Aggressive angiomyxoma (AAM) is a rare mesenchymal tumour of pelvis and perineum, almost exclusively occurring in females. We are reporting a case of a 53-year-old gentleman who presented with a long standing inguinoscrotal swelling misdiagnosed as inguinal hernia, for which he underwent incomplete excision at local hospital and then was referred to our centre for completion surgery.
The suitability of a chairside aMMP-8 test in determination of periodontal inflammation and caries in adolescents was assessed. Secondly, the influence of orthodontic treatment on aMMP-8 test result was analyzed.
Within the LIFE Child study, 434 adolescents (10 to 18 years) were included. Clinical dental examinations comprised caries experience (DMF/T-Index), signs of periodontal inflammation (probing pocket depth, PPD; community periodontal index of treatment needs; CPITN) at six index teeth and oral hygiene (OH). Information about orthodontic appliances (OA) and socioeconomic status (SES) were obtained by validated questionnaires. Test's sensitivity and specificity to detect periodontal inflammation and carious lesions were evaluated. The influence of OA on the test result was analyzed (multivariate model).
No associations between age, gender, SES or OH, and test outcome were found (p > 0.05). Positive test results correlated to periodontal findings (CPITN, mean PPD; p < 0.001). However, for the detection of ≥ 1 site(s) with PPD ≥ 4 mm, the test's sensitivity and specificity were found to be 61 and 69%, respectively. Multivariate analysis revealed a higher probability for a positive test result in cases of fixed OA (odds ratio 5.02, 95% confidence interval 1.90–13.19). The test had no diagnostic value considering carious lesions.
The chairside aMMP-8 test does not reliably identify adolescents with periodontal inflammation. Positive test results were more frequent in case of OA.
The chairside aMMP-8 test is no appropriate tool to screen children and adolescents neither for periodontal inflammation nor for carious lesions.
Increasing interest in climate engineering in recent years has led to calls by the international research community for international research collaboration as well as global public engagement. But making such collaboration a reality is challenging. Here, we report the summary of a 2016 workshop on the significance and challenges of international collaboration on climate engineering research with a focus on the Asia-Pacific region. Because of the region's interest in benefits and risks of climate engineering, there is a potential synergy between impact research on anthropogenic global warming and that on solar radiation management. Local researchers in the region can help make progress toward better understanding of impacts of solar radiation management. These activities can be guided by an ad hoc Asia-Pacific working group on climate engineering, a voluntary expert network. The working group can foster regional conversations in a sustained manner while contributing to capacity building. An important theme in the regional conversation is to develop effective practices of dialogues in light of local backgrounds such as cultural traditions and past experiences of large-scale technology development. Our recommendation merely portrays one of several possible ways forward, and it is our hope to stimulate the debate in the region.
We aimed to analyse the nailfold capillaryscopy findings morphologically and examine their relationship with disease activity and demographic characteristics in patients with rheumatoid arthritis. In accordance with the 2010 ACR/EULAR classification criteria, 201 patients diagnosed with Romatoiad artrit (RA) and 50 healthy controls were included. We analysed capillaroscopic abnormalities such asmegacapillaries, haemorrhages, ramifications and avascular areas in patients affected with rheumatoid arthritis. The findings in our study are as follows: in 45.77% of the RA patients, there were nonspecific capillaryscopy findings. When compared to control group, the incidence of tortuosity, dilated capillary and bushy capillary was higher in RA patients (p values, respectively, 0.110, 0.330, 0.440 and 0.516). In RA patients with Raynaud's phenomenon, the incidence of nonspecific capillaryscopy findings was higher. While there is a weak relationship between tortuosity and the duration of disease, no significant relation was detected between capillaryscopy findings and parameters such as RF, anti-CCP positivity and disease activity score (DAS28). When compared to controls, we have detected that RA patients have more nonspecific capillaryscopic findings. We could not find a relationship between nonspecific capillaryscopic findings and RA'a clinical findings and laboratory parameters. There is a need for a long-term wider-scale follow-up study to investigate whether there is a capillaryscopic pattern that can be correlated with RA's clinical findings.
The aim of this study was to study the process of intestinal adaptation in the three limbs of the small intestine after malabsorptive bariatric surgery: the biliopancreatic limb, the alimentary limb, and the common channel. These limbs are exposed to different stimuli, namely, gastrointestinal transit and nutrients in the alimentary limb, biliopancreatic secretions in the biliopancreatic limb, and a mix of both in the common channel. We also wished to investigate the effect of glutamine supplementation on the adaptation process.
Three types of surgery were performed using a porcine model: biliopancreatic bypass (BPBP), massive (75%) short bowel resection as the positive control, and a sham operation (transection) as the negative control. We measured the height and width of intestinal villi, histidine decarboxylase (HDC) activity, and amount of HDC messenger RNA (mRNA) (standard diet or a diet supplemented with glutamine).
An increase in HDC activity and mRNA expression was observed in the BPBP group. This increase coincided with an increase in the height and width of the intestinal villi. The increase in villus height was observed immediately after surgery and peaked at 2 weeks. Levels remained higher than those observed in sham-operated pigs for a further 4 weeks.
The intestinal adaptation process in animals that underwent BPBP was less intense than in those that underwent massive short bowel resection and more intense than in those that underwent transection only. Supplementation with glutamine did not improve any of the parameters studied, although it did appear to accelerate the adaptive process.
We aimed to analyse the nailfold capillaryscopy findings morphologically and examine their relationship with disease activity and demographic characteristics in patients with rheumatoid arthritis. In accordance with the 2010 ACR/EULAR classification criteria, 201 patients diagnosed with Romatoiad artrit (RA) and 50 healthy controls were included. We analysed capillaroscopic abnormalities such asmegacapillaries, haemorrhages, ramifications and avascular areas in patients affected with rheumatoid arthritis. The findings in our study are as follows: in 45.77% of the RA patients, there were nonspecific capillaryscopy findings. When compared to control group, the incidence of tortuosity, dilated capillary and bushy capillary was higher in RA patients (p values, respectively, 0.110, 0.330, 0.440 and 0.516). In RA patients with Raynaud's phenomenon, the incidence of nonspecific capillaryscopy findings was higher. While there is a weak relationship between tortuosity and the duration of disease, no significant relation was detected between capillaryscopy findings and parameters such as RF, anti-CCP positivity and disease activity score (DAS28). When compared to controls, we have detected that RA patients have more nonspecific capillaryscopic findings. We could not find a relationship between nonspecific capillaryscopic findings and RA'a clinical findings and laboratory parameters. There is a need for a long-term wider-scale follow-up study to investigate whether there is a capillaryscopic pattern that can be correlated with RA's clinical findings.
There is marked bone loss after spinal cord injury (SCI); however, its pathogenesis and clinical management remain unclear. The increased circulating levels of receptor activator of nuclear factor kB ligand (RANKL) associated with bone loss shortly after SCI and the prevention of bone loss with denosumab treatment suggest a contributory role of RANKL in SCI-induced osteoporosis.
Bone turnover and bone loss are markedly increased shortly after SCI. However, the pathogenesis and clinical management of this process remain unclear, especially the role of the osteoprotegerin (OPG)/RANKL system in this disorder. The aim of this study was to analyze serum levels of OPG and RANKL in bone loss associated with recent SCI and the effect of denosumab treatment on these mediators.
Twenty-three males with recent complete SCI were prospectively included. Serum OPG and RANKL levels, bone turnover markers (PINP, bone ALP, CTX), and bone mineral density (BMD) were assessed at baseline, at 6 months of follow-up, prior to initiating denosumab, and 6 months after treatment. The results were compared with a healthy control group.
At baseline, SCI patients showed higher RANKL levels vs. controls which were correlated with days-since-SCI and total hip BMD loss at 6 months. OPG levels were similar to controls at baseline. After denosumab treatment, OPG showed no changes, whereas RANKL levels became undetectable in 67% of patients. Patients with undetectable RANKL during treatment showed better response in femoral BMD and bone markers vs. patients with detectable RANKL at 6 months of denosumab. Increased parathormone (PTH) levels during treatment were negatively correlated with RANKL changes.
RANKL levels are increased after SCI and related to BMD loss at the proximal femur, becoming undetectable after denosumab treatment. The effect of denosumab on preventing sublesional bone loss, especially in patients with undetectable levels during treatment, suggests a contributory role of RANKL in this process.
Language assessment has a critical role in the clinical diagnosis of neurodegenerative diseases, in particular, in the case of Primary Progressive Aphasia (PPA). The current diagnostic criteria (Gorno-Tempini et al., 2011) identify three main variants on the basis of clinical features and patterns of brain atrophy. Widely accepted tools to diagnose, clinically classify, and follow up the heterogeneous language profiles of PPA are still lacking. In this study, we develop a screening battery, composed of nine tests (picture naming, word and sentence comprehension, word and sentence repetition, reading, semantic association, writing and picture description), following the recommendations of current diagnostic guidelines and taking into account recent research on the topic. All tasks were developed with consideration of the psycholinguistic factors that can affect performance, with the aim of achieving sensitivity to the language deficit to which each task was relevant, and to allow identification of the selective characteristic impairments of each PPA variant. Normative data on 134 Italian subjects pooled across homogeneous subgroups for age, sex, and education are reported. Although further work is still needed, this battery represents a first step towards a concise multilingual standard language examination, a fast and simple tool to help clinicians and researchers in the diagnosis of PPA.
Toxoplasma gondii is an obligate intracellular protozoan that causes toxoplasmosis in warm-blooded animals. Most mammals, including humans, can become intermediate host, resulting in subclinical infection or even death. Generally, there is limited information on the epidemiology of T. gondii of game species in Germany. As omnivores, raccoons, which are particularly widespread and abundant in Germany, are particularly exposed to infection the parasite. Here, we report the seroprevalence of T. gondii antibodies from 15 study sites located in Luxembourg and Germany. Using the indirect modified agglutination test (MAT), 170 (37.4%; 95% CI: 33.0–41.9) out of 454 raccoons were surveyed to be T. gondii seropositive. While values ranged from 19.0% to 53.3%, there was no significant difference in seroprevalence between study areas. Animal weight had a strong influence on the presence of T. gondii antibodies in raccoon sera, with heavier animals more likely to be seropositive. Our results show that T. gondii infection is widespread in central European raccoons, suggesting a high degree of ecosystem circulation of the parasite.
Previous studies showed recombinant annexin A2 (rA2) in combination with low-dose tissue-type plasminogen activator (tPA) improved thrombolytic efficacy and long-term neurological outcomes after embolic focal ischemia in rats. The objective of this study was to investigate the effects and mechanisms of the combination in early BBB integrity and cerebrovascular patency in the rat focal embolic stroke model. Ischemic brain infarct volume and hemorrhagic transformation were quantified at 24 h after stroke. At an earlier time point, 16 h after stroke, BBB integrity was evaluated by IgG extravasation, and the involved mechanisms were assessed for tight junction ZO-1 and adhesion junction ve-cadherin protein expression, matrix metalloproteinase activation, extracellular matrix collagen IV and endothelial barrier antigen expression, and activation of microglia/macrophages and astrocytes. While at the same time point, cerebrovascular patency was assessed by intravascular fibrin and platelet depositions. At 24 h after stroke, the combination showed significant reduction in brain infarction and intracerebral hemorrhage. At 16 h after stroke onset, the combination therapy significantly reduced BBB disruption, and improved preservation of the junction proteins ZO-1 and ve-cadherin, decreased activation of matrix metalloproteinase, inhibited degradation of extracellular matrix collagen IV and endothelial barrier antigen, and reduced microglia/macrophage and astrocytes activations. Meanwhile, the combination also significantly improved cerebrovascular patency by reducing intravascular fibrin and platelet depositions in the peri-infarct brain tissues. These results suggest the beneficial effects of the rA2 plus low-dose tPA combination may be mediated in part by the amelioration of BBB disruption and improvement of cerebrovascular patency.
The journal impact factor (IF) is often used as a surrogate marker for methodological quality. The objective of this study is to evaluate the relation between the journal IF and methodological quality of surgical randomized controlled trials (RCTs).
Surgical RCTs published in PubMed in 1999 and 2009 were identified. According to IF, RCTs were divided into groups of low (<2), median (2–3) and high IF (>3), as well as into top-10 vs all other journals. Methodological quality characteristics and factors concerning funding, ethical approval and statistical significance of outcomes were extracted and compared between the IF groups. Additionally, a multivariate regression was performed.
The median IF was 2.2 (IQR 2.37). The percentage of 'low-risk of bias' RCTs was 13% for top-10 journals vs 4% for other journals in 1999 (P < 0.02), and 30 vs 12% in 2009 (P < 0.02). Similar results were observed for high vs low IF groups. The presence of sample-size calculation, adequate generation of allocation and intention-to-treat analysis were independently associated with publication in higher IF journals; as were multicentre trials and multiple authors.
Publication of RCTs in high IF journals is associated with moderate improvement in methodological quality compared to RCTs published in lower IF journals. RCTs with adequate sample-size calculation, generation of allocation or intention-to-treat analysis were associated with publication in a high IF journal. On the other hand, reporting a statistically significant outcome and being industry funded were not independently associated with publication in a higher IF journal.
An enzyme with broad substrate specificity would be an asset for industrial application. T1 lipase apparently has the same active site residues as polyhydroxyalkanoates (PHA) depolymerase. Sequences of both enzymes were studied and compared, and a conserved lipase box pentapeptide region around the nucleophilic serine was detected. The alignment of 3-D structures for both enzymes showed their active site residues were well aligned with an RMSD value of 1.981 Å despite their sequence similarity of only 53.8%. Docking of T1 lipase with P(3HB) gave forth high binding energy of 5.4 kcal/mol, with the distance of 4.05 Å between serine hydroxyl (OH) group of TI lipase to the carbonyl carbon of the substrate, similar to the native PhaZ7Pl . This suggests the possible ability of T1 lipase to bind P(3HB) in its active site. The ability of T1 lipase in degrading amorphous P(3HB) was investigated on 0.2% (w/v) P(3HB) plate. Halo zone was observed around the colony containing the enzyme which confirms that T1 lipase is indeed able to degrade amorphous P(3HB). Results obtained in this study highlight the fact that T1 lipase is a versatile hydrolase enzyme which does not only record triglyceride degradation activity but amorphous P(3HB) degradation activity as well.
The knowledge on systemic autoinflammatory disorders (SAID) is expanding rapidly and new signalling pathways are being decrypted. The concept of autoinflammation has been proposed since 1999, to define a group of diseases with abnormal innate immunity activation. Since then, more than 30 monogenic SAID have been described. In this review, we first describe inflammasomopathies and SAID related to the interleukin-1 pathway. Recent insights into the pathogenesis of familial Mediterranean fever and the function of Pyrin are detailed. In addition, complex or polygenic SAID, such as Still's disease or PFAPA syndrome, are also discussed. Then, major players driving autoinflammation, such as type-1 interferonopathies (including the recently described haploinsuffiency in A20 and otulipenia), TNF-associated periodic syndromes, defects in ubiquitination, and SAID with overlapping features of autoimmunity or immunodeficiency. Discoveries of the pathogenic role of mosaicism, intronic defects coupled to the likelihood to identify digenic or polygenic diseases are providing new challenges for physicians and geneticists. This comprehensive review depicts the various SAID, presenting them according to their predominant pathophysiological mechanism, with a particular emphasis on recent findings. Epidemiologic data are also presented. Finally, we propose a practical diagnostic approach to the most common monogenic SAID, based on the most characteristic clinical presentation of these disorders.
Bone loss in rheumatoid arthritis (RA) is a key feature both local and systemic. Anti-citrullinated protein antibodies (ACPA) have recently been found to directly induce differentiation and activation of osteoclasts and therefore contribute to periarticular bone loss. The aim of this study was to analyze the effect of ACPA on systemic bone mineral density (BMD) in patients with established RA. This is a cross-sectional study with a single-center RA population. BMD was measured with Dual X-ray absorptiometry at lumbar and femoral sites. ACPA were measured by EIA. Multivariate analysis was performed adjusting for the main confounding variables. One hundred twenty-seven RA patients were enrolled. In univariate analysis, ACPA-positive patients showed lower BMD Z-score (SD below the age- and gender-matched mean reference value) at femoral sites (p < 0.01). A negative correlation between ACPA titer and BMD Z-score at all sites was observed (p < 0.01). The multivariate analysis adjusted for the main confounding variables confirmed the negative effect of ACPA at femoral sites (p < 0.05), but not at lumbar spine BMD. No significant effect of rheumatoid factor has been observed. ACPA have a negative titer-dependent effect on BMD at femoral sites, mainly constituted by cortical bone. ACPA-positive patients, especially if at high titer, should undergo bone investigations and be treated with bone protecting agents. Disease-modifying anti-rheumatic drugs lowering ACPA titer might have positive effects on systemic bone mass.
Penetrating cardiac injuries are uncommon and lethal. The objectives of this study are to examine the national profile of cardiac injuries, identify independent predictors of outcome, generate, compare and validate previous predictive models for outcomes. We hypothesized that National Trauma Data Bank (NTDB) given its large number of patients, would validate these models.
The NTDB was queried for data on cardiac injuries, using survival as the main outcome measure. Statistical analysis was performed utilizing univariate and stepwise logistic regression. The stepwise logistic regression model was then compared with other predictive models of outcome.
There were 2016 patients with penetrating cardiac injuries identified from 1,310,720 patients. Incidence: 0.16%. Mechanism of injury: GSWs—1264 (63%), SWs—716 (36%), Shotgun/impalement—19/16 (1%). Mean RTS 1.75, mean ISS 27 ± 23. Overall survival 675 (33%). 830 patients (41%) underwent ED thoracotomy, 47 survived (6%). Survival stratified by mechanism: GSWs 114/1264 (10%), SWs 564/717 (76%). Predictors of outcome for mortality—univariate analysis: vital signs, RTS, ISS, GCS: Field CPR, ED intubation, ED thoracotomy and aortic cross-clamping (p < 0.001). Stepwise logistic regression identified cardiac GSW's (p < 0.001; AOR 26.85; 95% CI 17.21–41.89), field CPR (p = 0.003; AOR 3.65; 95% CI 1.53–8.69), the absence of spontaneous ventilation (p = 0.008; AOR 1.08, 95% CI 1.02–1.14), the presence of an associated abdominal GSW (p = 0.009; AOR 2.58, 95% CI 1.26–5.26) need for ED airway (p = 0.0003 AOR 1386.30; 95% CI 126.0–15251.71) and aortic cross-clamping (p = 0.0003 AOR 0.18; 95% CI 0.11–0.28) as independent predictors for mortality. Overall predictive power of model—93%.
Predictors of outcome were identified. Overall survival rates are lower than prospective studies report. Predictive model from NTDB generated larger number of strong independent predictors of outcomes, correlated and validated previous predictive models.
Rugby league is a collision team sport played at junior and senior levels worldwide, whereby players require highly developed anthropometric and physical qualities (i.e. speed, change-of-direction speed, aerobic capacity, muscular strength and power). Within junior levels, professional clubs and national governing bodies implement talent identification and development programmes to support the development of youth (i.e. 13–20 years) rugby league players into professional athletes. This review presents and critically appraises the anthropometric and physical qualities of elite male youth rugby league players aged between 13 and 20 years, by age category, playing standard and playing position. Height, body mass, body composition, linear speed, change-of-direction speed, aerobic capacity, muscular strength and power characteristics are presented and demonstrate that qualities develop with age and differentiate between playing standard and playing position. This highlights the importance of anthropometric and physical qualities for the identification and development of youth rugby league players. However, factors such as maturity status, variability in development, longitudinal monitoring and career attainment should be considered to help understand, identify and develop the physical qualities of youth players. Further extensive research is required into the anthropometric and physical qualities of youth rugby league players, specifically considering national standardised testing batteries, links between physical qualities and match performance, together with intervention studies, to inform the physical development of youth rugby league players for talent identification and development purposes.
Valbenazine (Ingrezza™) is an orally bioavailable, selective, vesicular monoamine transporter 2 (VMAT2) inhibitor being developed by Neurocrine Biosciences for the treatment of various central nervous system disorders. Valbenazine has been approved in the USA for the treatment of adults with tardive dyskinesia (TD), is at various stages of development in other countries for TD and is in phase 2 development in the USA for Tourette syndrome. This article summarizes the milestones in the development of valbenazine leading to its first global approval in the USA for the treatment of adults with TD.
This study compares the diagnostic performance of a second generation anti-cyclic citrullinated peptide antibody (CCP2) with a third generation anti-CCP antibodies assay (CCP3), as well as the combination of both tests. Serum samples of 127 patients were analyzed. IgG anti-CCP 2 and IgM rheumatoid factor were determined by EliA™ technique on a Phadia 250 instrument (Thermo Fisher Scientific), anti-CCP3 by the Quanta Flash™ anti-CCP3 IgG kit, BIO-FLASH Rapid Response Chemiluminscence Analyzer (INOVA Diagnostics). Diagnostic performance was compared using ROC-curves, sensitivity, specificity, likelihood ratios, and predictive values. Logistic regressions were used to investigate whether using both tests (anti-CCP2 and anti-CCP3) gives a better prediction of rheumatoid arthritis. At the manufacturer's cut-offs sensitivity and specificity were 79.4 and 61.0% for CCP3 and 80.9 and 69.5% for CCP2. No significant differences could be observed regarding the areas under the curve (AUC) of both ROC-curves. The optimal cut-off point for CCP2 was 10.5 U/ml (sensitivity of 75.0% and specificity of 80.0%) and 5.6 U/ml for CCP3 (sensitivity of 86.9% and specificity of 61.0%). Binary logistic regressions indicated that the likelihood of having rheumatoid arthritis (RA) is significantly higher when testing positive on both CCP2 and CCP3 compared to CCP2 or CCP3 alone. In our cohort, comparable performance was found between the two CCP assays. Positivity for both CCP2 and CCP3 resulted in the most specific identification of RA patients. In patients with joint complaints suspected of having RA and with a weakly positive CCP 2 (≥7 and ≤16 U/ml) CCP3 testing could be of additive value for diagnosing RA.
To investigate coronal plane trunk asymmetry (TA) and its association with sagittal postural alignment in healthy subjects before pubertal peak growth.
In this cross-sectional baseline study, 1190 healthy pre-peak growth velocity subjects were included. Coronal plane TA was evaluated using back surface topography. Whole-body sagittal alignment (previously validated and objectively classified as neutral, sway-back or leaning-forward) and sagittal spinopelvic profile (trunk lean, lumbar lordosis, thoracic kyphosis, sacral inclination and length of the posteriorly inclined thoracolumbar segment) were determined, as were height, proportion of trunk to body length, body mass index, generalized joint laxity, and handedness.
Logistic regression analysis yielded overall sagittal posture class to be independently associated with coronal plane TA: having a leaning-forward posture associated with a nearly three times higher odds of coronal TA (p < 0.001) compared to neutrals. A sway-back was 2.2 times more likely to show TA (p = 0.016) than a neutral, yet only in boys. Significant associations with coronal TA were also found for trunk lean, thoracic kyphosis and body mass index. These correlations, however, were gender and posture class specific. The spinal region where asymmetry is seen, varies according to the whole-body sagittal alignment type: primary thoracic curves were the most frequent in leaning-forwards, whereas primary curves in the lumbar or declive thoracolumbar segment were the most common in sway-backs.
In immature spines without known scoliosis, coronal plane TA is associated with whole-body sagittal alignment. It is more often seen in non-neutral than neutral sagittal posture types. Whether adolescent idiopathic scoliosis is related with postural characteristics before pubertal growth peak, should be addressed in future prospective studies.
Giardia is a prevalent intestinal parasitic infection. The trophozoite structural protein a1-giardin (a1-g) and the cyst protein cyst wall protein 2 (CWP2) have shown promise as Giardia vaccine antigen candidates in murine models. The present study assesses the genetic diversity of a1-g and CWP2 between and within assemblages A and B in human clinical isolates. a1-g and CWP2 sequences were acquired from 15 Norwegian isolates by PCR amplification and 20 sequences from German cultured isolates by whole genome sequencing. Sequences were aligned to reference genomes from assemblage A2 and B to identify genetic variance. Genetic diversity was found between assemblage A and B reference sequences for both a1-g (90.8% nucleotide identity) and CWP2 (82.5% nucleotide identity). However, for a1-g, this translated into only 3 amino acid (aa) substitutions, while for CWP2 there were 41 aa substitutions, and also one aa deletion. Genetic diversity within assemblage B was larger; nucleotide identity 92.0% for a1-g and 94.3% for CWP2, than within assemblage A (nucleotide identity 99.0% for a1-g and 99.7% for CWP2). For CWP2, the diversity on both nucleotide and protein level was higher in the C-terminal end. Predicted antigenic epitopes were not affected for a1-g, but partially for CWP2. Despite genetic diversity in a1-g, we found aa sequence, characteristics, and antigenicity to be well preserved. CWP2 showed more aa variance and potential antigenic differences. Several CWP2 antigens might be necessary in a future Giardia vaccine to provide cross protection against both Giardia assemblages infecting humans.
As one of the most common mental disorders and the most important precursor of suicide in Alzheimer's disease (AD), depression is associated with a decline in both well-being and daily functioning. At present, the diagnosis of AD patients with depression (D-AD) is largely dependent on clinical signs and symptoms, and the precise neural correlate underlying D-AD is still not fully understood.
The current study sought to investigate low-frequency oscillations at the voxel level in D-AD patients based on the amplitude of low-frequency fluctuations (ALFF) measured using resting-state functional magnetic resonance imaging. We examined 22 D-AD patients and 21 non-depressed AD (nD-AD) patients.
The results revealed that D-AD patients exhibited increased ALFF values in the left caudate and thalamus and decreased ALFF values in the left middle temporal pole compared with nD-AD patients.
These findings may provide further insight into the underlying neuropathophysiology of AD with depression.
This paper aims to evaluate a new iterative metal artifact reduction algorithm for post-interventional evaluation of brain tissue and intracranial arteries.
The data of 20 patients that underwent follow-up cranial CT and cranial CT angiography after clipping or coiling of an intracranial aneurysm was retrospectively analyzed. After the images were processed using a novel iterative metal artifact reduction algorithm, images with and without metal artifact reduction were qualitatively evaluated by two readers, using a five-point Likert scale. Moreover, artifact strength was quantitatively assessed in terms of CT attenuation and standard deviation alterations.
The qualitative analysis yielded a significant increase in image quality (p = 0.0057) in iteratively processed images with substantial inter-observer agreement (ĸ = 0.72), while the CTA image quality did not differ (p = 0.864) and even showed vessel contrast reduction in six cases (30%). The mean relative attenuation difference was 27% without metal artifact reduction vs. 11% for iterative metal artifact reduction images (p = 0.0003).
The new iterative metal artifact reduction algorithm enhances non-enhanced CT image quality after clipping or coiling, but in CT-angiography images, the contrast of adjacent vessels can be compromised.
Recently, multiple randomised controlled trials showed efficacy of endovascular treatment over traditional care in patients with acute ischemic stroke due to an intracranial anterior circulation occlusion. Internal carotid artery (ICA) dissection with a concomitant intracranial occlusion is a rare but important cause of severe acute ischemic stroke. Although this subtype of acute ischemic stroke is mostly treated with endovascular treatment, treatment outcomes are still sparsely studied. This study assesses the clinical outcome and reperfusion rates by means of a systematic review.
Electronic databases of PubMed, EMBASE and Web of Science were searched up to October 1, 2016 for articles describing endovascular treatment in patients with intracranial artery occlusion and ICA dissection.
Sixteen studies were included in the analysis. Most studies showed favourable outcome and successful reperfusion. However, most included studies had a high risk of bias.
In the reviewed studies, endovascular treatment in patients with ICA dissection and concomitant proximal intracranial occlusion was associated with favourable outcome. This could point in the direction of endovascular treatment being a beneficial treatment method for these patients. However, this review has only taken data of a limited group of patients into account. A pooled analysis of patients from recently published endovascular treatment trials and running registries is therefore recommended.
The aim of this study is to study the age, gender and lateral asymmetry-related white matter changes of long association tracts throughout late childhood and adolescence into adulthood using diffusion tensor tractography (DTT).
DTT was performed in 44 healthy subjects aged 7–45 years. Fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), Trace, density and volume were calculated for long association tracts, namely the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), uncinate fasciculus, superior longitudinal fasciculus (SLF) and its arcuate fibres. FA and diffusivity indices were correlated as function of age using Pearson correlation test. Comparison between males and females, and comparison between both hemispheres among all participants were also performed. A p value less than .01 was considered significant.
The majority of the examined tracts (SLF and IFOF of both hemispheres, and the arcuate fasciculus, uncinate fasciculus, and ILF of the left hemisphere) followed a common pattern of metric changes with age. This pattern was characterized by significant FA increase accompanied by reduction in RD, Trace without significant AD changes. The right arcuate fasciculus showed similar pattern but without significant FA changes. The right uncinate and right ILF fasciculus demonstrated significant reduction in RD, Trace and AD, with and without significant FA increase, respectively. Left hemispheric dominance regarding the FA and diffusivity indices was demonstrated in uncinate fasciculus with no significant gender-related differences.
Significant microstructural tract-specific maturation processes continue throughout late childhood into adulthood. These processes may represent stages in a cascade of age-related maturation in white matter microstructure.
Blood–brain barrier (BBB) damage aggravates perihematomal edema, and edema volume predicts prognosis independently. But the BBB permeability at the late stage of acute intracerebral hemorrhage (ICH) patients is uncertain. We aimed to assess the BBB permeability of spontaneous basal ganglia ICH using computed tomographic perfusion (CTP) and investigates its relationship with hematoma and perihematomal edema volume.
We performed CTP on 54 consecutive ICH patients within 24 to 72 h after symptom onset. Permeability-surface area product (PS) derived from CTP imaging was measured in hematoma, "high-PS spot," perihematoma, normal-appearing, hemispheric, and contralateral regions. Hematoma and edema volumes were calculated from non-contrast CT.
"High-PS spot" and perihematoma regions had higher PS than the contralateral regions (p < 0.001). Hematoma PS was lower than that in the contralateral regions (p < 0.001). Perihematoma PS of the large-hematoma group was higher than that of the small-hematoma group (p = 0.011). Perihematomal edema volume correlated positively with hematoma volume (β = 0.864, p < 0.001) and perihematoma PS (β = 0.478, p < 0.001). Perihematoma PS correlated positively with hematoma volume (β = 0.373, p = 0.005).
Locally elevated perihematoma PS was found in most spontaneous basal ganglia ICH patients within 24 to 72 h after symptom onset. Perihematoma PS was higher in larger hematomas and was associated with larger edema volume. At this period, BBB leakage is likely to be an important factor in edema formation.
In this study, a hydrothermal method was successfully used to prepare a reduced graphene oxide (RG)–titanium dioxide (TiO2) hybrid in 10–20 nm, starting from commercial TiO2 P25 nanoparticles and liquid-exfoliated graphene oxide (GO). Compared to TiO2, an obvious red shift of light absorption (from 3.1 to 2.6 eV) of the as-prepared RG–TiO2 was observed by UV–Vis analysis, and an enhanced photocatalytic degradation of the Rhodamine B (Rh. B) was also observed under Xe lamp exposure test by using the as-prepared RG–TiO2. Multiple characterizations of this RG–TiO2 nanocomposite confirmed that its photocatalytic enhancement could be ascribed to two approaches. Firstly, RG extended the mean free path and photogenerated electrons' lifetime of TiO2, which minimized electron–hole pairs' recombination. Secondly, RG expanded the light absorption spectrum of TiO2 from UV range to UV and visible light range. The explication of these improvements was concluded as the energy gap changing and a likelihood of up-conversion photoluminescence mechanism (UCPL). Due to the low-cost, nonpoisonous and excellent photocatalytic properties of RG–TiO2, this material can be applied well in sewage treatment and other related fields.
Graphical abstract
Non-occlusive mesenteric ischemia (NOMI) is a devastating complication after cardiac surgery. Once patients develop NOMI, intra-mesenteric infusion of vasodilators and/or emergent laparotomy is usually required, but the mortality is extraordinarily high even with intensive treatment. We present a case of salvage of a patient with NOMI complicated with severe right ventricular dysfunction after left ventricular assist device (LVAD) implantation using maximum treatment with emergent laparotomy and temporary right ventricular assist device implantation. To the best of our knowledge, this is the first successful salvage case of NOMI in a LVAD patient. We believe that hemodynamic optimization using maximum treatment is critically important to achieve salvage.
We performed a meta-analysis to evaluate the femoral neck and lumbar spine bone mineral density (BMD) in adults with type 1 diabetes (T1D) compared with controls. Adults with T1D have modestly lower BMD at femoral neck and lumbar spine than adults without diabetes.
Fracture risk is four to sixfold higher in adults with T1D. Since BMD is one of the major contributors for fracture risk, we performed a meta-analysis to evaluate differences in femoral neck and lumbar spine BMD between adults with T1D and controls.
MEDLINE, Ovid, and the Cochrane library and abstracts from various scientific meetings were searched. Studies reporting the femoral neck and/or lumbar spine BMD in adults (age > 20 years) with T1D in comparison with people without diabetes were selected. General linear mixed models were used to assess differences in BMD at femoral neck and lumbar spine between subjects with T1D and controls adjusting for age, sex, and dual x-ray absorptiometry (DXA) instruments.
Sixteen studies met the inclusion criteria. The femoral neck BMD was modestly lower in adults with T1D compared to controls (−0.055 g/cm2; 95% CI: −0.065, −0.045). There were no differences in lumbar spine BMD between adults with T1D and controls (0.0062 g/cm2; 95% CI −0.04, 0.016). However, in a sensitivity analysis, lumbar spine BMD was modestly lower in adults with T1D compared to controls (−0.035 g/cm2; −0.049, −0.02). Studies using Lunar DXA instruments have reported higher lumbar spine and femoral neck BMD compared to studies using Hologic DXA instruments.
Femoral neck and lumbar spine BMD were modestly lower in adults with T1D compared to controls. However, this modest reduction in femoral neck and lumbar spine BMD cannot explain much higher observed fracture risk in adults with T1D.
This study compares the diagnostic performance of a second generation anti-cyclic citrullinated peptide antibody (CCP2) with a third generation anti-CCP antibodies assay (CCP3), as well as the combination of both tests. Serum samples of 127 patients were analyzed. IgG anti-CCP 2 and IgM rheumatoid factor were determined by EliA™ technique on a Phadia 250 instrument (Thermo Fisher Scientific), anti-CCP3 by the Quanta Flash™ anti-CCP3 IgG kit, BIO-FLASH Rapid Response Chemiluminscence Analyzer (INOVA Diagnostics). Diagnostic performance was compared using ROC-curves, sensitivity, specificity, likelihood ratios, and predictive values. Logistic regressions were used to investigate whether using both tests (anti-CCP2 and anti-CCP3) gives a better prediction of rheumatoid arthritis. At the manufacturer's cut-offs sensitivity and specificity were 79.4 and 61.0% for CCP3 and 80.9 and 69.5% for CCP2. No significant differences could be observed regarding the areas under the curve (AUC) of both ROC-curves. The optimal cut-off point for CCP2 was 10.5 U/ml (sensitivity of 75.0% and specificity of 80.0%) and 5.6 U/ml for CCP3 (sensitivity of 86.9% and specificity of 61.0%). Binary logistic regressions indicated that the likelihood of having rheumatoid arthritis (RA) is significantly higher when testing positive on both CCP2 and CCP3 compared to CCP2 or CCP3 alone. In our cohort, comparable performance was found between the two CCP assays. Positivity for both CCP2 and CCP3 resulted in the most specific identification of RA patients. In patients with joint complaints suspected of having RA and with a weakly positive CCP 2 (≥7 and ≤16 U/ml) CCP3 testing could be of additive value for diagnosing RA.
Recent studies show that the frequencies of circulating follicullar helper T (cTfh) cells are significantly higher in myasthenia gravis (MG) patients compared with healthy controls (HC). And, they are positively correlated with levels of serum anti-acetylcholine receptor antibody (anti-AchR Ab). It is unclear whether cTfh cell subset frequencies are altered and what role they play in MG patients. In order to clarify this, we examined the frequencies of cTfh cell counterparts, their subsets, and circulating plasmablasts in MG patients by flow cytometry. We determined the concentrations of serum anti-AChR Ab by enzyme-linked immunosorbent assay (ELISA). We assayed the function of cTfh cell subsets by flow cytometry and real-time polymerase chain reaction (RT-PCR). We found higher frequencies of cTfh cell counterparts, cTfh-Th17 cells, and plasmablasts in MG patients compared with HC. The frequencies of cTfh cell counterparts and cTfh-Th17 cells were positively correlated with the frequencies of plasmablasts and the concentrations of anti-AChR Ab in MG patients. Functional assays showed that activated cTfh-Th17 cells highly expressed key molecular features of Tfh cells including ICOS, PD-1, and IL-21. Results indicate that, just like cTfh cell counterparts, cTfh-Th17 cells may play a role in the immunopathogenesis and the production of anti-AChR Ab of MG.
It is well described that patients with pulmonary arteriovenous malformations (PAVMs) and Hereditary Hemorrhagic Telangiectasia (HHT) have an increased risk of cerebral abscess (CA). However, as both CA and HHT are rare, the proportion of patients with CA who are diagnosed with HHT has not been previously described. A retrospective study was carried out of all patients treated surgically for CA between January 1995 and September 2014 at the Department of Neurosurgery, Odense University Hospital. The cases were then cross-referenced with the Danish HHT database. Eighty patients aged 5–79 years were included. The incidence of CA was 0.33/100,000/year. Two patients (2.5%) were registered as having HHT. Bacterial pathogens were identified in 70% of all cases, most frequently streptococci species (46.3%). The most common predisposing condition was odontogenic infection (20%), followed by post-operative infection (13.8%) and post-trauma (6.3%). Patients undergoing a full diagnostic program to determine predisposing conditions causing CA increased over the 20-year period from 11.8% to 65.2%. The 3-month and 1-year mortality rates were 7.5% and 11.25%, respectively. There is an overrepresentation of HHT patients in a cohort of patients with CA, and HHT should be investigated as the cause of the CA if no other apparent cause can be identified.
Prasugrel, a P2Y12 adenosine diphosphate (ADP) receptor antagonist, inhibits ADP-mediated platelet activation and aggregation in patients with sickle cell anemia (SCA). We developed a population pharmacokinetic (popPK) model in pediatric patients from 2 to <18 years of age with SCA, and performed exposure–response evaluations to characterize the effects of prasugrel in a subset of these patients who weighed 19 kg or more and experienced at least two episodes of vaso-occlusive crises (VOC) in the past year.
A three-compartment popPK model adapted from that used in adults with acute coronary syndrome was used to describe the relationship between plasma concentrations of prasugrel's active metabolite (Pras-AM) and time using data from phase II and III clinical studies in children. A VOC event rate model was developed from the phase III study to explore the exposure–response relationship between Pras-AM exposure and VOC, and included evaluation of covariates.
The final popPK model for children with SCA provided a reasonable fit to Pras-AM plasma concentrations over time, with estimates of apparent clearance (CL/F) (172 L/h) and apparent volume of distribution (Vd/F) (51.7 L) that were comparable to previous studies in adults. The final model included weight as a covariate on both CL/F and Vd/F, and age as a covariate on CL/F. Analyses of safety (bleeding events requiring medical intervention) and efficacy (VOC event rate) variables showed no apparent relationship to model-predicted Pras-AM exposure quartiles, and no statistically significant effects of intrinsic or extrinsic factors on the VOC event rate were identified in the VOC event rate model. The effect of post hoc exposures on the VOC event rate did not reach statistical significance.
A popPK model was developed that provided reasonable parameter estimates, goodness-of-fit diagnostics, and visual predictive checks when applied to Pras-AM plasma concentrations in pediatric patients with SCA. Post hoc exposures obtained from this model did not correlate with measures of VOC or bleeding events in this population.
In this work, the β-galactosidase from Enterobacter cloacae B5 (BgaB5) exhibited excellent transglycosylation activity toward tyrosol (p-hydroxyphenethyl alcohol) when using lactose as the glycosyl donor, generating a series of tyrosol glycosides with potential pharmacological properties. The effects of substrate concentration, temperature, pH, and reaction time on the transglycosylation reaction catalyzed by the enzyme BgaB5 were studied in detail. Three tyrosol derivatives were produced in a total high yield of 50.0% when incubating the enzyme with 250 mM tyrosol and 1000 mM lactose (pH 7.5) at 50 °C for 5 min. These derivatives were subsequently purified by column chromatography and preparative thin-layer chromatography. MS analysis of the purified compounds suggested one monogalactoside (M r 300) and two digalactoside derivatives (M r 462). The following NMR analysis further identified them to be p-hydroxyphenethyl β-D-galactopyranoside, p-hydroxyphenethyl β-D- galactopyranosyl-(1 → 3′)-β-D-galactopyranoside, and p-hydroxyphenethyl β-D- galactopyranosyl-(1 → 6′)-β-D-galactopyranoside, respectively. The yield of the tyrosol monogalactoside which was known to possess potent bioactivities reached 39.4%, higher than other enzymatic yields reported so far. The two digalactosides, which were expected to have potential applications for novel drug screening and discovery, were artificially obtained with 10.6% yield for the first time.
Laryngeal squamous cell carcinoma (LSCC), one of the most common malignancies in the head and neck, has poor prognosis and high mortality. The need of novel and effective treatment for LSCC is urgent. Asparaginase, an enzyme-depriving asparagine, has been employed for the treatment of various cancers. In this study, we reported for the first time that asparaginase could induce remarkable cytotoxicity and caspase-dependent apoptosis in human LSCC Tu212 and Tu686 cells. Meanwhile, autophagy was triggered by asparaginase in LSCC cells, which was confirmed by accumulation of autophagosomes and the conversion of light chain 3-I (LC3-I) to LC3-II. Importantly, inhibition of autophagy by chloroquine (CQ) significantly enhanced asparaginase-induced cytotoxicity, indicating that autophagy has a cytoprotective role in asparaginase-treated LSCC cells. Meanwhile, we found that mitochondrial-originated reactive oxygen species (ROS) participated in asparaginase-induced autophagy and cytotoxicity. N-acetyl-L-cysteine (NAC), a common antioxidant, was employed to scavenge ROS, and our results demonstrated that NAC could significantly block asparaginase-induced autophagy and attenuate asparaginase-induced cytotoxicity, indicating that intracellular ROS played a crucial role in asparagine deprivation therapy. Furthermore, western blot analysis showed that asparaginase-induced autophagy was mediated by inactivation of Akt/mTOR and activation of the Erk signaling pathway in Tu212 and Tu686 cells. Therefore, these results indicated the protective role of autophagy in asparaginase-treated LSCC cells and provided a new attractive therapeutic strategy for LSCC by asparaginase alone or in combination with autophagic inhibitors.
The surfactant sodium lauryl ether sulfate (SLES) is widely used in the composition of detergents and frequently ends up in wastewater treatment plants (WWTPs). While aerobic SLES degradation is well studied, little is known about the fate of this compound in anoxic environments, such as denitrification tanks of WWTPs, nor about the bacteria involved in the anoxic biodegradation. Here, we used SLES as sole carbon and energy source, at concentrations ranging from 50 to 1000 mg L−1, to enrich and isolate nitrate-reducing bacteria from activated sludge of a WWTP with the anaerobic-anoxic-oxic (A2/O) concept. In the 50 mg L−1 enrichment, Comamonas (50%), Pseudomonas (24%), and Alicycliphilus (12%) were present at higher relative abundance, while Pseudomonas (53%) became dominant in the 1000 mg L−1 enrichment. Aeromonas hydrophila strain S7, Pseudomonas stutzeri strain S8, and Pseudomonas nitroreducens strain S11 were isolated from the enriched cultures. Under denitrifying conditions, strains S8 and S11 degraded 500 mg L−1 SLES in less than 1 day, while strain S7 required more than 6 days. Strains S8 and S11 also showed a remarkable resistance to SLES, being able to grow and reduce nitrate with SLES concentrations up to 40 g L−1. Strain S11 turned out to be the best anoxic SLES degrader, degrading up to 41% of 500 mg L−1. The comparison between SLES anoxic and oxic degradation by strain S11 revealed differences in SLES cleavage, degradation, and sulfate accumulation; both ester and ether cleavage were probably employed in SLES anoxic degradation by strain S11.
Skull radiography (SR) and Computed Tomography (CT) are still proposed as the first-line imaging choice for the diagnosis of craniosynostosis (CS) in children with abnormal head shape, but both techniques expose infants to ionizing radiation. Several studies shown that ultrasound may play an important role in the diagnosis of craniosynostosis. The aim of our study is to assess the diagnostic accuracy of cranial ultrasound scan (CUS) and confirm if it is a reliable first step imaging evaluation for the diagnosis of craniosynostosis in newborn.
A cohort of 196 infants (122/74 males/females), with a mean age of 4 months, clinically suspected to have abnormal closure of cranial sutures, were firstly examined by CUS and then referred to neuroradiologists to perform volumetric CT scan if the suspicion of stenosis was ecographically confirmed; otherwise, a routine follow-up and physical treatment was performed, to observe the evolution of the head shape.
Of the 196 children studied by CUS, only two had inconclusive studies due to age limitation (>12 months). Thirty children were diagnosed with cranial synostosis at CUS and verified by CT; all the CUS results were confirmed, except two cases, that were revealed as false positives in the starting phase of the study. Twelve patients with very prominent head deformity and negative CUS underwent CT, which confirmed the CUS results in all of them; one case of closure of both temporal sutures, not studied by CUS, was documented by CT. All the 148 children with poor clinical suspicion and negative CUS underwent just a prolonged clinical follow-up. In all of them, a progressive normalization of head shape was observed, and the craniosynostosis was excluded on a clinical base.
CUS is a highly specific and sensitive imaging technique. In referral centers, expert hands can use it as a reliable first-step screening for infants younger than 1 year, suspected to have a craniosynostosis, thus avoiding unnecessary exposure to ionizing radiation. The "golden age" to obtain the best CUS results is under 6 months of life. Because the method is operator-dependent and there is a learning curve, a case centralization is advisable.
Colloid cysts are the most common pathologic lesions of the third ventricle. Although they are histologically benign, they may grow and can cause the hydrocephalus.
A 5-year-old male patient underwent to surgery with the diagnosis of colloid cyst. In operation, after the anterior transcallosal approach, the cyst was punctured by syringe and obviously pus aspirated.
Colloid cysts mostly remain silent and detected incidentally. Although it is rarely defined, rhinorrhea, hypopituitarism, diabetes insipidus, spasmodic torticollis, drop attack, aseptic meningitis, and coexistence with neurocysticercosis have been reported, but this is the first reported case of an infected colloid cyst.
Phase II monitoring with intracranial electroencephalography (ICEEG) occasionally requires bilateral placement of subdural (SD) strips, grids, and/or depth electrodes. While phase I monitoring often demonstrates a preponderance of unilateral findings, individual studies (video EEG, single photon emission computed tomography [SPECT], and positron emission tomography [PET]) can suggest or fail to exclude a contralateral epileptogenic onset zone. This study describes previously unreported techniques of trans-falcine and sub-frontal insertion of contralateral SD grids and depth electrodes for phase II monitoring in pediatric epilepsy surgery patients when concern about bilateral abnormalities has been elicited during phase I monitoring.
Pediatric patients with medically refractory epilepsy undergoing stage I surgery for phase II monitoring involving sub-frontal and/or trans-falcine insertion of SD grids and/or depth electrodes at the senior author's institution were retrospectively reviewed. Intra-operative technical details of sub-frontal and trans-falcine approaches were studied, while intra-operative complications or events were noted. Operative techniques included gentle subfrontal retraction and elevation of the olfactory tracts (while preserving the relationship between the olfactory bulb and cribriform plate) to insert SD grids across the midline for coverage of the contralateral orbito-frontal regions. Trans-falcine approaches involved accessing the inter-hemispheric space, bipolar cauterization of the anterior falx cerebri below the superior sagittal sinus, and sharp dissection using a blunt elevator and small blade scalpel. The falcine window allowed contralateral SD strip, grid, and depth electrodes to be inserted for coverage of the contralateral frontal regions.
The study cohort included seven patients undergoing sub-frontal and/or trans-falcine insertion of contralateral SD strip, grid, and/or depth electrodes from February 2012 through June 2015. Five patients (71%) experienced no intra-operative events related to contralateral ICEEG electrode insertion. Intra-operative events of frontal territory venous engorgement (1/7, 14%) due to sacrifice of anterior bridging veins draining into the SSS and avulsion of a contralateral bridging vein (1/7, 14%), probably due to prior anterior corpus callosotomy, each occurred in one patient. There were no intra-operative or peri-operative complications in any of the patients studied. Two patients required additional surgery for supplemental SD strip and/or depth electrodes via burr hole craniectomy to enhance phase II monitoring. All patients proceeded to stage II surgery for resection of ipsilateral epileptogenic onset zones without adverse events.
Trans-falcine and sub-frontal insertion of contralateral SD strip, grid, and depth electrodes are previously unreported techniques for achieving bilateral frontal coverage in phase II monitoring in pediatric epilepsy surgery. This technique obviates the need for contralateral craniotomy and parenchymal exposure with limited, remediable risks. Larger case series using the method described herein are now necessary.
Congenital thrombophilia is associated with an increased intraventricular hemorrhage (IVH) risk among newborns, but it may also play a protective role. The role of genetic polymorphisms involved in the coagulation pathway of IVH pathogenesis is probably a consequence of an increased risk of thrombosis in the fine blood vessels in the germinal matrix region.
The aim of this study was to evaluate the possible relationship between Factor V (FV) 1691G>A, Factor II (FII) 20210G>A mutations and methylenetetrahydrofolate reductase (MTHFR) 677C>T; 1298A>C and Factor XIII (FXIII) 103G>T gene polymorphisms and the occurrence of IVH in 100 infants born from 24 + 0 to 32 + 0 weeks of gestation, born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroid therapy, and without congenital abnormalities.
IVH developed 45 (45%) infants, including 15 (33.33%) diagnosed with IVH stage I, 20 (42.22%) with stage II, 8 (17.77%) with stage III, and 3 (6.66%) with stage IV. Analysis showed a prevalence 4.5 times higher of IVH stages II to IV in infants with the genotype CC (OR 4511 (1147–17.75); p = 0.026) of MTHFR 1298A>C gene polymorphism. Our investigation did not confirm any significant prevalence of IVH development in other studied mutations/polymorphisms.
This study confirmed that the MTHFR 1298A>C polymorphism is associated with the risk of IVH. IVH is a significant problem for preterm infants. In addition to little progress in preventing IVH in preterm babies, substantial research that is focused on understanding the etiology, mechanism, and risk factors for IVH is imperative. In the era of personalized medicine, identification of genetic risk factors creates opportunities to generate preventative strategies.
A novel lipase gene lip256 was cloned and identified from the genomic library of hot spring strain Bacillus sp. HT19. The deduced amino acid sequence of lip256 has less than 32% identity to a predicted esterase (Cog1752) from Photobacterium leiognathi lrivu.4.1 and contains a novel motif (GTSAG) that differs from other clusters in the lipase superfamily. Following purification, a single band was obtained with a molecular mass of 33 kDa by SDS-PAGE, and the optimal temperature and pH for lipolytic activity of Lip25 were 70 °C and 9.0, respectively. Lip256 exhibited high activity at high temperatures, with 40% maximum activity at 80 °C and good stability at temperatures ranges between 50 and 80 °C. Additionally, the enzyme was highly stable in the presence of butyl-alcohol, glycerol, acetonitrile, pyridine, and urea. However, the presence of acetone, methanol, trichloromethane, petroleum ether, hexane, tert-butanol, isopropanol, dithiothreitol, ethylenediaminetetraacetic acid, polyhexamethylene biguanide, dimethyl sulfoxide, benzene, Triton X-100, Tween-20, Tween-80, and sodium dodecyl sulfate suppressed or absolutely inhibited enzyme activity. Furthermore, Ca2+, Mg2+, and Cu2+ suppressed enzyme activity, whereas Na+, Fe3+, K+, Fe2+, and Sr2+ enhanced enzyme activity. The unique characteristics of novel lipase Lip256, including its thermo-alkaliphilic performance, high tolerance toward metal ions, inhibitors, and detergents, and high stability in organic solvents, implied that this enzyme might be an interesting candidate for industrial processes.
Edible brown algae have attracted interest as a source of beneficial allenic carotenoid fucoxanthin, and glyco- and phospholipids enriched in polyunsaturated fatty acids. Unlike green algae, brown algae contain no or little phosphatidylserine, possessing an unusual aminophospholipid, phosphatidyl-O-[N-(2-hydroxyethyl) glycine], PHEG, instead. When our routinely used technique of 31P-NMR analysis of phospholipids was applied to the samples of edible New Zealand brown algae, a number of signals corresponding to unidentified phosphorus-containing compounds were observed in total lipids. NI (negative ion) ESI QToF MS spectra confirmed the presence of more familiar phospholipids, and also suggested the presence of PHEG or its isomers. The structure of PHEG was confirmed by comparison with a synthetic standard. An unusual MS fragmentation pattern that was also observed prompted us to synthesise a number of possible candidates, and was found to follow that of phosphatidylhydroxyethyl methylcarbamate, likely an extraction artefact. An unexpected outcome was the finding of ceramidephosphoinositol that has not been reported previously as occurring in brown algae. An uncommon arsenic-containing phospholipid has also been observed and quantified, and its TLC behaviour studied, along with that of the newly synthesised lipids.
Patients with chronic kidney disease (CKD) have an increased risk of comorbid conditions, including cardiovascular disease (CVD). Anemia is prevalent in the CKD population and worsens as kidney function declines, resulting in a diminished quality of life and increased morbidity/mortality. The purpose of this secondary analysis was to determine the real-world prevalence of CVD among patients with non-dialysis-dependent CKD (NDD-CKD), with and without comorbid anemia, and to assess the impact of these conditions on quality of life (QoL) and work productivity.
Data were drawn from the Adelphi CKD Disease-Specific Programme, conducted in France, Germany, Italy, Spain, and the UK (2012). Anonymized data were collected via patient record forms and patient-completed questionnaires. Patient data were stratified by anemic status and the presence of CVD comorbidity.
Data were collected by physicians for 1993 patients, of whom 867 completed a patient-completed questionnaire. A total of 61.4% of patients had anemia, and the prevalence of anemia increased with CKD stage. Patients with anemia had a higher mean number of cardiovascular comorbidities than non-anemic patients (1.27 vs 0.95, respectively; P < 0.001). The presence of cardiovascular conditions was associated with a significantly reduced QoL (EuroQol EQ-5D-3L visual analog scale: coefficient, −5.68 in anemic patients; P = 0.028) and work productivity and activity impairment (WPAI activity impairment: coefficient, +8.04 in anemic patients; P = 0.032), particularly among anemic patients.
The presence of anemia in this cohort of NDD-CKD patients was high. The presence of concomitant cardiovascular conditions was more common in NDD-CKD patients with comorbid anemia, and was associated with reduced QoL and work productivity outcomes.
Crizotinib is recommended as first-line therapy for ALK-positive non-small cell lung cancer (NSCLC), but within a year of treatment initiation many patients develop resistance. With the recent approval of second-generation ALK inhibitors, this study assessed how physicians monitor for and diagnose progression and how they alter treatment following progression on crizotinib.
A panel of oncologists from the United States were surveyed regarding their monitoring practices and criteria for diagnosing progression on crizotinib. The physicians also retrospectively provided data (March–June 2016) from the medical charts of their adult patients with locally advanced or metastatic ALK-positive NSCLC who progressed on crizotinib after the approval (April 2014) of the first second-generation ALK inhibitor, ceritinib.
A total of 28 physicians responded to the survey. Data was abstracted on 74 patients. In the physician survey, most physicians (71%) reported monitoring for radiographic progression every 3–4 months. When new lesions were detected, physician response varied. Following a symptomatic isolated lesion, most physicians (75%) would add local therapy and resume crizotinib. Following multiple symptomatic lesions, 96% and 64% of physicians would switch to a new therapy depending on whether the lesions were extracranial or isolated to the brain, respectively. For the patient cohort, physician-defined progression on crizotinib was diagnosed after a median of 10 months, and within 30 days of diagnosis, 86% of patients discontinued crizotinib. Among all patients who discontinued crizotinib, 77% switched to ceritinib, 14% to chemotherapy, and 1% to alectinib. The remaining 7% did not receive additional systemic antineoplastic therapy.
The findings from this physician survey and retrospective chart review study suggest that physician response to the development of new lesions in crizotinib-treated ALK-positive NSCLC patients varies with location and extent of the lesions. Once patients were considered to have progressed, most of them were immediately switched to ceritinib.
Novartis Pharmaceuticals Corporation.
Dopamine (DA) is a neurotransmitter in the central nervous system as well as in peripheral tissues. Emerging evidence however points to DA also as a key transmitter between the nervous system and the immune system as well as a mediator produced and released by immune cells themselves. Dopaminergic pathways have received so far extensive attention in the adaptive branch of the immune system, where they play a role in health and disease such as multiple sclerosis, rheumatoid arthritis, cancer, and Parkinson's disease. Comparatively little is known about DA and the innate immune response, although DA may affect innate immune system cells such as dendritic cells, macrophages, microglia, and neutrophils. The present review aims at providing a complete and exhaustive summary of currently available evidence about DA and innate immunity, and to become a reference for anyone potentially interested in the fields of immunology, neurosciences and pharmacology. A wide array of dopaminergic drugs is used in therapeutics for non-immune indications, such as Parkinson's disease, hyperprolactinemia, shock, hypertension, with a usually favorable therapeutic index, and they might be relatively easily repurposed for immune-mediated disease, thus leading to innovative treatments at low price, with benefit for patients as well as for the healthcare systems.
We report the effect of microwaves sintering on the crystal domain and electrical properties of TiO2 nanoparticles. Commercially available TiO2 nanoparticles of 25 nm size were coated on ITO (indium tin oxide) substrates, which were then sintered at 450 °C employing microwave and conventional sintering approaches. The structural properties of the sintered coatings were examined using atomic force microscopy (AFM), scanning electron microscope (SEM), X-ray diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDS), whereas the charge transfer properties were investigated using electrochemical impedance spectroscopy (EIS). Structural analysis reveals that the microwave sintering of TiO2-coated substrates results in the formation of more ordered crystal structure as compared to the conventionally sintered samples. Nyquist plots demonstrate the improved charge transfer characteristics of TiO2 nanoparticles in microwave-sintered layers. Also, the application of the microwave-sintered TiO2-coated ITO substrates as photoanode in dye-sensitized solar cells (DSSCs) confirms superior electrical properties compared to conventionally sintered samples.
