Nasogastric enteral feeding tubes modulate preterm colonization in early life.

BACKGROUND: Preterm infants are generally fed through nasogastric enteral feeding tubes (NEFTs). The aim of this work was to evaluate the role of NEFTs in the initial colonization of the preterm gut and its evolution within the first 2 weeks after birth. METHODS: For this purpose, fecal and NEFT-derived samples from 30 preterm infants hospitalized in a neonatal intensive care unit (NICU) were collected from birth to the second week of life. Samples were cultivated in ten culture media, including three for the isolation of antibiotic-resistant microorganisms. RESULTS: Isolates (561) were identified by 16S ribosomal RNA gene sequencing. Although the first NEFTs inserted into the neonates after birth were rarely colonized, analysis of NEFTs and fecal samples over time revealed a significant increase in bacterial abundance, diversity, and detection frequency. Results showed a parallel colonization between time-matched NEFTs and fecal samples, suggesting an ongoing bidirectional transfer of bacteria from the neonatal gut to the NEFTs and vice versa. CONCLUSIONS: In short-term hospitalization, length is by far the determinant factor for the early colonization of preterm infants. As NEFT populations reflect the bacterial populations that are colonizing the preterm in a precise moment, their knowledge could be useful to prevent the dissemination of antibiotic-resistant strains. IMPACT: The hospital environment modulates preterm colonization immediately after birth. The colonization of preterm feces and NEFTs occurs in parallel. There is an ongoing bidirectional transfer of microorganisms from the neonatal gut to the NEFTs and vice versa. Bacterial communities inside NEFTs could act as reservoirs of antibiotic resistance genes. NEFT populations reflect the bacteria that are colonizing the preterm at a precise moment.

Digital microscopic image application (DMIA), an automatic method for particle size distribution analysis in waste activated sludge.

An important physical property in environmental samples is particle size distribution. Several processes exist to measure particle diameter, including change in electrical resistance, blocking of light, the fractionation of field flow and laser diffraction (these being the most commonly used). However, their use requires expensive and complex equipment. Therefore, a digital microscopic imaging application (DMIA) method was developed adapting the algorithms used in the helminth egg automatic detector software coupled with a neural network (NN) and Bayesian algorithms. This allowed the determination of particle size distribution in samples of waste activated sludge (WAS), recirculated sludge (RCS), and pre-treated sludge (PTS). The recirculation and electro-oxidation pre-treatment processes showed an effect in increasing the degree of solubilization, decreasing particle size and breakage factor with ranges between 44.29%, and 31.89%. Together with a final NN calibration process, it was possible to compare results. For example, the 90th percentile of equivalent diameter value obtained by the DMIA with the corresponding result for the laser diffraction method. DMIA values: 228.76 µm (WAS), 111.18 µm (RCS), and 84.45 µm (PTS). DMIA processing has advantages in terms of reducing complexity, cost and time, and offers an alternative to the laser diffraction method.

Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.

BACKGROUND: Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. METHODS: We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. RESULTS: We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. CONCLUSIONS: Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.

Patient self-management of oral anticoagulation with vitamin K antagonists in everyday practice: clinical outcomes in a single centre cohort after long-term follow-up.

BACKGROUND: Patient self-management (PSM) of vitamin K antagonists (VKA) seems a very promising model of care for oral anticoagulation in terms of efficacy and safety. In comparison with other management models of VKA therapy, the number of scientific publications supporting the advantages of PSM is more limited. Currently, most of the scarce information comes from randomized clinical trials. Moreover, a small number of studies have assessed PSM of VKA therapy in real life conditions. METHODS: We analyzed clinical outcomes of 927 patients in a single center (6018.6 patient-years of follow-up). Recruitment took place between 2002 and 2017. All patients followed a structured training program, conducted by specialized nurses. RESULTS: Fifty percent of individuals had a mechanical heart valve (MHV), 23% suffered from recurrent venous thromboembolism (VTE) or high-risk thrombophilia, and 13% received VKA therapy because of atrial fibrillation (AF). Median follow-up was 6.5 years (range 0.1-15.97 years), median age was 58.1 years (IQR 48-65.9) and 46.5% were women. The incidence of major complications (either hemorrhagic or thromboembolic) was 1.87% patient-years (pt-ys) with a 95% CI of 1.54-2.27. The incidence of major thromboembolic events was 0.86% pt-ys (95% CI 0.64-1.13) and that of major hemorrhagic events was 1.01% pt-ys (95% CI 0.77-1.31). The incidence of intracranial bleeding was 0.22% pt-ys (95% CI 0.12-0.38). In terms of clinical indication for VKA therapy, the incidence of total major complications was 2.4% pt-ys, 2.0% pt-ys, 0.9% pt-ys and 1.34% pt-ys for MHV, AF, VTE and other (including valvulopathies and myocardiopathies), respectively. Clinical outcomes were worse in patients with multiple comorbidities, previous major complications during conventional VKA therapy, and in older individuals. The percentage of time in therapeutic range (TTR) was available in 861 (93%) patients. Overall, the mean (SD) of TTR was 63.6 ± 13.4%, being higher in men (66.2 ± 13.1%) than women (60.6 ± 13.2%), p < 0.05. CONCLUSIONS: In terms of clinically relevant outcomes (incidence of major complications and mortality), PSM in real life setting seems to be a very good alternative in properly trained patients.

Helminth Egg Automatic Detector (HEAD): Improvements in development for digital identification and quantification of helminth eggs and their application online.

Helminths are parasitic worms that constitute a major public health problem. Conventional analytical techniques to evaluate helminth eggs in environmental samples rely on different steps, namely sedimentation, filtration, centrifugation, and flotation, to separate the eggs from a variety of particles and concentrate them in a pellet for direct observation under an optical microscope. To improve this process, a new approach was implemented in which various image processing algorithms were developed and implemented by a Helminth Egg Automatic Detector (HEAD). This allowed identification and quantification of pathogenic helminth eggs of global medical importance and it was found to be useful for relatively clean wastewater samples. After the initial version, two improvements were developed: first, a texture verification process that reduced the number of false positive results; and second, the establishment of the optimal thresholds (morphology and texture) for each helminth egg species. This second implementation, which was found to improve on the results of the former, was developed with the objective of using free software as a platform for the system. This does not require the purchase of a license, unlike the previous version that required a Mathworks® license to run. After an internal statistical verification of the system was carried out, trials in internationally recognized microbiology laboratories were performed with the aim of reinforcing software training and developing a web-based system able to receive images and perform the analysis throughout a web service. Once completed, these improvements represented a useful and cheap tool that could be used by environmental monitoring facilities and laboratories throughout the world; this tool is capable of identifying and quantifying different species of helminth eggs in otherwise difficult environmental samples: wastewater, soil, biosolids, excreta, and sludge, with a sensitivity and specificity for the TensorFlow (TF) model in the web service values of 96.82% and 97.96% respectively. Additionally, in the case of Ascaris, it may even differentiate between fertile and non-fertile eggs.

Quick incubation process to determine inactivation of Ascaris and Toxocara eggs.

Helminth eggs are among the most important biological contaminants in environmental engineering. They pose a significant health risk associated with poor sanitation, the use of contaminated water for irrigation, and the disposal of excreta or sludge to land. Helminths are parasitic worms transmitted to humans via their eggs, which is the infective stage of their life cycle. They are therefore relevant to public health and environmental fields due to their low infectious dose, their persistence in the environment (up to several years), and their high resistance to conventional disinfection processes. The evaluation of the efficiency of any process of inactivation, through the determination of the viability of these parasites, is fundamental, but the traditional incubation technique requires 20 days to determine both the viability and the infectivity of nematode eggs. However, the present study found that, using an inactivation process at a temperature of 60 °C for 1 hour and incubation at 28 °C and 34 °C, the absence of division of the nucleus of eggs of species from two genera, Ascaris lumbricoides and Toxocara canis, showed them to be inactivated following only 48 hours of incubation. Similar inactivation results were observed using an automatic system as long as the eggs were inactivated. The minimum time required to evaluate the inactivation of nematode eggs through the incubation technique was 48 hours.

9/11-related PTSD among highly exposed populations: a systematic review 15 years after the attack.

BACKGROUND: The 11 September 2001 (9/11) attacks were unprecedented in magnitude and mental health impact. While a large body of research has emerged since the attacks, published reviews are few, and are limited by an emphasis on cross-sectional research, short time frame, and exclusion of treatment studies. Additionally, to date, there has been no systematic review of available longitudinal information as a unique data set. Consequently, knowledge regarding long-term trajectories of 9/11-related post-traumatic stress disorder (PTSD) among highly exposed populations, and whether available treatment approaches effectively address PTSD within the context of mass, man-made disaster, remains limited. METHODS: The present review aimed to address these gaps using a systematic review of peer-reviewed reports from October 2001 to May 2016. Eligible reports were of longitudinal studies of PTSD among highly exposed populations. We identified 20 reports of 9/11-related PTSD, including 13 longitudinal prevalence studies and seven treatment studies. RESULTS: Findings suggest a substantial burden of 9/11-related PTSD among those highly exposed to the attack, associated with a range of sociodemographic and back-ground factors, and characteristics of peri-event exposure. While most longitudinal studies show declining rates of prevalence of PTSD, studies of rescue/recovery workers have documented an increase over time. Treatment studies were few, and generally limited by methodological shortcomings, but support exposure-based therapies. CONCLUSION: Future directions for research, treatment, and healthcare policy are discussed.

Identification and quantification of pathogenic helminth eggs using a digital image system.

A system was developed to identify and quantify up to seven species of helminth eggs (Ascaris lumbricoides -fertile and unfertile eggs-, Trichuris trichiura, Toxocara canis, Taenia saginata, Hymenolepis nana, Hymenolepis diminuta, and Schistosoma mansoni) in wastewater using different image processing tools and pattern recognition algorithms. The system was developed in three stages. Version one was used to explore the viability of the concept of identifying helminth eggs through an image processing system, while versions 2 and 3 were used to improve its efficiency. The system development was based on the analysis of different properties of helminth eggs in order to discriminate them from other objects in samples processed using the conventional United States Environmental Protection Agency (US EPA) technique to quantify helminth eggs. The system was tested, in its three stages, considering two parameters: specificity (capacity to discriminate between species of helminth eggs and other objects) and sensitivity (capacity to correctly classify and identify the different species of helminth eggs). The final version showed a specificity of 99% while the sensitivity varied between 80 and 90%, depending on the total suspended solids content of the wastewater samples. To achieve such values in samples with total suspended solids (TSS) above 150 mg/L, it is recommended to dilute the concentrated sediment just before taking the images under the microscope. The system allows the helminth eggs most commonly found in wastewater to be reliably and uniformly detected and quantified. In addition, it provides the total number of eggs as well as the individual number by species, and for Ascaris lumbricoides it differentiates whether or not the egg is fertile. The system only requires basically trained technicians to prepare the samples, as for visual identification there is no need for highly trained personnel. The time required to analyze each image is less than a minute. This system could be used in central analytical laboratories providing a remote analysis service.

Complications of hyperglycaemia with PI3K-AKT-mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials.

BACKGROUND: PI3K-AKT-mTOR inhibitors (PAMi) are promising anticancer treatments. Hyperglycaemia is a mechanism-based toxicity of these agents and is becoming increasingly important with their use in larger numbers of patients. METHODS: Retrospective case-control study comparing incidence and severity of hyperglycaemia (all grades) between a case group of 387 patients treated on 18 phase I clinical trials with PAMi (78 patients with PI3Ki, 138 with mTORi, 144 with AKTi and 27 with PI3K/mTORi) and a control group of 109 patients treated on 10 phase I clinical trials with agents not directly targeting the PAM pathway. Diabetic patients were excluded in both groups. RESULTS: The incidence of hyperglycaemia was not significantly different between cases and controls (86.6% vs 80.7%, respectively, P=0.129). However, high grade (grade 3-4) hyperglycaemia was more frequent in the PAMi group than in controls (6.7% vs 0%, respectively, P=0.005). The incidence of grade 3-4 hyperglycaemia was greater with AKT and multikinase inhibitors compared with other PAMi (P<0.001). All patients with high-grade hyperglycaemia received antihyperglycemic treatment and none developed severe metabolic complications (diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic state). High-grade hyperglycaemia was the cause of permanent PAMi discontinuation in nine patients. CONCLUSIONS: PI3K-AKT-mTOR inhibitors are associated with small (6.7%) but statistically significant increased risk of high-grade hyperglycaemia compared with non-PAM targeting agents. However, PAMi-induced hyperglycaemia was not found to be associated with severe metabolic complications in this non-diabetic population of patients with advanced cancers.

Histological alterations in the structure of the testis in tench (Tinca tinca) after exposure to 17 alpha-ethynylestradiol.

Environmental pollution with synthetic estrogens may pose a serious threat to reproduction of aquatic wildlife species. The current study describes the effects of 17α-ethynylestradiol (EE2 ) on the structure of the testis in tench (Tinca tinca). Adult male tench were exposed to sublethal doses of EE2 (50, 100, and 500 µg/Kg t.w.) under semistatic conditions for a period of 30 days. The condition factor (CF), testicular somatic index (TSI), and histology (including a morphometric analysis) of the testis were examined. No consistent differences were observed in the CF of EE2 -exposed tench when compared with nonexposed fish. A significant decrease in TSI could only be observed at a 50 µg/Kg t.w. EE2 dose (p < 0.05) when compared with the control group. The histopathology of the testis was associated with loss of normal tubular structure with increased doses of exposure, decrease of tubule number, degeneration in Sertoli and Leydig cells, increase in necrotic testicular cells including formation of syncytia structures and, finally, a high incidence of fish with early primary oocytes at 100 and 500 µg/Kg t.w. EE2 . These results indicate that long-term exposure to EE2 may produce clear negative effects on testicular structure in tench.

Essure® and chronic pelvic pain: a population-based cohort.

The aim of this study was to assess the incidence of chronic pelvic pain in women after placement of Essure® microinserts. This was a case series study at the hysteroscopy unit in a teaching hospital. We included 4,274 patients undergoing permanent sterilisation with Essure® microinserts from January 2005 to December 2011. Essure devices were removed in all patients reporting pelvic pain after insertion. All data were collected from the hysteroscopy unit database with later review of medical records in cases of chronic pelvic pain and a telephone survey after microinsert removal. Main outcome measures were: grade of procedure difficulty perceived by the surgeon; tolerance described by the patient after placement; the need for analgesics during or immediately after the procedure; side-effects; average time between device placement and the onset of symptoms; time between device placement and removal; technique for device removal and any symptoms thereafter. A total of seven women (0.16%) presented with chronic pelvic pain requiring microinsert removal, with four classifying the pain perceived during the procedure as medium-high. Six patients did not require analgesics after the procedure and a vasovagal syndrome requiring intravenous analgesia and monitoring occurred in only one case. Six women reported pain immediately after the procedure, with a mean time between placement and removal of 29.4 months. In all cases, the symptoms disappeared after Essure removal. We conclude that the development of chronic pelvic pain is very uncommon after placement of Essure microinserts. Removal of these devices usually improves the pain.

Levels of persistent organic pollutants (POPs) and the role of anthropic subsidies in the diet of avian scavengers tracked by stable isotopes.

Persistent Organic Pollutants (POPs) have been identified as a significant factor driving declines in wildlife populations. These contaminants exhibit a dual tendency to biomagnify up the food chains and persist within tissues, rendering long-lived vertebrates, such as raptors, highly vulnerable to their adverse effects. We assessed the concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in fledglings of two vulture species, the Egyptian vulture (Neophron percnopterus) and the griffon vulture (Gyps fulvus), coexisting in northern Spain. Vultures, currently facing a severe threat with a population decline exceeding 90%, represent one of the most critically endangered avian groups in the Old World. Despite this critical situation, there remains a scarcity of research examining the intricate relationship between contaminant levels and individual foraging behaviors. In parallel, we analyzed stable isotope levels (δ15N and δ13C) in fledgling's feathers and prey hair to determine the association between individual dietary and contaminant burdens. Our findings revealed higher levels of PCBs in Egyptian vultures, while pesticide concentrations remained very similar between focal species. Furthermore, higher individual values of δ13C, indicating a diet based on intensive farming carcasses and landfills, were associated with higher levels of PCBs. While the levels of POPs found do not raise immediate alarm, the presence of individuals with unusually high values reveals the existence of accessible contamination sources in the environment for avian scavengers. The increasing reliance of these birds on intensive livestock farming and landfills, due to the decline of extensive livestock farming, necessitates long-term monitoring of potential contaminant effects on their populations.

Characterization of workers or population percentage affected by low-back pain (LPB), sciatica and herniated disc due to whole-body vibrations (WBV).

Whole-body vibrations have several harmful effects on the population's health. The most suitable way to characterize the vibrations is to use the daily vibration exposure A (8) and Vibration Dose Value as specified in Directive 2002/44/EC. Therefore, based on the existing literature, we propose Probit equations that allow us to relate the population percentage affected by the vibration effects (low-back pain, sciatica, and herniated disc) with the A (8) and the Vibration Dose Value. It is worth noting that there is a good correlation between the experimental data and the expressions obtained, especially for low-back pain and herniated discs. Once the expressions have been validated, we analyze the limit values given in the aforementioned legislation, showing that the percentage of the affected population is significant for them. Therefore, this study also proposes new limits based on their own definitions, which are more in line with the results shown in the bibliography.

Expression of non-replicating persistence associated genes of Mycobacterium bovis in lymph nodes from skin test-reactor cattle.

Upon oxygen shift-down, Mycobacterium tuberculosis complex bacteria can induce a genetic program characterized by halted duplication, which is called Non-replicating persistence (NRP). During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions. It remains unclear whether expression of NRP genes occurs within the tissue of Mycobacterium bovis naturally infected cattle. In order to start dissecting this question, total RNA from bovine lymph node tissues of sacrificed tuberculin reacting animals was isolated and transcription of genes required for in vivo duplication (esxB and fbpB) and in vitro NRP (hspX, pfkB, and mb2660c) were analyzed by RT-PCR approaches. Detection of transcripts was positive in bovine tissue samples for genes hspX, pfkB, and mb2660c in 84, 32, and 21%, respectively. NRP genes were upregulated even in animals with a negative IFN-γ in vitro test, and the expression of NRP genes occurred more often than expression of the esxB gene.

Differential immune response in mice immunized with the A, R or C domain from TcSP protein of Trypanosoma cruzi or with the coding DNAs.

In a murine model of experimental Trypanosoma cruzi (H8 strain) infection, we investigated the induction of protective immunity against the domains [amino (A), repeats (R) and carboxyl (C)] of the surface protein (SP), a member of the trans-sialidase (TS) superfamily. Recombinant proteins and plasmid DNA coding for the respective proteins were used to immunize BALB/c mice, and the humoral response and cytokine levels were analysed. Immunization with the recombinant proteins induced higher levels of anti-TcSP antibodies than immunization with the corresponding DNAs, and analysis of serum cytokines showed that immunization with both recombinant proteins and naked DNA resulted in a Th1-Th2 mixed T-cell response. Mice immunized with either recombinant proteins or plasmid DNA were infected with blood trypomastigotes. The recombinant protein-immunized mice showed a variable reduction in peak parasitemia, and most died by day 60. Only the pBKTcSPR-immunized mice exhibited a significant reduction in peak parasitemia and survived the lethal challenge. DNA-based immunization with DNA coding for the repeats domain of TcSP is a good candidate for the development of a vaccine against experimental T. cruzi infection.

Performic acid for advanced wastewater disinfection.

The disinfection efficiency of performic acid (PFA) against various microbial contaminants has been studied in municipal secondary effluent. The study demonstrated that PFA provides rapid, efficient and safe disinfection, degrading both bacteria and viruses even at low doses. The resistance order starting from the most resistant microorganism is as follows: MS2-coliphages > DNA-coliphages > enterococci and Escherichia coli. PFA is also efficient in the elimination of Salmonella spp., Clostridium perfringens spores and Giardia cysts. The results showed that a PFA dose as low as 0.5-1 mg L(-1) with contact time of 10 min was efficient in achieving and maintaining for 72 h the disinfection level required for unrestricted agricultural water reuse (≤3 log units for faecal coliforms). However, the optimal dose will depend on the quality of wastewater. Regarding the formation of by-products during disinfection with PFA, very low amounts of hydrogen peroxide and organic per-acids were observed; active oxygen was not detected. The amounts of adsorbable organically bound halogens (AOX) compounds formed were significantly lower compared to the amounts generated during chlorine disinfection. This chlorine-free solution enables compliance with microbiological criteria for various water reuse applications and is already on the market for advanced disinfection.

Histological alterations on the structure of the excretory renal system in tench (Tinca tinca) after exposure to 17-alpha-ethynylestradiol.

This study describes the effects of 17-alpha-ethynylestradiol (EE2) on the structure of the excretory system of the kidney in tench. Adult male tench were exposed to sub-lethal doses of EE2 (50, 100 and 500 µg/kg b.w.) under semistatic conditions for a period of 30 days. The nephrosomatic index and histology (including a morphometric analysis) of the kidney were examined. Histopathological lesions in the kidney of exposed tench were: dilation of glomerular capillaries and increase in the area of the renal corpuscle, hyaline degeneration in the epithelial cells of the proximal tubules leading to necrotic changes, hemorrhages in the interstitial tissue and deposits of eosinophilic material. These lesions were observed with a greater degree of severity as the exposure doses were increased. These results indicate that long-term exposure to EE2 could produce clear negative effects on the excretory system of the kidney in tench and consequently on their physiological functions.

[Elastofibroma dorsi: Diagnosis and follow-up in primary care]. / Elastofibroma dorsi: diagnóstico y seguimiento en atención primaria.

OBJECTIVE: To present a series of patients with elastofibroma dorsi (ED) in order to recall the pathology and justify its diagnostic and therapeutic management in the primary care setting. MATERIALS AND METHODS: Retrospective observational and longitudinal study of 12 patients with 18ED. Epidemiological, clinical and imaging characteristics were analysed. Treatment outcomes were assessed in terms of pain (VAS scale), shoulder function (Constant and Murley scale) and quality of life (EuroQol-5 dimension scale, EQ-5D). The mean follow-up of the cases was 60.5months (5years, range 1-161months). RESULTS: Six patients were male and six were female, with a mean age at diagnosis of 59years. The diagnosis of suspicion in all cases was based in clinical and imaging findings. Only three required surgery. The results of all were satisfactory. CONCLUSIONS: Both the diagnosis and the indication for treatment of an ED can be made in the primary care setting. In typical cases, which are the majority, the clinical history and an ultrasound study allow a diagnosis of certainty. The indication for conservative or surgical treatment depends on the informed patient. When there are diagnostic doubts or the patient wishes surgical resection of the tumour, the patient should be referred to a hospital specialist.