Molecular Insights of Cholestasis in MDR2 Knockout Murine Liver Organoids.

MDR3 (multidrug resistance 3) deficiency in humans (MDR2 in mice) causes progressive familial intrahepatic cholestasis type 3 (PFIC3). PFIC3 is a lethal disease characterized by an early onset of intrahepatic cholestasis progressing to liver cirrhosis, a preneoplastic condition, putting individuals at risk of hepatocellular carcinoma (HCC). Hepatocyte-like organoids from MDR2-deficient mice (MDR2KO) were used in this work to study the molecular alterations caused by the deficiency of this transporter. Proteomic analysis by mass spectrometry allowed characterization of 279 proteins that were differentially expressed in MDR2KO compared with wild-type organoids. Functional enrichment analysis indicated alterations in three main cellular functions: (1) interaction with the extracellular matrix, (2) remodeling intermediary metabolism, and (3) cell proliferation and differentiation. The affected cellular processes were validated by orthogonal molecular biology techniques. Our results point to molecular mechanisms associated with PFIC3 that may drive the progression to liver cirrhosis and HCC and suggest proteins and cellular processes that could be targeted for the development of early detection strategies for these severe liver diseases.

Primary neonatal and pediatric ECMO transport: First experience in Spain.

INTRODUCTION: The organization of primary Extracorporeal membrane oxygenation (ECMO) transport is highly variable. METHODS: To present the experience of the first mobile pediatric ECMO program in Spain, we designed a prospective descriptive study of all primary neonatal and pediatric (0-16 years) ECMO transports carried out over 10 years. The main variables recorded include demographic information, patient background, clinical data, ECMO indications, adverse events, and main outcomes. RESULTS: 39 primary ECMO transports were carried out with a 66.7% survival to hospital discharge. The median age was 1.24 months[IQR: 0.09-96]. Cannulation was mostly peripheral venoarterial (33/39). The mean response time from the call from the sending center to the departure of the ECMO team was 4 h[2.2-8]. The median inotropic score at the time of cannulation was 70[17.2-206.5], with a median oxygenation index of 40.5[29-65]. In 10% of the cases, ECMO-CPR was performed. Adverse events occurred in 56.4%, mostly related to the means of transport (40% overall). On arrival at the ECMO center, 44% of the patients underwent interventions. The median PICU stay was 20.5 days[11-32]. 5 patients developed neurological sequels. Statistically significant differences between survivors and deceased patients were not found. CONCLUSIONS: A good survival rate, with a low prevalence of serious adverse events, suggests a clear benefit of primary ECMO transport when conventional therapeutic measures are exhausted and the patient is too unstable to undergo conventional transport. A nationwide primary ECMO-transport program must therefore be offered to all patients regardless of their location.

Does imbalance in chest X-ray datasets produce biased deep learning approaches for COVID-19 screening?

BACKGROUND: The health crisis resulting from the global COVID-19 pandemic highlighted more than ever the need for rapid, reliable and safe methods of diagnosis and monitoring of respiratory diseases. To study pulmonary involvement in detail, one of the most common resources is the use of different lung imaging modalities (like chest radiography) to explore the possible affected areas. METHODS: The study of patient characteristics like sex and age in pathologies of this type is crucial for gaining knowledge of the disease and for avoiding biases due to the clear scarcity of data when developing representative systems. In this work, we performed an analysis of these factors in chest X-ray images to identify biases. Specifically, 11 imbalance scenarios were defined with female and male COVID-19 patients present in different proportions for the sex analysis, and 6 scenarios where only one specific age range was used for training for the age factor. In each study, 3 different approaches for automatic COVID-19 screening were used: Normal vs COVID-19, Pneumonia vs COVID-19 and Non-COVID-19 vs COVID-19. The study was validated using two public chest X-ray datasets, allowing a reliable analysis to support the clinical decision-making process. RESULTS: The results for the sex-related analysis indicate this factor slightly affects the system in the Normal VS COVID-19 and Pneumonia VS COVID-19 approaches, although the identified differences are not relevant enough to worsen considerably the system. Regarding the age-related analysis, this factor was observed to be influencing the system in a more consistent way than the sex factor, as it was present in all considered scenarios. However, this worsening does not represent a major factor, as it is not of great magnitude. CONCLUSIONS: Multiple studies have been conducted in other fields in order to determine if certain patient characteristics such as sex or age influenced these deep learning systems. However, to the best of our knowledge, this study has not been done for COVID-19 despite the urgency and lack of COVID-19 chest x-ray images. The presented results evidenced that the proposed methodology and tested approaches allow a robust and reliable analysis to support the clinical decision-making process in this pandemic scenario.

Physical capability in a rural birth cohort at the age of 52: association with early environmental, nutritional, and developmental factors.

INTRODUCTION: Midlife physical capability (PC) is associated with developmental factors in the populations of economically developed countries. As far as we know, there is no information for rural populations of low- and middle-income countries. The aim of the study was to investigate the influence of pre- and postnatal factors on midlife objective measures of PC in a 1966-67 birth cohort from a Mexican rural community. The hypothesis was that adverse developmental conditions are associated with low midlife PC. METHODS: In 1966-67, a birth cohort of all children from a poor Mexican rural community was assembled. Data on family socioeconomic status (SES), parental health and nutritional status, birth weight, postnatal growth and feeding patterns were registered. In 2018, out of the 336 cohort members, 118 were living in the community, and eighty-two of them underwent a comprehensive clinical evaluation. The evaluation included grip strength, gait velocity and chair-stand PC tests. In multivariable linear models, PC tests were the dependent variables, and prenatal, birth and postnatal factors were the independent variables. Adjustment for confounding was made with adult anthropometric, body composition, clinical and ageing status variables. RESULTS: Independent of adult health status and other ageing indicators, lower PC was associated with family organization and SES, parental nutritional status, birth weight, infant postnatal growth velocity, and weaning time. These results indicate that adverse family and environmental conditions that are prevalent in poor rural communities are associated with low midlife PC.

The Application of Ultrasound in Honey: Antioxidant Activity, Inhibitory Effect on α-amylase and α-glucosidase, and In Vitro Digestibility Assessment.

In the present study, the effects of ultrasound (10, 20, and 30 min) on the bioactive compounds, antioxidant capacity, enzymatic inhibition, and in vitro digestion of six honey extracts from the Oaxaca state, Mexico, were analyzed. Significant differences were found in each honey extract with respect to the ultrasonic treatment applied (p < 0.05). In the honey extract P-A1 treated with 20 min of ultrasound, the phenols reached a maximum concentration of 29.91 ± 1.56 mg EQ/100 g, and the flavonoids of 1.92 ± 0.01 mg EQ/100 g; in addition, an inhibition of α-amylase of 37.14 ± 0.09% was noted. There were also differences in the phases of intestinal and gastric digestion, presenting a decrease in phenols (3.92 ± 0.042 mg EQ/100 g), flavonoids (0.61 ± 0.17 mg EAG/100 mg), antioxidant capacity (8.89 ± 0.56 mg EAG/100 mg), and amylase inhibition (9.59 ± 1.38%). The results obtained from this study indicate that, in some honeys, the processing method could increase the concentration of bioactive compounds, the antioxidant capacity, and the enzymatic inhibition; however, when subjected to in vitro digestion, the properties of honey are modified. The results obtained could aid in the development of these compounds for use in traditional medicine as a natural source of bioactive compounds.

C apsicum fruits as functional ingredients with antimicrobial activity: an emphasis on mechanisms of action.

Capsicum spp. fruits (CFs) are a basic ingredient in the diet and have been used as active ingredients in the pharmaceutical, cosmetic, and food products, due to their antioxidant, anti-inflammatory, antiseptic, and antimicrobial properties. The antimicrobial activity is the most studied property due to its effectiveness against pathogenic species, however, few studies have focused on the mechanisms of action involved. Therefore, this review discusses the effects generated by the CFs compounds on the viability and metabolism of microorganisms, highlighting the mechanisms by which these compounds exert their antimicrobial effects. The information provided shows that CFs are mainly source of capsaicinoids and phenolic compounds responsible for the inhibition of bacteria, yeasts, and fungi, through an increase in the permeabilization of the membrane and cell wall. Also, these compounds show an antiviral effect associated with the inactivation of virus binding proteins, preventing their replication and infection. Despite this, there is still a lack of information about the mechanisms that regulate the interactions between CFs compounds and food-important-microorganisms. Therefore, future research should focus on new antimicrobial compounds from CFs for their subsequent use against novel infectious agents, mainly virus of importance in health such as SARS-CoV-2.

Fructose Malabsorption in Chilean Children Undergoing Fructose Breath Test at a Tertiary Hospital.

ABSTRACT: Fructose is a highly abundant carbohydrate in western diet and may induce bowel symptoms in children as in adults. The main objective of this study is to describe the frequency of fructose malabsorption (FM) in symptomatic patients 18 years or younger undergoing fructose breath test in a single tertiary center between 2013 and 2018, and to evaluate whether certain symptoms are related to positivity of the test. Out of 273 tests 183 (67%) were compatible with FM. The most frequent pretest symptom in the overall study population was bloating (83%), followed by abdominal pain (73%). Patients with positive test were younger than those with a negative test (median 5 vs 8 years, P < 0.001). In multivariate analysis, which included age, sex, and symptoms (diarrhea, abdominal pain, bloating, nausea), only age <6 years (odds ratio 2.93, 95% confidence interval 1.64-5.23) and absence of nausea (odds ratio = 3.32, 95% confidence interval 1.56-7.05) were associated with FM.

Cattle seroprevalence and risk factors associated with bovine viral diarrhea in the northeastern of Colombia.

Bovine viral diarrhea (BVD) is one of the most common and economically significant viral infections in cattle. Different risk factors have been associated with viral exposure and transmission, generating endemic regions with different biotype circulations. To find the BVD status in the northeastern region of Colombia, this study aimed to determine the seroprevalence and risk factors associated with the disease in non-vaccinated farms. For this purpose, a two-time point sampling strategy was developed, obtaining serum from 1157 animals housed in 25 farms distributed in 46 townships, thus for antibody detection against non-structural protein 3 (NS3, p80) of bovine viral diarrhea virus (BVDV) using an indirect ELISA test. For the first time in Colombia, the presence of serological persistent cattle was evaluated in 1047 animals 3 weeks later of first sampling. The information on a standardized questionnaire with closed and dichotomic answers was used to calculate the putative risk factors. The association analysis by univariate and multivariate logistic regression reported odds ratios (OR) with a 95% of confidence interval (C.I). The overall seroprevalence was 65% (95% CI 62.5-72.9%), with variations according to age ranges. The prevalence of persistent serological positive corresponded to 37.7% (95% CI 34.2-41.5). The risk factors found by multivariate analyses were the lease of pastures (OR = 2.071 CI 1.485-3.690), the use of the same needle (OR = 2.249 CI 1.354-3.736), the molasses supplementation (OR = 2.742 CI 1.156-5.807), and the native Creole breed (OR = 1.895 CI 1.416-2.804). The results of this study confirmed the endemism and higher common exposure to BVDV, as well as the presence of serological persistent cattle in Valledupar, Colombia.

Seroprevalence and risk factors for Leptospira spp. in small ruminants of semi-arid zone in northeastern Colombia.

Leptospirosis in small ruminants is an economically important disease that causes important losses by pathologies of the reproductive tract. The present study aimed to estimate the seroprevalence and risk factors associated with Leptospira spp. in small ruminants under traditional husbandry systems. A cross-sectional epidemiological study was carried out in a sample of 1039 animals which included 793 sheep and 245 goats from 49 farms of 10 municipalities of northeastern areas of Colombia. The MAT test using a panel of 13 laboratory serovars was performed to diagnose the Leptospira spp. antibodies in the serum samples of animals. A structured questionnaire was filled in each farm to obtain information on putative risk factors, and its association with Leptospira spp. infection was detected by univariate and multivariate logistic regression. The general seroprevalence showed a rate of 13.9%, the 79.6% of farms showed at least one positive animal, the 14.2% and 0.4% of positive animals showed titers ≥ 1:100 and 1:200, respectively. The seroprevalence in sheep and goats showed a rate of 13.1% and 16.2%, respectively. The most common serovars in positive animals were Autumnalis (3.6%), Tarassovi (3.4%), Bratislava (2.9%), Mini (2.9%), Bataviae (1.4%), Canicola (0.3%), and Grippotyphosa (0.3%). The univariate and multivariate analysis showed as risk factors the absence of housing system (OR = 3.412 CI: 1.347-8.152), the absence of quarantine measures to new animals (OR = 1.371 CI: 0.943-1.978), and the protective factor identified was the use of Toggenburg breed (OR = 0.571 CI: 0.249-1.074). This exploratory study showed the Leptospira spp. positive small ruminants located in the northeastern areas of Colombia with titer associated with chronic and subclinical infection.

Association of Cow's Milk Protein Allergy Prevalence With Socioeconomic Status in a Cohort of Chilean Infants.

OBJECTIVES: The aim of the study was to compare the cow's milk protein allergy (CMPA) prevalence in 2 cohorts of children from different socioeconomic strata. METHODS: Prospective birth cohort that included patients from 2 hospitals providing care for a low- and high-income population, respectively. Healthy newborns ≥34 gestational weeks were recruited and followed up to 12 months by a monthly telephone survey. If ≥2 predefined symptoms/signs suggestive of CMPA were detected, the patient was evaluated by a pediatric gastroenterologist. Diagnosis was confirmed by exclusion diet followed by open oral food challenge. RESULTS: Overall the prevalence of CMPA was 5.2%, with a 6 times higher prevalence in the high income cohort (9.2%) compared with the low-income group (1.5%; relative risk 6.2; 95% confidence interval 1.8-20.7; P = 0.0005). All the cases were non-immunoglobulin E-mediated with predominantly gastrointestinal symptoms. High-income cohort did have higher frequency of C-section, mother's previous chronic disease, mother's history of atopy/food allergy, older age, and higher educational level of parents. Parent smoking and presence of pets at home were more frequent in the low-income cohort. Multiple logistic regression showed that the high-income cohort did have older age and higher educational level of both parents. CONCLUSION: In these cohorts the prevalence of CMPA was higher than reported previously in other developing countries and significantly higher in the high-income group. Our findings were associated with sociodemographic characteristics of the parents.

Endoscopic Findings Associated With Button Battery Ingestion in Children: Do We Need to Change the Protocol for Managing Gastric Location?

BACKGROUND: Ingested button batteries (BB) can cause corrosive damage of digestive mucosa within minutes. Immediate endoscopic removal of esophageal BB has been clearly established, but the management of BB located in the stomach is still controversial. AIM: To describe demographic, clinical, radiologic, and endoscopic characteristics of a series of pediatric patients evaluated for BB ingestion. METHODS: Retrospective analysis of clinical charts belonging to children younger than 15 years, who underwent endoscopic removal of BB at Clínica Alemana of Santiago, between November 2007 and November 2011. RESULTS: Twenty-five patients subjected to upper endoscopy were analyzed; median age, 31 months; 15 were male (60%), and 11 patients (46%) were symptomatic after ingestion. The BB ingestion was confirmed by radiograph. Endoscopy revealed 10 patients with BB in the esophagus, 12 patients in the stomach and 3 distal to duodenum. Range time between ingestion and endoscopy was 2 to 10 hours for esophageal BB and 2 hours to 3 days for gastric BB. Eight of the 22 BBs removed had a diameter of 20 mm or greater, 6 of them were located in the esophagus and 2 in stomach. The BB color changes were observed in 14 of the 22 BBs. Breakage of battery edges was present in 11 of the 22 batteries. All patients with esophageal BB and 6 of those 12 with gastric BB presented mucosal damage. CONCLUSION: Esophageal BB cause damage within hours. The BB located in the stomach may also cause damage early. Extraction of gastric BB before 48 hours should be considered.

Effectiveness of ceftazidime/avibactam as salvage therapy for treatment of infections due to OXA-48 carbapenemase-producing Enterobacteriaceae.

Background: Experience in real clinical practice with ceftazidime/avibactam is limited, and there are even fewer data on infections due to OXA-48-producing Enterobacteriaceae. Methods: We designed an observational study of a prospectively collected cohort of adult patients receiving ceftazidime/avibactam in our centre. Only the first treatment course of each patient was analysed. Efficacy and safety were evaluated as 14 and 30 day mortality, recurrence rate at 90 days, resistance development and occurrence of adverse effects. Results: Fifty-seven patients were treated with ceftazidime/avibactam. The median age was 64 years (range 26-86), 77% were male and the median Charlson index was 3. The most frequent sources of infection were intra-abdominal (28%), followed by respiratory (26%) and urinary (25%). Thirty-one (54%) patients had a severe infection (defined as presence of sepsis or septic shock). Most patients received ceftazidime/avibactam as monotherapy (81%) and the median duration of treatment was 13 days. Mortality at 14 days was 14%. In multivariate analysis, the only mortality risk factor was INCREMENT-CPE score >7 (HR 11.7, 95% CI 4.2-20.6). There was no association between mortality and monotherapy with ceftazidime/avibactam. The recurrence rate at 90 days was 10%. Ceftazidime/avibactam resistance was not detected in any case and only two patients developed adverse events related to treatment. Conclusions: Ceftazidime/avibactam shows promising results, even in monotherapy, for the treatment of patients with severe infections due to OXA-48-producing Enterobacteriaceae and limited therapeutic options. The emergence of resistance to ceftazidime/avibactam was not observed.

Peripheral B-Cell Subset Distribution in Primary Antiphospholipid Syndrome.

BACKGROUND: B-cell differentiation and B-cell tolerance checkpoints may be different in antiphospholipid syndrome (APS) from systemic lupus erythematosus (SLE) and can help to understand differences between them. Our aim was to define alterations of B-cell subsets in patients with primary APS (pAPS) and to compare them with SLE patients and healthy controls (HC). METHODS: Cross-sectional study including three study groups: 37 patients with pAPS, 11 SLE patients, and 21 age- and gender-matched HC. We determined the frequencies of different B-cell subsets in peripheral blood naïve and memory compartments. In addition, we measured serum B cell-activating factor (BAFF) levels and circulating pro-inflammatory cytokines, such as IL-6, by commercial ELISA and CBA, respectively. RESULTS: Patients with pAPS showed a lower percentage of immature and naïve B cells than patients with SLE (p = 0.013 and p = 0.010, respectively) and a higher percentage of non-switched memory B cells than patients with SLE (p = 0.001). No differences either in the percentage of switched memory cells or plasma cells were found among the different groups. Serum BAFF levels were higher in SLE patients than in healthy controls and pAPS patients (p = 0.001 and p = 0.017, respectively). A significant increase in the serum BAFF levels was also observed in pAPS patients compared to HC (p = 0.047). Circulating IL-6 levels were higher in SLE and pAPS patients than HC (p = 0.036 and p = 0.048, respectively). A positive correlation was found between serum BAFF and IL-6 levels in patients with SLE but not in pAPS (p = 0.011). CONCLUSIONS: Our characterization of peripheral blood B-cell phenotypes in pAPS demonstrates different frequencies of circulating B cells at different stages of differentiation. These differences in the naïve B-cell repertoire could explain the higher number and variety of autoantibodies in SLE patients in comparison to pAPS patients, especially in those with obstetric complications.

A Truncated Variant of ASCC1, a Novel Inhibitor of NF-κB, Is Associated with Disease Severity in Patients with Rheumatoid Arthritis.

Loss of the regulatory mechanisms that avoid excessive or constitutive activation of NF-κB may be associated with chronic inflammatory disorders, including rheumatoid arthritis (RA). After massive sequencing of 158 regulators of the NF-κB pathway in RA patients, we focused on a scarcely known gene, ASCC1, and showed that it potently inhibits the expression of NF-κB target genes (TRAIL, TNF-α, cIAP-1, IL8) and blocks activation of a NF-κB-luciferase reporter construct in five different human cell lines. Therefore, ASCC1 may contribute to avoiding a pathologic activation of this transcription factor. A truncated variant of ASCC1 (p.S78*) was found in RA patients and control individuals. Functional in vitro studies revealed that truncation abrogated the NF-κB inhibition capacity of ASCC1. In contrast with full-length protein, truncated ASCC1 did not reduce the transcriptional activation of NF-κB and the secretion of TNF-α in response to inflammatory stimuli. We analyzed the clinical impact of p.S78* variant in 433 patients with RA and found that heterozygous carriers of this variant needed more disease-modifying antirheumatic drugs, and more patients with this genotype needed treatment with corticoids and biologic agents. Moreover, the truncated allele-carrier group had lower rates of remission compared with the full-length variant carriers. Overall, our findings show for the first time, to our knowledge, that ASCC1 inhibits NF-κB activation and that a truncated and inactive variant of ASCC1 is associated with a more severe disease, which could have clinical value for assessing the progression and prognosis of RA.

[Intestinal cleaning for colonoscopy in children: effectiveness, adherence and adverse effects of schemes differentiated by age]. / Limpieza intestinal para colonoscopia en niños: efectividad, adherencia y efectos adversos de esquemas diferenciados por edad.

Adequate intestinal cleanliness is crucial to achieve optimal colonoscopy performance. Several bowel preparation (BP) schemes have been proposed, but there is still no consensus as regards which is the most suitable in paediatric patients. OBJECTIVE: To describe the effectiveness, adherence, and adverse effects of BP protocols differentiated by age group in paediatric patients subjected to colonoscopy. PATIENTS AND METHOD: Prospective, study that included patients < 18 years subjected to colonoscopy. BP protocols differentiated by age group were indicated as follows: < 6 m (glycerine suppository); 6 m-3y 11 m (poly-ethylene-glycol (PEG 3350 without electrolytes); 4y-9y 11 m (PEG 3350 without electrolytes + bisacodyl); 10 y-18 y (PEG 3350 with electrolytes). Demographic, clinical information, adherence and adverse effects were registered. Effectiveness was determined using a validated scale (Boston modified) during colonoscopy. RESULTS: A total of 159 patients were included, of which 87 (55%) were males, and with a median age of 4 years (range 1 m-17 years). Seventy eight percent of patients achieved successful BP. The higher effectiveness was observed in the groups of < 6 m (96%) and 10-18 y (91%). Constipation was significantly more frequent (29%) in the 4 yo-9 yo 11 m in which lower effectiveness was observed (69%). Good adherence was observed in 87% of patients. Adverse effects were observed in a third of patients, although they were mild and did not lead to the suspension of the BP. CONCLUSIONS: Satisfactory results were achieved with the BP schemes used, with a successful BP being obtained in 4 out of 5 patients. Results were different between groups, which is probably related to previous bowel transit and indicated medication.

Colorectal cancer risk factors in patients with serrated polyposis syndrome: a large multicentre study.

OBJECTIVE: Serrated polyposis syndrome (SPS) is associated with an increased colorectal cancer (CRC) risk, although the magnitude of the risk remains uncertain. Whereas intensive endoscopic surveillance for CRC prevention is advised, predictors that identify patients who have high CRC risk remain unknown. We performed a multicentre nationwide study aimed at describing the CRC risk in patients with SPS and identifying clinicopathological predictors independently associated with CRC. DESIGN: From March 2013 through September 2014, patients with SPS were retrospectively recruited at 18 Spanish centres. Data were collected from medical, endoscopy and histopathology reports. Multivariate logistic regression was performed to identify CRC risk factors. RESULTS: In 296 patients with SPS with a median follow-up time of 45 months (IQR 26-79.7), a median of 26 (IQR 18.2-40.7) serrated polyps and 3 (IQR 1-6) adenomas per patient were detected. Forty-seven patients (15.8%) developed CRC at a mean age of 53.9±12.8, and 4 out of 47 (8.5%) tumours were detected during surveillance (cumulative CRC incidence 1.9%). Patients with >2 sessile serrated adenomas/polyps (SSA/Ps) proximal to splenic flexure and ≥1 proximal SSA/P with high-grade dysplasia were independent CRC risk factors (incremental OR=2, 95% CI 1.22 to 3.24, p=0.006). Patients with no risk factors showed a 55% decrease in CRC risk (OR=0.45, 95% CI 0.24 to 0.86, p=0.01). CONCLUSIONS: Patients with SPS have an increased risk of CRC, although lower than previously published. Close colonoscopy surveillance in experienced centres show a low risk of developing CRC (1.9% in 5 years). Specific polyp features (SSA/P histology, proximal location and presence of high-grade dysplasia) should be used to guide clinical management.

Accuracy of a Genetic Test for the Diagnosis of Hypolactasia in Chilean Children: Comparison With the Breath Test.

BACKGROUND: Lactase nonpersistence (LNP) in humans is a genetically determined trait. This age-dependent decrease of lactase expression is most frequently caused by single nucleotide polymorphisms in the regulatory region of the lactase (LCT) gene. The homozygous LCT-13,910C/C genotype (rs 4988235) predominates in Caucasian adults with LNP, and is useful for its diagnosis in this population. The accuracy of this genetic test (GT) has not been completely established in children or in a Latin-American population. OBJECTIVES: The aim of the study was to determine diagnostic accuracy of GT for LNP in Chilean children using the lactose breath test (BT) as a reference, and to compare diagnostic yield in preschool- (<6 years) and in school-age (≥6 years) children. METHODS: Children referred for BT for diagnosis of lactose malabsorption to the Gastroenterology Laboratory at Clínica Alemana, Santiago, from October 2011 to March 2012 were invited to participate. After informed consent, symptom questionnaires, both historic and post lactose ingestion were completed. H2 and CH4 in expired air and -13,910 C>T single nucleotide polymorphism by polymerase chain reaction, restriction enzyme analysis, and/or Sanger sequencing were determined. GT accuracy was calculated compared to BT as reference method. Diagnostic yield of GT in preschool- and school-age children was compared. RESULTS: Lactose malabsorption was detected by BT in 42 of 60 children (70%). Genotype -13,910C/C was identified in 41 of 60 patients (68%). GT showed 80% sensitivity, 63% specificity, and 74% accuracy for LNP in the preschool population. In school-age children values were higher, 85%, 80%, and 84%, respectively. CONCLUSIONS: GT results were significantly concordant with BT results for hypolactasia detection in Chilean children, particularly in those of age 6 years and older.

The proto-oncogene c-myc regulates antibody secretion and Ig class switch recombination.

The immune response involves the generation of Ab-secreting cells and memory B cells through a process called terminal B lymphocyte differentiation. This program requires the transcriptional repressor Blimp-1, which inhibits c-myc expression and terminates proliferation. Although the role of c-Myc in cell proliferation is well characterized, it is not known whether it has other functions in terminal differentiation. In this study, we show that c-Myc not only regulates cell proliferation, but it is also essential for Ab-secreting cell function and differentiation in vivo. c-Myc-deficient B lymphocytes hypersecrete IgM and do not undergo Ig class switch recombination (CSR). CSR has been previously linked to proliferation, and in this study we mechanistically link class switching and proliferation via c-Myc. We observed that c-Myc regulates CSR by transcriptionally activating the B cell-specific factor activation-induced cytidine deaminase. By linking cell proliferation and CSR, c-Myc is thus a critical component for a potent immune response.

[Cervical cancer screening: Is active recruitment worth the effort?]. / Cribado de cáncer de cérvix: ¿merece la pena la búsqueda activa?

OBJECTIVES: To determine the percentage of women who have had a Pap smear in the last 5 years, and the place where it was carried out. To detect cytological abnormalities and precursors of cervical cancer in un-screened or inadequately screened women and the prevalence of HPV-positive determinations. DESIGN: Cross sectional study. SETTING: Natahoyo Health Centre, Gijón (Spain). PARTICIPANTS: Women aged 40-50 years living in the area and assigned to the Health Centre. METHODS: The information was collected from databases, telephone and home surveys. There was active recruitment of unscreened women or inadequately screened in Primary Care as well as offering to perform cytology and HPV determination. RESULTS: Of the 1420 women aged 40 to 50 years, 1236 (87%) had cytology in the last 5 years, and 184 women (13%) had no screening or it was inadequate. Of these 184 women, 108 (58.7%) agreed to have cytology and HPV test performed. No high-grade cervical dysplasia was diagnosed. The prevalence of HPV-positive was 8.3%. CONCLUSIONS: In our population there is a high coverage of opportunistic screening for cervical cancer. The active recruitment of women who were not in the screening program was not useful.