The Consensus Definition of Bronchopulmonary Dysplasia Is an Adequate Predictor of Lung Function at Preschool Age

Bronchopulmonary dysplasia; Lung function; Preschool ageDisplasia broncopulmonar; Función pulmonar; Edad preescolarDisplàsia broncopulmonar; Funció pulmonar; Edat preescolarBackground: Recent attempts to refine the definition bronchopulmonary dysplasia (BPD) have based its predictive capacity on respiratory outcome in the first 2 years of life, eliminating the pre-existing requirement of 28 days of oxygen therapy prior to 36 weeks postmenstrual age (PMA). The objective of this study was to assess the utility of the 2001 consensus definition in predicting impaired lung function at preschool age. Methods: This cohort study included children aged 4–6 years old who were born at gestational age (GA) <32 weeks or bodyweight <1500 g. Univariate and multivariate analyses were performed to assess differences in antenatal and neonatal variables between BPD and non-BPD children. All participants underwent incentive spirometry. Lung function parameters were contrasted with the Global Lung Function Initiative (GLI-2012) reference equations and, together with antenatal and neonatal variables, compared among the different subgroups (no BPD, mild BPD, and moderate-to-severe BPD). A multivariate model was generated to identify independent risk factors for impaired lung function. Results: GA, hemodynamically significant patent ductus arteriosus, and late sepsis were independent risk factors for the development of BPD. A total of 119 children underwent incentive spirometry. All lung function parameters were significantly altered relative to reference values. Greater impairment of lung function was observed in the mild BPD vs. the no BPD group (forced expiratory volume in the first 0.75 seconds [FEV0.75]: −1.18 ± 0.80 vs. −0.55 ± 1.13; p = 0.010), but no difference in forced vital capacity (FVC) was observed (−0.32 ± 0.90 vs. −0.18 ± 1; p = 0.534). The moderate-to-severe BPD group exhibited the most severe FEV0.75 reduction (FEV0.75: −2.63 ± 1.18 vs. −0.72 ± 1.08; p = 0.000) and was the only condition with FVC impairment (FVC: −1.82 ± 1.12 vs. −0.22 ± 0.87; p = 0.000). The multivariate analysis identified a diagnosis of moderate-to-severe BPD as an independent risk factor for lung function impairment. Conclusion: The 2001 consensus definition of BPD has adequate predictive capacity for lung function measured by spirometry at 4–6 years of age. Moderate-to-severe BPD was the best predictor of respiratory impairment. Children with mild BPD showed greater alteration of FEV0.75 than those without BPD.This study was partially financed with funds from the IDIS research group C012 (Santiago de Compostela) and Miguel Servet Biomedical Foundation (Zaragoza)

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Prevalence of Same-Sex Sexual Behavior and Associated Characteristics among Low-Income Urban Males in Peru

Peru has a concentrated HIV epidemic in which men who have sex with men are particularly vulnerable. We describe the lifetime prevalence of same-sex sexual contact and associated risk behaviors of men in Peru's general population, regardless of their sexual identity.A probability sample of males from low-income households in three Peruvian cities completed an epidemiologic survey addressing their sexual risk behavior, including sex with other men. Serum was tested for HSV-2, HIV, and syphilis. Urine was tested for chlamydia and gonorrhea. A total of 2,271 18-30 year old men and women were contacted, of whom 1,645 (72.4%) agreed to participate in the study. Among the sexually experienced men surveyed, 15.2% (85/558, 95% CI: 12.2%-18.2%) reported a history of sex with other men. Men ever reporting sex with men (MESM) had a lower educational level, had greater numbers of sex partners, and were more likely to engage in risk behaviors including unprotected sex with casual partners, paying for or providing compensated sex, and using illegal drugs. MESM were also more likely to have had previous STI symptoms or a prior STI diagnosis, and had a greater prevalence of HSV-2 seropositivity.Many low-income Peruvian men have engaged in same-sex sexual contact and maintain greater behavioral and biological risk factors for HIV/STI transmission than non-MESM. Improved surveillance strategies for HIV and STIs among MESM are necessary to better understand the epidemiology of HIV in Latin America and to prevent its further spread

Characterizing the Role of Cell-Wall β-1,3-Exoglucanase Xog1p in Candida albicans Adhesion by the Human Antimicrobial Peptide LL-37

Candida albicans is the major fungal pathogen of humans. Its adhesion to host-cell surfaces is the first critical step during mucosal infection. Antimicrobial peptides play important roles in the first line of mucosal immunity against C. albicans infection. LL-37 is the only member of the human cathelicidin antimicrobial peptide family and is commonly expressed in various tissues, including epithelium. We previously showed that LL-37 significantly reduced C. albicans adhesion to plastic, oral epidermoid OECM-1 cells, and urinary bladders of female BALB/c mice. The inhibitory effect of LL-37 on cell adhesion occurred via the binding of LL-37 to cell-wall carbohydrates. Here we showed that formation of LL-37–cell-wall protein complexes potentially inhibits C. albicans adhesion to polystyrene. Using phage display and ELISA, we identified 10 peptide sequences that could bind LL-37. A BLAST search revealed that four sequences in the major C. albicans cell-wall β-1,3-exoglucanase, Xog1p, were highly similar to the consensus sequence derived from the 10 biopanned peptides. One Xog1p-derived peptide, Xog1p90–115, and recombinant Xog1p associated with LL-37, thereby reversing the inhibitory effect of LL-37 on C. albicans adhesion. LL-37 reduced Xog1p activity and thus interrupted cell-wall remodeling. Moreover, deletion of XOG1 or another β-1,3-exoglucanase-encoding gene EXG2 showed that only when XOG1 was deleted did cellular exoglucanase activity, cell adhesion and LL-37 binding decrease. Antibodies against Xog1p also decreased cell adhesion. These data reveal that Xog1p, originally identified from LL-37 binding, has a role in C. albicans adhesion to polystyrene and, by inference, attach to host cells via direct or indirect manners. Compounds that target Xog1p might find use as drugs that prevent C. albicans infection. Additionally, LL-37 could potentially be used to screen for other cell-wall components involved in fungal cell adhesion

Chronic allograft nephropathy

Chronic allograft nephropathy (CAN) is the leading cause of renal allograft loss in paediatric renal transplant recipients. CAN is the result of immunological and nonimmunological injury, including acute rejection episodes, hypoperfusion, ischaemia reperfusion, calcineurin toxicity, infection and recurrent disease. The development of CAN is often insidious and may be preceded by subclinical rejection in a well-functioning allograft. Classification of CAN is histological using the Banff classification of renal allograft pathology with classic findings of interstitial fibrosis, tubular atrophy, glomerulosclerosis, fibrointimal hyperplasia and arteriolar hyalinosis. Although improvement in immunosuppression has led to greater 1-year graft survival rates, chronic graft loss remains relatively unchanged and opportunistic infectious complications remain a problem. Protocol biopsy monitoring is not current practice in paediatric transplantation for CAN monitoring but may have a place if new treatment options become available. Newer immunosuppression regimens, closer monitoring of the renal allograft and management of subclinical rejection may lead to reduced immune injury leading to CAN in the paediatric population but must be weighed against the risk of increased immunosuppression and calcineurin inhibitor nephrotoxicity

Pch2 Acts through Xrs2 and Tel1/ATM to Modulate Interhomolog Bias and Checkpoint Function during Meiosis

Proper segregation of chromosomes during meiosis requires the formation and repair of double-strand breaks (DSBs) to form crossovers. Repair is biased toward using the homolog as a substrate rather than the sister chromatid. Pch2 is a conserved member of the AAA+-ATPase family of proteins and is implicated in a wide range of meiosis-specific processes including the recombination checkpoint, maturation of the chromosome axis, crossover control, and synapsis. We demonstrate a role for Pch2 in promoting and regulating interhomolog bias and the meiotic recombination checkpoint in response to unprocessed DSBs through the activation of axial proteins Hop1 and Mek1 in budding yeast. We show that Pch2 physically interacts with the putative BRCT repeats in the N-terminal region of Xrs2, a member of the MRX complex that acts at sites of unprocessed DSBs. Pch2, Xrs2, and the ATM ortholog Tel1 function in the same pathway leading to the phosphorylation of Hop1, independent of Rad17 and the ATR ortholog Mec1, which respond to the presence of single-stranded DNA. An N-terminal deletion of Xrs2 recapitulates the pch2Δ phenotypes for signaling unresected breaks. We propose that interaction with Xrs2 may enable Pch2 to remodel chromosome structure adjacent to the site of a DSB and thereby promote accessibility of Hop1 to the Tel1 kinase. In addition, Xrs2, like Pch2, is required for checkpoint-mediated delay conferred by the failure to synapse chromosomes

First Colombian Multicentric Newborn Screening for Congenital Toxoplasmosis

Congenital toxoplasmosis can result in permanent sequel as blindness or neurological damage in children and it seems to be more severe in South America than in other continents. There is a lack of information about this frequency in Colombia, where no control program is established, although it is a recognized cause of potentially preventable congenital blindness. We propose the first Colombian multicentric study to determine the frequency and impact of congenital toxoplasmosis. More than 15,000 newborns in seven cities were studied. Newborns were tested at birth by doing a cord blood test for toxoplasmosis. Additionally, children from mothers with history of toxoplasmosis acquired during pregnancy were recalled for a follow-up. The program identified fifteen children otherwise undiagnosed; three of these children died as consequence of congenital toxoplasmosis. The frequency of the congenital infection varied significantly between cities, being higher in Armenia and Florencia, intermediate in Bogota, Bucaramanga and Barranquilla and very low in western cities such as Cucuta and Riohacha. For the first time a significant correlation was found between mean rainfall at the city and the incidence of this congenital infection

History-Dependent Excitability as a Single-Cell Substrate of Transient Memory for Information Discrimination

Neurons react differently to incoming stimuli depending upon their previous history of stimulation. This property can be considered as a single-cell substrate for transient memory, or context-dependent information processing: depending upon the current context that the neuron “sees” through the subset of the network impinging on it in the immediate past, the same synaptic event can evoke a postsynaptic spike or just a subthreshold depolarization. We propose a formal definition of History-Dependent Excitability (HDE) as a measure of the propensity to firing in any moment in time, linking the subthreshold history-dependent dynamics with spike generation. This definition allows the quantitative assessment of the intrinsic memory for different single-neuron dynamics and input statistics. We illustrate the concept of HDE by considering two general dynamical mechanisms: the passive behavior of an Integrate and Fire (IF) neuron, and the inductive behavior of a Generalized Integrate and Fire (GIF) neuron with subthreshold damped oscillations. This framework allows us to characterize the sensitivity of different model neurons to the detailed temporal structure of incoming stimuli. While a neuron with intrinsic oscillations discriminates equally well between input trains with the same or different frequency, a passive neuron discriminates better between inputs with different frequencies. This suggests that passive neurons are better suited to rate-based computation, while neurons with subthreshold oscillations are advantageous in a temporal coding scheme. We also address the influence of intrinsic properties in single-cell processing as a function of input statistics, and show that intrinsic oscillations enhance discrimination sensitivity at high input rates. Finally, we discuss how the recognition of these cell-specific discrimination properties might further our understanding of neuronal network computations and their relationships to the distribution and functional connectivity of different neuronal types

Pooled analysis of who surgical safety checklist use and mortality after emergency laparotomy

Background: The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods: In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results: Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89⋅6 per cent) compared with that in countries with a middle (753 of 1242, 60⋅6 per cent; odds ratio (OR) 0⋅17, 95 per cent c.i. 0⋅14 to 0⋅21, P &lt; 0⋅001) or low (363 of 860, 42⋅2 percent; OR 0⋅08, 0⋅07 to 0⋅10, P &lt; 0⋅001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference −9⋅4 (95 per cent c.i. −11⋅9 to −6⋅9) per cent; P &lt; 0⋅001), but the relationship was reversed in low-HDI countries (+12⋅1 (+7⋅0 to +17⋅3) per cent; P &lt; 0⋅001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0⋅60, 0⋅50 to 0⋅73; P &lt; 0⋅001). The greatest absolute benefit was seen for emergency surgery in low-and middle-HDI countries. Conclusion: Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries