Dissociable Contributions of Basolateral Amygdala and Ventrolateral Orbitofrontal Cortex to Flexible Learning Under Uncertainty.

Reversal learning measures the ability to form flexible associations between choice outcomes with stimuli and actions that precede them. This type of learning is thought to rely on several cortical and subcortical areas, including the highly interconnected orbitofrontal cortex (OFC) and basolateral amygdala (BLA), and is often impaired in various neuropsychiatric and substance use disorders. However, the unique contributions of these regions to stimulus- and action-based reversal learning have not been systematically compared using a chemogenetic approach particularly before and after the first reversal that introduces new uncertainty. Here, we examined the roles of ventrolateral OFC (vlOFC) and BLA during reversal learning. Male and female rats were prepared with inhibitory designer receptors exclusively activated by designer drugs targeting projection neurons in these regions and tested on a series of deterministic and probabilistic reversals during which they learned about stimulus identity or side (left or right) associated with different reward probabilities. Using a counterbalanced within-subject design, we inhibited these regions prior to reversal sessions. We assessed initial and pre-/post-reversal changes in performance to measure learning and adjustments to reversals, respectively. We found that inhibition of the ventrolateral orbitofrontal cortex (vlOFC), but not BLA, eliminated adjustments to stimulus-based reversals. Inhibition of BLA, but not vlOFC, selectively impaired action-based probabilistic reversal learning, leaving deterministic reversal learning intact. vlOFC exhibited a sex-dependent role in early adjustment to action-based reversals, but not in overall learning. These results reveal dissociable roles for BLA and vlOFC in flexible learning and highlight a more crucial role for BLA in learning meaningful changes in the reward environment.

Adaptation of sea turtles to climate warming: Will phenological responses be sufficient to counteract changes in reproductive output?

Sea turtles are vulnerable to climate change since their reproductive output is influenced by incubating temperatures, with warmer temperatures causing lower hatching success and increased feminization of embryos. Their ability to cope with projected increases in ambient temperatures will depend on their capacity to adapt to shifts in climatic regimes. Here, we assessed the extent to which phenological shifts could mitigate impacts from increases in ambient temperatures (from 1.5 to 3°C in air temperatures and from 1.4 to 2.3°C in sea surface temperatures by 2100 at our sites) on four species of sea turtles, under a "middle of the road" scenario (SSP2-4.5). Sand temperatures at sea turtle nesting sites are projected to increase from 0.58 to 4.17°C by 2100 and expected shifts in nesting of 26-43 days earlier will not be sufficient to maintain current incubation temperatures at 7 (29%) of our sites, hatching success rates at 10 (42%) of our sites, with current trends in hatchling sex ratio being able to be maintained at half of the sites. We also calculated the phenological shifts that would be required (both backward for an earlier shift in nesting and forward for a later shift) to keep up with present-day incubation temperatures, hatching success rates, and sex ratios. The required shifts backward in nesting for incubation temperatures ranged from -20 to -191 days, whereas the required shifts forward ranged from +54 to +180 days. However, for half of the sites, no matter the shift the median incubation temperature will always be warmer than the 75th percentile of current ranges. Given that phenological shifts will not be able to ameliorate predicted changes in temperature, hatching success and sex ratio at most sites, turtles may need to use other adaptive responses and/or there is the need to enhance sea turtle resilience to climate warming.

[Registry of perioperative cardiac arrests in a clinical hospital in the period 2006-2017]. / Registro de paro cardiorrespiratorio perioperatorio en un hospital universitario en el período 2006-2017.

BACKGROUND: Perioperative cardiac arrest (PCA) is a rare but important event in the operating room. AIM: To describe PCA events at a Clinical Hospital in Santiago, Chile. MATERIAL AND METHODS: Registry of PCA that occurred in the operating room (OR) and during procedures not carried out in the OR between September 2006 and November 2017. Precipitating events, type of anesthesia and results of resuscitation maneuvers were described. RESULTS: Eighty events (five outside of the OR) during 170,431 surgical procedures were recorded, resulting in an incidence of 4.4 events per 10,000 interventions. Hypotension/hypoperfusion was the most frequently found preexisting condition (42.5%). The main cause was the presence of preoperative complications (57.5%). Nineteen cases (23.8%) were attributable to anesthesia, with an incidence of 1.11 per 10,000 anesthetic procedures. Survival rate at hospital discharge was 52.5%. The figure for PCA caused by anesthesia was 84.2%. CONCLUSIONS: The incidence of PCA and its survival is similar to that reported abroad. In general, PCA has a better prognosis than other types of cardiac arrest, especially if it has an anesthetic cause.

Prevalence of human papillomavirus types in North and Central regions of Mexico.

Human papillomavirus (HPV) is a DNA virus linked to mucosal and cutaneous carcinogenesis. More than 200 different HPV types exist. We carried out a transversal study to investigate the prevalence of HPV types in two regions of Mexico. A total of 724 genital and non-genital samples from women (F) and men (M) were studied; 241 (33%) from North-Eastern (NE) and 483 (66%) from South-Central (SC) Mexico. The overall prevalence was 87%. In genital lesions from females, the NE group showed a prevalence of HPV types 16 (37%), 6 (13%), 59 (6%), 11, 18 and 66 (5.4% each); and the SC group showed types 6 (17%), 16 (15%), 11 (14.5%), 18 (12%) and 53 (6%). In the genital lesions from males, NE group showed types 16 (38%), 6 (21%), 11 (13%) and 59 plus 31 (7.5%) and the SC group showed types 6 (25%), 11 (22%), 18 (17%) and 16 (11.5%). When the two regions were compared, a higher prevalence of low-risk HPV 6 and 11 was found in the SC region and of high-risk HPV 59, 31 and 66 (the latter can also be present in benign lesions) in the NE region. Our findings complement efforts to understand HPV demographics as a prerequisite to guide and assess the impact of preventive interventions.

Hiccups in Parkinson's disease: an analysis of cases reported in the European pharmacovigilance database and a review of the literature.

BACKGROUND: Some reports have suggested an association between dopamine agonists and hiccups, involuntary contractions that merit full clinical attention because they can be very debilitating. Many drugs frequently used to treat hiccups are formally contraindicated in Parkinson's disease due to their liability to worsen motor symptoms, making the treatment of hiccups problematic in this disease. The objective of the present study was to analyze all spontaneous reports of hiccups from the European Pharmacovigilance Database in patients with Parkinson's disease and/or on dopaminergic drugs. Finally, we sought to identify evidence-based recommendations on the management of hiccups in Parkinson's disease. METHODS: We searched for all reports of hiccups in the European Pharmacovigilance Database (EudraVigilance) and calculated proportional reporting ratios for dopamine agonists and hiccups. We reviewed the literature on Parkinson's disease, dopamine agonists, and hiccups, searching for specific treatment recommendations for hiccups in this disease. RESULTS: Both rotigotine and pramipexole fulfilled the criteria to generate a safety signal. We found 32 and 13 cases of hiccups associated with dopamine agonists in EudraVigilance and the literature, respectively. There were no specific recommendations for the management of hiccups in Parkinson's disease in the clinical guidelines consulted. CONCLUSIONS: We have found evidence that rotigotine and pramipexole are associated with the appearance of hiccups and that this adverse reaction occurs predominantly in males. Given the scarce information available, specific recommendations are needed in clinical guidelines for the adequate management of hiccups in Parkinson's disease.

How to improve the diagnosis of eosinophilic esophagitis: Experience from a case series in Mexico. / Cómo mejorar el diagnóstico de esofagitis eosinofílica: experiencia de una serie de casos en México.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic, immune disorder mediated largely by food antigens. It shares nonspecific symptoms with gastroesophageal reflux disease (GERD). EoE is rarely reported in Mexico, perhaps due to the racial characteristics of the population or because of insufficient diagnostic suspicion. AIMS: Our aim was to describe a Mexican cohort with EoE and evaluate the usefulness of the clinical history and endoscopy in the EoE diagnosis, in comparison with GERD patients. MATERIALS AND METHODS: A retrospective study was carried out on the clinical characteristics and endoscopic and histopathologic findings in patients with EoE, along with a case-control study on patients with GERD. The endoscopic images obtained were interpreted in a blind and randomized manner by 4 gastroenterologists, before and after providing them with information on the characteristic alterations of EoE. The esophageal biopsies were also blinded to 2 pathologists that evaluated their diagnostic correlation. The Fisher's exact test and Mann-Whitney U test were used in the statistical analysis. RESULTS: Fourteen patients with EoE were included in the study. Ten (71%) of them were men and the mean age of the patients was 35 years. There were more subjects with a personal history of asthma (p=0.0023) and food impaction (p=0.04) in the EoE group. The initial evaluation of the endoscopic findings showed 53% correct EoE interpretations and rose to 96% in the second revision (sensitivity 100%, specificity 71%, PPV 65%, NPV 100%). CONCLUSIONS: Mexican patients with EoE have similar characteristics to those of patients in western case series. Clinical awareness of the disorder increases endoscopic diagnosis in up to 40% of cases.

Serum 25-Hydroxyvitamin D associated with indicators of body fat and insulin resistance in prepubertal chilean children.

BACKGROUND: Consistent data on the relation between vitamin D, body fat and insulin resistance (IR) in children are lacking. OBJECTIVES: (1) To evaluate the association between serum 25-Hydroxyvitamin D [25(OH)D] and key indicators of: adiposity (total and central), IR, and (2) to estimate serum 25(OH)D cut-offs that best reflect IR and total and central adiposity in children. SUBJECTS/METHODS: Prepubertal children (n=435, ~53% girls; ~age 7 years) from the Growth and Obesity Chilean Cohort Study were evaluated for potential associations between serum 25(OH)D and indicators of: (1) total adiposity (body mass index by age (BAZ), body fat (including three-component model)), central adiposity (waist circumference and trunk fatness); (2) IR (homeostasis model assessment of IR) and insulin sensitive (quantitative insulin sensitivity check index) using standardized multiple regression models with standardized coefficients and receiver operating characteristic curves. RESULTS: Overall, mean serum 25(OH)D was 32.1±9.2 ng ml(-1), while 19.4% of children were obese (BAZ⩾2 s.d.). Serum 25(OH)D was inversely associated with indicators of total and central adiposity and with IR indicators. Effect sizes were moderate in girls (~0.3 for adiposity and IR indicators), while, weaker values were found in boys. Serum 25(OH)D estimated cut-offs that best predicted total, central adiposity and IR were~30 ng ml(-1). Children with suboptimal serum 25(OH)D (<30 ng ml(-1)) had a higher risk (two to three times) of being obese (high BAZ, body fat percent and/or central adiposity); and three to four times greater risk for IR. CONCLUSIONS: Serum 25(OH)D was inversely associated with adiposity (total and central) and IR indicators in prepubertal Chilean children. The conventional cut-off of vitamin D sufficiency (⩾30 ng ml(-1)) was adequate to assess obesity and IR risk in this age group.

Dipeptidyl peptidase-IV inhibitors induced bullous pemphigoid: a case report and analysis of cases reported in the European pharmacovigilance database.

WHAT IS KNOWN AND OBJECTIVE: Bullous pemphigoid has been reported in association with gliptins. We describe a case, review the literature and analyse all cases of bullous pemphigoid recorded in the European pharmacovigilance database, EudraVigilance. CASE SUMMARY: A 74-year-old woman, treated with vildagliptin/metformin for 12 months, developed bullous pemphigoid, confirmed by skin biopsy. The symptoms resolved within 7 months after vildagliptin/metformin withdrawal. WHAT IS NEW AND CONCLUSION: A search in EudraVigilance showed a disproportionality for bullous pemphigoid and gliptins, except alogliptin. These findings extend the evidence associating gliptins with this potentially serious disease.

Failure of deactivation in the default mode network: a trait marker for schizophrenia?

BACKGROUND: Functional imaging studies in relatives of schizophrenic patients have had inconsistent findings, particularly with respect to altered dorsolateral prefrontal cortex activation. Some recent studies have also suggested that failure of deactivation may be seen. METHOD: A total of 28 patients with schizophrenia, 28 of their siblings and 56 healthy controls underwent functional magnetic resonance imaging during performance of the n-back working memory task. An analysis of variance was fitted to individual whole-brain maps from each set of patient-relative-matched pair of controls. Clusters of significant difference among the groups were then used as regions of interest to compare mean activations and deactivations among the groups. RESULTS: In all, five clusters of significant differences were found. The schizophrenic patients, but not the relatives, showed reduced activation compared with the controls in the lateral frontal cortex bilaterally, the left basal ganglia and the cerebellum. In contrast, both the patients and the relatives showed significant failure of deactivation compared with the healthy controls in the medial frontal cortex, with the relatives also showing less failure than the patients. Failure of deactivation was not associated with schizotypy scores or presence of psychotic-like experiences in the relatives. CONCLUSIONS: Both schizophrenic patients and their relatives show altered task-related deactivation in the medial frontal cortex. This in turn suggests that default mode network dysfunction may function as a trait marker for schizophrenia.

A PCR-Based Diagnostic System for Differentiating Two Weevil Species (Coleoptera: Curculionidae) of Economic Importance to the Chilean Citrus Industry.

A PCR-based method was developed to identify Naupactus cervinus (Boheman) and Naupactus xanthographus (Germar), two curculionids affecting the citrus industry in Chile. The quarantine status of these two species depends on the country to which fruits are exported. This identification method was developed because it is not possible to discriminate between these two species at the egg stage. The method is based on the species-specific amplification of sequences of internal transcribed spacers, for which we cloned and sequenced these genome fragments from each species. We designed an identification system based on two duplex-PCR reactions. Each one contains the species-specific primer set and a second generic primer set that amplify a short 18S region common to coleopterans, to avoid false negatives. The marker system is able to differentiate each Naupactus species at any life stage, and with a diagnostic sensitivity to 0.045 ng of genomic DNA. This PCR kit was validated by samples collected from different citrus production areas throughout Chile and showed 100% accuracy in differentiating the two Naupactus species.

The influence of process parameters in production of lipopeptide iturin A using aerated packed bed bioreactors in solid-state fermentation.

The strain Bacillus iso 1 co-produces the lipopeptide iturin A and biopolymer poly-γ-glutamic acid (γ-PGA) in solid-state fermentation of substrate consisting of soybean meal, wheat bran with rice husks as an inert support. The effects of pressure drop, oxygen consumption, medium permeability and temperature profile were studied in an aerated packed bed bioreactor to produce iturin A, diameter of which was 50 mm and bed height 300 mm. The highest concentrations of iturin A and γ-PGA were 5.58 and 3.58 g/kg-dry substrate, respectively, at 0.4 L/min after 96 h of fermentation. The low oxygen uptake rates, being 23.34 and 22.56 mg O2/kg-dry solid substrate for each air flow rate tested generated 5.75 W/kg-dry substrate that increased the fermentation temperature at 3.7 °C. The highest pressure drop was 561 Pa/m at 0.8 L/min in 24 h. This is the highest concentration of iturin A produced to date in an aerated packed bed bioreactor in solid-state fermentation. The results can be useful to design strategies to scale-up process of iturin A in aerated packed bed bioreactors. Low concentration of γ-PGA affected seriously pressure drop, decreasing the viability of the process due to generation of huge pressure gradients with volumetric air flow rates. Also, the low oxygenation favored the iturin A production due to the reduction of free void by γ-PGA production, and finally, the low oxygen consumption generated low metabolic heat. The results show that it must control the pressure gradients to scale-up the process of iturin A production.

Management of cerebral venous thrombosis in Spain: MOTIVATE descriptive study.

INTRODUCTION: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke that mainly affects young adults. Early, accurate diagnosis can reduce the rate and severity of complications. OBJECTIVE: The aim of this study was to analyse the clinical characteristics, management, and treatment of CVT in different centres in Spain. METHODS: We conducted a multicentre, retrospective, descriptive study of patients hospitalised due to CVT between 2008 and 2017 at 10 Spanish centres. RESULTS: We included 256 patients, with a mean age (SD) of 49.8 (18.7) years; 51% of patients were women. The most frequent symptoms were headache (73%), focal deficits (50%), epileptic seizures (33%), and encephalopathy (21%). The most frequent localisations were the superior sagittal sinus (12.5%), the transverse sinus (10.9%), and 2 or more sinuses or veins (66.4%). Thrombophilia was the most frequent known aetiology (24%), and was most commonly associated with the prothrombin G20210A mutation (19%). Forty-six percent of patients were treated with antithrombotics for 3 to 6 months, 21% for one year, and 22.6% required indefinite anticoagulation. Endovascular therapy was performed in 5% of cases, and 33% required neurosurgery. Regarding outcomes, 75% of patients were independent at 3 months (modified Rankin Scale [mRS] score ≤ 2), with papilloedema (P =  .03), focal deficits (P = .001), and encephalopathy (P < .001) showing a statistically significant association with poor prognosis (mRS > 3). The in-hospital mortality rate was 4.3%, with a 3-month mortality rate of 6.3%. CONCLUSION: The diverse risk factors and variable presentation of CVT represent a challenge in the diagnosis and treatment of this condition. To improve prognosis and reduce mortality, it is essential to establish management protocols for this entity.

4-Hydroxydibenzyl: a novel metabolite from the human gut microbiota after consuming resveratrol.

Resveratrol (RSV) was known to be metabolised by the gut microbiota to dihydroresveratrol, lunularin (LUNU), and (or) 3,4'-dihydroxy-trans-stilbene (DHST). We describe here for the first time that LUNU can be further dehydroxylated, but only at the 3-position, to yield 4-hydroxydibenzyl, a novel metabolite found in human urine after RSV intake in 41 out of 59 healthy participants. In contrast, DHST was not further dehydroxylated, and thus, 4-hydroxy-trans-stilbene was not detected as a gut microbial metabolite of RSV. Faecal in vitro incubations confirmed the in vivo results.

[Multi-tissue donor: a reachable option]. / El donante multitejido: una opción a nuestro alcance.

The clinical use of human tissues is a therapeutic reality in many diseases, observing a spectacular increase in their demand in recent years. This has also generated an increase in the demand for donors which, in regarding to obtaining tissues, is not limited to brain death donors. Consequently, tissues obtained from cardiorespiratory arrest donors must be promoted in our hospitals. With this purpose, we present our experience in the last five years and the mechanisms we used to reach these goals. During this period, an awareness and health care staff information campaign was carried out in the Emergency and Hemodynamic areas. The next step will be to extend this campaign to the rest of the hospital staff. We believe that the mechanisms needed to obtain hospital staff collaboration in the detection of multi-tissue donors is to offer updated information on the indications and therapeutic advantages of clinical use of human tissues, favoring hospital awareness on this subject and therefore the detection of potential donors.

Hepatocellular carcinoma in the noncirrhotic liver: Clinical features and outcomes in Veracruz, Mexico. / Carcinoma hepatocelular en hígado no cirrótico: características clínicas y resultados en Veracruz, México.

INTRODUCTION AND AIM: Hepatocellular carcinoma (HCC) is the most frequent primary tumor of the liver. HCC in the noncirrhotic liver accounts for 15-20% of all HCC. Noncirrhotic HCC is a clinically different entity because of the non-neoplastic liver parenchyma involved. Our aim was to describe the presentation, treatment, and predictive survival results of noncirrhotic HCC in Veracruz. MATERIAL AND METHOD: A retrospective study, spanning 13 years, was conducted on patients with noncirrhotic HCC. It analyzed their clinical characteristics, fibrosis/cirrhosis biologic index (NAFLD, MELD, ALBI, APRI, CDS, FIB-4, GUCI, Lok) results, disease treatment, and survival. RESULTS: From a total of 168 cases of HCC, 33 (19.6%) noncirrhotic patients were included in the study. Of those patients, the mean patient age was 67.3 years (51.5% men), 9.1% had hepatitis C virus infection, and 27.3% were alcoholics. Less than 20% of the patients had biologic indexes suggestive of fibrosis/cirrhosis. Mean tumor size was 7.7cm and 42.4% of the patients had alpha-fetoprotein levels>15ng/ml. A total of 52.5% of the tumors were classified as Okuda II and 30.3% of the patients had advanced disease (the Milan criteria). Liver resection was performed on 51.5% of the patients, radiofrequency ablation on 18.2%, and transarterial chemoembolization on 9.1%. The overall 5-year survival rate was 55.4%. Liver resection resulted in the best 5-year survival rate (72.7%). Age>67 years and elevated alpha-fetoprotein levels were associated with poorer survival (P<.05, log-rank). CONCLUSIONS: The characteristics and survival rate of HCC in the noncirrhotic liver were similar to those reported in other studies. Liver resection provided the highest survival rates. The liver fibrosis biologic indexes were not risk factors for survival.

Management of cerebral venous thrombosis in Spain: MOTIVATE descriptive study. / Manejo de la trombosis venosa cerebral en España: estudio descriptivo MOTIVATE.

INTRODUCTION: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke that mainly affects young adults. Early, accurate diagnosis can reduce the rate and severity of complications. OBJECTIVE: The aim of this study was to analyse the clinical characteristics, management, and treatment of CVT in different centres in Spain. METHODS: We conducted a multicentre, retrospective, descriptive study of patients hospitalised due to CVT between 2008 and 2017 at 11 Spanish centres. RESULTS: We included 256 patients, with a mean age (SD) of 49.8 (18.7) years; 51% of patients were women. The most frequent symptoms were headache (73%), focal deficits (50%), epileptic seizures (33%), and encephalopathy (21%). The most frequent localisations were the superior sagittal sinus (12.5%), the transverse sinus (10.9%), and 2 or more sinuses or veins (66.4%). Thrombophilia was the most frequent known aetiology (24%), and was most commonly associated with the prothrombin G20210A mutation (19%). Forty-six percent of patients were treated with antithrombotics for 3-6 months, 21% for one year, and 22.6% required indefinite anticoagulation. Endovascular therapy was performed in 5% of cases, and 33% required neurosurgery. Regarding outcomes, 75% of patients were independent at 3 months (modified Rankin Scale [mRS] score ≤ 2), with papilloedema (P=.03), focal deficits (P=.001), and encephalopathy (P <.001) showing a statistically significant association with poor prognosis (mRS> 3). The in-hospital mortality rate was 4.3%, with a 3-month mortality rate of 6.3%. CONCLUSION: The diverse risk factors and variable presentation of CVT represent a challenge in the diagnosis and treatment of this condition. To improve prognosis and reduce mortality, it is essential to establish management protocols for this entity.

COMT Val158Met polymorphism in relation to activation and de-activation in the prefrontal cortex: A study in patients with schizophrenia and healthy subjects.

The Val158Met polymorphism in the COMT gene has been found to be associated with differences in brain activation in both healthy subjects and patients with schizophrenia. The predominant finding has been increased prefrontal activation associated with the Val allele; however, genotype-related de-activations have not been studied. In this study 42 schizophrenia patients and 31 controls underwent fMRI while performing the n-back task. Brain differences related to presence/absence of disease and presence/absence of the Val/Val genotype were examined. Both disease and Val/Val genotype were associated with failure of de-activation in a cluster centred in the medial prefrontal cortex. There was no interaction between disease and genotype at this location, but clusters where there were significant interactions emerged in the right prefrontal cortex and left temporal/parietal cortex. These findings suggest that Val158Met polymorphism influences task-related de-activations in the default mode network in both healthy subjects and schizophrenia patients to an equivalent extent. However the Val158Met polymorphism also has disease-specific effects on DLPFC activation in schizophrenia.

Carbon nanotubes as injection electrodes for organic thin film transistors.

We have investigated the charge injection efficiency of carbon nanotube electrodes for organic semiconducting layers and compared their performance to that of traditional noble metal electrodes. Our results reveal that charge injection from a single carbon nanotube electrode is more than an order of magnitude more efficient than charge injection from metal electrodes. Moreover, organic thin film transistors that use arrays of carbon nanotube electrodes display considerable effective mobilities (0.14 cm(2)/(V.s)) and nearly ideal linear output characteristics. These results indicate that carbon nanotubes should be considered a viable alternative to metal electrodes for next-generation organic field-effect transistors.

[Whipple's disease: a case report and review of the literature]. / Enfermedad de Whipple. Presentación de un caso y revisión de la literatura.

Whipple's disease is a systemic infectious condition caused by a gram-positive bacteria belonging to the family of actinomycetes called Tropherima whipplei. It presents most often in males and 13% of patients present with severe diarrhea, fever, adenopathy, weight loss and pigmentation of the skin. Diagnosis is made through duodenal biopsy by which shows foamy macrophages PAS positive. In cases where the histology is negative, we can make the identification of the infectious agent by polymerase-chain reaction (PCR). We describe a 47 years old woman with Whipple's disease whose diagnosis was made through the duodenum and colon biopsies showing infiltration by PAS-positive macrophages.