only the groups treated with the two higher doses continued responding. The results indicate that recovery of the extinguished response produced by muscarinic blockade follows dose- and time-dependent curves, and can be achieved long after a single training session. These data suggest that the inhibitory avoidance memory trace is retained in the brain after behavioural extinction of this response, thus supporting the view of extinction as new learning that affects the retrieval of the original memory, but does not modify its storage.

Reduction in anxiety after ejaculation in the rat.

The anxiety levels, tested in the conditioned defensive burying behaviour paradigm, were analyzed after various phases of copulatory behaviour. No differences in anxiety were found between the group of animals without sexual activity and the group of animals tested after five intromissions of the first ejaculatory series. A decrease in anxiety, reflected as a reduction in the burying behaviour, was found in the group of animals tested during the first and the second postejaculatory intervals or after two intromissions from the second series of copulation. The possible involvement of the GABAergic system mediating the reduction in anxiety during these phases of copulation is discussed.

Tetrodotoxin inactivation of the gustatory cortex disrupts the effect of the N-methyl-D-aspartate antagonist ketamine on latent inhibition of conditioned taste aversion in rats.

The effect of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine on latent inhibition of taste aversion learning was studied in rats. Systemic injections of ketamine (50 mg/kg) applied after each of three preexposures to sodium saccharin (0.1%) disrupted the latent inhibition effect. The blockade was not due to aversive properties of ketamine, because three saccharin-ketamine pairings did not produce saccharin aversion. Moreover, the ketamine-induced blockade of latent inhibition was disrupted by tetrodotoxin injections (10 ng/microl)-induced reversible inactivation of gustatory cortex, applied after each preexposure. A specific gustatory cortex mediation of the ketamine effect is discussed.

Selective M1 muscarinic receptor antagonists disrupt memory consolidation of inhibitory avoidance in rats.

The effect of three different M1 muscarinic antagonists, pirenzepine, biperiden, and trihexyphenidyl on memory consolidation was investigated. Rats were trained in a one-trial step-through inhibitory avoidance task and injected intraperitoneally immediately afterwards, either with pirenzepine, biperiden, or trihexyphenidyl (dose range from 0 to 16 mg/kg). The non-selective antimuscarinic compound scopolamine, was also administered for comparison. One day later, rats were tested for retention. Results show that biperiden, trihexyphenidyl and scopolamine produced a dose-dependent impairment of inhibitory avoidance consolidation, while pirenzepine had no effect. The amnestic state produced by biperiden and trihexyphenidyl was comparable to that observed after the administration of scopolamine. These results indicate that the selective blockade of the central M1 muscarinic receptors interfere with memory consolidation of inhibitory avoidance and suggest that this receptor subtype is critically involved in mnemonic functions.

Survival of patients with medulloblastoma treated with carboplatin and etoposide before and after radiotherapy.

BACKGROUND: Medulloblastoma represents 20% of all tumors of the central nervous system. Patients with partial resection of the tumor and those with extension into the neuraxis at diagnosis have been identified as high-risk patients. The objective of our study was to determine tumor response, survival rates and toxicity with a new scheme of treatment with carboplatin, etoposide and radiotherapy. METHODS: All patients received chemotherapy with carboplatin and etoposide every 4 weeks for four courses, hyperfractionated radiotherapy, and another four courses of the above chemotherapy scheme. Tumor response was classified, and global and disease-free survival rates were calculated according to the actuarial survival method. RESULTS: A total of 26 patients were included, with a median age of 6.9 years. Nineteen achieved complete response after the first four courses of chemotherapy, and two more had a complete response after radiotherapy. A total of seven children have died, three of whom did not respond to initial treatment. Global and disease-free survival rates were 69% and 64%, respectively, at 60 months of follow-up. There was no renal or auditory toxicity. Hematological toxicity was transitory and reversible. CONCLUSIONS: This scheme of treatment is effective and can be safely used for pediatric patients with high-risk medulloblastomas. Toxicity was not significant, and survival is similar to other reports.

Reversal of extinction by scopolamine.

The aim of this experiment was to determine the effects of muscarinic blockade on extinction of passive avoidance conditioning. Rats were trained with a foot shock of 2.5, 3.0, or 6.0 mA and were tested for retention for 8 weeks (once weekly). Five minutes before the seventh test they were injected with 8 mg/kg scopolamine. The groups that had been trained with 2.5 and 3.0 mA showed extinction, which was reversed by the scopolamine; the overreinforced group (6.0 mA) did not show extinction and the scopolamine did not alter the conditioned response. The data support the hypothesis that extinction represents the learning of a new response sustained by a set of cholinergic neurons, different from that which mediated original passive avoidance learning.

Reliable variables in the exsanguinated patient which indicate damage control and predict outcome.

BACKGROUND: Exsanguination as a syndrome is ill defined. The objectives of this study were to investigate the relationship between survival and patient characteristics--vital signs, factors relating to injury and treatment; determine if threshold levels of pH, temperature, and highest estimated blood loss can predict survival; and identify predictive factors for survival and to initiate damage control. MATERIAL AND METHODS: A retrospective 6-year study was conducted, 1993 to 1998. In all, 548 patients met one or more criteria: (1) estimated blood loss > or =2,000 mL during trauma operation; (2) required > or =1,500 mL packed red blood cells (PRBC) during resuscitation; or (3) diagnosis of exsanguination. Analysis was made in two phases: (1) death versus survival in emergency department (ED); (2) death versus survival in operating room (OR). Statistical methods were Fisher's exact test, Student's t test, and logistic regression. RESULTS: For 548 patients, mean Revised Trauma Score 4.38, mean Injury Severity Score 32. Penetrating injuries 82% versus blunt injuries 18%. Vital statistics in emergency department: mean blood pressure 63 mm Hg, heart rate 78 beats per minute. Mean OR pH 7.15 and temperature 34.3 degrees C. Mortality was 379 of 548 (69%). Predictive factors for mortality (means): pH < or =7.2, temperature <34 degrees C, OR blood replacement >4,000 mL, total OR fluid replacement >10,000 mL, estimated blood loss >15 mL/minute (P <0.001). Analysis 1: death versus survival in ED, logistic regression. Independent risk factors for survival: penetrating trauma, spontaneous ventilation, and no ED thoracotomy (P <0.001; probability of survival 0.99613). Analysis 2: death versus survival in OR, logistic regression. Independent risk factors for survival: ISS < or =20, spontaneous ventilation in ED, OR PRBC replacement <4,000 mL, no ED or OR thoracotomy, absence of abdominal vascular injury (P <0.001, max R(2) 0.55, concordance 89%). CONCLUSIONS: Survival rates can be predicted in exsanguinating patients. "Damage control" should be performed using these criteria. Knowledge of these patterns can be valuable in treatment selection.