Miracle-dz/UniFAR-FTUs huggingface dataset:
Recurrences, vaccinations and long‐term symptoms in GBS and CIDP

Abstract We determined the frequency of recurrent Guillain–Barré syndrome (GBS), whether vaccinations led to recurrences of GBS or an increase of disability in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and we assessed the prevalence of pain, fatigue and the impact on quality of life after GBS and CIDP. Additionally, we assessed the presence of common auto‐immune disorders. Four hundred and sixty‐one members of the Dutch society of neuromuscular disorders received a questionnaire. Two hundred and forty‐five GBS and seventy‐six CIDP patients were included (response rate 70%). Nine patients had a confirmed recurrent GBS, and two patients had experienced both GBS and CIDP. Common auto‐immune diseases were reported in 9% of GBS and 5% of CIDP patients. None of the 106 GBS patients who received a flu vaccination (range 1–37 times, total 775 vaccinations) reported a recurrence thereafter. Five out of twenty‐four CIDP patients who received a flu vaccination (range 1–17 times) reported an increase in symptoms. Pain or severe fatigue was reported in about 70% of patients after the diagnosis of GBS (median 10 years) or after onset of CIDP (median 6 years), and quality of life was significantly reduced. Flu vaccinations seem relatively safe. GBS and CIDP patients often experience pain, fatigue and a reduced quality of life for many years after the diagnosis.
The Fes Protein-Tyrosine Kinase Phosphorylates a Subset of Macrophage Proteins That Are Involved in Cell Adhesion and Cell-Cell Signaling*

The c-fps/fes proto-oncogene encodes a 92-kDa protein-tyrosine kinase that is expressed at high levels in macrophages. We have previously shown that overexpression of c-fps/fes in a CSF-1-dependent macrophage cell line (BAC1.2F5) partially released these cells from their factor dependence and that this correlated with the tyrosine phosphorylation of a subset of proteins in a tissue-specific manner. We have now identified one of the macrophage substrates of Fes as the crk-associated substrate (Cas) and a second substrate as a 130-kDa protein that has been previously described as a T cell activation-dependent substrate and is unrelated to Cas. Both of these proteins, which have optimal consensus sequences for phosphorylation by Fes, were tightly associated with this kinase through its SH2 domain, suggesting that they were direct substrates of Fes. Remarkably, when the Fes SH2 domain was used as an affinity reagent to identify potential substrates of endogenous Fes in control BAC1.2F5 cells, the phosphotyrosyl proteins that were recognized were the same as those that were specifically phosphorylated when Fes was overexpressed in the same cells. We conclude that the substrates we identified may be structurally related or identical to the physiological targets of this kinase in macrophages. The known functions of Cas and p130 suggest that Fes kinase may play a role in signaling triggered by cell adhesion and cell-cell interactions during immune responses of macrophages.
Serum levels of soluble IL‐2 receptor, IL‐4 and IgE‐binding factors in childhood allergic diseases

The serum levels of soluble IL‐2 receptor (sIL‐2R), IL‐4 and IgE‐binding factors were examined in children with allergic diseases, and compared with those in non‐allergic controls of the same age and sex. The results showed age‐related decreases in the serum levels of sIL‐2R and IgE‐binding factors, but not in that of IL‐4 in both allergic and non‐allergic individuals. Significant elevation of sIL‐2R was observed in sera from children with atopic eczema or history of an anaphylactic reaction to food, as compared with that in non‐allergic controls. The serum concentration of IL‐4 was elevated in all allergic groups, including cases of atopic eczema, bronchial asthma and anaphylaxis to food, compared with non‐allergic controls, and was correlated significantly with the serum level of IgE (r= 0.59). The IgE‐binding factor levels in sera from patients aged 6‐10 years with bronchial asthma, or patients aged 1‐5 years with a history of food anaphylaxis were elevated as compared with those in non‐allergic controls of same age. There was no significant correlation between the serum levels of IgE‐binding factors and IgE. Since sIL‐2R is released by activated T cells, the present study is in favour of T cell activation causing allergic skin disorders. The serum levels of IL‐4 as well as IgE did not differ among allergic patients of different clinical categories. The role of IgE in atopic eczema and other allergic diseases is not clearly established; however, it seems likely that IL‐4 is deeply involved in the increased production of IgE seen in allergic individuals. The possible involvement of IgE‐binding factors in the age‐related changes of clinical manifestations in childhood allergic diseases was also discussed.
Systems‐wide analysis and engineering of metabolic pathway fluxes in bio‐succinate producing Basfia succiniciproducens

Basfia succiniciproducens has been recently isolated as novel producer for succinate, an important platform chemical. In batch culture, the wild type exhibited a high natural yield of 0.75 mol succinate (mol glucose)−1. Systems‐wide 13C metabolic flux analysis identified undesired fluxes through pyruvate‐formate lyase (PflD) and lactate dehydrogenase (LdhA). The double deletion strain B. succiniciproducens ΔldhA ΔpflD revealed a 45% improved product yield of 1.08 mol mol−1. In addition, metabolic flux analysis unraveled the parallel in vivo activity of the oxidative and reductive branch of the TCA cycle in B. succiniciproducens, whereby the oxidative part mainly served for anabolism. The wild type re‐directed surplus NADH via a cycle involving malic enzyme or via transhydrogenase, respectively, to supply NADPH for anabolism, because the fluxes through the oxidative PPP and isocitrate dehydrogenase, that also provide this cofactor, were not sufficient. This was not observed for the deletion mutants, B. succiniciproducens ΔpflD and ΔldhA ΔpflD, where PPP and isocitrate dehydrogenase flux alone matched with the reduced anabolic NADPH demand. The integration of the production performance into the theoretical flux space, computed by elementary flux mode analysis, revealed that B. succiniciproducens ΔldhA ΔpflD reached 62% of the theoretical maximum yield. Biotechnol. Bioeng. 2013;110: 3013–3023. © 2013 Wiley Periodicals, Inc.
The Impact of the Heptavalent Pneumococcal Conjugate Vaccine on Risk Factors for Streptococcus pneumoniae Carriage in Children

Background: The aim of the study was to investigate whether the 7-valent pneumococcal conjugate vaccine (PCV7) alters common risk factors of nasopharyngeal carriage by Streptococcus pneumoniae in children. Methods: From July 2005 through December 2010, we performed a cross-sectional study investigating risk factors associated with pneumococcal carriage in children. Parents of participating children completed questionnaires including whether or not the children received PCV7 vaccination. Results: Among 9705 children, 20.2% of them received at least 1 dose of the PCV7 vaccine. Multivariate logistic regression models identified older age, having 1 sibling in a family, history of acute otitis media and household exposure to smoking as independent risk factors for pneumococcal carriage in the unvaccinated group, but not associated with pneumococcal carriage in the vaccinated group. The number of siblings ≥2 in a family, history of upper respiratory tract infection and child-care attendance were strong factors associated with pneumococcal carriage in children, regardless of vaccination. In vaccinated group, breast-feeding was associated with increased nonvaccine type pneumococcal carriage, mainly in children with upper respiratory tract infection. Conclusions: PCV7 decreased the association between pneumococcal carriage and older age, 1 sibling in a family, history of acute otitis media and household exposure to smoking, but increased the association between pneumococcal carriage and breast-feeding.
Identification of novel chromosomal loci affecting Yersinia enterocolitica pathogenesis

Pathogenic species of the genus Yersinia have a marked tropism for lymphoid tissue during the early stages of infection. Bacterial survival at this site determines whether the disease is localized or progresses systemically, leading to a high rate of mortality. Several plasmid‐encoded virulence genes are known to be required for survival and pathogenesis, but the contribution of chromosomal genes has been largely unexplored. This study represents the first intensive effort to characterize and determine the function of Yersinia chromosomal genes expressed in lymphoid tissue after intragastric infection. Strains harbouring cat fusions expressed in the host were isolated from Peyer’s patch tissue of mice intragastrically infected and treated with chloramphenicol (Cm); genes identified in this manner were designated hre for host responsive element. The hre::cat strains that were Cm resistant in vivo (in mouse tissue) and Cm sensitive in vitro (on laboratory media at 26°C) were identified and shown to consist of 61 different allelic groups. The hre::cat fusions from 48 of the allelic groups were cloned and characterized by DNA sequence analysis. The results identified genes necessary for iron acquisition, protection from environmental stresses, biosynthesis of cell envelope components and other diverse metabolic activities. However, the DNA sequence of many clones had no homology to other known genes. Insertion mutations were constructed for four hre genes and the resulting Y. enterocolitica mutants were tested in the mouse model for effects on pathogenesis. All of the mutant strains were affected for virulence when assayed for survival in host tissues and LD50 analysis.
Injectable and biodegradable poly(organophosphazene) hydrogel as a delivery system of docetaxel for cancer treatment

Abstract Although docetaxel (DTX) is an advanced taxoid, further augmentation of its properties is still required, such as improvement in its low aqueous solubility. Herein, we report the development of biodegradable/injectable poly(organophosphazene) (PPZ) hydrogels for the delivery of DTX without the use of organic solvents. An aqueous solution of PPZ containing α-amino-ω-methoxy-poly(ethylene glycol) (AMPEG) 750 instead of AMPEG 550 was prepared, thereby increasing the erosion capacity of the hydrogel by judicious balance of the hydrophobic/hydrophilic moieties. The safety of the hydrogel was demonstrated using a biocompatibility test. The PPZ aqueous solution (8 wt%) containing DTX exhibited a thermosensitive sol–gel–sol transition that was independent of the concentration of DTX (1–3 mg/mL). The in vitro release study indicated that the dominant release mechanism was either erosion or diffusion/erosion-controlled release depending on the DTX content of the hydrogel. The in vivo anticancer effect of the intratumorally injected PPZ system in human gastric cancer cell-xenografted mice was evaluated, which demonstrated a significantly (p < 0.01) enhanced effect of the DTX-PPZ hydrogel system compared to the control (DTX solution, i.v.). In conclusion, the PPZ hydrogel may be a promising candidate for DTX delivery, affecting a decrease in the size of tumors with little toxicity prior to exeresis.
ACUTE KIDNEY INJURY IN THE ICU: TIME HAS COME FOR AN EARLY BIOMARKER KIT!

Abstract Early recognition of acute kidney injury (AKI) in the intensive care unit (ICU) remains a critical problem, with a rising incidence and a high mortality rate. As a consequence, the actual lack of an early and effective biomarker results in a significant delay in initiating appropriate therapy. The accurate diagnosis of AKI is especially problematic in critically-ill patients, in whom we know that renal function is in an unsteady state; therefore the validity of creatinine- based baseline assessment measures is reduced. Because the rationale for assessing AKI markers in critically-ill patients is strong at the present time, researchers are stimulated to establish a multidimensional AKI classification system. This system should in essence grade AKI severity. The most widely referenced classification is the RIFLE system. Thus, early recognition of AKI, well before changes in serum creatinine occur, has come under intensive research, because it is evidenced that even small increases in serum creatinine are associated with an increase in patient mortality. The development of a biomarker kit in which several early markers with different characteristics are combined, is essential. Multi-centre, randomized studies indicate a potential for early biomarkers able to diagnose AKI 48 hours before creatinine changes. In conclusion, time has come to leave serum creatinine behind as a marker of renal function in patients with AKI on the ICU. Only then will we be able to offer early goal-directed therapy for the kidney in the ICU setting.
Spinal cord repair in neonatal rats: a correlation between axonal regeneration and functional recovery

The present study aimed to analyse how anatomical regeneration contributes to functional recovery after experimental spinal cord repair. Thoracic spinal cord of neonatal rats was completely transected to make a gap and repaired by grafting a section of embryonic spinal cord. Six weeks after surgery, outcome of locomotor performance was assessed using an open field locomotor scale (BBB scale). Axonal regeneration across the repaired site was quantitatively assessed in the raphe, vestibular, and red nuclei and the sensorimotor cortex by a retrograde tracing method. The rats that had no labelled neurons in any of the supraspinal nuclei showed no hind–forelimb coordination. The rats that had labelled neurons in the brainstem nuclei but not in the sensorimotor cortex showed hind–forelimb coordination of varying grades depending on the amount of regeneration. The rats that had labelled neurons in all of the examined nuclei showed almost normal locomotion. In addition to a relationship between distribution of the labelled neurons and functional recovery, a positive correlation was observed between number of the labelled neurons in each of the supraspinal nuclei and locomotor performance of the rat. Thus the grade of restored function appeared to be regulated by distribution and number of fibres regenerated across the repaired site and into the target region. These results suggest that accurate reconstruction of neural connections is essential for significant functional recovery after spinal cord repair.
Use of an Olmesartan Medoxomil‐Based Treatment Algorithm for Hypertension Control

Hypertension guidelines recommend a steppedcare approach that starts with titration of the initial agent followed by the addition of other agents, as necessary, to achieve goal blood pressure. This study assessed the effectiveness of an antihypertensive treatment algorithm with olmesartan medoxomil as the initial agent. This was a 24‐week, open‐label trial in patients (N=201) with mean seated diastolic blood pressure of 90–109 mm Hg. Following placebo run‐in, all patients received olmesartan medoxomil 20 mg/d for 4 weeks. At subsequent 4‐week intervals, the regimen was modified in patients with blood pressure >130/85 mm Hg: up‐titration of olmesartan medoxomil to 40 mg/d; addition of hydrochlo‐rothiazide 12.5 mg/d; up‐titration of hydrochlo‐rothiazide to 25 mg/d; addition of amlodipine besylate 5 mg/d; and up‐titration of amlodipine besylate to 10 mg/d. Patients who achieved blood pressure ≤130/85 mm Hg at any point exited the study with no further follow‐up. At Week 24, reductions in blood pressure from baseline were 33.7/18.2 mm Hg. Altogether, 87.7% of patients reached the goal blood pressure of ≤130/85 mm Hg and 93.3% achieved a blood pressure of ≤140/90 mm Hg. Thus, an antihypertensive algorithm with olmesartan medoxomil as the initial agent controlled blood pressure in the majority of patients, but with >60% of patients also requiring the use of a thiazide diuretic or a thiazide and a calcium channel blocker.
Taxonomic challenges in freshwater fishes: a mismatch between morphology and DNA barcoding in fish of the north‐eastern part of the Congo basin

This study evaluates the utility of DNA barcoding to traditional morphology‐based species identifications for the fish fauna of the north‐eastern Congo basin. We compared DNA sequences (COI) of 821 samples from 206 morphologically identified species. Best match, best close match and all species barcoding analyses resulted in a rather low identification success of 87.5%, 84.5% and 64.1%, respectively. The ratio ‘nearest‐neighbour distance/maximum intraspecific divergence’ was lower than 1 for 26.1% of the samples, indicating possible taxonomic problems. In ten genera, belonging to six families, the number of species inferred from mtDNA data exceeded the number of species identified using morphological features; and in four cases indications of possible synonymy were detected. Finally, the DNA barcodes confirmed previously known identification problems within certain genera of the Clariidae, Cyprinidae and Mormyridae. Our results underscore the large number of taxonomic problems lingering in the taxonomy of the fish fauna of the Congo basin and illustrate why DNA barcodes will contribute to future efforts to compile a reliable taxonomic inventory of the Congo basin fish fauna. Therefore, the obtained barcodes were deposited in the reference barcode library of the Barcode of Life Initiative.
Uterine rupture after the uterine fundal pressure maneuver

Abstract Objective: To clarify the incidence of uterine fundal pressure at delivery and its effect on uterine rupture. Study design: A questionnaire was sent to 2518 institutions in Japan. We received a response from 1430. Results: Of reporting institutions, 89.4% used fundal pressure in at least some of their deliveries. Among the 347,771 women who delivered vaginally in this study, 38,973 (11.2%) were delivered with the assistance of fundal pressure. There were six cases of uterine rupture associated with uterine fundal pressure, with one case resulting in maternal death secondary to amniotic fluid embolism. Conclusion: Since uterine fundal pressure may potentially cause serious injury to either the mother and/or neonates, the indications for application need to be clearly elucidated, and obstetric care providers also need comprehensive education and training.
Relations between the residential fast-food environment and the individual risk of cardiovascular diseases in The Netherlands: A nationwide follow-up study

Background The food environment has been hypothesized to influence cardiovascular diseases such as hypertension and coronary heart disease. This study determines the relation between fast-food outlet density (FFD) and the individual risk for cardiovascular disease, among a nationwide Dutch sample. Methods After linkage of three national registers, a cohort of 2,472,004 adults (≥35 years), free from cardiovascular disease at January 1st 2009 and living at the same address for ≥15 years was constructed. Participants were followed for one year to determine incidence of cardiovascular disease, including coronary heart disease, stroke and heart failure. Street network-based buffers of 500 m, 1000 m and 3000 m around residential addresses were calculated, while FFD was determined using a retail outlet database. Logistic regression analyses were conducted. Models were stratified by degree of urbanization and adjusted for age, sex, ethnicity, marital status, comorbidity, neighbourhood-level income and population density. Results In urban areas, fully adjusted models indicated that the incidence of cardiovascular disease and coronary heart disease was significantly higher within 500 m buffers with one or more fast-food outlets as compared with areas with no fast-food outlets. An elevated FFD within 1000 m was associated with an significantly increased incidence of cardiovascular disease and coronary heart disease. Evidence was less pronounced for 3000 m buffers, or for stroke and heart-failure incidence. Conclusions Elevated FFD in the urban residential environment (≤1000 m) was related to an increased incidence of cardiovascular heart disease and coronary heart disease. To better understand how FFD is associated with cardiovascular disease, future studies should account for a wider range of lifestyle and environmental confounders than was achieved in this study.
Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial.

OBJECTIVE To assess the effect of an individualized treatment regimen on the intensity and duration of medication treatment for alcohol withdrawal. DESIGN A randomized double-blind, controlled trial. SETTING An inpatient detoxification unit in a Veterans Affairs medical center. PATIENTS One hundred one patients admitted for the treatment of alcohol withdrawal who could give informed consent and had no history of seizures or medication use that might alter the clinical course of withdrawal. INTERVENTION Patients were randomized to either a standard course of chlordiazepoxide four times daily with additional medication as needed (fixed-schedule therapy) or to a treatment regimen that provided chlordiazepoxide only in response to the development of the signs and symptoms of alcohol withdrawal (symptom-triggered therapy). The need for administration of "as-needed" medication was determined using a validated measure of the severity of alcohol withdrawal. MAIN OUTCOME MEASURES Duration of medication treatment and total chlordiazepoxide administered. RESULTS The median duration of treatment in the symptom-triggered group was 9 hours, compared with 68 hours in the fixed-schedule group (P < .001). The symptom-triggered group received 100 mg of chlordiazepoxide, and the fixed-schedule group received 425 mg (P < .001). There were no significant differences in the severity of withdrawal during treatment or in the incidence of seizures or delirium tremens. CONCLUSIONS Symptom-triggered therapy individualizes treatment, decreases both treatment duration and the amount of benzodiazepine used, and is as efficacious as standard fixed-schedule therapy for alcohol withdrawal.