Early universal screening of gestational diabetes in a university hospital in Thailand.
A total of 1016 pregnant women attending antenatal clinic before 20 weeks of gestation during September 2018 to February 2019 were included in a cohort study with repeated cross-sectional assessments. The study was aimed to determine prevalence and characteristics of gestational diabetes mellitus (GDM) and pregnancy outcomes by early universal screening approach. GDM screening was performed during first visit and repeated during 24-28 weeks of gestation, as necessary, using a 50-g glucose challenge test followed by a 100-g oral glucose tolerance test for GDM diagnosis. Overall prevalence of GDM was 18.6%. A significantly higher prevalence of GDM was observed among high-risk than low-risk women (21.3% vs. 13.1%, p = 0.002). GDM among low-risk women contributed to 23.3% of all GDM cases. The majority of GDM (76.2%) were diagnosed before 20 weeks of gestation, with 74.5% occurring in high-risk women and 81.8% occurring in low-risk women. When initial screening tests were normal, risk of GDM diagnosed during 24-28 weeks was 6.0% (7.5% among high-risk women and 3.1% among low-risk women). Compared to those without GDM, women with GDM significantly had lower gestational weight gain (p < 0.001), higher prevalence of preeclampsia (p = 0.001), large for gestational age (LGA) (p = 0.034) and macrosomia (p = 0.004). These outcomes were more pronounced among high-risk women with GDM. Impact StatementWhat is already known on this subject? Universal GDM screening is recommended during 24-28 weeks of gestation, either by 1- or 2-step approach. Some also recommend early GDM screening among high-risk women. Prevalence of early-onset GDM varies between studies and benefits of early diagnosis and treatment are still controversial.What do the results of this study add? Early universal GDM screening identified more women with GDM and majority could be diagnosed before 20 weeks of gestation. GDM among low-risk women contributed to 23.3% of all cases. Adverse pregnancy outcomes were more common among high-risk women with GDM. This approach could be useful and can be implemented in other settings, especially those that serve high-risk population or with high GDM prevalence.What are the implications of these findings for clinical practice and/or further research? Early universal GDM screening should be considered in settings with high prevalence of GDM and high-risk women. However, benefits of early detection and treatment of GDM should be determined in more details in the future, especially in terms of cost-effectiveness and improvement in pregnancy outcomes.


Analysis of the Structure of the PsbO Protein and its Implications.
The PsbO protein is a ubiquitous extrinsic subunit of Photosystem II (PS II), the water splitting enzyme of photosynthesis. A recently determined 3D X-ray structure of a cyanobacterial protein bound to PS II has given an opportunity to conduct complete analyses of its sequence and structural characteristics using bioinformatic methods. Multiple sequence alignments for the PsbO family are constructed and correlated with the cyanobacterial structure. We identify the most conserved regions of PsbO and the mapping of their positions within the structure indicates their functional roles especially in relation to interactions of this protein with the lumenal surface of PS II. Homologous models for eukaryotic PsbO were built in order to compare with the prokaryotic protein. We also explore structural homology between PsbO and other proteins for which 3D structures are known and determine its structural classification. These analyses contribute to the understanding of the function and evolutionary origin of the PS II manganese stabilising protein.


Direct demonstration of the productive capability of cytokines at the single cell level in lung sarcoidosis using multicolor cytometry.
Sarcoidosis is a chronic systemic disorder of unknown etiology characterized by noncaseating epithelioid cell granulomatous lesions, around which an increasing number of CD4+ T cells infiltrate. These CD4+ T cells may release interferon-gamma (IFN-gamma) and interleukin-2 (IL-2). These cytokines are considered to play an important role in pathogenesis of sarcoidosis. We employed a modification of Jung's method using multicolor flow cytometry to assess the capability of single cells obtained from bronchoalveolar lavage (BAL) fluid to produce various cytokines. BAL CD4+ T cell production of IFN-gamma, IL-2 and IL-4 after phorbol ester and ionomycin stimulation were studied. The percentage of IFN-gamma- and IL-2-producing CD4+ T cells was significantly higher in patients with sarcoidosis compared to healthy volunteers [84.7 +/- 7.5 vs. 51.2 +/- 14.8% (p < 0.005), and 75.3 +/- 8.7 vs. 39.8 +/-11.0% (p < 0.001), respectively]. No significant difference in the percentage of IL-4-producing CD4+ T cells was noted (1.2 +/- 0.6 vs. 3.5 +/- 2.6%; not significant), whereas the absolute number of IL-4-producing CD4+ T cells was significantly higher in patients with sarcoidosis compared to healthy volunteers (563.6 +/- 330.2 vs. 50.9 +/- 66.9/ml; p < 0.005). In the IL-4-producing CD4+ T cells, about 80% of cells concomitantly produced IFN-gamma and more than 60% of cells also produced IL-2. We demonstrate that Th1-like-producing cells are predominant in the CD4+ as well as in the CD8+ T cell subset of patients with sarcoidosis. We for the first time demonstrated concomitant capabilities of BAL CD4+ T cells to produce Th1 and Th2 cytokines at the single cell level by multicolor flow cytometry.


Generation of biologically active interleukin-1 beta by proteolytic cleavage of the inactive precursor.
Interleukin-1 beta (IL-1 beta) is derived from an inactive precursor by proteolytic cleavage. To study IL-1 beta processing, we expressed the precursor in Escherichia coli, partially purified it, and used it as a substrate for various potentially relevant protease preparations. The precursor alone was virtually inactive, but incubation with membranes from human monocytes or myeloid cell lines yielded a 500-fold increase in IL-1 bioactivity. Western blot analysis of the incubated material showed that the 31,000-Da precursor is broken down to three major products, ranging from 17,400 to about 19,000 Da. The most active of these products is the smallest one, and it co-migrates during electrophoresis with mature IL-1 beta. Four purified known proteases were also tested for their effect on precursor IL-1 beta, and none of these products co-migrated with the mature protein. Chymotrypsin and Staphylococcus aureus protease yielded slightly larger products, which were highly active. Elastase and trypsin yielded substantially larger products, and these had little IL-1 activity. The products of three of the known proteases were identified by NH2-terminal sequencing. These results show conclusively that proteolysis of precursor IL-1 beta generates biological activity and that the cleavage must occur close to the mature NH2 terminus.


Anti-neuropeptide Y plasma immunoglobulins in relation to mood and appetite in depressive disorder.
Depression and eating disorders are frequently associated, but the molecular pathways responsible for co-occurrence of altered mood, appetite and body weight are not yet fully understood. Neuropeptide Y (NPY) has potent antidepressant and orexigenic properties and low central NPY levels have been reported in major depression. In the present study, we hypothesized that in patients with major depression alteration of mood, appetite and body weight may be related to NPY-reactive autoantibodies (autoAbs). To test this hypothesis, we compared plasma levels and affinities of NPY-reactive autoAbs between patients with major depression and healthy controls. Then, to evaluate if changes of NPY autoAb properties can be causally related to altered mood and appetite, we developed central and peripheral passive transfer models of human autoAbs in mice and studied depressive-like behavior in forced-swim test and food intake. We found that plasma levels of NPY IgG autoAbs were lower in patients with moderate but not with mild depression correlating negatively with the Montgomery-Åsberg Depression Rating Scale scores and with immobility time of the forced-swim test in mice after peripheral injection of autoAbs. No significant differences in NPY IgG autoAb affinities between patients with depression and controls were found, but higher affinity of IgG autoAbs for NPY was associated with lower body mass index and prevented NPY-induced orexigenic response in mice after their central injection. These data suggest that changes of plasma levels of anti-NPY autoAbs are relevant to altered mood, while changes of their affinity may participate in altered appetite and body weight in patients with depressive disorder.


Essay: the political logic of regulatory error.
Regulatory error is an issue that has come to the fore following the withdrawal of rofecoxib (Vioxx; Merck) a year ago. Here, we provide a theoretical discussion of the factors that could influence regulatory error, drawing on the Vioxx episode in particular as a possible example of error, and consider the implications for future regulatory policy.


Medical Education Adaptations Post COVID-19: An Egyptian Reflection.
Coronavirus (COVID19) appears to be an inflection point that is forcing a disruption in medical education. The study aims to explore how medical schools in Egypt responded to COVID-19 pandemic regarding teaching and learning/assessment for undergraduate students. A mixed method exploratory 2-phase study was conducted. Data was collected through a questionnaire and focus groups. The responses of the participants were categorized according to main themes; University preparedness, Role of faculty in the transition, Role of ME units/Departments/National/Regional bodies in the transition, Role of Egyptian Knowledge Bank, New teaching methods/strategies, New assessment methods/strategies and Projection into the future. The staff level of preparedness for that unexpected shift was evaluated as optimum to high and a good leadership support was reported by 70% of them. They reported conflicting views about the proper role of medical education units but reinforced the idea of Egyptian Knowledge Bank's crucial role in this transition. Additionally, 64.1% of the participants identified a clinical skills teaching challenge and 76.3% of them reported absence of alternative methods for summative assessment. Finally, there is a communication problem with the students that leads to their detachment. Individuals moved faster than bodies and relied on support existing outside the universities when catastrophe happened. Many recommendations emerged including the need to integrate online learning into the curriculum at favorable percentages.


Adapting an emotional regulation and social communication skills group programme to teletherapy, in response to the COVID-19 pandemic.
The COVID-19 pandemic created an unprecedented situation, whereby essential services within child and adolescent mental health services (CAMHS) were suspended. This created a need to modify regular methods of treatment at a rapid pace, to avoid cessation of clinical intervention and prevent potential regression in mental health. Eighteen children with moderate-to-severe mental health disorders and their parents were attending weekly group cognitive behaviour therapy-based sessions ('The Secret Agent Society' programme) when the Irish Department of Health suspended face-to-face intervention. This report describes how the group sessions were adapted to individualised, online therapeutic triads between each child, his/her parent and their clinician. Whilst internet technology has emerged as a promising solution to shortfalls in therapy services, in-depth exploration is needed to confirm the efficacy of telehealth for children attending CAMHS.


Craniofacial and Craniocervical Features in Cartilage-Hair Hypoplasia: A Radiological Study of 17 Patients and 34 Controls.
Biallelic mutations in the non-coding RNA gene RMRP cause Cartilage-hair hypoplasia (CHH), a rare skeletal dysplasia in which the main phenotypic characteristic is severe progressive growth retardation. This study compared the cranial dimensions of individuals with CHH to healthy subjects. Lateral skull radiographs of 17 patients with CHH (age range 10 to 59 years) and 34 healthy individuals (age range 10 to 54 years) were analyzed for relative position of the jaws to skull base, craniofacial height and depth, as well as vertical growth pattern of the lower jaw, anterior cranial base angle, and the relationship between the cervical spine and skull base. We found that the length of the upper and lower jaws, and clivus were significantly decreased in patients with CHH as compared to the controls. Anterior cranial base angle was large in patients with CHH. Basilar invagination was not found. This study found no severe craniofacial involvement of patients with CHH, except for the short jaws. Unexpectedly, mandibular deficiency did not lead to skeletal class II malocclusion. Although the jaws were shorter in patients with CHH, they were proportional to each other. A short posterior cranial base was not associated with craniocervical junction pathology.


Metastasectomy in older adults with urothelial carcinoma: Population-based analysis of use and outcomes.
Metastatic urothelial carcinoma of the bladder, ureter, or renal pelvis is a highly aggressive disease with poor outcomes. Even with platinum-based chemotherapy, the median overall survival is 15 months and the 5-year survival is only 15%. The role of metastasectomy in urothelial carcinoma is currently undefined. To examine the use and outcomes of metastasectomy in older patients with urothelial carcinoma in a large population-based dataset. We conducted a SEER-Medicare study, and from 70,648 urothelial carcinoma patients who met inclusion criteria, we identified 497 patients who had at least 1 metastasectomy during a median follow-up of 40 months. The primary study endpoints were metastasectomy use, the length of stay for metastasectomy, complications, and overall survival following metastasectomy. Secondary outcomes included 30-day mortality and readmission rate following metastasectomy. We identified 497 patients meeting inclusion criteria who had at least 1 metastasectomy during the study period including 24 patients who had more than 1 procedure resulting in a total of 523 metastasectomies. The median overall survival after the first metastasectomy was 19 months (95% CI: 15-23; interquartile range: 4-74). In this selected patient population, over a third of patients were alive at 3 years. In the 476 patients who had evaluable discharge dates, the median length of stay after metastasectomy was 7 days (IQR: 4-12), and 10% of patients had at least 1 complication within 30 days of discharge. Thirty-day mortality after metastasectomy was 10% (n = 53/523) and was largely driven by the mortality associated with resections of urothelial cancer brain metastases. In well-selected patients with urothelial carcinoma with a reasonable life expectancy, resection of metastatic lesions is safe and is associated with long-term survival and potential cures.


Modern Total Knee Arthroplasty Bearing Designs and the Role of the Posterior Cruciate Ligament.
The role of the posterior cruciate ligament (PCL) in total knee arthroplasty (TKA) surgery continues to be a source of debate among the adult reconstruction community. In native knee flexion, the PCL is comprised of an anterolateral and posteromedial bundle that work together to limit posterior tibial translation and allow adequate femoral rollback for deep flexion. In the arthritic knee, the PCL can often become dysfunctional and attenuated, which led to the development of posterior stabilized (PS) TKA bearing options. PS TKAs implement a cam-post construct to functionally replace a resected PCL. While PS designs may facilitate balancing knees with significant deformity, they are associated with complications such as postfracture, increased wear, and patellar clunk/crepitus. In recent years, newer designs have been popularized with greater degrees of congruency and incorporation of medial and lateral pivoting to better recreate native knee kinematics. The American Joint Registry has confirmed the recent predilection for ultra-congruent and cruciate-retaining TKA inserts over PS TKAs during the last decade. Studies have failed to identify an overall clinical superiority between the cruciate substituting and sacrificing designs. The literature has also failed to identify clinical consequences from PCL resection with modern, more conforming TKA designs. In this article, we review modern PCL sacrificing designs and discuss the impact of each on the kinematics after TKA. We also will delineate the role of the PCL in modern TKA in the hopes to better understand the recent surge in sacrificing but not substituting knee implants.


Reduction of beta-endorphin-containing immune cells in inflamed paw tissue corresponds with a reduction in immune-derived antinociception: reversible by donor activated lymphocytes.
The functional integrity of the immune system is essential for peripheral antinociception. Previous studies have demonstrated that immune cells elicit potent antinociception in inflamed tissues and that corticotropin-releasing factor-induced antinociception is significantly inhibited in animals that have undergone cyclosporin A (CsA)-induced immunosuppression. In this study, we examined the effect of a single bolus of CsA on inflammatory nociception. CsA-treated rats had substantially increased nociception compared with nonimmunosuppressed rats, consistent with a reduction in circulating and infiltrating lymphocytes. Furthermore, CsA-treated rats had inhibition of corticotropin-releasing factor-induced immune-derived antinociception, which was dose-dependently reversed by IV injection of concanavalin A-activated donor lymphocytes (1.0-7.0 x 10(6) cells/0.1 mL). In conclusion, our findings provided further evidence that opioid-containing immune cells are essential for peripheral analgesia. It is evident from these findings that control of inflammatory pain relies heavily on a functioning immune system. The immune system not only contributes to inflammation, but also provides localized analgesia. A depleted immune system results in a reduction of immune-derived analgesia and a potentiation of inflammatory pain. Donor activated lymphocytes reverse these effects, highlighting the importance of a functional immune system in inflammatory pain.


Simplification or simulation: Power calculation in clinical trials.
A justifiable sample size is essential at trial design stage. Generally this task is completed by forming the main research question into a statistical procedure and then implementing the published formulae or software packages. When these standard statistical formulae/software packages become unavailable for studies with complex statistical procedures, some statisticians choose to fill this gap by assuming an alternative simplified sample size calculation. Monte Carlo simulations can also be deployed, particularly for complex trials. However, it is still unclear on how to determine the appropriate approach under certain practical scenarios. We adopted real clinical trials as examples and investigated on simplification and simulation-based sample size calculation approaches. Compared to simplified sample size calculation, the simulation approach can better address the non-ignorable impact of baseline/follow-up outcome correlation on study power. For studies with multiple endpoints and multiple co-primary endpoints, the sample sizes calculated by simplification approach should be scrutinized. Directly using the simplification approach for sample size calculation should be restricted. We recommend to utilize the simulation approach, particularly for complex trials, at least as a sensitivity checking and a useful triangulation to the simplification approach outlined.


Acute transverse myelitis in a child with Lyme disease and a review of literature.
Acute transverse myelitis is a rare Borellia burgdorferi-related neurologic complication in childhood. We present a 12-year-old girl who was diagnosed with acute transverse myelitis associated with a borreliosis infection. We also review clinical features in all five cases of Borellia burgdorferi-related transverse myelitis in children. We describe here the sixth child with borreliosis-related transverse myelitis.


Predictive formula for acute liver failure is useful for predicting the prognosis of patients with acute-on-chronic liver failure.
The prognosis of acute-on-chronic liver failure (ACLF) is extremely poor in comparison to acute liver failure (ALF). We aimed to establish methods for the early diagnosis of ACLF and its severity to identify the patients with a poor prognosis. The laboratory data at admission of 30 ACLF and 46 ALF patients were compared. Three established prognosis prediction models (Model for End-Stage Liver Disease [MELD]; MELD modified by serum sodium concentration, [MELD-Na]; and the Japan hepatic encephalopathy prediction model [J-HEPM]) were assessed using area under the receiver-operator curve (AUROC) values. No significant difference was found in the laboratory data of the two patient groups. J-HEPM was able to predict the outcome of the ACLF subjects (AUROC = 0.93). Although ACLF could not be differentially diagnosed from ALF at admission from the laboratory data alone, the J-HEPM effectively predicted the prognosis of liver failure in patients with ACLF. These findings indicate that ACLF patients with high J-HEPM scores require earlier and more intensive care than ALF patients.


Indium 111-labeled white blood cell scans after vascular prosthetic reconstruction.
The clinical value of indium 111-labeled white blood cell (WBC) scanning done after vascular graft procedures was investigated to differentiate noninfectious postoperative inflammation associated with graft incorporation from early prosthetic graft infection. Indium 111-labeled WBC scans were initially obtained in 30 patients before discharge from the hospital and during the subsequent follow-up period (334 days). Fourteen of 30 patients (47%) had normal predischarge scans that included all 10 patients who had grafts confined to the abdomen and 4 of 20 patients (20%) who had grafts arising or terminating at the femoral arteries (p less than 0.05). Sixteen of 30 patients (53%) discharged with abnormal initial indium 111 WBC scans underwent serial scanning until the scan normalized or a graft complication developed. All of the 16 patients had grafts involving the groin region. Abnormal indium 111 uptake in the femoral region continued for a mean 114 days without the development of prosthetic graft infections. The sensitivity of indium 111-labeled WBC scans for detecting wound complications was 100%, whereas the specificity was 50%. Thus, the accuracy of the test was only 53%. We conclude that (1) abnormal indium 111 WBC scans are common after graft operations involving the groin region but are unusual after vascular procedures confined to the abdomen, and (2) in the absence of clinical suspicion, the indium 111-labeled WBC scan does not reliably predict prosthetic graft infection because of the low specificity of the test in the early postoperative period.


SDBP-Pred: Prediction of single-stranded and double-stranded DNA-binding proteins by extending consensus sequence and K-segmentation strategies into PSSM.
Identification of DNA-binding proteins (DNA-BPs) is a hot issue in protein science due to its key role in various biological processes. These processes are highly concerned with DNA-binding protein types. DNA-BPs are classified into single-stranded DNA-binding proteins (SSBs) and double-stranded DNA-binding proteins (DSBs). SSBs mainly involved in DNA recombination, replication, and repair, while DSBs regulate transcription process, DNA cleavage, and chromosome packaging. In spite of the aforementioned significance, few methods have been proposed for discrimination of SSBs and DSBs. Therefore, more predictors with favorable performance are indispensable. In this work, we present an innovative predictor, called SDBP-Pred with a novel feature descriptor, named consensus sequence-based K-segmentation position-specific scoring matrix (CSKS-PSSM). We encoded the local discriminative features concealed in PSSM via K-segmentation strategy and the global potential features by applying the notion of the consensus sequence. The obtained feature vector then input to support vector machine (SVM) with linear, polynomial and radial base function (RBF) kernels. Our model with SVM-RBF achieved the highest accuracies on three tests namely jackknife, 10-fold, and independent tests, respectively than the recent method. The obtained prediction results illustrate the superlative prediction performance of SDBP-Pred over existing studies in the literature so far.


Emotional Changes and Protective Factors of Emotional Workers in the Public and Private Sector.
Emotional labor is known to be a risk factor for emotional distress. This study aimed to evaluate specific stressors according to the type of occupation and identify protective and adverse factors. We recruited 349 workers engaged in emotional labor in a suburban city. They were assessed using scales regarding emotional status, job stress, resilience, and job satisfaction. Correlation and regression analyses were performed to evaluate their emotional state according to their stress level. A mediation model using structural equation modeling was utilized to identify the mediating effects of resilience and workplace satisfaction. The correlation analysis indicated that the level of workplace stress was statistically correlated with depressed mood and anxiety and showed a significant inverse correlation with individuals' resilience and job satisfaction. According to the regression analysis, in private institution workers, "emotional disharmony and hurt" had a statistically significant negative effect on their emotional state, and in public institution workers, "emotional demands and regulation" were prominent. Resilience partially mediated the relationship between emotional stress and anxiety/depressive symptoms. Our findings indicate that the causes of stress differed according to the working environment. Preventive strategies such as resilience training and relieving stress on individual factors are needed to promote mental health.


Nosocomial infection rates during a one-year period in a nursing home care unit of a Veterans Administration hospital.
Infections in long-term care institutions are a constant source of morbidity in residents in these facilities. We report our experience with infection rates during a 1-year surveillance period in a 120-bed nursing home care unit of a Veterans Administration hospital. Our purpose was (1) to establish our own infection rate and (2) to ascertain the relationships (a) between infection rate and level of required nursing care and (b) between infection rate and staffing adequacy. Our overall nosocomial infection rate for 1987 was 4.6 infections/1000 patient days. The majority of infections were urinary tract infections, with the predominant pathogen Proteus mirabilis. One ward in the nursing home care unit had a significantly higher infection rate compared with that of the other wards (p less than 0.05), and there was a significantly higher infection rate in residents who required total nursing care versus less dependent residents (p less than 0.05). We were unable to find a direct relationship between the degree of staff shortages and infection rate. This prolonged infection control surveillance indicated our nosocomial infection rates were similar to those in previously published reports. We also identified problem infections in certain areas, which led us to develop staff in-service programs to address these problems. In summary, we believe this information is useful not only for us but for others involved in the care of residents in long-term care facilities inasmuch as there are little published data on yearly infection rates per patient days.


Random electromagnetic model beams with correlations described by two families of functions.
The electromagnetic Schell-model beams whose cross-spectral matrices have elements belonging to different families of functions are considered for the first time. The spatial distributions of polarization properties of such beams are shown to be made completely or partially different from that of the average intensity.


Evidence for mitochondrial K+ channels and their role in cardioprotection.
Twenty years after the discovery of sarcolemmal ATP-sensitive K+ channels and 12 years after the discovery of mitochondrial K(ATP) (mitoK(ATP)) channels, progress has been remarkable, but many questions remain. In the case of the former, detailed structural information is available, and it is well accepted that the channel couples bioenergetics to cellular electrical excitability; however, in the heart, a clear physiological or pathophysiological role has yet to be defined. For mitoK(ATP), structural information is lacking, but there is abundant evidence linking the opening of the channel to protection against ischemia-reperfusion injury or apoptosis. This review updates recent progress in understanding the physiological role of mitoK(ATP) and highlights outstanding questions and controversies, with the intent of stimulating additional investigation on this topic.


Essential role of choline for pneumococcal virulence in an experimental model of meningitis.
The goal of the present study was to elucidate the contribution of the newly recognized virulence factor choline to the pathogenesis of Streptococcus pneumoniae in an animal model of meningitis. The choline containing strain D39Cho(-) and its isogenic choline-free derivative D39Cho(-)licA64--each expressing the capsule polysaccharide 2--were introduced intracisternally at an inoculum size of 10(3) CFU into 11 days old Wistar rats. During the first 8 h post infection both strains multiplied and stimulated a similar immune response that involved expression of high levels of proinflammatory cytokines, the matrix metalloproteinase 9 (MMP-9), IL-10, and the influx of white blood cells into the CSF. Virtually identical immune response was also elicited by intracisternal inoculation of 10(7) CFU equivalents of either choline-containing or choline-free cell walls. At sampling times past 8 h strain D39Cho(-) continued to replicate accompanied by an intense inflammatory response and strong granulocytic pleiocytosis. Animals infected with D39Cho(-) died within 20 h and histopathology revealed brain damage in the cerebral cortex and hippocampus. In contrast, the initial immune response generated by the choline-free strain D39Cho(-)licA64 began to decline after the first 8 h accompanied by elimination of the bacteria from the CSF in parallel with a strong WBC response peaking at 8 h after infection. All animals survived and there was no evidence for brain damage. Choline in the cell wall is essential for pneumococci to remain highly virulent and survive within the host and establish pneumococcal meningitis.


Clinical relevance of the lnc-HNF1B-3:1 genetic polymorphisms in Western Chinese tuberculosis patients.
Tuberculosis remains a global public health problem. Genetic polymorphisms may affect the susceptibility, clinical characteristics, and adverse drug reactions of patients with TB. The present study aimed to examine the association of single nucleotide polymorphisms of lncRNA-HNF1B-3:1 with the clinical manifestation of TB in a Western Chinese population. A total of 526 tuberculosis patients and 561 healthy subjects were recruited in Western China. The correlation between lnc-HNF1B-3:1 polymorphism and tuberculosis susceptibility was investigated. Moreover, the influence on adverse drug reactions following treatment was explored. A total of 7 SNPs within the lnc-HNF1B-3:1 locus was genotyped by the improved multiplex ligation detection reaction method. No significant associations were noted between TB susceptibility and the presence of all 7 SNPs of the lnc-HNF1B-3:1 as determined by single-locus analysis (All P > .05). The AA genotype of rs12939622 (in the dominant model) and the AA genotype of rs4262994 (in the recessive model) caused increased susceptibility of the subjects to fever (P < .001 and P = .008, respectively). The Rs2542670 G allele was associated with increased risk of thrombocytopenia, leukopenia, and chronic kidney damage following drug administration (P = .007, .029, .003, respectively). The present study reported for the first time that the rs12939622, rs4262994 and rs2542670 genotypes in lnc-HNF1B-3:1 locus may influence the clinical manifestations of tuberculosis.


Prognostic Model That Predicts Benefits of Adjuvant Radiotherapy in Patients With High Grade Meningioma.
Adjuvant radiotherapy is the main treatment modality for high grade meningioma after surgical resection; however, recurrence and survival outcomes vary. The aim of this study was to create a new "prognostic score" that allows personalized recommendations for post-operative adjuvant radiotherapy in patients with high grade meningioma. Clinical data were collected from 115 patients with high grade meningioma treated with surgical resection and adjuvant radiotherapy. A prognostic model was built based on the hazards ratios of independent prognostic factors yielded by multivariate cox proportional analysis. Calibration and discrimination of the prognostic score was evaluated using good of fit test and Harrel's C index, respectively. A total of 115 high grade meningioma patients (72 atypical and 43 anaplastic meningiomas) were enrolled. Three factors were independently associated with progression-free survival (PFS): extent of resection (GTR vs. STR), recurrent status (de novo vs. recurrent), and Ki-67 labeling index (<5% vs. ≥ 5%). The respective β-coefficients were used to generate the "prognostic score". The cohort was divided into low-risk and high-risk groups based on the median prognostic score. Good of fit test showed strong calibration (P = 0.7133) and Harrel's C index 0.766 indicated a strong discrimination capability of the prognostic score. The Harrel's C index for OS was 0.60. Our prognostic model using three basic clinical parameters robustly separated high grade meningioma patients who benefit vs. do not benefit from adjuvant radiotherapy. External validation of our model is warranted to help improve patient selection suitable for adjuvant radiotherapy.


Cooking up a culinary identity for Belgium. Gastrolinguistics in two Belgian cookbooks (19th century).
The notion of cookbooks as socio-historic markers in a society is generally accepted within food studies. As both representations and prescriptions of food practices, perceived habits and attitudes towards food, they represent a certain identity for their readers. This paper investigates the nature of the identity that Belgian cookbooks constructed through their rhetoric. An important part of this study is to explore how and to what extent explicit reference to Belgium was made. To this end recipe titles/labels and recipe comments used in two leading bourgeois cookbooks from nineteenth-century Belgium were subjected to a quantitative and qualitative content analysis. The analysis showed that clear attention was paid to national culinary preferences. In terms of a domestic culinary corpus, it became apparent that both the Dutch and French editions of these cookbooks promoted dishes that were ascribed a Belgian origin. Internationality, however, was also an important building block of Belgian culinary identity. It was part of the desire of Belgian bourgeoisie to connect with an international elite. It fit into the 'search for sophistication', which was also expressed through the high representation of the more costly meats and sweet dishes. In addition, other references associated with bourgeois norms and values, such as family, convenience and frugality, were additional building blocks of Belgian culinary identity. Other issues such as tradition, innovation and health, were also matters of concerns to these Belgian cookbooks.


Expression of complement regulatory proteins [membrane cofactor protein (CD46), decay accelerating factor (CD55), and protectin (CD59)] in endometrial stressed cells.
In the female reproductive tract, the complement system represents a defense mechanism that can act directly against pathogens and cells, and mediates inflammatory response. Endometrial cells are protected from autologous complement attack by membrane-bound complement regulatory proteins (CRPs) that prevent complement activation: membrane cofactor protein (CD46), decay accelerating factor (CD55), and protectin (CD59). In this work we show that all CRPs were overexpressed after LPS exposure. Maximal stimulatory effect was detected after 6h, and was declining after 12h, reaching control levels in 24h. CD59 was the protein showing the more prominent effect. There seems to be a slight increase of CRP expression in the endometrium of sterile patients that have anti-endometrial antibodies (AEA) in their serum. Our results suggest that under stress, the high expression of CRPs (CD46, CD55, and CD59) could protect endometrial injured cells against complement mediated lysis. The survival of these cells with some biochemical modifications would enable autoimmune response.


Identification of novel putative alleles related to important agronomic traits of wheat using robust strategies in GWAS.
Principal component analysis (PCA) is widely used in various genetics studies. In this study, the role of classical PCA (cPCA) and robust PCA (rPCA) was evaluated explicitly in genome-wide association studies (GWAS). We evaluated 294 wheat genotypes under well-watered and rain-fed, focusing on spike traits. First, we showed that some phenotypic and genotypic observations could be outliers based on cPCA and different rPCA algorithms (Proj, Grid, Hubert, and Locantore). Hubert's method provided a better approach to identifying outliers, which helped to understand the nature of these samples. These outliers led to the deviation of the heritability of traits from the actual value. Then, we performed GWAS with 36,000 single nucleotide polymorphisms (SNPs) based on the traditional approach and two robust strategies. In the conventional approach and using the first three components of cPCA as population structure, 184 and 139 marker-trait associations (MTAs) were identified for five traits in well-watered and rain-fed environments, respectively. In the first robust strategy and when rPCA was used as population structure in GWAS, we observed that the Hubert and Grid methods identified new MTAs, especially for yield and spike weight on chromosomes 7A and 6B. In the second strategy, we followed the classical and robust principal component-based GWAS, where the first two PCs obtained from phenotypic variables were used instead of traits. In the recent strategy, despite the similarity between the methods, some new MTAs were identified that can be considered pleiotropic. Hubert's method provided a better linear combination of traits because it had the most MTAs in common with the traditional approach. Newly identified SNPs, including rs19833 (5B) and rs48316 (2B), were annotated with important genes with vital biological processes and molecular functions. The approaches presented in this study can reduce the misleading GWAS results caused by the adverse effect of outlier observations.


Association between Clostridioides difficile ribotypes, restriction endonuclease analysis types, and toxin gene expression.
Clostridioides difficile strains cause severe infection. Previous studies suggested that the virulence of C. difficile is dependent on ribotype; however, this hypothesis is still controversial. We aim to investigate the relationship between ribotypes, restriction endonuclease analysis (REA) types, and toxin gene expression in C. difficile strains. We utilized 53 clinical C. difficile strains. All strains were assigned a molecular strain type using PCR ribotyping and REA typing and classified into 17 ribotypes and six REA types. The expression of toxin genes (tcdA, tcdB, and cdtB) in C. difficile strains were quantified by real-time PCR using each specific primer set, and expression was normalized to that of the housekeeping gene rpoA. All 53 strains expressed tcdB and four strains expressed cdtB. Five strains did not express tcdA. Most ribotype and REA type strains expressed tcdA and tcdB similar to the BAA-1870 strain. In cdtB-positive strains, the cdtB expression levels were similar to those in the BAA-1870 strain. tcdA and tcdB expression levels were similar in the cdtB-positive and cdtB-negative strains. Toxin gene expression was not associated with the ribotype. Production of binary toxin C. difficile transferase was not related to tcdA and tcdB expression levels.


Dietary intervention in adult rats exposed to a high-sugar diet early in life permanently impairs sperm quality.
Childhood obesity predicts the presence of adult obesity. Obesity is associated with poor sperm quality. We hypothesized that exposure to a high-sugar diet (HSD) in early life would cause permanent histomorphology damage to the testes, resulting in reduced sperm quality in adult life. Wistar rats (aged 21days) were divided into four groups (n=6). In the first experiment, the rats received tap water (control) and a 30% sucrose diet for two months (S30). In the second experiment, the control and 30% sucrose diets were fed for two months, followed by replacement with tap water for two months (IS30). Eating and drinking were monitored. Animals were then euthanized, visceral and gonadal fat tissue and testes were collected, and epididymal spermatozoa were excised. Testicular samples were used for morphological description by H&E staining and for quantifying triacylglycerol content, caspase activity, and oxidative stress. Serum testosterone concentration was evaluated. Spermatozoa were used to assess sperm quality. Our results show that sperm quality was impaired by consuming HSD and could not be restored by dietary intervention. HSD feeding induced hyperplasia of visceral adipose tissue, increased testicular weight, and serum testosterone levels. The dietary intervention increased visceral adipose tissue, serum, and testicular triacylglycerol levels and normalized serum testosterone levels. Overall, the HSD diet caused permanent changes in seminiferous tubule cross-sectional area, caspase activity, oxidative stress, and sperm quality. Therefore, a high-sugar diet in early life causes permanent damage to sperm quality in adulthood.


Characterization of hindlimb motoneuron membrane properties in acute and chronic spinal cats.
The purpose of this study was to determine if changes in hindlimb motoneuron membrane electrical properties occur 4-6 months after spinal transection in the adult animal. Eight acute and nine chronic animals were spinalized at T12. Intracellular recordings from motoneurons innervating the triceps surae were performed. Membrane electrical properties, including resting potential, action potential peak amplitude, afterhyperpolarization duration, rheobasic current, input resistance and axonal conduction velocity were measured. There were no statistical differences found between group means or frequency distributions in the membrane properties of motoneurons assessed from acute and chronic spinal animals. Thus, alteration of motoneuron membrane properties does not appear to be a major contributing factor to the hyperexcitable hindlimb reflex activity demonstrated by chronic spinal animals.


Baseline PET features to predict prognosis in primary mediastinal B cell lymphoma: a comparative analysis of different methods for measuring baseline metabolic tumour volume.
This study assessed the performance of four different methods for the estimation of metabolic tumour volume (MTV) in primary mediastinal B cell lymphoma (PMBCL). MTV was estimated using either a region growing automatic software program (RG) or a fixed threshold (FT) segmentation algorithm with the three most common cut-offs proposed in the literature (i.e., 25% and 41% of the SUVmax and SUV value ≥2.5). We compared these four methods using phantoms that simulated different set-ups of the main imaging characteristics of PMBCL (volume, shape, 18-FDG uptake and intra-lesion distribution) and assessed their performance in 103 PMBCL patients enrolled in the International Extranodal Lymphoma Study Group-26 (IELSG-26) study. There was good correlation between MTV values estimated in vitro and in vivo using the different methods. The 25% FT cut-off (FT25%) provided the most accurate MTV evaluation in the phantoms. The cut-off at SUV 2.5 (FT2.5) resulted in MTV overestimation that particularly increased with high SUV values. The 41% cut-off (FT41%) showed MTV underestimation that was more evident when there were high levels of heterogeneity in tracer distribution. Shape of the lesion did not affect MTV computation. The RG algorithm provided a systematic slight MTV underestimation without significant changes due to lesion characteristics. We observed analogous trends for the MTV estimation in patients, with very different derived thresholds for the four methods. Optimal cut-offs for predicting progression-free survival (PFS) ranged from 213 to 831 ml. All methods predicted PFS with similar negative predictive values (94-95%) but different positive predictive values (23-45%). The different methods result in significantly different MTV cut-off values. All allow risk stratification in PMBCL, but FT25% showed the best capacity to predict disease progression in the patient cohort and provided the best accuracy in the phantom model.


The inventory for déjà vu experiences assessment. Development, utility, reliability, and validity.
In this article the development, utility, reliability, and validity of the Inventory for Déjà vu Experiences Assessment (IDEA) are described. The IDEA is a 23-item self-administered questionnaire consisting of a general section of nine questions and qualitative section of 14 questions. The latter questions comprise 48 topics. The questionnaire appeared to be a user-friendly instrument with satisfactory to good reliability and validity. The IDEA permits the study of quantitative and qualitative characteristics of déjà vu experiences.


Does a history of mild traumatic brain injury increase suicide risk in veterans with PTSD?
Research shows that posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) independently increase suicide risk; however, scant research has investigated whether mTBI increases suicide risk above and beyond the risk associated with PTSD alone. The current research compared suicide risk factors among a matched sample of Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) military personnel and veterans with PTSD alone or PTSD and a history of an mTBI. Differences in the assessed risk factors were small and suggest that if PTSD and mTBI are associated with elevations in suicide risk relative to PTSD alone, the added risk is likely mediated or confounded by PTSD symptom severity. This finding highlights the importance of screening and treating military personnel and veterans for PTSD. Future explication of the impact of TBI-related impairments on suicide risk will be critical as we strive to ensure safety and optimize care for our military personnel and veterans.


Non-invasive elevation of circulating corticosterone increases the rejection of foreign eggs in female American robins (Turdus migratorius).
Avian obligate brood parasites rely on other species to raise their offspring. In turn, many brood parasite hosts have evolved defensive behaviors to reduce the costs of brood parasitism, yet the proximate bases underlying these defenses remain poorly understood. Recent studies regarding the potential endocrine mechanisms of foreign-egg rejection have implicated corticosterone as a physiological mediator of anti-parasitic defenses. For example, corticosterone is elevated in response to non-mimetic eggs in an egg rejecter thrush, the Eurasian blackbird (Turdus merula) and this hormone's suppression reduces egg rejection rates in the congeneric American robin (T. migratorius). American robins are also among the few host species of obligate brood parasitic brown-headed cowbirds (Molothrus ater) that readily reject foreign eggs from their nests. We non-invasively elevated corticosterone levels in incubating female robins by dissolving it in DMSO gel which was then applied onto eggs already in the clutch. Relative to controls treated with pure DMSO gel, corticosterone-treated female robins were more likely to reject a non-mimetic, cowbird-sized foreign egg (72 %) than control females (50 %) when accounting for the known effect of lower clutch sizes on greater egg rejection. Future studies are needed to assess the sensory and cognitive impact(s) of corticosterone, as well as other hormones essential for parental care, in this and other hosts' defense behaviors against avian brood parasitism.


EMS-induced reversion studies in the white locus of Drosophila melanogaster.
5 white-locus mutants of Drosophila melanogaster, respresenting 5 different sub-sites, were treated with EMS and tested for reversion to wild-type. 4 of them were genuine mutants and one was not. Moreover, the ability of the 4 mutants to revert to wild-type differed from one another which therefore reflects a qualitatively distinct alteration in the genetic material delimited by each mutant.


Differentiating stage 1 epithelial ovarian cancer from benign ovarian tumours using a combination of tumour markers HE4, CA125, and CEA and patient's age.
Evaluating the presence of possible malignant disease in women with ovarian masses relies on medical imaging and serum marker findings. This study considers the role of serum Human Epididymal Protein 4 (HE4) antigen in combination with other serum markers to more effectively estimate the risk of malignancy in patients with isolated pelvic masses. We used prospectively collected biospecimens held by the Australian Ovarian Cancer Study (AOCS). Serum samples of patients with FIGO stage 1 epithelial ovarian cancer or with a benign condition were analysed for levels of circulating HE4 antigen, CA 125, and CEA, and test results were used to predict the presence of malignancy and to differentiate benign from malignant pelvic masses. HE4 levels were significantly elevated amongst postmenopausal women and amongst patients with malignancy compared to premenopausal women and those with benign disease (p<0.001 for both). The combination of CA125 and age, achieved an area under the ROC curve of 0.677 (95% CI: 0.584 to 0.770, p=0.778), whilst HE4+CA125+CEA in combination with patient's age showed significantly higher AUC of 0.797 (95% CI: 0.721 to 0.874, p=0.0052). By adjusting the ROMA cut-off values the percentage of correctly classified premenopausal patients into low and high risk groups increased from 36.99% to 69.86%. In patients with isolated pelvic masses, the combination of HE4, CA 125 and age with or without CEA provides higher diagnostic value compared to CA125 and age alone. It may therefore be considered for continuous evaluation in patients with adnexal masses.


Clinical Practice Guideline for the Treatment of Pediatric Acute Gastroenteritis in the Outpatient Setting.
Acute gastroenteritis (AGE) is a common illness in childhood that usually can be treated in the outpatient setting. Inaccurate assessment or delayed treatment of AGE can lead to an increased risk for invasive interventions. A literature search was conducted using PubMed, CINAHL Plus, the Cochrane Library, and Embase. Results of the query were refined to narrow the focus of relevant studies for the provider caring for dehydrated children in the outpatient setting. Use of clinical dehydration scales to assess the level of dehydration and early initiation of oral rehydration therapy promote optimal patient outcomes. Oral rehydration therapy remains the best means of rehydrating, and ondansetron is a safe and effective adjunct to help children with persistent vomiting. The purpose of this practice guideline is to identify best practices for AGE in children older than 6 months with symptoms for less than 7 days who are being cared for in the outpatient setting.


Management of the deviated nose. The importance of septal reconstruction.
The key to the correction of severely deviated noses is straightening the nasal septum. An emphasis is placed on conservative management of the external nasal framework while being prepared to perform extensive surgery on the deviated septum. If the septum can be modified and repositioned in the midline without losing support to the nose, consistently good functional and aesthetic results are obtained. Several techniques that we have found to be of value in achieving this goal have been discussed and illustrated and three representative cases have been presented.


Successive non-radical and radical process of peroxymonosulfate-based oxidation using various activation methods for enhancing mineralization of sulfamethoxazole.
To enhance the mineralization of toxic organic pollutants is crucial for the alleviation of environmental pollution. In this study, the successive non-radicals and radicals process (SNRP) of peroxymonosulfate (PMS)-based oxidation was performed using various methods for PMS activation, including UV, ozone, gamma radiation and biochar and applied for enhancing the mineralization of sulfamethoxazole (SMX). The results showed that SNRP-UV could improve the mineralization of SMX, and both SNRP-UV and PMS/UV could completely mineralize SMX. For SNRP-Ozone, SNRP-Radiation and SNRP-Biochar, compared to the sole radical oxidation, all SNRPs could enhance the mineralization of SMX. The biochar-induced SNRP obtained the maximum mineralization increment, followed by gamma irradiation-induced SNRP and ozone-induced SNRP. Sulfate radicals were mainly responsible for SMX mineralization for SNRP-Biochar, while hydroxyl radicals for SNRP-Radiation, and the synergetic effect of ozone and sulfate radicals for SNRP-Ozone. Different degradation intermediate products were identified in different SNRP, further revealing that SNRP induced by different methods had different mineralization capacity. This study further demonstrated that SNRP could be a new strategy for enhancing the mineralization of SMX.


Foveal avascular zone and foveal pit formation after preterm birth.
Vascularisation of the macula takes place between 24 and 27 weeks post-conception. Preterm birth may affect the formation of the foveal avascular zone (FAZ) and foveal depression, and displacement of inner retinal layers away from the incipient fovea. To examine whether vascular abnormalities accompany an inner retinal abnormality, and whether they are coincident. High-density spectral domain optical coherence tomography volume scans were obtained from 24 preterm children and 34 full-term controls (5-16 years). Matlab programs were used to quantify total retinal thickness, thickness of individual retinal layers and metrics of foveal morphology. Summed voxel projections for the ganglion cell layer-inner nuclear layer were used to identify the FAZ. Preterm children had significantly smaller FAZ diameters than controls (p<0.0001). The foveal pits of preterm children were significantly shallower and less steep (p<0.0001) and total retinal thickness at the fovea was significantly increased (p<0.0001) compared to controls. The ganglion cell layer-inner plexiform layer and outer nuclear layer were significantly (p≤0.0001) thicker in preterm children than in controls. Preterm birth results in abnormal foveal vascularisation, a failure of the inner retinal neurons to migrate away from the fovea, and an elevated outer nuclear layer ratio. The spatial coincidence of inner retinal and vascular abnormalities in preterm children supports the hypothesis that aspects of foveal development are interdependent.


Decrease in the expression level of the gene encoding the putative Bombyx mori bidensovirus receptor during virus infection.
Bombyx mori bidensovirus (BmBDV) is a pathogen that replicates only in the midgut columnar cells of silkworms, causing fatal disease. Resistance to BmBDV, which does not depend on the viral dose, is determined by a single gene, nsd-2 (resistance gene). Previously, we identified nsd-2 by positional cloning using B. mori genome information and found that this gene encodes a putative amino acid transporter that may function as a receptor for BmBDV. In this study, to understand the relationship between BmBDV and the putative virus receptor, we performed expression analysis of +nsd-2 (allele of nsd-2; susceptibility gene) after virus infection. Quantitative RT-PCR analysis using total RNA isolated from the midgut of an uninfected and a virus-infected silkworm revealed no change in the expression levels of +nsd-2 in the uninfected silkworm, whereas the expression levels of +nsd-2 drastically decreased in the virus-infected silkworm. Moreover, comparison of the expression pattern between the BmBDV-derived transcript and +nsd-2 revealed that the expression level of +nsd-2 decreased with an increase in the virus-derived transcript. In addition, expression analysis of 26 genes encoding other transporters in the midgut demonstrated that the expression levels of three other genes also decreased similarly to the decrease of the expression levels of +nsd-2 after virus infection. Thus, our results suggest that some transporters, including +nsd-2, are affected by BmBDV infection.


Moon, Mars and Minds: Evaluating Parkinson's disease mortality among U.S. radiation workers and veterans in the million person study of low-dose effects.
Radiation is one of the most important stressors related to missions in space beyond Earth's orbit. Epidemiologic studies of exposed workers have reported elevated rates of Parkinson's disease. The importance of cognitive dysfunction related to low-dose rate radiation in humans is not defined. A meta-analysis was conducted of six cohorts in the Million Person Study (MPS) of low-dose health effects to learn whether there is consistent evidence that Parkinson's disease is associated with radiation dose to brain. The MPS evaluates all causes of death among U.S. radiation workers and veterans, including Parkinson's disease. Systematic and consistent methods are applied to study all categories of workers including medical radiation workers, industrial radiographers, nuclear power plant workers, atomic veterans, and Manhattan Projects workers at the Los Alamos National Laboratory and at Rocky Flats. Consistent methods for all cohorts are used to estimate organ-specific doses and to obtain vital status and cause of death. The meta-analysis include 6 cohorts within the MPS, consisting of 517,608 workers and 17,219,001 person-years of observation. The mean dose to brain ranged from 6.9 to 47.6 mGy and the maximum dose from 0.76 to 2.7 Gy. Five of the 6 cohorts revealed positive associations with Parkinson's disease. The overall summary estimate from the meta-analysis was statistically significant based on 1573 deaths due to Parkinson's disease. The summary excess relative risk at 100 mGy was 0.17 (95% CI: 0.05; 0.29). Parkinson's disease was positively associated with radiation in the MPS cohorts indicating the need for careful evaluation as to causality in other studies, delineation of possible mechanisms, and assessing possible implications for space travel as well as radiation protection guidance for terrestrial workers.


Immunity to intestinal parasites.
Intestinal parasites are common in man and animals and can cause severe disease. Knowledge of immunity to such infections is limited and comes largely from studies using laboratory host-parasite systems. Understanding how immunity can operate, and why it often does not, is not only of intrinsic interest but necessary for the development of immunological methods of control.


Efficiency curve of the ionization chamber of the SIR.
The efficiency of the SIR ionization chamber versus photon energy has been obtained by an iterative method, starting from a few monoenergetic gamma-ray emitters. The relative standard uncertainty on the efficiency curve obtained is lower than 10(-2) above 65 keV. An efficiency curve for beta particles has been deduced in a similar manner, from measurements of (quasi-) pure beta emitters. The possible uses of the efficiency curve to identify inconsistent SIR data or discrepant decay scheme data are discussed.


Effectiveness of cyanoacrylate glue in the fixation of midline catheters and peripherally inserted central catheters in hospitalised adult patients: Randomised clinical trial (CIANO-ETI).
The objective of the study was to assess the efficacy of the use of cyanoacrylate glue (CAG) as a means of securing midline catheters and peripherally inserted central catheters with the modified micro-Seldinger technique in adult hospitalised patients. Randomised clinical trial with two groups (1:1): control and intervention. The control group received a securement method with a sutureless device plus transparent dressing and the intervention group received the same securement method plus the CAG. The study was approved by the Drug Research Ethics Committee of the Lleida Health Region. A total of 216 patients were assessed. The two groups of the trial were homogenously distributed in terms of sociodemographic and clinical variables. The intervention group had a statistically significant lower incidence of peri-catheter bleeding and/or oozing during the 7-day study period (odds ratio (OR), 0.6; 95% confidence level (CI), 0.44-0.81; p < 0.001) and a statistically significant lower incidence of catheter dislodgements during the first 24 h (OR, 0.2; 95% CI, 0.04-0.91; p = 0.03). There were no statistically significant differences in the incidence of phlebitis (OR, 1.30; 95% CI, 0.60-2.83; p = 0.56) or catheter-related pain (OR, 0.88; 95% CI, 0.40-1.94; p = 0.84). Midline catheters and peripherally inserted central catheters secured with CAG had fewer complications than catheters not secured with this adhesive.


The importance of checking the assumptions of the professional referral source.
Behavior therapy has at times been portrayed as simply an assemblage of therapeutic "techniques". However, central to its practice is a behavioral analysis which eventually leads to the selection of the most efficacious intervention. Wolpe has repeatedly warned against reliance upon either patients' assumptions or one's own "too facile" interpretations. From this excerpt from an initial consultation it is apparent that one must also be wary of the assumptions made by professional referral sources. It is easy to be led astray by seductively "obvious" correlations between environmental events and psychophysiological reactions. Different etiologies call for different treatment strategies, and careful behavioral analysis is needed for an appropriate decision.


Parasomnias and Sleep-Related Movement Disorders in Older Adults.
Sleep paralysis is rare in the elderly but may occur particularly in families suffering from this phenomenon. In a minority of patients with disorders of arousal, the episodes persist until the age of 70. Zolpidem and other medications may induce sleepwalking and sleep eating-related syndrome. Most patients with idiopathic REM sleep behavior disorder (RBD) eventually develop Parkinson disease and dementia with Lewy bodies. Anti-IgLON5 disease includes abnormal behaviors in both nonrapid eye movement sleep and rapid eye movement sleep (REM) sleep. Restless legs syndrome prevalence increases with age until the sixth decade. A severe form of periodic limb movements in sleep may clinically mimic REM sleep behavior disorder (RBD).


Physicochemical studies on the interaction of serum albumin with pulmonary surfactant extract in films and bulk bilayer phase.
Functionality, structure and composition of the adsorbed films of bovine lipid extract surfactant (BLES), in the absence and presence of bovine serum albumin (BSA), at the air-buffer interface was characterized through surface tension, atomic force microscopy and time of flight secondary ion mass spectrometric methods. Gel and fluid domains of BLES films were found to be altered significantly in the presence of BSA. Differential scanning calorimetric studies on BLES dispersions in presence of BSA revealed that the perturbations of the lipid bilayer structures were significant only at higher amount of BSA. FTIR studies on the BLES dispersions in buffer solution revealed that BSA could affect the lipid head-group hydrations in bilayer as well as the methylene and methyl vibration modes of fatty acyl chains of the phospholipids present in BLES. Serum albumin could perturb the film structure at pathophysiological concentration while higher amount of BSA was required in perturbing the bilayer structures. The studies suggest a connected perturbed bilayer to monolayer transition model for surfactant inactivation at the alveolar-air interface in dysfunctional surfactants.


Extracellular matrix alterations in the skin of patients affected by psoriasis.
Psoriasis is a chronic inflammatory disease dependent upon a complex interaction between genetic predisposition and immunological factors. It is characterized by skin lesions throughout the body, causing great morbidity and affecting life quality. The present study aimed to evaluate the protein and mRNA expression of heparanase-1 (HPSE), heparanase-2 (HPSE2), syndecan-1 (SYND1), metalloproteinases (MMP2, MMP9), and tissue inhibitor metalloproteinases 2 (TIMP2) in skin samples. From each psoriasis patient, two samples were collected, one sample from a psoriasis plaque (n = 23) and the other sample from non-affected skin (n = 23), as well as tissue collected by blepharoplasty from control individuals (n = 18). Protein expression was investigated by immunohistochemistry, followed by digital quantification. Quantitative RT-PCR obtained mRNA expression. Statistical analyses were done, and p values < 0.05 were considered significant. A significant increase in protein and mRNA expression was observed in both heparanases (HPSE and HPSE2), and higher protein levels of MMP9 and TIMP2 were observed in the psoriasis plaque compared to the non-affected skin. The data point to a probable activation of MMP2 by TIMP2. Moreover, there was a significant increase in HPSE2, SYND1, MMP9, and TIMP2 in non-affected skin samples from patients with psoriasis than in the control sample (tissue obtained by individuals who do not have psoriasis). These results show a possible correlation between the characteristic inflammatory process and alterations in the expression of the extracellular matrix in psoriasis. The increased expression of HPSE2, SYND1, MMP9, and TIMP2, even in the absence of psoriatic plaque, indicates that these molecules may be involved with extracellular matrix changes in the initial alterations the psoriatic process and may be candidates for the development of target treatments.


The effect of gamma radiation and neocarzinostatin on NAD and ATP levels in mouse leukaemia cells.
When mouse leukemia cells are treated with gamma-radiation or neocarzinostatin the intracellular NAD and ATP levels fall rapidly. We have shown that the ATP response is a consequence of the decreased NAD level. We suggest that this low NAD level results in decreased glycolytic activity and that there is a subsequent accumulation of phosphorylated sugars associated with the fall in ATP. Under these extreme conditions, therefore, the NAD level probably regulates the rate of glycolysis in cells which are utilising a rapidly metabolisable sugar as their energy source.


Effects of acrylamide and some other sulfhydryl reagents on spontaneous and pathologically induced terminal sprouting from motor end-plates.
The innervation of the normal rat sternocostalis muscle exhibits a constant low level of short spontaneous terminal sprouts visible in zinc iodide-osmium (ZIO) and in methylene blue-stained preparations. Acrylamide inhibits these spontaneous sprouts in a dose-dependent manner. This inhibition is mimicked by N-ethylmaleimide (a sulfhydryl group blocking agent) and can be nullified when acrylamide is given after the sulfhydryl group protecting agent, dithiothreitol (DTT). This could not be reversed by giving DTT 3 hours after acrylamide. Furthermore, when given alone DTT increases the level of spontaneous terminal sprouting seen in ZIO and in methylene blue-stained preparations. These findings suggest that the binding of acrylamide to sulfhydryl groups is involved in the inhibitory process. Acrylamide also reduces the number and length of the reactionary terminal sprouts, seen in ZIO and in methylene blue-stained preparations, that follow partial denervation or local injection of botulinum toxin. These inhibitory effects are long-lasting; recovery still has not fully occurred 4 weeks after a single dose of acrylamide (50 mg/kg). The roles of glutathione and other sulfhydryl components of axons are discussed in relation to the mechanism of acrylamide neurotoxicity.


Estimating Risk for Future Intracranial, Fully Implanted, Modular Neuroprosthetic Systems: A Systematic Review of Hardware Complications in Clinical Deep Brain Stimulation and Experimental Human Intracortical Arrays.
A new age of neuromodulation is emerging: one of restorative neuroengineering and neuroprosthetics. As novel device systems move toward regulatory evaluation and clinical trials, a critical need arises for evidence-based identification of potential sources of hardware-related complications to assist in clinical trial design and mitigation of potential risk. The objective of this systematic review is to provide a detailed safety analysis for future intracranial, fully implanted, modular neuroprosthetic systems. To achieve this aim, we conducted an evidence-based analysis of hardware complications for the most established clinical intracranial modular system, deep brain stimulation (DBS), as well as the most widely used intracranial human experimental system, the silicon-based (Utah) array. Of 2328 publications identified, 240 articles met the inclusion criteria and were reviewed for DBS hardware complications. The most reported adverse events were infection (4.57%), internal pulse generator malfunction (3.25%), hemorrhage (2.86%), lead migration (2.58%), lead fracture (2.56%), skin erosion (2.22%), and extension cable malfunction (1.63%). Of 433 publications identified, 76 articles met the inclusion criteria and were reviewed for Utah array complications. Of 48 human subjects implanted with the Utah array, 18 have chronic implants. Few specific complications are described in the literature; hence, implant duration served as a lower bound for complication-free operation. The longest reported duration of a person with a Utah array implant is 1975 days (~5.4 years). Through systematic review of the clinical and human-trial literature, our study provides the most comprehensive safety review to date of DBS hardware and human neuroprosthetic research using the Utah array. The evidence-based analysis serves as an important reference for investigators seeking to identify hardware-related safety data, a necessity to meet regulatory requirements and to design clinical trials for future intracranial, fully implanted, modular neuroprosthetic systems.


Dose escalation study of intravenous and intra-arterial N-acetylcysteine for the prevention of oto- and nephrotoxicity of cisplatin with a contrast-induced nephropathy model in patients with renal insufficiency.
Cisplatin neuro-, oto-, and nephrotoxicity are major problems in children with malignant tumors, including medulloblastoma, negatively impacting educational achievement, socioemotional development, and overall quality of life. The blood-labyrinth barrier is somewhat permeable to cisplatin, and sensory hair cells and cochlear supporting cells are highly sensitive to this toxic drug. Several chemoprotective agents such as N-acetylcysteine (NAC) were utilized experimentally to avoid these potentially serious and life-long side effects, although no clinical phase I trial was performed before. The purpose of this study was to establish the maximum tolerated dose (MTD) and pharmacokinetics of both intravenous (IV) and intra-arterial (IA) NAC in adults with chronic kidney disease to be used in further trials on oto- and nephroprotection in pediatric patients receiving platinum therapy. Due to ethical considerations in pediatric tumor patients, we used a clinical population of adults with non-neoplastic disease. Subjects with stage three or worse renal failure who had any endovascular procedure were enrolled in a prospective, non-randomized, single center trial to determine the MTD for NAC. We initially aimed to evaluate three patients each at 150, 300, 600, 900, and 1200 mg/kg NAC. The MTD was defined as one dose level below the dose producing grade 3 or 4 toxicity. Serum NAC levels were assessed before, 5 and 15 min post NAC. Twenty-eight subjects (15 men; mean age 72.2 ± 6.8 years) received NAC IV (N = 13) or IA (N = 15). The first participant to experience grade 4 toxicity was at the 600 mg/kg IV dose, at which time the protocol was modified to add an additional dose level of 450 mg/kg NAC. Subsequently, no severe NAC-related toxicity arose and 450 mg/kg NAC was found to be the MTD in both IV and IA groups. Blood levels of NAC showed a linear dose response (p < 0.01). Five min after either IV or IA NAC MTD dose administration, serum NAC levels reached the 2-3 mM concentration which seemed to be nephroprotective in previous preclinical studies. In adults with kidney impairment, NAC can be safely given both IV and IA at a dose of 450 mg/kg. Additional studies are needed to confirm oto- and nephroprotective properties in the setting of cisplatin treatment. Clinical Trial Registration URL: https://eudract.ema.europa.eu . Unique identifier: 2011-000887-92.


Anthropogenic mercury signals in lake sediments from southernmost Patagonia, Chile.
Atmospheric mercury fluxes to terrestrial and aquatic surfaces in the Northern Hemisphere have increased since the Industrial Revolution. However fluxes are not well characterized for the Southern Hemisphere, since environmental archives are comparatively scarce. Mercury records from (210)Pb-dated sediment cores of three South Patagonian lakes were investigated in order to reveal the influence of anthropogenic activities on atmospheric mercury deposition in remote lakes of the Southern Hemisphere. Comparison with indicators of organic matter sources (carbon and nitrogen/carbon ratios) and a conservative mineral soil element (zirconium) in the sediments revealed that soil erosion is an important process contributing mercury to these lakes and influenced variation in concentrations through time. However, at ~1900 AD mercury accumulation increased independent from soil erosion and peaked from 1980 to 2000 AD. We attribute this to an increase in atmospheric mercury deposition in this remote region of the Southern Hemisphere. Mean flux ratios, which reflect the increase in modern mercury accumulation compared to pre-1850 AD, lie within a range of 1.4 to 2.4. These values indicate an increase in atmospheric mercury deposition slightly lower than predictions derived from global mercury models that suggest an increase in Hg deposition by a factor of 2 to 3.


Elevated plasma interleukin-17A in a subgroup of Myasthenia Gravis patients.
To better define the role of IL-17A in myasthenia gravis (MG), we assessed plasma concentrations in 69 adult patients with MG prior to initiation of immunosuppression and monitored their clinical course for the subsequent 2years with quantitative MG scores (QMGS) and Osserman classification. IL-17A was higher among patients than healthy control subjects. Early-onset women without thymoma had greater elevations of IL-17A. Logistic regression analysis indicated that the absence of thymoma rather than women gender or early-onset was the significant determinant associated with IL-17A elevation. Elevated IL-17A levels were associated with more severe MG. In summary, IL-17A has role in the pathogenesis of a subgroup of patients with early-onset women with MG with greater disease severity who are most likely to have thymic hyperplasia. This subgroup may be a target for IL-17 treatments, which are under development.


Sequence variability of Rhizobiales orthologs and relationship with physico-chemical characteristics of proteins.
Chromosomal orthologs can reveal the shared ancestral gene set and their evolutionary trends. Additionally, physico-chemical properties of encoded proteins could provide information about functional adaptation and ecological niche requirements. We analyzed 7080 genes (five groups of 1416 orthologs each) from Rhizobiales species (S. meliloti, R. etli, and M. loti, plant symbionts; A. tumefaciens, a plant pathogen; and B. melitensis, an animal pathogen). We evaluated their phylogenetic relationships and observed three main topologies. The first, with closer association of R. etli to A. tumefaciens; the second with R. etli closer to S. meliloti; and the third with A. tumefaciens and S. meliloti as the closest pair. This was not unusual, given the close relatedness of these three species. We calculated the synonymous (dS) and nonsynonymous (dN) substitution rates of these orthologs, and found that informational and metabolic functions showed relatively low dN rates; in contrast, genes from hypothetical functions and cellular processes showed high dN rates. An alternative measure of sequence variability, percentage of changes by species, was used to evaluate the most specific proportion of amino acid residues from alignments. When dN was compared with that measure a high correlation was obtained, revealing that much of evolutive information was extracted with the percentage of changes by species at the amino acid level. By analyzing the sequence variability of orthologs with a set of five properties (polarity, electrostatic charge, formation of secondary structures, molecular volume, and amino acid composition), we found that physico-chemical characteristics of proteins correlated with specific functional roles, and association of species did not follow their typical phylogeny, probably reflecting more adaptation to their life styles and niche preferences. In addition, orthologs with low dN rates had residues with more positive values of polarity, volume and electrostatic charge. These findings revealed that even when orthologs perform the same function in each genomic background, their sequences reveal important evolutionary tendencies and differences related to adaptation.


Treatment of angular deformities of the tibia in children: acute versus gradual correction.
This is a retrospective review of 25 tibial osteotomies (in 19 patients) performed with either acute or gradual correction to determine the outcome of treatment and incidence of neurovascular complications. Patients undergoing gradual correction had fewer neurovascular complications and greater correction than those undergoing acute correction (27 degrees vs. 18 degrees, respectively). It was concluded that gradual correction tends to be a safer technique for the treatment of tibial deformities and allows greater correction.


Copulation increases offensive attack in male rats.
Twenty-four adult male rats with previous sexual experience were tested for aggression against intruders after one of four treatments (n = 6 per treatment): exposure to inaccessible estrous females; exposure to anestrous females; no female exposure, or copulation to ejaculation. Although both exposure to inaccessible estrous females and copulation significantly decreased latency to attack only copulation produced significant elevation of intensity and duration of attack. Results are discussed in reference to the role of aggression in maintaining priority of access to females, and as a means of assuring paternity of offspring by dominant males.


Vanadium oxide, vanadium oxynitride, and cobalt oxynitride as electrocatalysts for the nitrogen reduction reaction: a review of recent developments.
The electrocatalytic reduction of molecular nitrogen to ammonia-the nitrogen reduction reaction (NRR)-is of broad interest as an environmentally- and energy-friendly alternative to the Haber-Bosch process for agricultural and emerging energy applications. Herein, we review our recent findings from collaborative electrochemistry/surface science/theoretical studies that counter several commonly held assumptions regarding transition metal oxynitrides and oxides as NRR catalysts. Specifically, we find that for the vanadium oxide, vanadium oxynitride, and cobalt oxynitride systems, (a) there is no Mars-van Krevelen mechanism and that the reduction of lattice nitrogen and N2to NH3occurs by parallel reaction mechanisms at O-ligated metal sites without incorporation of N into the oxide lattice; and (b) that NRR and the hydrogen evolution reaction do occur in concert under the conditions studied for Co oxynitride, but not for V oxynitride. Additionally, these results highlight the importance of both O-ligation of the V or Co center for metal-binding of dinitrogen, and the importance of N in stabilizing the transition metal cation in an intermediate oxidation state, for effective N≡N bond activation. This review also highlights the importance and limitations ofex situandin situphotoemission-involving controlled transfer between ultra-high vacuum and electrochemistry environments, and ofoperandonear ambient pressure photoemission coupled within situstudies, in elucidating the complex chemistry relevant to the electrolyte/solid interface.


Visualizing macromolecular complexes with in situ liquid scanning transmission electron microscopy.
A central focus of biological research is understanding the structure/function relationship of macromolecular protein complexes. Yet conventional transmission electron microscopy techniques are limited to static observations. Here we present the first direct images of purified macromolecular protein complexes using in situ liquid scanning transmission electron microscopy. Our results establish the capability of this technique for visualizing the interface between biology and nanotechnology with high fidelity while also probing the interactions of biomolecules within solution. This method represents an important advancement towards allowing future high-resolution observations of biological processes and conformational dynamics in real-time.


Activation of peroxisome proliferator-activated receptor gamma is crucial for antitumoral effects of 6-iodolactone.
Molecular iodine (I2) exhibits antiproliferative and apoptotic effects on in vivo and in vitro cancer models. These effects are thought to be mediated by an iodinated arachidonic acid derivative, 6-iodolactone (6IL), and one of the proposed mechanisms is that 6IL activates Peroxisome Proliferator-Activated Receptors type gamma (PPARG). These receptors have been implicated in the inhibition of carcinogenic processes, in addition to their classical role in maintaining lipid and glucose homeostasis. The aim of this study was to determine whether PPARG participates in the 6IL antiproliferative and apoptotic effects on the mammary cancer cell line MCF-7. The 6IL/PPARG complex was inhibited by the PPARG antagonist GW9662, in both an endogenous and overexpressed (adenoviral vector infection) context, and stable PPARG-knockdown MCF-7 cells (RNA interference, confirmed with hydrolysis probes and Western blot), were used to corroborate the PPARG participation. 6IL effects on proliferation (measured by Trypan Blue exclusion) and apoptosis (phosphatidylserine identification by flow cytometer) were evaluated in conditions of chemical inhibition (GW9662) and silencing (RNA interference). A wound-healing assay was conducted on wild-type and stable PPARG-knockdown MCF-7 cells to evaluate the antimigrational effect of 6IL. Caspase-8 activity was evaluated to determine if the extrinsic pathway is involved in the effects of 6IL and I2 treatment. Antiproliferative and pro-apoptotic 6IL effects require the activation of PPARG. In addition, wound-healing assays show that 6IL is able to inhibit MCF-7 cell migration and that PPARG plays a role in this phenomenon. Finally, the data exclude the participation of the extrinsic apoptotic pathway in 6IL- and I2-induced apoptosis. These results support the previously proposed mechanism, in which the I2 effects are mediated by 6IL, and they provide further support for the use of I2 as coadjuvant in breast cancer treatment.


The variations of human sex ratio at birth during and after wars, and their potential explanations.
Data on wartime sex ratios (proportions male at birth) are reviewed. Two sorts of variation are empirically well supported viz. (a) rises during and just after both World Wars and (b) a fall in Iran during the Iran-Iraq War. Potential explanations are offered here for these rises and fall. The fall seems plausibly explained by psychological stress causing pregnant women disproportionately to abort male fetuses. The rises may be explained by either or both of two different forms of hypothesis viz. (i) Kanazawa's "returning soldier" hypothesis and (ii) variation in coital rates. The coital rate hypothesis potentially accounts, in slightly different ways, for the rises both during, and just after, some wars. The argument that coital rate affects sex ratio just after wars seems to be supported by evidence that in some combatant countries, dizygotic (DZ) twinning rates (which also reportedly vary with coital rate) peaked after the World Wars. The suggestion that war is associated with rises in sex ratio at birth was first made more than two centuries ago. However, I have been unable to locate direct supporting sex ratio data relating to any conflict before World War One. So it would be useful if historical demographers were to search for such data relating to these earlier wars.


Neural Substrates of Psychomotor Speed Deficits in Cerebral Small Vessel Disease: A Brain Disconnectome Mapping Study.
It remains unknown which factors influence how brain disconnectivity derived from White Matter Hyperintensity (WMH) lesions leads to psychomotor speed dysfunction, one of the earliest and most common cognitive manifestations in the cerebral Small Vessel Disease (cSVD) population. While the burden of WMH has been strongly linked to psychomotor speed performance, the effect that different locations and volumes of WMH may have on cSVD-related cognitive impairment remains unclear. Therefore, we aimed to explore (1) whether global WMH, deep WMH (DWMH), and periventricular (PVWMH) volumes display different psychomotor speed associations; (2) whether tract-specific WMH volume shows stronger cognitive associations compared with global measures of WMH volume; (3) whether specific patterns of WMH location lead to different degrees of disconnectivity. Using the BCBToolkit, we investigated which pattern of distribution and which locations of WMH lesion result in impaired psychomotor speed in a well-characterized sample (n = 195) of cSVD patients without dementia. Two key findings emerge from our study. First, global (and not tract-specific) measures of WMH volume were associated with psychomotor speed performance. Second, disconnection maps revealed the involvement of callosal tracts, association and projection fibers, and frontal and parietal cortical brain areas related to psychomotor speed, while the lesion location influenced such associations. In conclusion, psychomotor deficits are affected differently by WMH burden and topographic distribution through brain disconnection in non-demented cSVD patients.


[Neonatal renal vein thrombosis in a heterozygous carrier of both factor V Leiden and the MTHFR gene mutation].
Renal vein thrombosis (RVT) is a rare but potentially serious neonatal disease. Its epidemiology and its clinical and biological expression are currently well known, but its etiological exploration, like that of venous thromboembolism, is increasingly complex. Perinatal risk factors such as prematurity, dehydration, and birth asphyxia have lost their direct accountability at the expense of their interaction with constitutional disorders of hemostasis. We report a case of RVT in a newborn who was a heterozygous carrier of both factor V Leiden and the methylene tetrahydrofolate reductase (MTHFR) gene mutation. We recall the clinical and epidemiological characteristics. A search for inborn blood coagulation disorders should be systematic in the newborn infant with venous thrombosis because of the risk of recurrence, taking into account perinatal factors and maternal thrombophilia (especially if RVT is established during the prenatal period).


Hemophiliac patient's knowledge and educational needs concerning acquired immunodeficiency syndrome.
The Patient Knowledge Assessment Study (PKAS) was conducted among 107 male hemophilic patients, aged 15 to 67 years, at 19 hemophilia treatment centers (HTC). Participants were given a 30-item questionnaire concerning the cause of acquired immunodeficiency syndrome (AIDS), the groups at risk, and modes of transmission. The questionnaire included questions on the participant's status in regard to antibody to human T-lymphotropic retrovirus, type III/lymphadenopathy-associated virus (HTLV-III/LAV), and the meaning of this test result. HTC health-care providers were asked to complete a separate questionnaire containing 17 questions about information given patients concerning their HTLV-III/LAV antibody status and its meaning. Overall, patients had a good base of knowledge about AIDS; however, there were gaps in this knowledge. Twenty-nine percent of patients did not know that spouses of AIDS patients were at risk for AIDS; 47% did not know that sexual partners of persons with hemophilia were at risk; and 32% did not know that hemophilic children were at risk. Further, only 69% understood that antibody-positive individuals had had contact with the AIDS virus. Identifying these and other areas of misunderstanding will provide the information needed to design educational strategies and psychosocial support programs appropriate for the hemophilic population, and which may serve as a model for other populations.


Getting into the brain: Potential of nanotechnology in the management of NeuroAIDS.
In spite of significant advances in antiretroviral (ARV) therapy, the elimination of human immunodeficiency virus (HIV) reservoirs from the periphery and the central nervous system (CNS) remains a formidable task. The incapability of ARV to go across the blood-brain barrier (BBB) after systemic administration makes the brain one of the dominant HIV reservoirs. Thus, screening, monitoring, and elimination of HIV reservoirs from the brain remain a clinically daunting and key task. The practice and investigation of nanomedicine possesses potentials for therapeutics against neuroAIDS. This review highlights the advancements in nanoscience and nanotechnology to design and develop specific size therapeutic cargo for efficient navigation across BBB so as to recognize and eradicate HIV brain reservoirs. Different navigation and drug release strategies, their biocompatibility and efficacy with related challenges and future prospects are also discussed. This review would be an excellent platform to understand nano-enable multidisciplinary research to formulate efficient nanomedicine for the management of neuroAIDS.


Sustained pressure-controlled inflation or intermittent mandatory ventilation in preterm infants in the delivery room? A randomized, controlled trial on initial respiratory support via nasopharyngeal tube.
To prove the hypothesis that sustained pressure-controlled inflation compared to intermittent mandatory ventilation for lung recruitment via nasopharyngeal tube after delivery is more effective in reducing the rate of endotracheal intubation and mechanical ventilation in very preterm infants. The study was designed as a randomized, controlled trial. The setting was the delivery room and neonatal intensive care unit of a university hospital in Germany. Subjects were 61 infants (25.0-28.9 wk of gestation) with signs of respiratory distress immediately after birth. The infants were randomized in the delivery room to two different respiratory interventions: either to sustained pressure-controlled inflation (15 s) or to intermittent mandatory ventilation (rate 60 min(-1)). This respiratory support was given by a nasopharyngeal tube. The inflation pressure or peak inspiratory pressure was increased stepwise (20-25-30 cm H2O) according to the response of heart rate and oxygenation. The main outcome measure was treatment failure, i.e., endotracheal intubation and mechanical ventilation according to given intubation criteria. Treatment failure occurred in 61% (95% CI, sustained pressure-controlled inflation: 42-78) and 70% (95% CI, intermittent mandatory ventilation: 51-85) (p = 0.59). The rates of mortality (3/61), severe intraventricular haemorrhage (5/61) and chronic lung disease (10/58) were not different between groups. Sufficient spontaneous breathing within the first 48 h of life without endotracheal intubation and mechanical ventilation was achieved in about 30% with both methods of initial respiratory support.


[Normal values of osteocalcin in the blood over the course of life].
This study tends to settle the standard values of BGP circulating amount, which - attesting osteoblastic activity - varies according life periods. The lowest amounts are to be found in twenty five to forty five years adults; though varying all the day and night long, these amounts remain included between 3-7 ng/ml; particularly if the blood-test took place between 8 and 10 a.m.


The dispersion state of milk fat influences triglyceride metabolism in the rat--a 13CO2 breath test study.
Milk fat, which has different structures in the various dairy products, is a major and controversial lipid source in the Western diet. However, information about the digestion fate of milk fat depending on its supramolecular structure for a given composition is scarce. In this study, 13CO2 breath tests were performed with fasted rats force-fed different dairy preparations of similar composition but differing in fat suprastructure in order to highlight differences of general lipid metabolism. Each preparation consisted of a NaCl solution, anhydrous milk fat labelled with a 13C mixed triacylglycerol, casein (as native phosphocaseinate powder with some lactose), and dipalmitoylphosphatidylcholine. Milk fat was either fed (i) unemulsified consecutively to the aqueous phase, or emulsified as (ii) coarse droplets of approximately 10 microm covered mainly with the phospholipid, or (iii-iv) fine droplets of approximately 1 microm covered mainly with casein, force-fed either in the liquid state or in a semi-crystallized state. 13C abundance in expired air samples was measured by isotope ratio mass spectrometry; results were expressed as 13C enrichment and were submitted to an ANOVA analysis. The 13CO2 excretion curves of the unemulsified preparation and the coarse emulsion were similar and presented a sharp peak, both significantly different from the fine emulsion curves characterized by a nearly linear cumulative recovery. The crystalline state of the fine emulsion droplets and the viscosity of these emulsions did not affect significantly their excretion curves. The lipid metabolization (indicated by the 13C recovery) was significantly slower for the fine droplets coated with casein than for the large droplets coated with the phospholipid and the unemulsified fat. For the latter, a single 13C peak rapidly appeared, while for small droplets coated with caseins, 13C excretion was continuous up to 6 h. Global lipid metabolism based on oxidation to CO2 was decreased with smaller compared to larger emulsified milk fat particles with different coatings. These data support the concept that dairy products with different fat suprastructures are digested and metabolized differently.


The clinical and molecular taxonomy of t(14;18)-negative follicular lymphomas.
Follicular lymphoma (FL) is a neoplasm derived from germinal center B cells, composed of centrocytes and centroblasts, with at least a focal follicular growth pattern. The t(14;18) translocation together with epigenetic deregulation through recurrent genetic alterations are now recognized as the hallmark of FL. Nevertheless, FL is a heterogeneous disease, clinically, morphologically, and biologically. The existence of FL lacking the t(14;18) chromosomal alteration highlights the complex pathogenesis of FL, and indicates that there are alternative pathogenetic mechanisms that can induce a neoplasm with follicular center B-cell phenotype. Based on their clinical presentation, t(14;18)-negative FLs can be divided into 3 broad groups: nodal presentation, extranodal presentation, and those affecting predominantly children and young adults. Recent studies have shed some light into the genetic alterations of t(14;18)-negative FL. Within the group of t(14;18)-negative FL with nodal presentation, cases with STAT6 mutations are increasingly recognized as a distinctive molecular subgroup, often cooccurring with CREBBP and/or TNFRSF14 mutations. FL with BCL6 rearrangement shows clinicopathological similarities to its t(14;18)-positive counterpart. In contrast, t(14;18)-negative FL in extranodal sites is characterized mainly by TNFRSF14 mutations in the absence of chromatin modifying gene mutations. FL in children have a unique molecular landscape when compared with those in adults. Pediatric-type FL (PTFL) is characterized by MAP2K1, TNFRSF14, and/or IRF8 mutations, whereas large B-cell lymphoma with IRF4 rearrangement is now recognized as a distinct entity, different from PTFL. Ultimately, a better understanding of FL biology and heterogeneity should help to understand the clinical differences and help guide patient management and treatment decisions.