Chronic full-band recordings with graphene microtransistors as neural interfaces for discrimination of brain states.

Brain states such as sleep, anesthesia, wakefulness, or coma are characterized by specific patterns of cortical activity dynamics, from local circuits to full-brain emergent properties. We previously demonstrated that full-spectrum signals, including the infraslow component (DC, direct current-coupled), can be recorded acutely in multiple sites using flexible arrays of graphene solution-gated field-effect transistors (gSGFETs). Here, we performed chronic implantation of 16-channel gSGFET arrays over the rat cerebral cortex and recorded full-band neuronal activity with two objectives: (1) to test the long-term stability of implanted devices; and (2) to investigate full-band activity during the transition across different levels of anesthesia. First, we demonstrate it is possible to record full-band signals with stability, fidelity, and spatiotemporal resolution for up to 5.5 months using chronic epicortical gSGFET implants. Second, brain states generated by progressive variation of levels of anesthesia could be identified as traditionally using the high-pass filtered (AC, alternating current-coupled) spectrogram: from synchronous slow oscillations in deep anesthesia through to asynchronous activity in the awake state. However, the DC signal introduced a highly significant improvement for brain-state discrimination: the DC band provided an almost linear information prediction of the depth of anesthesia, with about 85% precision, using a trained algorithm. This prediction rose to about 95% precision when the full-band (AC + DC) spectrogram was taken into account. We conclude that recording infraslow activity using gSGFET interfaces is superior for the identification of brain states, and further supports the preclinical and clinical use of graphene neural interfaces for long-term recordings of cortical activity.

Typical values of z-resolution for different Digital Breast Tomosynthesis systems evaluated in a multicenter study.

PURPOSE: The aim of the present study, conducted by a working group of the Italian Association of Medical Physics (AIFM), was to define typical z-resolution values for different digital breast tomosynthesis (DBT) models to be used as a reference for quality control (QC). Currently, there are no typical values published in internationally agreed QC protocols. METHODS: To characterize the z-resolution of the DBT models, the full width at half maximum (FWHM) of the artifact spread function (ASF), a technical parameter that quantifies the signal intensity of a detail along reconstructed planes, was analyzed. Five different commercial phantoms, CIRS Model 011, CIRS Model 015, Modular DBT phantom, Pixmam 3-D, and Tomophan, were evaluated on reconstructed DBT images and 82 DBT systems (6 vendors, 9 models) in use at 39 centers in Italy were involved. RESULTS: The ASF was found to be dependent on the detail size, the DBT angular acquisition range, the reconstruction algorithm and applied image processing. In particular, a progressively greater signal spread was observed as the detail size increased and the acquisition angle decreased. However, a clear correlation between signal spread and angular range width was not observed due to the different signal reconstruction and image processing strategies implemented in the algorithms developed by the vendors studied. CONCLUSIONS: The analysis led to the identification of typical z-resolution values for different DBT model-phantom configurations that could be used as a reference during a QC program.

Electrochemical biosensor for aerobic acetate detection.

There is an increasing demand on alternatives methods to animal testing. Numerous health parameters have been already studied using in vitro devices able to mimic the essential functions of the organs, being the real-time monitoring and response to stimuli their main limitations. Regarding the health of the gut, the short chain fatty acids, and particularly acetate, have emerged as key biomarkers to evaluate gut healthiness and disease development, although the number of acetate biosensors is still very low. This article presents a microbial biosensor based on fully biocompatible materials which is able to detect acetate in aerobic conditions in the range between 11 and 50 mM, and without compromising the viability and function of either bacteria (>90% viability) or mammalian cells (>80% viability). The detection mechanism is based on the metabolism of acetate by Escherichia coli bacteria immobilized on the transducer surface. Ferricyanide is used as a redox mediator to transfer electrons from the acetate metabolism in the bacterial cells to the transducer. High bacterial concentrations are immobilized in the transducer surface (109 cfu mL-1) by electrodeposition of conductive alginate hydrogels doped with reduced graphene oxide. The results show successful outcomes to exploit bacteria as a biosensing tool, based on the use of inkjet printed transducers, biocompatible materials and cell entrapment technologies.

Laparoscopic transperitoneal hernia repair (TAPP) in emergency: long-term follow-up in a high volume centre.

PURPOSE: Aim of this study was to analyse feasibility, safety and effectiveness of laparoscopic transperitoneal hernia repair (TAPP) approach to inguinal hernias in the emergency setting, with a longer follow-up than the studies present in literature. METHODS: We retrospectively analysed all patients who underwent emergency TAPP hernia repair in San Marco Hospital (Zingonia, Italy), from September 2010 to June 2020. A prospectively collected database of 685 consecutive TAPP hernia repair was reviewed. Feasibility and safety were evaluated through operative time, conversion rate, perioperative mortality, morbidity and prosthesis infection rate. Effectiveness was assessed by recurrence and complication rate, acute (during admission) and chronic (during follow-up) pain by Visual Analogic Scale (VAS), and recovery to normal activity in a long-term follow-up (mean period 1718 days). RESULTS: The final study group included 47 patients. The mean age was 59.6 years (range 22-89), 29 patients were male and 18 were female. The mean operation time was 64 min. Two cases were converted to open approach (4%). In four cases bowel resection became necessary (8.5%). Appendicectomy and omentectomy occurred once and twice, respectively (2% and 4%), and orchiectomy was required in two patients (4%). Seroma was the only postoperative complication that we registered in four patients. During a mean follow-up period of 1718 days, there was no recurrence of the hernia or other complications. Five patients referred mild occasional groin pain (VAS < 3), with quick relief without taking any pain killers. CONCLUSION: TAPP approach is a safe, feasible and effective therapeutic option for groin hernias in emergency setting. No recurrence or severe complications were reported in over 4 years of follow-up.

Contingency management for smoking cessation among individuals with substance use disorders: In-treatment and post-treatment effects.

INTRODUCTION: Smokers with substance use disorders (SUDs) show elevated tobacco prevalence, and smoking abstinence rates are considerably low. This randomized controlled trial sought to compare the effect of a cognitive behavioral treatment (CBT) that includes an episodic future thinking (EFT) component with the same treatment protocol plus contingency management (CM). This study aims to examine the effect of CM on smoking outcomes and in-treatment behaviors (i.e., retention, session attendance and adherence to nicotine use reduction guidelines), and to analyze whether these in-treatment variables predicted days of continuous abstinence at end-of-treatment. METHOD: A total of 54 treatment-seeking participants (75.9% males, M = 46.19 years old) were allocated to CBT + EFT (n = 30) or CBT + EFT + CM (n = 24). Intervention consisted of eight weeks of group-based sessions. Tobacco abstinence was verified biochemically by testing levels of carbon monoxide (≤4ppm) and urine cotinine (≤80 ng/ml). RESULTS: CM intervention increased 24-hour tobacco abstinence (50% vs. 20%, χ2(1) = 5.4; p = .021) and days of continuous abstinence (M = 5.92 ± 7.67 vs. 5.53 ± 12.42; t(52) = -0.132; p = 0.89) at end-of-treatment in comparison with CBT + EFT intervention. Although not statistically significant, CBT + EFT + CM enhanced in-treatment behaviors, in terms of retention (83.3% vs. 70%; χ2(1) = 0.255; p = .208), sessions attended (12.29 ± 3.22 vs. 10.93 ± 3.26; t(52) = -1.527; p = .133) and adherence to weekly nicotine use reduction targets (41.07% ± 31.96 vs. 35% ±2 6.28; t(52) = -0.766; p = .447). A higher percentage of samples meeting reduction guidelines (ß = 0.609; p<.001) predicted days of continuous abstinence at end-of-treatment. CONCLUSION: Combining CM with CBT + EFT improves short-term quitting rates. Findings suggest the need to incorporate strategies for improving adherence to nicotine reduction guidelines.

Severe Cutaneous Adverse Reactions to Drugs in Latin America: The RACGRAD Study.

BACKGROUND AND OBJECTIVE: Severe cutaneous adverse reactions to drugs (SCARs) are associated with high morbidity and mortality and with sequelae. Objective: To characterize patients with SCARs in 8 health care institutions in Latin America. METHODS: We performed a cross-sectional, descriptive, multicenter study of patients diagnosed with SCARs in Latin America between January 2009 and December 2018. The analysis was carried out using a database in BD Clinic. RESULTS: We collected 70 patients, of whom 42 (60%) were women. Mean age was 38.7 years. Forty-two patients (60%) had DRESS-DIHS, 12 (17.1%) TEN, 5 (7.1%) SJS, 6 (8.5%) AGEP, 4 (5.7%) other reactions not classified as SCARs, and 1 (1.4%) overlapping SJS-TEN. The main causative drugs were aromatic anticonvulsants in 31 cases (44.3%), ß-lactam antibiotics in 11 cases (15.7%), and non-ß-lactam antibiotics in 6 cases (8.6%). In all of the cases, the suspected drug was withdrawn at the first sign of a SCAR. Sixty-six patients (94.2%) received anti-inflammatory treatment, mostly systemic corticosteroids. Complications occurred in 53 cases (75.7%), and 3 patients died (4.3%). Thirteen patients (18.6%) had sequelae. CONCLUSIONS: This is the first multicenter report on SCARs in Latin America. DRESS-DIHS was the most frequently reported clinical entity, and anticonvulsants were the main triggers. Most of the patients received systemic corticosteroids. Complications were frequent, and 3 patients died.

Incidental finding of cornea verticillata or lamellar inclusions in kidney biopsy: measurement of lyso-Gb3 in plasma defines between Fabry disease and drug-induced phospholipidosis.

INTRODUCTION: Therapy with cationic amphiphilic drugs (Amiodarone or hydroxychloroquine) may result in biochemically and ultrastructurally similar lipid inclusions in many cells also affected by Fabry disease (FD). In addition, it often results in similar clinical manifestations such as cornea verticillata. This may lead to a FD misdiagnosis, especially when a complete medical history is not available to the ophthalmologist confronted with cornea verticillata or to the pathologist examining a kidney biopsy. When enzymatic/genetic test or pathological studies are not conclusive, a specific biomarker may help clarify this dilemma. The plasma globotriaosylsphingosine (lyso-Gb3) assay has high sensitivity and specificity and is elevated above normal levels in FD. MATERIALS AND METHODS: We measured plasma lyso-Gb3 levels in male patients receiving Amiodarone or hydroxychloroquine and compared it with male patients with classic and late onset variant of FD. RESULTS: In all Fabry patients (classic and late onset variant) α-GalA activity was deficient in dried blood spot and plasma lyso-Gb3 was above normal levels. Patients on treatment with Amiodarone or hydroxychloroquine had normal values for α-GalA activity and lyso-Gb3 in plasma. CONCLUSIONS: Even when Amiodarone or hydroxychloroquine may decrease α-GalA activity in vitro or in cell culture, our results showed that in all patients lyso-Gb3 plasma levels remain normal with no evidence of reduction in α-GalA activity, confirming the specificity of this biomarker for the diagnosis of FD.

Severe Cutaneous Adverse Reactions to Drugs in Latin America: The RACGRAD Study

Background: Severe cutaneous adverse reactions to drugs (SCARs) are associated with high morbidity and mortality and with sequelae. Objective: To characterize patients with SCARs in 8 health care institutions in Latin America. Methods: We performed a cross-sectional, descriptive, multicenter study of patients diagnosed with SCARs in Latin America between January 2009 and December 2018. The analysis was carried out using a database in BD Clinic. Results: We collected 70 patients, of whom 42 (60%) were women. Mean age was 38.7 years. Forty-two patients (60%) had DRESS-DIHS, 12 (17.1%) TEN, 5 (7.1%) SJS, 6 (8.5%) AGEP, 4 (5.7%) other reactions not classified as SCARs, and 1 (1.4%) overlapping SJS-TEN. The main causative drugs were aromatic anticonvulsants in 31 cases (44.3%), ß-lactam antibiotics in 11 cases (15.7%), and non–ß-lactam antibiotics in 6 cases (8.6%). In all of the cases, the suspected drug was withdrawn at the first sign of a SCAR. Sixty-six patients (94.2%) received anti-inflammatory treatment, mostly systemic corticosteroids. Complications occurred in 53 cases (75.7%), and 3 patients died (4.3%). Thirteen patients (18.6%) had sequelae. Conclusions: This is the first multicenter report on SCARs in Latin America. DRESS-DIHS was the most frequently reported clinical entity, and anticonvulsants were the main triggers. Most of the patients received systemic corticosteroids. Complications were frequent, and 3 patients died (AU)

Structural brain anomalies in Cri-du-Chat syndrome: MRI findings in 14 patients and possible genotype-phenotype correlations.

INTRODUCTION: Cri-du-Chat Syndrome (CdCS) is a genetic condition due to deletions showing different breakpoints encompassing a critical region on the short arm of chromosome 5, located between p15.2 and p15.3, first defined by Niebuhr in 1978. The classic phenotype includes a characteristic cry, peculiar facies, microcephaly, growth retardation, hypotonia, speech and psychomotor delay and intellectual disability. A wide spectrum of clinical manifestations can be attributed to differences in size and localization of the 5p deletion. Several critical regions related to some of the main features (such as cry, peculiar facies, developmental delay) have been identified. The aim of this study is to further define the genotype-phenotype correlations in CdCS with particular regards to the specific neuroradiological findings. PATIENTS AND METHODS: Fourteen patients with 5p deletions have been included in the present study. Neuroimaging studies were conducted using brain Magnetic Resonance Imaging (MRI). Genetic testing was performed by means of comparative genomic hybridization (CGH) array at 130 kb resolution. RESULTS: MRI analyses showed that isolated pontine hypoplasia is the most common finding, followed by vermian hypoplasia, ventricular anomalies, abnormal basal angle, widening of cavum sellae, increased signal of white matter, corpus callosum anomalies, and anomalies of cortical development. Chromosomal microarray analysis identified deletions ranging in size from 11,6 to 33,8 Mb on the short arm of chromosome 5. Then, we took into consideration the overlapping and non-overlapping deleted regions. The goal was to establish a correlation between the deleted segments and the neuroradiological features of our patients. CONCLUSIONS: Performing MRI on all the patients in our cohort, allowed us to expand the neuroradiological phenotype in CdCS. Moreover, possible critical regions associated to characteristic MRI findings have been identified.

Understanding why fat, oil and grease (FOG) bioremediation can be unsuccessful.

Commercial kitchen wastewaters are typically strong organic and fat-rich effluents, often identified as major contributors to fatberg formation and associated blockages in sewers. Experimental trials were done using synthetic kitchen wastewater to understand the complex reactions involved in microbial remediation in grease traps/separators prior discharge in sewers. The principle organic components (FOG, carbohydrate and protein nitrogen), were varied using ranges observed in a previous study on real kitchen wastewater characterisation. A model bacterium, Bacillus licheniformis NCIMB 9375, was used to evaluate microbial utilisation of the different organic fractions in relation to fat, oil and grease (FOG) degradation. Novel results in the treatment of these effluents showed that, the presence and concentration of alternative carbon sources and the ratio of carbon to nitrogen (COD:N) had great influence on FOG-degradation response. For example, FOG removal decreased from 24 to 10 mg/l/h when glucose was substitute for starch at equivalent concentrations (500 mg/l); and from 26 to 5 mg/l/h when initial COD:N increased from 45:1 to 147:1. The dominant influence of COD:N was validated using a commercial bioadditive and real kitchen wastewater adjusted to different COD:N ratios, confirming the strong influence of kitchen wastewater composition on bioremediation outcomes. These results can therefore have major implications for biological management of FOG in kitchens and sewers as they provide a scientific explanation for bioremediation success or failure.

First case of fatal equine meningoencephalitis caused by Halicephalobus gingivalis in Mexico.

Aberrant nematode larval migration in the CNS of horses is rare but frequently fatal; one of the main etiological agents involved in this illness is Halicephalobus gingivalis. This soil nematode has been associated with several fatal equine meningoencephalitis reports worldwide; however, it had never been diagnosed in horses of Mexico. A 10 year-old Andalusian horse presented dysphagia, fever, weakness, prostration and ataxia; the patient expired during the medical attention. Post mortem examination was performed and no gross alterations were found. Histopathology revealed meningoencephalitis, vasculitis and intralesional adult nematodes, larvae and eggs compatible with Halicephalobus spp. A polymerase chain reaction (PCR) for the nuclear large subunit ribosomal RNA gene (LSU rDNA) of nematodes was performed from formalin-fixed and paraffin wax-embedded sections of brain. Posterior nucleotide sequence analysis of the amplified fragment identified the agent as H. gingivalis. To our knowledge, this is the first confirmed report of Halicephalobiasis in Mexico.

A new conceptual model of pesticide transfers from agricultural land to surface waters with a specific focus on metaldehyde.

Pesticide losses from agricultural land to water can result in the environmental deterioration of receiving systems. Mathematical models can make important contributions to risk assessments and catchment management. However, some mechanistic models have high parameter requirements which can make them difficult to apply in data poor areas. In addition, uncertainties in pesticide properties and applications are difficult to account for using models with long run-times. Alternative, simpler, conceptual models are easier to apply and can still be used as a framework for process interpretation. Here, we present a new conceptual model of pesticide behaviour in surface water catchments, based on continuous water balance calculations. Pesticide losses to surface waters are calculated based on the displacement of a limited fraction of the soil pore water during storm events occurring after application. The model was used to describe the behaviour of metaldehyde in a small (2.2 km2) under-drained catchment in Eastern England. Metaldehyde is a molluscicide which has been regularly detected at high concentrations in many drinking water supply catchments. Measured peak concentrations in stream water (to about 9 µg L-1) occurred in the first few storm events after application in mid-August. In each event, there was a quasi-exponential decrease in concentration during hydrograph recession. Peak concentrations decreased in successive events - responding to rainfall but reflecting an effective exhaustion in soil supply due to degradation and dissipation. Uncertain pesticide applications to the catchment were estimated using land cover analysis of satellite data, combined with a Poisson distribution to describe the timing of application. Model performance for both the hydrograph (after calibration of the water balance) and the chemograph was good and could be improved via some minor adjustments in assumptions which yield general insights into the drivers for pesticide transport. The use of remote sensing offers some promising opportunities for estimating catchment-scale pesticide applications and associated losses.

Characterisation of food service establishment wastewater and its implication for treatment.

Essential for the selection of a reliable treatment system is the characterisation of the effluent to treat. Kitchen wastewater (KWW) from food service establishments (FSEs) is a strong organic and fat-rich effluent whose characterisation has not been sufficiently addressed. KWW composition is highly variable and linked to the FSE's size, the type of meals prepared and the amount of water used during the cleaning. COD, TSS and fat content (FOG) are the most common parameters found in literature. However, other physical and chemical parameters (e.g. temperature, pH, oil droplets characteristics and trace elements), correlated to commercial kitchen cleaning practices rather than the specific effluent, but equally influential on the treatment efficiencies of both physical and biological methods, have hardly been investigated. A comprehensive characterisation of wastewaters from three food service establishments was used to generate data to support the selection of appropriate FOG mitigation methods. Two novel analytical methods were used to quantify the proportion of emulsified FOG and associated droplet size from different kitchen washing effluents. The results showed that more than 90% of the FOG from the dishwasher effluent and around 35% of sink one was emulsified, with droplet sizes less than 100 µm, well below the removal capabilities of conventional grease interceptors, but easily removed using biological means. From the WW composition results, a formula for predictive modelling was derived to represent average organic matter composition for kitchen wastewater as C20H38O10N, applicable in remediation processes. These results offer a good starting point for the design, operation, and optimisation of wastewater treatment systems of oil-rich KWW.

Learnings from real-life experience of using omalizumab for chronic urticaria in Latin America.

BACKGROUND: Updated urticaria guidelines recommend that patients should be assessed for disease activity, severity, control, and quality of life at baseline and follow up. Regarding treatment, guidelines consider second generation antihistamines as the cornerstone in therapy for chronic urticaria (CU), while other drugs, such as omalizumab, are conceived as second-line alternatives. In regards to omalizumab, despite advances in the management of CU, there are still open questions about timing, dosing, and objective measures for clinical response. This study was designed to portray the use of patient-reported outcomes (PROs) in chronic urticaria management, as well as the effectiveness and treatment patterns of omalizumab in CU, as seen in a real-life setting in Latin America. METHODS: This is a retrospective observational study, involving 72 Latin American patients with chronic urticaria treated with omalizumab. Patient reported outcomes and treatment patterns, response, quality of life improvement and discontinuation were analyzed. RESULTS: From the 72 patients, 91.7% (n = 66) were assessed through PROs, where urticaria control test (UCT) was the most used (79.2%; n = 57). Overall, 80.0% (n = 44) responded to omalizumab at some point of the treatment. Omalizumab 300 mg was associated with earlier response compared to lower doses. Regardless of dosage, most patients assessed with CU-Q2oL improved quality of life (80.8%; n = 21). With respect to omalizumab discontinuation, 20.8% (n = 15) patients interrupted omalizumab before the 3rd month of treatment (p = .000). CONCLUSIONS: The present study highlights how the use of PROs and omalizumab in Latin America differ from guidelines' recommendations and clinical trials. Even though most patients were initiated under omalizumab 300 mg, most of them finished with lower doses. Regardless of dosage, most patients responded to omalizumab and improved quality of life at some point during treatment. However, such features were seen earlier with omalizumab 300 mg. Regarding treatment discontinuation, one-fifth of patients interrupted omalizumab before the third month.

Color tunable pressure sensors based on polymer nanostructured membranes for optofluidic applications.

We demonstrate an integrated optical pressure sensing platform for multiplexed optofluidics applications. The sensing platform consists in an array of elastomeric on-side nanostructured membranes -effectively 2D photonic crystal- which present colour shifts in response to mechanical stress that alter their nanostructure characteristical dimensions, pitch or orientation. The photonic membranes are prepared by a simple and cost-effective method based on the infiltration of a 2D colloidal photonic crystal (CPC) with PDMS and their integration with a microfluidic system. We explore the changes in the white light diffraction produced by the nanostructured membranes when varying the pneumatic pressure in the microfluidics channels as a way to achieve a power-free array of pressure sensors that change their reflective colour depending on the bending produced on each sensor. The structural characterization of these membranes was performed by SEM, while the optical properties and the pressure-colour relation were evaluated via UV-Vis reflection spectrometry. Maximum sensitivities of 0.17 kPa-1 is obtained when measuring at Littrow configuration (θin = -θout), and close to the border of the membranes. The reflected colour change with pressure is as well monitorized by using a smartphone camera.

Quality of life and clinical characterization of patients with vernal keratoconjunctivitis in a pediatric population in Colombia

Vernal keratoconjunctivitis is one of the most serious ocular allergies that have the potential to induce large ocular morbidity and significant visual changes affecting the quality of life of these individuals. Methodology: This study was conducted in two phases. The first phase consisted of the clinical characterization of 32 patients from the Clinical Allergology center of the I.P.S. Universitaria from July 2014 to February 2015. A retrospective analysis of medical records was performed. In the second phase, the evaluation of quality of life was conducted using the questionnaire KIDSCREEN 27, which was validated in our population and evaluated as recommended by the creators of this instrument. Results: A total of 24 patients (75%) were men, mean age of 12.1 (SD 2.6) years. 100% of the patients had clinical evaluation and were monitored by Allergology and Ophthalmology, 12 patients (37.5%) were found in mild level, 5 patients (15.6%) were moderate and 14 patients (43.8%) were severe level. The most common symptoms were pruritus (75%), photophobia (50%), lacrimation (37.5%), and secretions (28.1%). 5.6% had a family history of atopy and 84.4% had an allergic comorbidity. Aeroallergen skin tests were found positive in 25 patients (78.1%). All patients had initiated ocular treatment by the time the survey of quality of life was conducted; but, they still had low quality of life scores in the 5 domains assessed. When the scores were evaluated by gender, the only statistically significant difference was found in the domain of family life and free time, which was lower for women. Conclusion: The vernal keratoconjunctivitis is a disease more prevalent in men. It apparently has an important atopic base in our environment, which due to its severe ocular involvement causes a marked decrease in the quality of life of the children who present it

No disponible

Online oxygen monitoring using integrated inkjet-printed sensors in a liver-on-a-chip system.

The demand for real-time monitoring of cell functions and cell conditions has dramatically increased with the emergence of organ-on-a-chip (OOC) systems. However, the incorporation of co-cultures and microfluidic channels in OOC systems increases their biological complexity and therefore makes the analysis and monitoring of analytical parameters inside the device more difficult. In this work, we present an approach to integrate multiple sensors in an extremely thin, porous and delicate membrane inside a liver-on-a-chip device. Specifically, three electrochemical dissolved oxygen (DO) sensors were inkjet-printed along the microfluidic channel allowing local online monitoring of oxygen concentrations. This approach demonstrates the existence of an oxygen gradient up to 17.5% for rat hepatocytes and 32.5% for human hepatocytes along the bottom channel. Such gradients are considered crucial for the appearance of zonation of the liver. Inkjet printing (IJP) was the selected technology as it allows drop on demand material deposition compatible with delicate substrates, as used in this study, which cannot withstand temperatures higher than 130 °C. For the deposition of uniform gold and silver conductive inks on the porous membrane, a primer layer using SU-8 dielectric material was used to seal the porosity of the membrane at defined areas, with the aim of building a uniform sensor device. As a proof-of-concept, experiments with cell cultures of primary human and rat hepatocytes were performed, and oxygen consumption rate was stimulated with carbonyl-cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP), accelerating the basal respiration of 0.23 ± 0.07 nmol s-1/106 cells up to 5.95 ± 0.67 nmol s-1/106 cells s for rat cells and the basal respiration of 0.17 ± 0.10 nmol s-1/106 cells by up to 10.62 ± 1.15 nmol s-1/106 cells for human cells, with higher oxygen consumption of the cells seeded at the outflow zone. These results demonstrate that the approach of printing sensors inside an OOC has tremendous potential because IJP is a feasible technique for the integration of different sensors for evaluating metabolic activity of cells, and overcomes one of the major challenges still remaining on how to tap the full potential of OOC systems.

In-treatment cigarette demand among treatment-seeking smokers with depressive symptoms.

INTRODUCTION: Despite previous evidence supporting the use of the Cigarette Purchase Task (CPT) as a valid tool for assessing smoking reinforcement, research assessing how environmental changes affect CPT performance is scarce. AIMS: This study addressed for the first time the differential effect of treatment condition [Cognitive Behavioral Treatment (CBT) + Behavioral Activation (BA) versus CBT + BA + Contingency Management (CM)] on cigarette demand among treatment seeking smokers with depressive symptoms. It also sought to assess whether reductions in smoking consumption arranged over the course of an intervention for smoking cessation impact on in-treatment cigarette demand. METHOD: Participants were 92 smokers with depressive symptoms from a randomized clinical trial that received eight weeks of either CBT + BA or CBT + BA + CM. Individuals completed the CPT 8 times; the first during the intake visit and the remaining 7 scheduled once a week in midweek sessions. Cotinine samples were collected in each session. RESULTS: Participants receiving CBT + BA + CM showed higher reduction in cigarette demand across sessions than participants receiving CBT + BA, although this comparison was only significant for the intensity index (p = .004). Cotinine was positively related to cigarette demand (all p values < .001), although this association became less prominent across sessions. In-treatment cotinine decreases were associated with demand reductions (all p values < .001), but this association was not significant for elasticity. CONCLUSIONS: Reductions in nicotine intake arranged over the course of an intervention for smoking cessation impact in-treatment cigarette demand.

A balanced reciprocal translocation t(10;15)(q22.3;q26.1) interrupting ACAN gene in a family with proportionate short stature.

PURPOSE: Few examples of the involvement of a single gene in idiopathic short stature have been described until now. Our aim was to identify the causative gene of proportionate short stature in a large family showing co-segregation of the phenotype with the reciprocal translocation t(10;15)(q22;q24). METHODS: FISH mapping was carried out with BACs and long-range PCR probes to identify the smallest genomic regions harboring the translocation breakpoints. Real-Time RT-PCR was performed in blood after pre-amplification of target genes cDNA. RESULT: The affected family members presented with a final height of between - 2.41 and - 4.18 SDS and very mild skeletal dysmorphisms. Growth rates of the proband and of her cousin, whose childhood and pre-pubertal bone age corresponded to the chronological age, showed a poor growth spurt during treatment with rhGH. However, their adult height was greater than that of their untreated mothers, suggesting efficacy of GH therapy. Breakpoint mapping revealed that the translocation t(10;15)(q22.3;q26.1) disrupts, on 15q, the ACAN gene at intron 1, decreasing its transcriptional expression. CONCLUSIONS: This is the first description of a chromosome rearrangement disrupting ACAN and leading to its haploinsufficiency. ACAN loss of function should be considered a potential underpinning of short patients who display a poor growth spurt and belong to families with autosomal dominant segregation of proportionate short stature. Besides this core phenotype, literature review suggests that advanced bone age, early onset osteochondritis dissecans, osteoarthritis, intervertebral disc disease as well as craniofacial dysmorphisms can be important suggestive phenotypes in affected families.

Quality of life and clinical characterization of patients with vernal keratoconjunctivitis in a pediatric population in Colombia.

Vernal keratoconjunctivitis is one of the most serious ocular allergies that have the potential to induce large ocular morbidity and significant visual changes affecting the quality of life of these individuals. METHODOLOGY: This study was conducted in two phases. The first phase consisted of the clinical characterization of 32 patients from the Clinical Allergology center of the I.P.S. Universitaria from July 2014 to February 2015. A retrospective analysis of medical records was performed. In the second phase, the evaluation of quality of life was conducted using the questionnaire KIDSCREEN 27, which was validated in our population and evaluated as recommended by the creators of this instrument. RESULTS: A total of 24 patients (75%) were men, mean age of 12.1 (SD 2.6) years. 100% of the patients had clinical evaluation and were monitored by Allergology and Ophthalmology, 12 patients (37.5%) were found in mild level, 5 patients (15.6%) were moderate and 14 patients (43.8%) were severe level. The most common symptoms were pruritus (75%), photophobia (50%), lacrimation (37.5%), and secretions (28.1%). 65.6% had a family history of atopy and 84.4% had an allergic comorbidity. Aeroallergen skin tests were found positive in 25 patients (78.1%). All patients had initiated ocular treatment by the time the survey of quality of life was conducted; but, they still had low quality of life scores in the 5 domains assessed. When the scores were evaluated by gender, the only statistically significant difference was found in the domain of family life and free time, which was lower for women. CONCLUSION: The vernal keratoconjunctivitis is a disease more prevalent in men. It apparently has an important atopic base in our environment, which due to its severe ocular involvement causes a marked decrease in the quality of life of the children who present it.