Emerging of ptxP3 lineage in Bordetella pertussis strains circulating in a population in northeastern Mexico.

We determined the molecular epidemiology of Bordetella pertussis isolates to evaluate its potential impact on pertussis reemergence in a population of Mexico. Symptomatic and asymptomatic cases were included. Pertussis infection was confirmed by culture and real-time polymerase chain reaction (PCR). Selected B. pertussis isolates were further analysed; i.e. clonality was analysed by pulsed-field gel electrophoresis (PFGE) and ptxP-ptxA, prn, fim2 and fim3 typing was performed by PCR and sequencing. Out of 11 864 analysed samples, 687 (5.8%) were positive for pertussis, with 244 (36%) confirmed by both culture and PCR whereas 115 (17%) were positive only by culture and 328 (48%) were positive only by PCR. One predominant clone (clone A, n = 62/113; 55%) and three major subtypes (A1, A2 and A3) were identified by PFGE. All 113 selected isolates had the allelic combination ptxP3-ptxA1. The predominant clone A and the three major subtypes (A1, A2 and A3) corresponded to the emerging genotypes ptxP3-ptxA1-prn2-fim2-1-fim3-2 and ptxP3-ptxA1-prn2-fim2-1-fim3-1. In conclusion, the presence of an endemic clone and three predominant subtypes belonging to the genotypes ptxP3-ptxA1-prn2-fim2-1-fim3-2 and ptxP3-ptxA1-prn2-fim2-1-fim3-1 were detected. This finding supports the global spread/expansion reported for these outbreaks associated genotypes.

Free energy profiles for two ubiquitous damaging agents: methylation and hydroxylation of guanine in B-DNA.

DNA methylation and hydroxylation are two ubiquitous reactions in DNA damage induction, yet insights are scarce concerning the free energy of activation within B-DNA. We resort to multiscale simulations to investigate the attack of a hydroxyl radical and of the primary diazonium onto a guanine embedded in a solvated dodecamer. Reaction free energy profiles characterize two strongly exergonic processes, yet allow unprecedented quantification of the barrier towards this damage reaction, not higher than 6 kcal mol-1 and sometimes inexistent, and of the exergonicities. In the case of the [G(C8)-OH]˙ intermediate, we challenge the functional dependence of such simulations: recently-proposed functionals, such as M06-2X and LC-BLYP, agree on a ∼4 kcal mol-1 barrier, whereas the hybrid GGA B3LYP functional predicts a barrier-less pathway. In the long term, multiscale approaches can help build up a unified panorama of DNA lesion induction. These results stress the importance of DFT/MM-MD simulations involving new functionals towards the sound modelling of biomolecule damage even in the ground state.

Iodine status and thyroid function among Spanish schoolchildren aged 6-7 years: the Tirokid study.

I deficiency is still a worldwide public health problem, with children being especially vulnerable. No nationwide study had been conducted to assess the I status of Spanish children, and thus an observational, multicentre and cross-sectional study was conducted in Spain to assess the I status and thyroid function in schoolchildren aged 6-7 years. The median urinary I (UI) and thyroid-stimulating hormone (TSH) levels in whole blood were used to assess the I status and thyroid function, respectively. A FFQ was used to determine the consumption of I-rich foods. A total of 1981 schoolchildren (52 % male) were included. The median UI was 173 µg/l, and 17·9 % of children showed UI<100 µg/l. The median UI was higher in males (180·8 v. 153·6 µg/l; P<0·001). Iodised salt (IS) intake at home was 69·8 %. IS consumption and intakes of ≥2 glasses of milk or 1 cup of yogurt/d were associated with significantly higher median UI. Median TSH was 0·90 mU/l and was higher in females (0·98 v. 0·83; P<0·001). In total, 0·5 % of children had known hypothyroidism (derived from the questionnaire) and 7·6 % had TSH levels above reference values. Median TSH was higher in schoolchildren with family history of hypothyroidism. I intake was adequate in Spanish schoolchildren. However, no correlation was found between TSH and median UI in any geographical area. The prevalence of TSH above reference values was high and its association with thyroid autoimmunity should be determined. Further assessment of thyroid autoimmunity in Spanish schoolchildren is desirable.

Duddingtonia flagrans chlamydospores in nutritional pellets: effect of storage time and conditions on the trapping ability against Haemonchus contortus larvae.

The study evaluated the effect of storage time and conditions of nutritional pellets (NP) containing Duddingtonia flagrans chlamydospores on its in vitro trapping ability against Haemonchus contortus L3 larvae. The treated batch (200 NP) contained 4 × 106 chlamydospores of the FTH0-8 strain, whereas the control batch (200 NP) was produced without spores. Both NP batches were exposed to four experimental storage conditions: (T1) shelves (indoors); (T2) refrigeration (4°C); (T3) outdoors under a roof; and (T4) 100% outdoors. Each group comprised 48 NP with spores and 48 NP without spores (control). The ability of D. flagrans spores to trap H. contortus L3 larvae was evaluated for 8 weeks for each storage condition. For that purpose, six randomly selected NP with spores were compared to their respective control NP. Each NP was individually crushed. The crushed material (1 g) was placed on the surface of a 2% water agar plate with 200 H. contortus L3 larvae. Plates were sealed and were incubated at room temperature for 8 days. The whole content of every plate was transferred to a Baermann apparatus to recover the remaining larvae. There was a clear larval reduction in the NP with spores, compared to the respective control NP in the four storage conditions (P< 0.05). The mean reductions ( ± SEM) of the storage conditions were 67 ± 4.9 (T2), 77 ± 6.1 (T1), 81.5 ± 3.8 (T4) and 82.1 ± 2.5 (T3). Larval reductions were similar at all times and were not affected by storage conditions or storage time (R 20.05). The long-term shelf-life of the chlamydospores in the NP suggests that this spore dosage technology is a viable option.

The catalytic mechanism of carboxylesterases: a computational study.

The catalytic mechanism of carboxylesterases (CEs, EC 3.1.1.1) is explored by computational means. CEs hydrolyze ester, amide, and carbamate bonds found in xenobiotics and endobiotics. They can also perform transesterification, a reaction important, for instance, in cholesterol homeostasis. The catalytic mechanisms with three different substrates (ester, thioester, and amide) have been established at the M06-2X/6-311++G**//B3LYP/6-31G* level of theory. It was found that the reactions proceed through a mechanism involving four steps instead of two as is generally proposed: (i) nucleophilic attack of serine to the substrate, forming the first tetrahedral intermediate, (ii) formation of the acyl-enzyme complex concomitant with the release of the alcohol product, (iii) nucleophilic attack of a water or alcohol molecule forming the second tetrahedral intermediate, and (iv) the release of the second product of the reaction. The results agree very well with the available experimental data and show that the hydrolytic and the transesterification reactions are competitive processes when the substrate is an ester. In all the other studied substrates (thioester or amide), the hydrolytic and transesterification process are less favorable and some of them might not even take place under in vivo conditions.

Regression activity that is naturally present in vitreous becomes ineffective as patients develop proliferative diabetic retinopathy.

AIMS/HYPOTHESIS: The realisation that targeting agents in the vitreous is an effective approach to treating patients with diabetic retinopathy (DR) has increased awareness that changes in the composition/bioactivity of the vitreous is a contributor to the pathogenesis of DR. The overall goal of this study was to test the hypothesis that the vitreous has regression activity, and that lysophosphatidic acid (LPA) contributes to such activity. LPA is a bioactive phospholipid present in many biological fluids, and has been recently appreciated for its ability to promote regression of blood vessels. METHODS: Vitreous-mediated regression was monitored on tubes organised from primary retinal endothelial cells or neovessels that sprouted from retinal explants. LPA was quantified radioenzymatically. RESULTS: Bovine and human vitreous promoted regression of retinal explant vessels and of tubes organised from primary retinal endothelial cells. LPA was a substantial component of this regression activity. Comparing the regression activities of vitreous from patients with different stages of DR revealed that, as patients developed proliferative diabetic retinopathy (PDR), vitreous lost its ability to promote regression, even though the amount of LPA did not change. The underlying mechanism was a PDR-vitreous-mediated insensitivity to LPA, which could be overcome pharmacologically. CONCLUSIONS/INTERPRETATION: Our findings suggest that a decline in the responsiveness to regression factors such as LPA, which are naturally present in the vitreous, contributes to the pathogenesis of PDR.

The cryptic seismic potential of the Pichilemu blind fault in Chile revealed by off-fault geomorphology.

The first step towards assessing hazards in seismically active regions involves mapping capable faults and estimating their recurrence times. While the mapping of active faults is commonly based on distinct geologic and geomorphic features evident at the surface, mapping blind seismogenic faults is complicated by the absence of on-fault diagnostic features. Here we investigated the Pichilemu Fault in coastal Chile, unknown until it generated a Mw 7.0 earthquake in 2010. The lack of evident surface faulting suggests activity along a partly-hidden blind fault. We used off-fault deformed marine terraces to estimate a fault-slip rate of 0.52 ± 0.04 m/ka, which, when integrated with satellite geodesy suggests a 2.12 ± 0.2 ka recurrence time for Mw~7.0 normal-faulting earthquakes. We propose that extension in the Pichilemu region is associated with stress changes during megathrust earthquakes and accommodated by sporadic slip during upper-plate earthquakes, which has implications for assessing the seismic potential of cryptic faults along convergent margins and elsewhere.

Echocardiographic study of structure and functional cardiac profile of football referees.

AIM: The aim of this study was to analyze, through echocardiography, the structure and functional cardiac profile of national category Spanish soccer referees. METHODS: The sample consisted of 54 licensed referees, who belonged to the Football Inter-Insular Federation of Las Palmas. The sample presented a mean age of 28.52 ± 6.39 years, a height of 1.76 ± 0.07 m, a body mass of 77.26 ± 10.74 kg and a Body Mass Index of 24.90 ± 2-73 kg/m2. The diastolic and systolic dimensions of the left ventricle were 50.03 ± 4.79 mm and 33.74 ± 5.23 mm, respectively. The thicknesses of the interventricular septum and the posterior wall of the left ventricle were 9.77 ± 1.53 mm and 9.47 ± 1.54 mm, respectively. The left ventricular mass was 112.80 ± 26.53 g/m2, the diastolic volume of the left ventricle 135.09 ± 39.63 mL and the ejected volume 47.34 ± 12.44 mL/m2. RESULTS: This study shows that the echocardiographic profile of football referees is characterized by presenting an increase in the left ventricular mass caused by an increase of the cardiac chambers and a normal systolic and diastolic function. The values obtained by football referees were higher than those found in sedentary people and lower than in professional football players. CONCLUSION: These differences may be due to the different physical training workloads employed by football players and referees.

Psychosocial and pharmacologic interventions for methamphetamine addiction: protocol for a scoping review of the literature.

BACKGROUND: Methamphetamine use and harms are rising rapidly. Management of patients with methamphetamine use disorder (MUD) and problematic methamphetamine use (PMU) is challenging, with no clearly established best approach; both psychosocial and pharmacologic interventions have been described. Furthermore, given the diversity of individuals that use methamphetamines, there is a need to assess evidence for treatments for subgroups including youths; gay, bisexual, and other men who have sex with men; individuals with mental health comorbidities; and individuals in correction services. Establishing awareness of the messages regarding treatment from recent clinical practice guidelines (CPG) in the field is also of value. The first study objective will be to establish a greater understanding of the methods, populations, and findings of controlled studies for psychosocial and pharmacologic treatments for MUD and PMU. Investigation of this information can help establish the potential for advanced syntheses of the evidence (such as network meta-analysis) to compare therapies for this condition and to identify gaps related to key populations where more primary research is needed. Summarizing the recommendations regarding treatment of MUD/PMU from recent CPGs and systematic reviews will be an important secondary objective. METHODS: A scoping review will be performed. Using the OVID platform, MEDLINE, Embase, PsycINFO, and relevant Cochrane databases from EBM Reviews will be searched (from databases' inception onwards). Eligibility criteria will include individuals described as having MUD or PMU, with designs of interest including randomized trials, non-randomized trials, and controlled cohort studies with three or more months of follow-up; systematic reviews and CPGs will also be sought. Two reviewers (with support from automation tools) will independently screen all citations, full-text articles, and chart data. Different approaches to handling and summarizing the data will be implemented for each type of study design. Tables and graphics will be used to map evidence sources and identify evidence gaps. DISCUSSION: This research will enhance awareness of evidence addressing the effects of psychosocial and pharmacologic interventions for MUD/PMU overall and in sub-populations, both in terms of recent CPGs/reviews and primary studies; inspection of the latter will also help establish the feasibility of future syntheses to compare treatments, such as network meta-analysis. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: Open Science Framework ( https://osf.io/9wy8p ).

Metabolism of theophylline to caffeine in human fetal liver.

Caffeine (1,3,7-trimethylxanthine) is a biotransformation product of theophylline (1,3-dimethylxanthine) in the human fetus. Liver explants, obtained from human fetuses with gestational ages of 12 to 20 weeks, were incubated with theophylline and produced caffeine and, in lesser amounts, 1,3-dimethyluric acid and 3-methylxanthine. These findings suggest that the predominant pathway in theophylline metabolism in the fetus and newborn infant is the methylation reaction producing caffeine. This may contribute to the neonate's exceedingly slower elimination of caffeine relative to theophylline. Caffeine produced from theophylline may add to the pharmacologic effects of theophylline in newborn infants with apnea.

Physical demands of top-class soccer assistant refereeing during high-standard matches.

This study examined the physical demands experienced by top-class assistant referees during high-standard football matches. Computerized match analyses and heart rate recordings were performed on 18 international assistant referees during the FIFA Confederations Cup 2005. Total distance covered averaged 5752+/-554 m, of which 34% was covered at a high-intensity (>13 km.h (-1)). Sidewards movements represented 30% of total match distance. Both total distance (r=0.67; P<0.01) and high-intensity activities (r=0.52; P<0.05) were related to the displacements of the ball in the same match. The distance covered by high-speed running in this tournament was 255% greater (P<0.001) than that covered during the under-17 World Championship 2003. Mean heart rate during the game was 140+/-11 b.min (-1) (78+/-4% HR (max)). Mean heart rate during a 5-min interval of the match was related in part (r=0.31; P<0.001) to the amount of high-intensity activities performed within the same match-period. The results of this study show that the physical demands imposed on assistant referees are influenced by the movements of the ball and the standard of the competition.

[Use of ranitidine in children's before and after an educative intervention with resident's in a third level pediatric hospital]. / Uso de ranitidina en niños antes y despuésde una intervención educativa en residentes de un hospital pediátrico de tercer nivel.

BACKGROUND: The H2-receptor blockers are often prescribed, but its good tolerance and accessibility have contributed to the abuse of these drugs. The lack of medical knowledge of the precise use of ranitidine involves a higher cost of care and possible errors. OBJECTIVE: To evaluate the use of ranitidine in a pediatric hospital of third level before and after an educational intervention for medical residents. MATERIALS AND METHODS: We reviewed 240 clinical files, taken at random from hospital wards, excluding emergency room and intensive care unit. The correct indications and the precise dose of the drug were verified. Ninety-three medical residents of each grade of the Pediatric residency were evaluated with an initial survey (IS). Each resident was handed a document with the indications,dosage of medicine and pharmacology. A month later, a second survey (SS) to the medial resident and clinical file was performed. RESULTS: The justified indication of ranitidine increased from 52.1 to 66.6% and not justified fell from 47.8 to 33.3%, the error in the prescription increased from 10.8 to 19.0% in the (SS) despite the educational intervention. CONCLUSION: The educational intervention on residents decreased prescribing of the drug when it is not justified; however more training and assistance to doctors and nurses is needed to avoid errors in prescribing and to prevent adverse effects.

Inhalation of marijuana affects Drosophila heart function.

We investigated the effect of inhalation of vaporized marijuana on cardiac function in Drosophila melanogaster, a suitable genetic model for studying human diseases. Adult flies were exposed to marijuana for variable time periods and the effects on cardiac function were studied. Short treatment protocol incremented heart-rate variability. Contractility was augmented only under prolonged exposure to cannabis and it was associated with incremented calcium transient within cardiomyocytes. Neither the activity of the major proteins responsible for calcium handling nor the calcium load of the sarcoplasmic reticulum were affected by the cannabis treatment. The observed changes manifested in the cardiomyocytes even in the absence of the canonical cannabinoid receptors described in mammals. Our results are the first evidence of the in vivo impact of phytocannabinoids in D. melanogaster. By providing a simple and affordable platform prior to mammalian models, this characterization of cardiac function under marijuana exposure opens new paths for conducting genetic screenings using vaporized compounds.This article has an associated First Person interview with the first author of the paper.

Effect of ibuprofen L-lysinate on bilirubin binding to albumin as measured by saturation index and horseradish peroxidase assays.

OBJECTIVE: To demonstrate, in vitro, the influence of increasing ibuprofen (IBU) concentration on bilirubin-albumin (B-A) binding. STUDY DESIGN: The influence of IBU on B-A binding was measured by saturation index and horseradish peroxidase assays. B-A solutions were prepared at B:A ratios of 0.5, 1.0, 1.5 and 2.0 and bilirubin concentrations of 5 and 10 mg per 100 ml. Drug concentrations used were 142.5, 200 and 285 mg l(-1) for IBU and 100 and 200 mg l(-1) for acetyl salicylic acid (ASA). Similar tests were performed on premature newborn sera with bilirubin concentrations of 5 to 10 mg per 100 ml. RESULT: By the saturation index test, significant displacement of bilirubin from albumin with IBU was demonstrated only on B-A solution with high B:A ratio of 2.0 and IBU concentration of 285 mg l(-1) and was less as compared to ASA. No displacement was observed in the sera of jaundiced neonates. By the horseradish peroxidase assay using B-A solutions, free bilirubin was significantly increased at (1) increasing concentrations of bilirubin in solution and (2) increasing B:A ratios in a solution containing 5 mg per 100 ml of bilirubin. In the sera of jaundiced neonates, significantly higher free bilirubin concentrations were observed when IBU was added to serum with bilirubin concentration of 10 mg per 100 ml as compared to 5 mg per 100 ml (0.062+/-0.004 versus 0.026+/-0.005, P<0.001 by Student's t-test). CONCLUSION: Displacement of bilirubin was demonstrated only at high IBU concentration and high B:A ratio. However, free bilirubin levels were not shown to increase with increasing IBU concentration.

Impact of donor age on the results of liver transplantation in hepatitis C virus-positive recipients.

OBJECTIVE: Hepatitis C virus (HCV)-cirrhosis is the most frequent indication for orthotopic liver transplantation (OLT) among adults in most European and American transplant centers. The aim of this study was to analyze the impact of donor age on graft survival among HCV-positive cirrhotic transplant patients. MATERIALS AND METHODS: We performed an observational, retrospective study between March 1997 and December 2004, analyzing 340 liver transplantations. The patients were divided into 4 groups, considering whether the HCV infection was the indication for OLT and whether the age of the donor was older or younger than 48 years: group 1 (HCV, <48 years); group 2 (HCV, >48 years); group 3 (non-HCV, <48 years); and group 4 (non-HCV, >48 years). RESULTS: A univariate analysis showed that posttransplantation graft survival was clearly influenced by recipient HCV serologic status (P = .018). However, no graft survival differences were found when the analysis variable was age (>48 or <48 years). When both variables were studied, a positive HCV serology did not modify graft survival when the donor age was <48 years (P = .32), but had a statistically significant negative impact when the age was >48 years (P = .02). CONCLUSIONS: The use of older donors for HCV recipients resulted in worse graft and patient survivals in our study. This difference in survival was not present in non-HCV recipients or when grafts for HCV recipients were procured from younger donors. Donor age <30 years was a protective factor for graft survival among HCV recipients.

Inferior Vena Cava Agenesis: An Unusual Cause of Deep Vein Thrombosis and Pulmonary Embolism in Young Adult Patients.

INTRODUCTION: Inferior vena cava agenesis (IVCA) is one of the many anomalies of this vessel. It is one of the most uncommon anomalies, with an estimated prevalence of 0.0005-1% in the general population. Around 5% of the patients younger than 30 years with a diagnosis of deep vein thrombosis (DVT) have a total or segmental IVCA. REPORT: Here two unique cases of young and previously healthy male patients are reported: one with bilateral lower extremity DVT, the second with lower extremity DVT and pulmonary embolism. Both patients were found to have segmental agenesis of the inferior vena cava on computed tomography angiography (CTA). Treatment consisted of ultrasound enhanced thrombolysis (EKOS + alteplase) and venous angioplasty. Both patients were discharged with long-term (up to 24 months) oral anticoagulation and compression stockings. Follow up at 3 and 12 months revealed no new thrombotic episode. DISCUSSION: IVCA can be asymptomatic but the majority of the symptomatic patients present with DVT. IVCA confers a risk factor for DVT. IVCA should be considered and ruled out as a rare but important risk factor and cause of DVT in previously young healthy patients. Once diagnosed, aggressive treatment must be started because of the high risk of post-thrombotic syndrome.

Neonatal facial coding system scores and spectral characteristics of infant crying during newborn circumcision.

OBJECTIVE: To determine the relations between Neonatal Facial Coding System (NFCS) scores and measures of infant crying during newborn circumcision. METHODS: Video and audio recordings were made of infant facial activity and cry sounds, respectively, during the lysis phase of circumcisions of 44 healthy term males (<3 d of age). All infants received topical analgesia before circumcision. NFCS scores were determined by blinded assistant from video recordings of facial activity. Measures of infant crying were determined via spectrum analysis of audio recordings by a blinded, independent researcher. Pearson product-moment correlations were used to examine relationship between NFCS scores and measures of crying. Principal component factor analysis detected dimensions underlying related measures of crying. Factor scores from a factor analysis were used in stepwise linear regression to predict NFCS scores. RESULTS: Higher NFCS scores correlated with lower peak fundamental frequency of crying (P<0.01) and with higher amplitudes of crying at peak fundamental frequency and dominant frequency and in overall cry sample (P<0.01). The factor analysis showed 3 significant orthogonal dimensions underlying measures of crying: Power and Velocity (amplitude and rapidity), Pitch of Crying (frequency characteristics), and Infant Arousal (turbulence and intensity) accounting for 42.3%, 17.8%, and 14.6% of variance, respectively. A regression analysis showed all 3 factor scores accounted for significant and separate portions of variance (P<0.001). The best predictor of NFCS score was Power and Velocity (P<0.002), followed by Infant Arousal (P<0.002), and Pitch of Crying (P<0.007). DISCUSSION: These data provide some of the first known evidence linking specific measures of infant crying with an independent, validated measure of pain.

Predicting the bioconcentration factor through a conformation-independent QSPR study.

The ANTARES dataset is a large collection of known and verified experimental bioconcentration factor data, involving 851 highly heterogeneous compounds from which 159 are pesticides. The BCF ANTARES data were used to derive a conformation-independent QSPR model. A large set of 27,017 molecular descriptors was explored, with the main intention of capturing the most relevant structural characteristics affecting the studied property. The structural descriptors were derived with different freeware tools, such as PaDEL, Epi Suite, CORAL, Mold2, RECON, and QuBiLs-MAS, and so it was interesting to find out the way that the different descriptor tools complemented each other in order to improve the statistical quality of the established QSPR. The best multivariable linear regression models were found with the Replacement Method variable sub-set selection technique. The proposed QSPR model improves previous reported models of the bioconcentration factor in the present dataset.

[The Revista Médica del IMSS in the 2017 Healthcare Book Fair]. / La Revista Médica del IMSS en la Feria del Libro de Ciencias de la Salud 2017.

On August, the second edition of the Healthcare Book Fair took place, sponsored by the Facultad de Medicina of UNAM. Again, the Revista Médica del Instituto Mexicano del Seguro Social participated with a stand where we promoted it, talked about the different indexes where our journal is included, explained its objective and scope, and finally talked about its nature as an open access journal, which is aimed to the clinical staff of the different health institutions of our country.

El pasado mes de agosto tuvo lugar la segunda edición de la Feria del Libro de Ciencias de la Salud, auspiciada por la Facultad de Medicina de la UNAM. En ella de nueva cuenta tuvo participación la Revista Médica del Instituto Mexicano del Seguro Social con un stand donde se difundió la revista, su indexación en los diferentes índices en los que tenemos participación, se explicitó su objetivo y alcance y se manifestó como una revista de acceso abierto, gratuita, dirigida al personal clínico de las diferentes instituciones de salud del país.