Integrating Exposure Assessment and Process Hazard Analysis: The Nano-Enabled 3D Printing Filament Extrusion Case.
Nanoparticles are being used in novel applications of the thermoplastics industry, including automotive parts, the sports industry and leisure and consumer goods, which can be produced nowadays through additive manufacturing. However, there is limited information on the health and safety aspects during the production of these new materials, mainly from recycled sources. This study covers the exposure assessment to nano- and micro-size particles emitted from the nanocomposites during the production of filaments for 3D printing through a compounding and extrusion pilot line using recycled (post-industrial) thermoplastic polyurethane (TPU) and recycled polyamide 12 (PA12), which have been also upcycled through reinforcement with iron oxide nanoparticles (Fe3O4 NPs), introducing matrix healing properties triggered by induction heating. The assessment protocol included near- and far-field measurements, considering the extruder as the primary emission source, and portable measuring devices for evaluating particulate emissions reaching the inhalable zone of the lab workers. A Failure Modes and Effects Analysis (FMEA) study for the extrusion process line was defined along with a Failure Tree Analysis (FTA) process in which the process deviations, their sources and the relations between them were documented. FTA allowed the identification of events that should take place in parallel (simultaneously) or in series for the failure modes to take place and the respective corrective actions to be proposed (additional to the existing control measures).


Splicing signals and factors in plant intron removal.
Constitutive splicing of the potato invertase mini-exon 2 (9 nt long) requires a branchpoint sequence positioned around 50 nt upstream of the 5' splice site of the adjacent intron and a U(11) element found just downstream of the branchpoint in the upstream intron [Simpson, Hedley, Watters, Clark, McQuade, Machray and Brown (2000) RNA 6, 422-433]. The sensitivity of this in vivo plant splicing system has been used to demonstrate exon scanning in plants, and to characterize plant intronic elements, such as branchpoint and poly-pyrimidine tract sequences. Plant introns differ from their vertebrate and yeast counterparts in being UA- or U-rich (up to 85% UA). One of the key differences in splicing between plants and other eukaryotes lies in early intron recognition, which is thought to be mediated by UA-binding proteins. We are adopting three approaches to studying the RNA-protein interactions in plant splicing. First, overexpression of plant splicing factors and, in particular, UA-binding proteins, in conjunction with a range of mini-exon mutants. Secondly, the sequences of around 65% of vertebrate and yeast splicing factors have high-quality matches to Arabidopsis proteins, opening the door to identification and analysis of gene knockouts. Finally, to discover plant-specific proteins involved in splicing and in, for example, rRNA or small nuclear RNA processing, green fluorescent protein-cDNA fusion libraries in viral vectors are being screened.


A new completely flexible ring for mitral valve annuloplasty: the "Rama-Valvuloplasty-Ring". Five-year Pitié Salpétrière experience.
The aim of this study was to analyze the effects about the use of a new completely flexible ring for mitral valve anuloplasty, the "Rama-Valvuloplasty-ring", in 182 patients operated on in the Pitié-Salpétrière Hospital, Paris, France for mitral valve regurgitation (MVR). From January 1998 to December 2003, 182 patients with mitral regurgitation (MR) underwent mitral reconstructive surgery at our institution with the "Rama-Valvuloplasty-Ring". This group was made up of 117 men (64.3%) and 65 women (35.7%). The age ranged from 19 to 87 years (mean 62.51 +/- 8.2 years). The patients surviving the operation were the subject of a prospective follow-up. In the preoperative stage sinus rhythm was found in 71.97% (131) of patients and atrial fibrillation in the remaining 28.03% (51) of patients. The mean NYHA FC was 2.9 +/- 1.7 and subdivided as follows: 65 patients in FC I-II (35.72%), 104 patients in FC III (57.14%) and 13 patients in FC IV (7.14%). Most of the patients have shown, in the preoperative echocardiogram, grade II M.R. (46.15% N. 84) and grade III M.R. (29.12%, N.53); 24.72% of the patients (N. 45) had grade IV M.R. The mean E.F. was 42.8 +/- 9.7%. Left ventricular end diastolic diameter (LVEDD) was 57.7 +/- 9.7 mm. The causes of mitral valve insufficiency were degenerative disease in 141 patients (77.47%), post-ischemic disease in 21 patients (11.53%), rheumatic valvular disease in 11 patients (6.05%) and infectious endocarditis in 9 patients (4.95%). All the patients were operated using the Rama-Valvuloplasty-Ring. Ring sizes most commonly used were 30 mm and 32 mm, respectively in 92 patients (50.55%) and 41 patients (22.54%), followed by 28 mm (43 patients, 23.62%), 34 mm (5 patients, 2.74%), 36 mm (1 patient, 0.55%). The surgical tecnique was valve quadrangular resection in 103 patients (56.60%), triangular resection in 57 patients (31.32%) and no valve resection in 22 patients (12.08%). Among the above, 89 patients (48.90%) underwent an associated intervention as follows: 44 patients (24.18%) underwent coronary revascularization: 18 patients (9.89%) with single by-pass surgery, 21 patients (11.54%) with double by-pass, 5 patients with triple by-pass (2.75%); 42 patients (23.07) underwent aortic valve replacement (AVR); 3 patients (1.65%) underwent aortic repair. Early postoperative mortality was 2.19% (4 of 182 patients). Early postoperative echocardiographic control showed MR grade 0 in 142 patients (79.78%) and grade I in 36 (20.22%) with mean grade 0.4 +/- 0.12; no patients with grade III or IV. Therefore, there was no mitral annuloplasty failure requiring valve replacement (MVR). During the follow-up there were 12 late deaths (12 of 178 patients, 6.74%). Only one death was valve-related (thrombosis) whereas the other 11 ones were non cardiac-related deaths (subdural frontal haematoma, septic shock). Postoperative transthoracic echocardiogram data were available in 166 patients at 5 years: the presence of postoperative MR was evaluated and severity was graded as mild in 33 patients (19.88%), moderate in 18 patients (10.84%), severe in 3 (1.81%) patients. There was no MR in the other 112 patients (67.47%); LVEDD was 49.4 +/- 6.5 mm; EF was 51.8 +/- 4.3%. The mean NYHA FC was 0.8 +/- 0.4. Only one patient was reoperated on during the follow-up because of mitral annuloplasty failure with MVR. In conclusion, mid-term 5-years follow up is good for patients operated on with the new completely flexible Rama-Valvuloplasty-Ring for mitral annuloplasty. This study has also verified the advantage about the Rama-Valvuloplasty-Ring use in the preservation of native valve apparatus.


Integration of Advance Information about a Forthcoming Task Switch - Evidence from Eye Blink Rates.
We investigated task switching among four tasks by means of a modified cuing procedure with two types of cues. One type of cue consisted of a standard task cue indicating the next task. In half of the trials, this task cue was preceded by another type of cue that reduced the set of candidate tasks from four to two tasks. In addition, we measured participants' spontaneous eye blink rates (EBRs) at the beginning, in the middle, and at the end of the experiment. Whereas interindividual differences in mean EBR had no pronounced effect on task switching performance, changes in EBRs during the first half of the experiment significantly modulated the interaction of the effects of the two types of cues. We suggest that changes in EBRs in the early phase of the experiment reflect adaptations of dopaminergic projections serving to integrate advance information about a forthcoming task switch.


Finite Element Analysis of the Implantation Process of Overlapping Stents.
Overlapping stents are widely used in vascular stent surgeries. However, the rate of stent fractures (SF) and in-stent restenosis (ISR) after using overlapping stents is higher than that of single stent implantations. Published studies investigating the nature of overlapping stents rely primarily on medical images, which can only reveal the effect of the surgery without providing insights into how stent overlap influences the implantation process. In this paper, a finite element analysis of the overlapping stent implantation process was performed to study the interaction between overlapping stents. Four different cases, based on three typical stent overlap modes and two classical balloons, were investigated. The results showed that overlapping contact patterns among struts were edge-to-edge, edge-to-surface, and noncontact. These were mainly induced by the nonuniform deformation of the stent in the radial direction and stent tubular structures. Meanwhile, the results also revealed that the contact pressure was concentrated in the edge of overlapping struts. During the stent overlap process, the contact pattern was primarily edge-to-edge contact at the beginning and edge-to-surface contact as the contact pressure increased. The interactions between overlapping stents suggest that the failure of overlapping stents frequently occurs along stent edges, which agrees with the previous experimental research regarding the safety of overlapping stents. This paper also provides a fundamental understanding of the mechanical properties of overlapping stents.


Cytochromes P450 involved in bacterial RiPP biosyntheses.
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a large class of secondary metabolites that have garnered scientific attention due to their complex scaffolds with potential roles in medicine, agriculture, and chemical ecology. RiPPs derive from the cleavage of ribosomally synthesized proteins and additional modifications, catalyzed by various enzymes to alter the peptide backbone or side chains. Of these enzymes, cytochromes P450 (P450s) are a superfamily of heme-thiolate proteins involved in many metabolic pathways, including RiPP biosyntheses. In this review, we focus our discussion on P450 involved in RiPP pathways and the unique chemical transformations they mediate. Previous studies have revealed a wealth of P450s distributed across all domains of life. While the number of characterized P450s involved in RiPP biosyntheses is relatively small, they catalyze various enzymatic reactions such as C-C or C-N bond formation. Formation of some RiPPs is catalyzed by more than one P450, enabling structural diversity. With the continuous improvement of the bioinformatic tools for RiPP prediction and advancement in synthetic biology techniques, it is expected that further cytochrome P450-mediated RiPP biosynthetic pathways will be discovered. The presence of genes encoding P450s in gene clusters for ribosomally synthesized and post-translationally modified peptides expand structural and functional diversity of these secondary metabolites, and here, we review the current state of this knowledge.


Electroencephalogram and treatment of hospitalized aggressive children with haloperidol or lithium.
Electroencephalograms (EEGs) of 48 children ages 5.2 to 12.9 years were examined on baseline placebo and on optimal dosages of haloperidol, lithium, or placebo. These children represent a subgroup of 61 hospitalized aggressive and explosive patients diagnosed as Conduct Disorder, undersocialized, aggressive who completed a double-blind study comparing the efficacy of haloperidol, lithium, and placebo. EEGs were correlated across treatment groups with behavioral ratings, ratings of untoward effects, and optimal dosages of medication. During the baseline placebo period 58.3% of the children had abnormal EEGs. Children receiving haloperidol or lithium had a significant probability that their EEGs on optimal dose would worsen, and would be more likely to show paroxysmal or focal abnormalities than those children treated with placebo. It was possible to identify children treated with haloperidol, lithium, or placebo on the basis of EEG alone. Thus, despite limitations, visual evaluation of EEGs is of value. No statements can be made with confidence regarding associations between baseline EEGs and behavioral changes, side effects, or optimal dosages of haloperidol or lithium.


Age-associated increase in rat cardiac opioid production.
Several lines of evidence suggest that opioid peptide production in the heart may increase during aging from adulthood through senescence. We tested the hypothesis that cardiac opioid peptides and preproenkephalin (PNK) mRNA would increase with advancing age. Ventricles and atria from male Wistar rats, aged 2, 6, 18, and 22-24 mo of age, were acid extracted and assayed for methionine enkephalin (ME) and leucine enkephalin (LE). Total RNA was extracted from hearts of age-matched rats and probed for PNK mRNA by Northern blot analysis using a cDNA probe. ME and LE peptides were significantly elevated with advancing age in both ventricles [P < 0.001; by analysis of variance (ANOVA)]. Ventricular ME concentration exhibited a biphasic increase with approximately twofold higher peaks at 6 and 22-24 mo of age compared with the 2 mo value of 1.04 +/- 0.05 (SE) pmol/g wet wt. In contrast, ventricular LE concentration was largely unchanged until 22-24 mo of age when it increased approximately threefold over the 2-mo value of 2.19 +/- 0.14 pmol/g wet wt. Left ventricular PNK mRNA increased approximately fivefold between 2 and 18 mo of age (P < 0.01; ANOVA). Thus both enkephalins and the mRNA coding for them were increased in hearts of older vs. younger rats. Because opioid receptor stimulation can negatively modulate several characteristics of cardiac myocyte contraction, these results may have important functional implications for the senescent heart.


Red Blood Cell Distribution Width Is Increased in Patients with Pemphigus: A Case-Control Study.
Red blood cell distribution width (RDW) has recently emerged as an inflammatory marker in several inflammatory diseases but has not been investigated in patients with pemphigus. We aimed to examine RDW percentage in patients with pemphigus relative to control subjects and to assess the association between this biomarker and the morphological characteristics of the disease. This case-control study included 183 pemphigus patients and 915 age- and sex-matched control subjects. RDW, hemoglobin, and mean corpuscular volume (MCV) were measured for all study participants. The RDW was significantly higher in patients with pemphigus than in controls (13.7±1.3 vs. 13.4±1.1%, respectively; P=0.001). A significant association between RDW and pemphigus was demonstrated in multivariate analysis (odds ratio, 1.22; 95% confidence interval, 1.01-1.46; P=0.036). The RDW was higher in patients with pemphigus vulgaris (PV) than in pemphigus foliaceus (PF; P=0.043), and in those with mucocutaneous PV relative to those with mucosal only and cutaneous only PV. The RDW increased significantly following treatment (P<0.001). Pemphigus patients demonstrated elevated RDW as compared with healthy controls. RDW may be a feasible biomarker in patients with pemphigus. Although it clearly does not replace any of the accepted diagnostic immunopathological criteria, increased RDW may be more suggestive of PV than PF, and of mucocutaneous rather than cutaneous PV. The remarkable increase following treatment may be ascribed to the corticosteroid-induced erythropoiesis.


New Pneumococcal Carriage Acquired in Association with Acute Respiratory Infection Is Prone to Cause Otitis Media.
For considering vaccine-prevention of pneumococcal acute otitis media (PncAOM), relationships between pneumococcal carriage, respiratory infection and PncAOM need to be understood. We analyzed nasopharyngeal samples collected from 329 unvaccinated Finnish children aged 2-24 months at scheduled visits and at visits during respiratory infection in 1994-97. We assessed temporal associations of respiratory infection with pneumococcal acquisition and whether PncAOM hazard depends on the relative timing of acquisition and the infection onset. The data comprised 607 person-years of risk-time for acquisition, 245 person-months of concurrent respiratory infection and carriage, and 119 episodes of PncAOM. The acquisition hazard was 3-fold in the month preceding respiratory sickness (hazard ratio, HR 3.5, 90% credible interval CI 2.9, 4.1) as compared to acquisition in healthy children. Moreover, the PncAOM hazard was markedly higher (HR 3.7, 90% CI 2.4, 5.3) during the first month of carriage acquired around the acute phase of respiratory infection (between 1 month before and 1 week after the sickness onset), as compared to carriage acquired later during sickness. The high proportion (76%) of PncAOM events occurring within 1 month of acquisition was due to frequent acquisition being associated with respiratory infection as well as the susceptibility of such acquisition to cause otitis media.


CSF levels of angiogenesis-related proteins in patients with leptomeningeal metastases.
The authors determined the levels of vascular endothelial growth factor (VEGF) and urokinase-type plasminogen activator (uPA) in the CSF of patients with leptomeningeal metastases (LM; n = 53), cancer patients without LM (n = 18), and subjects without malignancy (n = 25). Median levels of uPA and VEGF were significantly higher in patients with LM, supporting the hypothesis that angiogenesis contributes to LM. VEGF was negatively correlated with survival in patients with LM, suggesting its use as a prognostic factor.


A novel, cleavable peroxisomal targeting signal at the amino-terminus of the rat 3-ketoacyl-CoA thiolase.
Several peroxisomal proteins do not contain the previously identified tripeptide peroxisomal targeting signal (PTS) at their carboxy-termini. One such protein is the peroxisomal 3-ketoacyl CoA thiolase, of which two types exist in rat [Hijikata et al. (1990) J. Biol. Chem., 265, 4600-4606]. Both rat peroxisomal thiolases are synthesized as larger precursors with an amino-terminal prepiece of either 36 (type A) or 26 (type B) amino acids, that is cleaved upon translocation of the enzyme into the peroxisome. The prepieces are necessary for import of the thiolases into peroxisomes because expression of an altered cDNA encoding only the mature thiolase, which lacks any prepiece, results in synthesis of a cytosolic enzyme. When appended to an otherwise cytosolic passenger protein, the bacterial chloramphenicol acetyltransferase (CAT), the prepieces direct the fusion proteins into peroxisomes, demonstrating that they encode sufficient information to act as peroxisomal targeting signals. Deletion analysis of the thiolase B prepiece shows that the first 11 amino acids are sufficient for peroxisomal targeting. We conclude that we have identified a novel PTS that functions at amino-terminal or internal locations and is distinct from the C-terminal PTS. These results imply the existence of two different routes for targeting proteins into the peroxisomal matrix.


Epilepsy associated with lupus anticoagulant.
Lupus anticoagulant (LA) is commonly present in patients with systemic lupus erythematosus (SLE) who present with an ischemic cerebral stroke. Reports have noted the presence of LA in patients with epilepsy who do not have SLE. These patients are usually elderly, and it has been postulated that their epilepsy is due to subclinical ischemic infarcts. Two cases are presented in young patients (age < 35 years) who developed epileptic seizures and were LA positive. These patients did not have SLE or have cerebral infarcts that could explain the presence of their seizures. A 28-year-old woman was admitted for aortic insufficiency and new onset seizures. The clinical history, physical examination and magnetic resonance imaging did not reveal an antecedent cortical ischemic event. Serological testing revealed the presence of LA. The second patient was a 33-year-old man with medically intractable epilepsy in whom serological testing revealed the presence of LA. The clinical history, physical examination, and MRI did not reveal any evidence of an antecedent ischemic event. Neither patient had SLE. In young patients without SLE and cerebral infarcts, LA may be associated with epileptic seizures.


Expression of interferon-gamma- inducible protein-10 and its receptor CXCR3 in chronic pancreatitis.
The role of CXC chemokine, interferon-gamma-inducible protein-10 and its receptor CXCR3 in pathophysiology of chronic pancreatitis (CP) is not very clear. Hence, this study was carried out to analyze the expression of CXCL10 and CXCR3 in CP tissues. Pancreatic tissues from 25 histopathologically graded CP cases (11 alcohol associated CP, 5 confirmed idiopathic and 9 of undefined nature) and 10 normal cases were studied. Tissues were subjected to real-time PCR, immunohistochemistry, and Western blot analysis for CXCL10 and CXCR3 expression. Real-time (RT)-PCR revealed increased expression of CXCL10 (13-fold) and CXCR3 (7-fold) in CP tissue. The immunohistochemistry and Western blot analysis of the same showed significant increased protein expression and correlated well with the histopathological grades. The CXCL10 was localized mainly in the cytoplasm of pancreatic acinar cells and expression increased from grade I to grade II and declined in grade III while no expression was recorded in normal. The CXCR3 was expressed strongly at the acinar cell membrane in CP as compared to normal. Further, comparative analysis by semiquantitative RT-PCR analysis was performed for other CXC/CC chemokines (CXCL9, CXCL11, CCL3, CCL4, CCL5) and receptor (CCR5) which revealed their upregulation in the diseased state. The existence of CXCL10 and CXCR3 with other CXC/CC chemokine signature in CP is suggestive of their vital role in the progression of chronic inflammation.


Parents mention sons more often than daughters on social media.
Gender inequality starts early in life. Parents tend to prefer boys over girls, which is manifested in reproductive behavior, marital life, and parents' pastimes and investments in their children. While social media and sharing information about children (so-called "sharenting") have become an integral part of parenthood, whether and how gender preference shapes the online behavior of users are not well known. In this paper we use public posts made by 635,665 users from Saint Petersburg on a popular Russian social networking site, to investigate public mentions of daughters and sons on social media. We find that both men and women mention sons more often than daughters in their posts. We also find that posts featuring sons receive more "likes" on average. Our results indicate that girls are underrepresented in parents' digital narratives about their children, in a country with an above-average ranking on gender parity. This gender imbalance may send a message that girls are less important than boys or that they deserve less attention, thus reinforcing gender inequality from an early age.


Endovascular treatment of a dural arteriovenous fistula in a patient with Loeys-Dietz syndrome: A case report.
Background Loeys-Dietz syndrome (LDS) is a recently recognized autosomal dominant connective tissue disease. The manifestations of LDS include vascular tortuosity, scoliosis, craniosynostosis, aneurysm and aortic dissections. Clinical presentation A 35-year-old woman treated with Stanford type B aortic dissection and breast cancer was referred to us for Borden type II dural arteriovenous fistula (dAVF) draining to the vein of Galen, involving the midline of tentorium cerebelli. The dAVF was treated successfully by combined transarterial and transvenous embolization. Because of tortuosity of vertebral arteries, a genetic test was conducted confirming LDS type 2. Conclusions To our knowledge, this is the first case report of dAVF associated with LDS. The relationship between LDS and dAVF is unknown but this report shows the possibility that mutation of transforming growth factor β receptors 2 ( TGFBR2) related to LDS may be related to shunt diseases. Because intervention in LDS seems to be feasible compared to Ehlers Danlos syndrome and Marfan syndrome, it is important to make the correct diagnosis.


Communication outcomes for groups of children using cochlear implants enrolled in auditory-verbal, aural-oral, and bilingual-bicultural early intervention programs.
The relative impact of early intervention approach on speech perception and language skills was examined in these 3 well-matched groups of children using cochlear implants. Eight children from an auditory verbal intervention program were identified. From a pediatric database, researchers blind to the outcome data, identified 23 children from auditory oral programs and 8 children from bilingual-bicultural programs with the same inclusion criteria and equivalent demographic factors. All child participants were male, had congenital profound hearing loss (pure tone average >80 dBHL), no additional disabilities, were within the normal IQ range, were monolingual English speakers, had no unusual findings on computed tomography/magnetic resonance imaging, and received hearing aids and cochlear implants at a similar age and before 4 years of age. Open-set speech perception (consonant-nucleus-consonant [CNC] words and Bamford-Kowal-Bench [BKB] sentences) and the Peabody Picture Vocabulary Test (PPVT) were administered. The mean age at cochlear implant was 1.7 years (range, 0.8-3.9; SD, 0.7), mean test age was 5.4 years (range, 2.5-10.1; SD, 1.7), and mean device experience was 3.7 years (range, 0.7-7.9; SD, 1.8). Results indicate mean CNC scores of 60%, 43%, and 24% and BKB scores of 77%, 77%, and 56% for the auditory-verbal (AV), aural-oral (AO), and bilingual-bicultural (BB) groups, respectively. The mean PPVT delay was 13, 19, and 26 months for AV, AO, and BB groups, respectively. Despite equivalent child demographic characteristics at the outset of this study, by 3 years postimplant, there were significant differences in AV, AO, and BB groups. Results support consistent emphasis on oral/aural input to achieve optimum spoken communication outcomes for children using cochlear implants.


Course and severity of bronchial asthma and chronic bronchitis in a local Swedish population sample.
A population sample between 35 and 54 years of age with chronic obstructive lung disease was investigated. The material consisted of 86 persons with bronchial asthma (without chronic bronchitis), 69 with chronic bronchitis (without asthma) and 30 with a combination of chronic bronchitis and bronchial asthma. Of the 116 asthmatics 51 had reaginic bronchial allergy. Twenty-three subjects developed bronchoconstriction on exercise testing: 14 of these had asthma, one bronchitis and eight had a combination of the two. Onset of disease before 15 years of age was unusual in pure bronchitis (9%), although more common in pure asthma and in asthma with bronchitis (23-29%). The mean number of days of incapacity during the preceding 12 months was only 6, both in pure asthma and pure bronchitis, but it was more frequent, 22-26, in asthma with bronchitis and in exercise-induced bronchoconstriction. In asthma the multiple regression analyses showed that impaired spirometric values before or after taking a bronchodilating drug were correlated with the duration of incapacity in days and with exercise-induced bronchoconstriction. In bronchitis, impaired spirometric values were found to be correlated with the number of symptomatic days (during the preceding 12 months) and with smoking.


Metabolic reprogramming in cancer: mechanistic insights from Drosophila.
Cancer cells constantly reprogram their metabolism as the disease progresses. However, our understanding of the metabolic complexity of cancer remains incomplete. Extensive research in the fruit fly Drosophila has established numerous tumor models ranging from hyperplasia to neoplasia. These fly tumor models exhibit a broad range of metabolic profiles and varying nutrient sensitivity. Genetic studies show that fly tumors can use various alternative strategies, such as feedback circuits and nutrient-sensing machinery, to acquire and consolidate distinct metabolic profiles. These studies not only provide fresh insights into the causes and functional relevance of metabolic reprogramming but also identify metabolic vulnerabilities as potential targets for cancer therapy. Here, we review the conceptual advances in cancer metabolism derived from comparing and contrasting the metabolic profiles of fly tumor models, with a particular focus on the Warburg effect, mitochondrial metabolism, and the links between diet and cancer.


A mental model of factors associated with subjective life expectancy.
The objective was to develop and test a framework based on a biopsychosocial model that can be used to identify factors associated with subjective (self-estimated) life expectancy (SLE). SLE predicts important work and retirement decisions so a better understanding of the factors that contribute to an individual's thoughts about their likely age at death is essential for late-career and financial planning and for developing interventions aimed at addressing inappropriate estimates. This is a sub-study of the Australian 45 and Up Study cohort. Survey data were collected at two time points (3 years apart) from 2579 participants aged over 55 years. Correlations and regression analyses tested the relationship of SLE with biomedical/genetic factors (age, health diagnoses, parental longevity), socioeconomic factors (income, education) health behaviors (exercise, smoking, alcohol use, diet), and psychosocial factors (optimism, distress, social connectedness). Variables within each set of factors except the socioeconomic set were significantly related to SLE. Healthy lifestyle behaviors significantly moderated the effect of parental longevity. The findings indicate that individuals construct an understanding of their personal life expectancy based on similar factors that predict actual life expectancy, but not all mortality risk factors appear to be weighted realistically. The findings imply that, at least to some extent, SLE is not a stable construct and might be amenable to intervention.


[Effect of GR24 on accumulation of diterpenoids in Tripterygium wilfordii suspension cells].
Terpenoids are main bioactive components in Tripterygium wilfordii,but the contents of some terpenoids are relatively low. In order to provide scientific evidence for the regulation of terpenoids in T. wilfordii,this research explored the effect of GR24 on accumulations of four diterpenoids( triptolide,tripterifordin,triptophenolide,and triptinin B) in T. wilfordii suspension cells by biological technology and UPLC-QQQ-MS/MS. The results indicated that 100 μmol·L-1 GR24 inhibited the accumulations of triptolide,tripterifordin,triptophenolide,and triptinin B to different degrees. Compared with the control group,the contents of 4 diterpenoids( in the induced group) were down to 96.59%,63.80%,61.02% and 33.59% in 240 h,respectively. Among them,the accumulation of triptinin B iswas significantly inhibited. In addition,the key time point of inhibitory effect was 120 h after induction with GR24 in some diterpenoids. This is the first systematic study focusing on the effect of GR24 on the accumulations of diterpenoids in T. wilfordii suspension cells. The dynamic accumulation ruleregularity of four diterpenoids after induced by GR24 was summarized,which laid a foundation for further study on the chemical response mechanism of terpenoids to GR24.


Predictive validity of the SAVRY, YLS/CMI, and PCL:YV is poor for intimate partner violence perpetration among adolescent offenders.
Despite advances in developing structured risk assessment instruments, there is currently no instrument to assess and manage the risk of intimate partner violence perpetration among adolescents. Given the empirical link between many forms of antisocial behavior, we tested whether structured tools commonly used by professionals to evaluate adolescents' risk of engaging in general violence and offending could be used to identify adolescents at risk for perpetrating intimate partner violence. Because researchers have not yet examined whether risk assessment tools for general violence and offending predict intimate partner violence perpetration, we did not have a priori hypotheses regarding the predictive validity of these tools for this purpose. Research assistants rated 156 adjudicated youth on the Structured Assessment of Violence Risk in Youth (SAVRY), Youth Level of Service/Case Management Inventory (YLS/CMI), and Psychopathy Checklist: Youth Version (PCL:YV) and recorded charges for intimate partner violence perpetration, any violent reoffending, and any reoffending over a 2-year follow-up period. Receiver operating characteristic analysis indicated that total scores and summary risk ratings on the SAVRY and YLS/CMI and total scores on the PCL:YV were significantly predictive of any violent reoffending and any reoffending, with moderate to large effect sizes, but were nonsignificantly associated with intimate partner violence perpetration. Further, penalized logistic regression analysis indicated that the SAVRY, YLS/CMI, and PCL:YV did not significantly add incremental validity to age, gender, race/ethnicity, and prior intimate partner violence perpetration and victimization for predicting future intimate partner violence perpetration. These findings suggest that the SAVRY, YLS/CMI, and PCL:YV could have limitations for assessing and managing intimate partner violence perpetration among adolescents. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Restricted V-(D)-J junctional regions in the T cell response to lambda-repressor. Identification of residues critical for antigen recognition.
The T cell response to lambda-repressor is directed to a 15 amino acid peptide (P12-26) of the protein in A/J mice. Previous studies have demonstrated a preferential use of V alpha 2 and V beta 1 amongst the T cell hybridomas specific for P12-26 in the context of I-Ek. By using the polymerase chain reaction, the sequences of a panel of the T cells using V alpha 2 and V beta 1 were determined. A highly conserved alpha-chain V-J junctional sequence was found in six of the eight T cell hybrids. This consensus alpha-chain VJ sequence may be combined with different members of V alpha 2, indicating a more restricted selection on the junctional region than on the V element in these T cells. In contrast, greater diversities were found on the V-D-J region of beta-chains despite the same V beta 1 and J beta 2.1 were used. However, a highly conserved glutamic acid residue was found at the same position of beta-chains where a similar conservation was identified in cytochrome c-specific T cells. The correlation of the TCR sequence with the fine specificities of these T cells suggests that a single amino acid deletion in the V alpha-J alpha region may reduce the P12-26 response and abolish the recognition of an altered peptide [Phe22] P12-26. In addition, three amino acid difference in the V-D-J region of the beta-chain also determine the P12-26 reactivity. Thus the V(D)J junctional regions of both alpha- and beta-chains may be critical for the recognition of the peptide Ag presented by the specific MHC molecule.


Separation and first structure elucidation of Cremophor EL-components by hyphenated capillary electrophoresis and delayed extraction-matrix assisted laser desorption/ionization-time of flight-mass spectrometry.
The polyethoxylated heterogeneous components of the so far poorly characterized nonionic emulsifier Cremophor EL (polyoxyl 35 castor oil) (CrEL) were fractionated by cyclodextrin-modified micellar electrokinetic capillary chromatography (CD-MEKC). Due to the low UV absorbance of most of the CrEL-components an indirect UV detection was used with phenobarbital-sodium as background absorber. For a precise assignment of the resulting peaks to the corresponding components capillary electrophoresis (CE) had to be combined with delayed extraction-matrix assisted laser desorption/ionization-time of flight-mass spectrometry (DE-MALDI-TOF-MS) as detection system. For this purpose, the fractionating robot Probot was employed which enables both the on-line fractionation of the CE eluate on a MALDI target during the electrophoretic separation and the simultaneous dosage of the MALDI matrix solution. The applied CrEL amount was optimized by varying the CE injection parameters time, pressure and concentration of the sample in order to obtain homologue peak series of sufficient intensity without decreasing the separation efficiency. Evaluation of the mass spectra was performed by comparing the residue masses of the homologue peak series with the calculated residue masses of potential CrEL-components. However, the high number of polyethoxylated components leads to overlapping of homologue peak series with isobaric residue masses. These isobaric interferences were detected by a high mass accuracy of the measurements (obtained by internal calibration with polyethylene glycol (PEG) 1000 and by means of the residue mass plot, the newly developed evaluation method. The combination of these techniques allowed the first detailed structure analysis of the CrEL-components showing glycerol polyoxyethylene (POE) monoricinoleate and POE monoricinoleate to be the two main components of the emulsifier. Furthermore, the coupling of CE with DE-MALDI-TOF-MS is generally applicable to the fractionation and identification of polymers.


Prevalence and seasonal variation of Fasciola hepatica in slaughtered cattle: the role of climate and environmental factors in Mexico.
The objective of this study is to determine the prevalence of Fasciola hepatica infection in cattle slaughterhouses, as well as its association with climatic/environmental factors (derived from satellite data), seasonality and climate regions in two states in Mexico. Condemned livers from slaughtered animals were obtained from three abattoirs in the states of Puebla and Veracruz. The overall prevalence of the parasite in cattle between January and December of 2017 was 20.6% (1407 out of 6834); the highest rate of condemnation was observed in Veracruz (26.3%; tropical climate), and the lowest rate was found in Puebla (15.5%; temperate climate). The seasonal prevalence of fluke infection was 18.6%, 14.8% and 28.4% during the wet season, and 17.1%, 12.4% and 22.8% during the dry season in the three abattoir sites, located in the districts of Zacatlán, Teziutlán and Ciudad Alemán, respectively. Liver condemnations due to bovine fasciolosis were prevalent in the Zacatlán, Teziutlán and Ciudad Alemán districts during summer, autumn and summer, respectively. Using generalized estimating equations analysis, we determined six variables - rainfall (wet/dry), land surface temperature day, land surface temperature night, normalized difference vegetation index, seasonality and climate regions (temperate/tropical) - to be significantly associated with the prevalence of condemned livers. Climate region was the variable most strongly associated with F. hepatica infection (odds ratio (OR) 266.59; 95% confidence interval (CI): 241.90-353.34), followed by wet and dry seasons (OR 25.56; 95% CI: 20.56-55.67).


Elevated levels of serum IL-36α in patients with systemic lupus erythematosus.
The present study aimed to investigate the levels of IL-36α and its association with disease activity in patients with systemic lupus erythematosus (SLE). A total of 60 patients with SLE and 29 healthy controls were enrolled in the present study. Disease activity was evaluated using the SLE disease activity index (SLEDAI). The serum levels of IL-36α, IL-36 receptor antagonist (IL-36Ra) and IL-17 were assessed using ELISA. The levels of IL-36α in patients with SLE were significantly higher compared with those of healthy controls. There was a significant increase in IL-36α in the active SLE group (SLEDAI score ≥5) compared with that of the healthy controls (P<0.001). The serum IL-36α levels were higher in patients with active SLE than in patients with quiescent disease (P=0.012). IL-36Ra was downregulated in patients with SLE (P=0.007). The serum IL-17 levels were elevated in patients with SLE (P=0.036), and a positive correlation was observed between the IL-36α and IL-17 levels (r=0.453, P=0.003). The serum IL-36α levels were associated with SLEDAI (r=0.374, P=0.003), proteinuria (r=0.329, P=0.010) and complement 3 (r=-0.336, P=0.009). Patients who were receiving glucocorticoid treatment had lower IL-36α levels than those who were not receiving glucocorticoid treatment (P=0.003). Patients with lupus nephritis had higher serum IL-36α levels compared with those found in patients without lupus nephritis (P=0.037). The serum IL-36α concentration was elevated in patients with SLE, and was correlated with disease activity and IL-17 levels. The aberrant serum IL-36α levels observed in the present study and its clinical association with SLE suggest the important role of IL-36α in onset and progression of SLE. In addition, the association of IL-36α with IL-17 level indicates its involvement in the regulation of T helper 17 cytokines.


Surveillance strategies for Classical Swine Fever in wild boar - a comprehensive evaluation study to ensure powerful surveillance.
Surveillance of Classical Swine Fever (CSF) should not only focus on livestock, but must also include wild boar. To prevent disease transmission into commercial pig herds, it is therefore vital to have knowledge about the disease status in wild boar. In the present study, we performed a comprehensive evaluation of alternative surveillance strategies for Classical Swine Fever (CSF) in wild boar and compared them with the currently implemented conventional approach. The evaluation protocol was designed using the EVA tool, a decision support tool to help in the development of an economic and epidemiological evaluation protocol for surveillance. To evaluate the effectiveness of the surveillance strategies, we investigated their sensitivity and timeliness. Acceptability was analysed and finally, the cost-effectiveness of the surveillance strategies was determined. We developed 69 surveillance strategies for comparative evaluation between the existing approach and the novel proposed strategies. Sampling only within sub-adults resulted in a better acceptability and timeliness than the currently implemented strategy. Strategies that were completely based on passive surveillance performance did not achieve the desired detection probability of 95%. In conclusion, the results of the study suggest that risk-based approaches can be an option to design more effective CSF surveillance strategies in wild boar.


New Medicare Diabetes Prevention Coverage May Limit Beneficiary Access and Widen Health Disparities.
The Centers for Medicare and Medicaid Services recently issued final rules for the Medicare Diabetes Prevention Program (MDPP), offering an unprecedented opportunity to provide lifestyle intervention to Medicare beneficiaries with prediabetes via a pay-for-performance model. The MDPP is based on the widely disseminated, yearlong National Diabetes Prevention Program (NDPP), which has lesser but still beneficial risk-reduction outcomes among minority and low-income participants. We compare projected payments based on outcomes of a diverse sample of Medicare beneficiaries to service delivery costs, and explore resulting implications for MDPP access and sustainability. We delivered NDPP in a safety-net health care system from 2013 to 2017 and conducted an analysis of service cost, beneficiary performance, and projected MDPP reimbursement. Among 1165 total participants, 213 (18.3%) were Medicare beneficiaries. Participating beneficiaries were 40.6% Hispanic, 31.6% non-Hispanic black, and 26.9% non-Hispanic white and 69.5% low-income. Overall beneficiary performance would result in an average reimbursement of $138.52 (interquartile range=162.50). Program delivery costs were $800 per participant, leaving an average gap of $661 per beneficiary. Findings from delivering the NDPP to diverse and undeserved patients show a large gap between service costs and projected reimbursement. Although many MDPP suppliers are needed to reach all Medicare beneficiaries with prediabetes, insufficient reimbursement may be a deterrent. Health disparities may also widen as suppliers serving diverse and low-income populations will likely receive especially low payments, threatening access. Higher payments are supported by strong return-on-investment findings and seem needed to reduce diabetes prevalence and related disparities.


CircSCAP interacts with SF3A3 to inhibit the malignance of non-small cell lung cancer by activating p53 signaling.
Circular RNA (circRNA) has been recently identified as a critical regulator during carcinogenesis. However, the biological function and potential underlying mechanisms of circRNAs in lung cancer remain to be further elucidated. Here, we first evaluated the differentially expressed circRNAs between tumor and the matched adjacent nontumor tissues (3 pairs) of lung cancer patients via circRNA microarray. The expression of top five dysregulated circRNAs were tested in lung cancer cell lines and the circSCAP with concordant alteration in microarray data and cell lines was selected for further investigation. Then we validated the expression level of circSCAP in tumor and corresponding adjacent tissues (161 pairs) from a lung cancer cohort by RT-PCR analysis followed by correlation and prognosis analysis between circSCAP and clinical characteristics. Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer diagnosis (about 80% in the cohort used in this study). Therefore, we focused the role of circSCAP in NSCLC in the present study. In vitro and in vivo assays were performed to study the biological function of circSCAP in NSCLC. Biotin-labeled RNA pulldown and RNA immunoprecipitation (RIP) assays were carried out to identify the proteins directly interacting with circSCAP. The molecular mechanism of circSCAP-driven tumor suppression was demonstrated by immunoblotting, immunoprecipitation and luciferase reporter assays. In vitro and in vivo rescue experiments were conducted to verify the role of the circSCAP/SF3A3/p53 signaling axis in NSCLC. We screened the expression profiles of human circRNAs in lung cancer tissues and found that hsa_circ_0065214 (termed as circSCAP) was significantly decreased. Kaplan-Meier analysis showed that patients with low level of circSCAP had a significantly poor prognosis. Gain- and loss-of-function experiments suggested that circSCAP played an important role in NSCLC cell proliferation, cell migration and apoptosis. Mechanistically, circSCAP directly binds to the SF3A3 protein, facilitating the reduction of SF3A3 by promoting its ubiquitin-proteasome-mediated degradation, which enhances the expression of MDM4-S to finally activate its downstream p53 signaling. These findings illustrate a novel circSCAP/SF3A3/p53 signaling axis involved in suppressing the malignance of NSCLC and provide a promising target for NSCLC prognosis prediction and treatment.


Application of serologic assays for diagnosing acute hepatitis E in national surveillance of a nonendemic area.
Variant performance of immunoglobulin M (IgM) and immunoglobulin G (IgG) hepatitis E virus (HEV) assays may impact the diagnosis. The present study aimed to evaluate four different IgM/IgG assays for HEV infection for application in national surveillance in nonendemic areas. Sera from 300 patients that were stored in the Centers for Disease Control (CDC) of Taiwan for suspected acute HEV infection from 2004 to 2008, and 18 serum samples from acute cases of HEV infection in Taipei Veteran General Hospital were evaluated. Performances of EIAgen HEV IgG/M (Adaltis, Bologna, Italy), recomWell HEV IgG/M (Mikrogen, Neuried, Germany), MP HEV IgG/M (MP Biomedicals, Singapore), and in-house kits, HEVLPs (HEV virus-like particles) IgG/M were compared. Positive results of serum RNA detected by reverse transcription-polymerase chain reaction were defined as the definite diagnosis. There were five genotype 1, one genotype 3, and nine genotype 4 HEV samples. The four different IgM/IgG assays had excellent performance in terms of negative predictive value (98.4-100%) and varying performance in relation to sensitivity (66.7-93.3%) and specificity (62.9-95.6%). RecomWell IgM had the best overall performance. In addition, the combination of anti-HEV IgM ELISA with anti-HEV IgG or another anti-HEV IgM ELISA provided better screening performance, especially the recomWell IgM and HEVLPs IgM combination (area under the receiver operating curve: 0.94; sensitivity: 100%, specificity 88.1%). In conclusion, anti-HEV IgM ELISA is a good screening test for the national surveillance of acute HEV infection in nonendemic areas and not limited by inconsistent performances of sensitivity and specificity among different assays.


[Ophthalmoplegia in a patient with prostate cancer and bone metastases].
Prognosis in prostate cancer is determined, in greater part, by the presence of metastases. Bone metastases can occur in any part of the skeleton even, for example, at the base of the skull. We present a case of a 78 year old male who, in December 2001, presented with paralysis of the third cranial nerve. The NMR and CAT scans were normal and circulating levels of PSA were elevated. He was referred to the Urology Service where the treatment guidelines included complete androgen block. Subsequently, he developed retro-orbital pain, divergent strabismus and palpebral ptosis. CAT and NMR indicated a soft tissue mass at the sphenoid level. Treatment was Gamma Knife Radio-surgery. Since August 2004, in conjunction with the latest rise in PSA, the patients general status deteriorated considerably and he was referred to the Oncology Service. There was an increase in the paralysis of the third, fourth and sixth cranial nerve (complete left ophthalmoplegia) and left-central facial paralysis. Metastases from prostate cancer can be disseminated via the lymphatic or the blood system. Currently, there are more metastases from large-size tumours. Metastases are critical in prostate cancer because of their adverse effect on the patients survival. Measurements of circulating levels of prostate specific antigen and prostate acid phosphatase are very useful in the clinical diagnosis of the primary tumour, or its metastases.


Contribution of the collagen I alpha1 and vitamin D receptor genes to the risk of hip fracture in elderly women.
Hip fracture is partially genetically determined. The present study was designed to examine the contributions of vitamin D receptor (VDR) and collagen I alpha1 (COLIA1) genotypes to the liability to hip fracture in postmenopausal women. The study was designed as a prospective population-based cohort investigation. Six hundred seventy-seven postmenopausal women of Caucasian background, aged 70 +/- 7 yr (mean +/- SD), have been followed for up to 14 yr. Sixty-nine women had sustained a hip fracture during the period. Atraumatic hip fractures were prospectively identified through radiologists' reports. Bone mineral density (BMD) at the hip and lumbar spine was measured by dual-energy x-ray absorptiometry. GENOTYPES: The TaqI and SpI COLIA1 polymorphisms of the VDR and COLIA1 genes were determined. Using the Single Nucleotide Polymorphism database, VDR TT, Tt, and tt genotypes were coded as TT, TC, and CC, whereas COLIA1 SS, Ss, and ss were coded as GG, GT, and TT. Women with VDR CC genotype (16% prevalence) and COLIA1 TT genotype (5% prevalence) had an increased risk of hip fracture [odds ratio (OR) associated with CC, 2.6; 95% confidence interval (CI), 1.2-5.3; OR associated with TT, 3.8; 95% CI, 1.3-10.8] after adjustment for femoral neck BMD (OR, 3.4 per SD; 95% CI, 2.3-5.0) and age (OR, 1.4 per 5 yr; 95% CI, 1.1-1.7). Approximately 20 and 12% of the liability to hip fracture was attributable to the presence of the CC genotype and TT genotype, respectively. The VDR CC genotype and COLIA1 TT genotype were associated with increased hip fracture risk in Caucasian women, and this association was independent of BMD and age.


[Mild hearing loss in children with communication disorders].
The prevalence of MHL in 202, 1 to 6 year-old children with communication disorders who visited our clinic in 1991 was investigated. 1) 31% of the subjects had MHL bilaterally. The prevalence of MHL was 44% at age 1 year, 20% at age 2 years, 36% at age 3 years, 24% at age 4 years, 39% at age 5 years, 33% at age 6 years. 2) 88% of children with MHL had OME, 10% had mild sensorineural hearing loss, and 2% had cerminous plug. 3) The prevalence of MHL in children with mental retardation and autistic disorders was 9%, that with stuttering was 9%, that of OME accompanied by moderate and severe hearing disorders was 6%. 4) The primary causes in 191, except for those with stuttering, were as follows; the prevalence of MHL was 30%, that of mental retardation and autistic disorders was 24%, and that of articulation disorders was 28%. 5) On the other hand, the prevalence of MHL in children with retarded language development and articulation disorders was 30%, which was significantly higher than that of the other communication disorders. Accordingly, the results of this study suggest that MHL in early childhood greatly influences communication disorders.


Goblet cell density in nasal polyps.
The goblet cell density was determined in 29 nasal polyps from 22 patients by use of the periodic acid Schiff-alcian blue whole-mount method. The distribution of goblet cells was found to be extremely irregular, ranging from areas completely devoid of goblet cells to areas with a relatively high density. The median density varied from 280 cells/mm2 to 10,000 cells/mm2. The total median density for all 15 polyps located anteriorly in the nose was 3,450 cells/mm2, compared with 6,050 cells/mm2 for 14 posteriorly located polyps. The density was highest in pseudostratified, cylindric epithelium, although great variations occurred among the different areas with this type of epithelium. The goblet cell density may be influenced by several factors, such as the airflow, type and thickness of the epithelium, and whether the genesis of the nasal polyps is infectious or allergic, in addition to polyp growth, size, and age.


Proposal for a new risk classification system for nasopharyngeal carcinoma patients with post-radiation nasopharyngeal necrosis.
To analyze the clinical outcomes of nasopharyngeal carcinoma (NPC) patients with post-radiation nasopharyngeal necrosis (PRNN) and construct a new risk classification system for predicting survival of PRNN. A total of 276 patients with PRNN were consecutively enrolled. Complete magnetic resonance (MR) images of the nasopharynx and neck were available for all patients and were used to assess nasopharyngeal necrosis status. After 2010, patients with PRNN were initially treated by radical endoscopic necrectomy followed by reconstruction with nasal flap (ENNF). The 1-year and 2-year overall survival (OS) was 65.0% and 51.6%, respectively. Three variables affected survival: osteoradionecrosis, re-irradiation, and internal carotid artery (ICA) exposure, and only two variables were found to be independent prognostic factors: re-irradiation (hazard ratio [HR] 1.75, P=0.001) and internal carotid artery (ICA) exposure (hazard ratio [HR] 1.80, P=0.001). These two variables were combined to create a new risk classification system for PRNN. 131 (47.5%), 110 (39.9%), and 35 (12.7%) patients were classified into low-, intermediate- and high-risk group, with the 2-year OS rates of 64.8%, 45.1%, and 22.5%, respectively (P<0.001). ENNF was associated with a better OS in these three group patients compared with conservative management with statistical or marginal statistical significance (2-year OS low-risk group, 90.9% vs 61.1%, p=0.081; intermediate-risk group: 100% vs 37.8%, P=0.001; and high-risk group, 57.1% vs 20.8%, p=0.066). The new risk classification system provides accurate estimates of prognosis. ENNF surgery may lead to better survival outcome than conservative management in PRNN patients.


Expression, refolding and spectroscopic characterization of fibronectin type III (FnIII)-homology domains derived from human fibronectin leucine rich transmembrane protein (FLRT)-1, -2, and -3.
The fibronectin leucine rich transmembrane (FLRT) protein family consists in humans of 3 proteins, FLRT1, -2, and -3. The FLRT proteins contain two extracellular domains separated by an unstructured linker. The most membrane distal part is a leucine rich repeat (LRR) domain responsible for both cis- and trans-interactions, whereas the membrane proximal part is a fibronectin type III (FnIII) domain responsible for a cis-interaction with members of the fibroblast growth factor receptor 1 (FGFR1) family, which results in FGFR tyrosine kinase activation. Whereas the structures of FLRT LRR domains from various species have been determined, the expression and purification of recombinant FLRT FnIII domains, important steps for further structural and functional characterizations of the proteins, have not yet been described. Here we present a protocol for expressing recombinant FLRT-FnIII domains in inclusion bodies in Escherichia coli. His-tags permitted affinity purification of the domains, which subsequently were refolded on a Ni-NTA agarose column by reducing the concentration of urea. The refolding was confirmed by circular dichroism (CD) and 1H-NMR. By thermal unfolding experiments we show that a strand-strand cystine bridge has significant effect on the stability of the FLRT FnIII fold. We further show by Surface Plasmon Resonance that all three FnIII domains bind to FGFR1, and roughly estimate a Kd for each domain, all Kd s being in the µM range.


Making tubes: step by step.
Branched hollow tubes form the architectural basis of many mammalian organs. The growth factor HGF/SF and its receptor, the Met receptor tyrosine kinase, stimulate epithelial cells to undergo tubulogenesis in vitro. In this issue of Developmental Cell, O'Brien et al. (2004) look at temporal regulation and the role of two HGF/SF effectors, the ERK 1/2 MAP kinases and matrix metalloproteases, in this process.


Treosulfan-Based Conditioning Regimen in Sibling and Alternative Donor Hematopoietic Stem Cell Transplantation for Children with Sickle Cell Disease.
Lack of suitable donors and regimen related toxicity are major barriers for hematopoietic stem cell transplantation (HSCT) in patients with sickle cell disease (SCD). The aim of the study is the assessment of efficacy and toxicity of Treosulfan-based conditioning regimen for SCD also when alternative donors such as mismatched unrelated donor and haploidentical donor are employed. We report our single-center experience: 11 patients with SCD received HSCT with a Treosulfan/Thiotepa/Fludarabine/Anti-thymoglobulin conditioning regimen between 2010 and 2015. The donor was a matched sibling donor (n= 7), a haploidentical parent (n= 2), a matched unrelated donor (n= 1) or a mismatched unrelated donor (n=1). The haploidentical and mismatched unrelated donor grafts were manipulated by removing TCRαβ and CD19 positive cells. All patients survived the procedure and achieved stable engraftment. Stable mixed chimerism was observed in 5/11 patients. Grade III-IV regimen related toxicity was limited to mucositis and no grade III-IV graft-versus-host disease (GvHD) occurred. No SCD manifestation was observed post transplant and cerebral vasculopathy improved in 3/5 evaluable patients. Organ function evaluation showed no pulmonary, cardiac or renal toxicity but gonadal failure occurred in 1/4 evaluable patients. Our data suggest that Treosulfan is associated with low toxicity and may be employed also for unrelated and haploidentical donor HSCT.


Pelvic fracture in the patient with multiple injuries: factors and lesions associated with mortality.
The main objective of this study was to identify demographic, clinical, analytical factors or injuries associated with 30-day mortality in patients with pelvic fractures. Prospective observational study of patients with multiple injuries including pelvic fractures between January 2009 and January 2017. We recorded demographic, clinical, and laboratory data on arrival at the emergency department; type of pelvic fracture; treatments; associated lesions; and 30-day mortality. Univariable and multivariable models were used to analyze the data. A total of 2061 multiple-injury patients were attended; 118 had pelvic fractures. Fifteen of the patients with pelvic fractures (12.7%) died within 30 days. Arterial blood pressure on admission was less than 90 mm Hg in 23.7%, heart rate was over 100 beats per minute in 41.52%, lactic acid level was 20 mg/dL or higher in 67.6%, and base excess of -6 or less was recorded for 26.3%. The mean Injury Severity Score was 20 points. Angiographic embolization was required in 80.6% and preperitoneal packing in 3.4%. The main associated lesions were rib fractures (35.6%), hemo-pneumothorax (31.3%), spinal injuries (35.6%), and head injuries (30%). The 6 independent variables associated with risk of death in multiple-injury patients with pelvic fractures are age, female sex, complex fractures (Tile type C), lactic acid level of 20 mg/dL or more, base excess of -6 or less, and bowel perforation.


Adherence to WHO breastfeeding guidelines among HIV positive mothers in Southern Ethiopia: implication for intervention.
Breastfeeding reduces major causes of infant mortality and morbidity. On the other hand, it is a major mode of vertical HIV transmission. In developing countries like Ethiopia, HIV positive mothers are advised to continue breastfeeding up to 12 months. But there is scarce literature regarding the mothers' adherence to continued breastfeeding recommendations. Therefore, the objective of this study is to assess HIV positive mothers' adherence to the infant feeding recommendations of the new World Health Organization (WHO) guidelines for HIV-exposed infants aged ≥6 months. A cross-sectional study was conducted in health institutions with antiretroviral therapy and prevention of mother to child transmission facilities in Sidama Zone, Southern Ethiopia. Health institutions were considered as clusters and cluster sampling technique was employed. A total of 184 HIV positive mothers with their infants registered at respective health institutions were recruited and assessed for their infant breastfeeding practices. Descriptive statistics (frequency, mean, median, and standard deviation) were computed to describe the breastfeeding practices of HIV positive mothers. Almost all (181 [98.4%]) of the HIV-exposed infants were "ever breastfed". Among those mothers who had ever breastfed, 158 (87.3%) initiated breastfeeding within an hour of delivery and 157 (85.8%) had fed their babies colostrum while 31 (16.8%) gave prelacteal food to their infants. The prevalence of continued breastfeeding at 1 year was (54.5%) (46.9% for urban mothers and 75% for rural mothers). Seventy-one percent (70.9%) of HIV positive mothers practiced "on demand" breastfeeding. Twenty nine percent of infants aged 6-11 months and 47.8% of infants aged ≥12 months were no longer breastfed. The mean (± standard deviation) duration of breastfeeding was 7.8 (±3.1) months (95% confidence interval: 6.9-8.7). The 2010 WHO guidelines and recommendations on breastfeeding duration for HIV positive mothers was not adhered to after 6 months of age. Promotion and counseling of optimal breastfeeding practice for HIV positive mothers based on the updated WHO guideline is an appropriate intervention. However, further research is recommended to evaluate the acceptance of the new 2010 WHO guideline by the health professionals and HIV positive mothers.


A segment of Myxococcus xanthus ops DNA functions as an upstream activation site for tps gene transcription.
A segment of DNA located between 131 and 311 base pairs (bp) upstream from the transcriptional start of the Myxococcus xanthus ops gene (-131 to -311) was shown to function as an upstream activation site (UAS) for developmentally regulated transcription from the tps gene promoter region. The activation of early developmental transcription by the ops UAS was independent of orientation and could be increased by the addition of a second copy of the UAS. The ops UAS segment continued to function when placed 1.5 kbp upstream from the transcription initiation site. DNA from the tps promoter region was required for transcriptional activation by the ops UAS, and a specific requirement for the sequence of tps DNA between -34 and -66 was demonstrated. Several specific ops UAS DNA-protein complexes were observed after incubation of this DNA segment with an extract of early developmental M. xanthus cells. Extracts of vegetative cells contained much less ops UAS-specific DNA-binding activity. When the distance between the tps and ops genes was increased from 2 to 15 kbp by insertion of a transduced segment of DNA, the amount of developmentally induced tps RNA was found to be about one-third that found in wild-type M. xanthus. Our observations suggest that the regulatory region of the ops gene functions not only to control ops gene expression but also to increase early developmental expression of the tps gene located about 2 kbp downstream on the M. xanthus chromosome.


The influence of ascorbic acid on the free-radical metabolism of xenobiotics: the example of diaziquone.
Diaziquone (AZQ) is a quinone-containing alkylating agent undergoing trials as an antitumor drug. The quinone moiety of this compound places it among a group of compounds whose activity is believed to be modulated by a redox cycle that activates the compounds to their free radicals (e.g., adriamycin). AZQ is unique among these compounds in that it can be reduced to its free radical (AZQH) by a variety of cells in culture, including human and murine cancer cells. Red blood cells (RBC) were also observed to reduce AZQ to its free radical. Using electron spin resonance (ESR), we observed that soon after the AZQ free radical appeared, it decayed and was replaced by a doublet with ESR parameters that suggested the presence of the ascorbyl radical (AH). The identity of AH was confirmed by adding exogenous ascorbic acid to AZQ free radicals generated by a suspension of L1210 murine leukemia cells. The endogenous ascorbic acid was shown to arise mostly from the "buffy coat" of an RBC preparation which contained leukocytes. Leukocytes are second only to the adrenals in level of ascorbic acid in humans. Cyclic voltammetry of ascorbic acid, AZQ, and adriamycin in Hank's Balanced Salt Solution (HBSS pH 7.5), the buffer used for biological measurements, showed that the oxidation peak potential for ascorbic acid (Eap = +0.43 V) is closer to the reduction peak potential for AZQ (Ecp = -0.36 V) than that for adriamycin (Ecp = -0.67 V). This may explain why the ascorbic acid redox system interacts with that of AZQ but not with that of ADR.


How a Culture of Kindness Can Improve Employee Engagement and Patient Experience - and Five Ways to Get There.
Aware of the evidence demonstrating how important employee engagement is to patient experience, outcomes and cost containment, leadership at Bluewater Health, Sarnia, was looking for strategic solutions to improve engagement. Work with compassion fatigue and resilience specialists suggested focusing on kindness. This article shares the hospital's experience designing and implementing their campaign - from a core committee that empowers and encourages teams to find their own creative ways to promote kindness, through to leadership's commitment to changing organizational culture. There's even a treat cart! Bluewater Health's employee engagement solution has an aspect of fun that is fresh and innovative.


Single nucleotide polymorphism barcoding of cytochrome c oxidase I sequences for discriminating 17 species of Columbidae by decision tree algorithm.
DNA barcodes are widely used in taxonomy, systematics, species identification, food safety, and forensic science. Most of the conventional DNA barcode sequences contain the whole information of a given barcoding gene. Most of the sequence information does not vary and is uninformative for a given group of taxa within a monophylum. We suggest here a method that reduces the amount of noninformative nucleotides in a given barcoding sequence of a major taxon, like the prokaryotes, or eukaryotic animals, plants, or fungi. The actual differences in genetic sequences, called single nucleotide polymorphism (SNP) genotyping, provide a tool for developing a rapid, reliable, and high-throughput assay for the discrimination between known species. Here, we investigated SNPs as robust markers of genetic variation for identifying different pigeon species based on available cytochrome c oxidase I (COI) data. We propose here a decision tree-based SNP barcoding (DTSB) algorithm where SNP patterns are selected from the DNA barcoding sequence of several evolutionarily related species in order to identify a single species with pigeons as an example. This approach can make use of any established barcoding system. We here firstly used as an example the mitochondrial gene COI information of 17 pigeon species (Columbidae, Aves) using DTSB after sequence trimming and alignment. SNPs were chosen which followed the rule of decision tree and species-specific SNP barcodes. The shortest barcode of about 11 bp was then generated for discriminating 17 pigeon species using the DTSB method. This method provides a sequence alignment and tree decision approach to parsimoniously assign a unique and shortest SNP barcode for any known species of a chosen monophyletic taxon where a barcoding sequence is available.


Atypical Hemolytic Uremic Syndrome (p.Gly1110Ala) with Autoimmune Disease.
BACKGROUND Hemolytic uremic syndrome (HUS) can be categorized as primary (typical or atypical) or secondary (with a coexisting diseases). Typical HUS usually means shiga-toxin-medicated and thrombotic thrombocytopenic purpura. Secondary HUS is often initiated by coexisting diseases or conditions such as infections, transplantation, cancer, and autoimmune disease. Atypical HUS (aHUS) is usually induced by genetic mutations of one or several complement-regulating genes and associated with dysregulated complement activation. In the era of compliment-inhibiting therapy, early recognition of aHUS is important for patient prognosis. However, compliment-inhibiting therapy is not always beneficial in patients with secondary HUS. CASE REPORT We present a case of a 49-year-old woman with aHUS, which was caused by a novel genetic point mutation of complement factor H gene (p.Gly1110Ala) mimicking secondary HUS with scleroderma. Instead of administering eculizumab treatment for C5 polymorphism, the patient was successfully treated with mycophenolate mofetil. CONCLUSIONS HUS has complex and mixed etiologies and requires genetic testing. Attention should be paid to new point mutations in aHUS.


[Inhibition of angiogenesis in pancreatic carcinoma by cyclooxygenase-2 antisense oligodeoxynucleotides].
To investigate the effect of cyclooxygenase-2 antisense oligodeoxynucleotides (COX-2 AS-ODNs) on the angiogenesis in pancreatic carcinoma and to evaluate the intermediary effect of prostaglandin 2 in this process. Specific targeting COX-2 AS-ODNs were designed and synthesized, and transfected into the PC3 human pancreatic carcinoma cells cultured in vitro. Fluorescence microscopy was used to observe the PC3 cells 0.12. 24, 40, and 72 hours after the transfection. the second cultured PC3 cells were divided into 5 groups: control group, Lipo group (transfected with Lipofectin only), C1 group (transfected with 1 micro g COX-2 AS-ODN + Lipo/well), C2 group (transfected with 2 micro g COX-2 AS-ODN + Lipo/well), and C3 group (transfected with 3 micro g COX-2 AS-ODN + Lipo/well). RT-PCR was used to observe the expression of COX-2 mRNA in the PC3 cells. The third batch of PC3 cells were transfected with 3 micro g COX-2 AS-ODN + Lipo/well, and the expression of COX-2 mRNA was observed 0, 12, 24, 48, and 72 hours later by RT-PCR. 3 micro g COX-2 AS-ODN + Lipo/bottle and 9 micro g COX-2 AS-ODN + Lipo/bottle were added into the cultured PC3 cells and Western blotting was used to observe the expression of COX-2 protein 24 hours later. 24 chicken eggs were inoculated with PC3 cells into the chorio-allantoic membrane and then divided equally into 5 groups; control group, Lipo group, COX-2 AS-ODN + Lipo group, and COX-2 AS-ODN + Lipo + PGE2 group. Leica microscopy was used to observe the angiogenesis in the transplanted carcinoma. RT-PCR showed that the downregulation of expression of COX-2 mRNA in the PC3 cells with the increase of the COX-2 AS-ODN concentration, peaking at the concentration of 0.2 micro mol/L. The effect of COX-2 AS-ODN was strongest by the 12th hour after transfection and then began to decrease and basically disappeared 48 hours after. Western blotting showed that COX-2 AS-ODN, especially that of the concentration of the expression of 9 micro g/bottle, inhibited the expression of COX-2 AS-ODN. The angiogenesis of the transplanted carcinoma in the eggs was significantly inhibited in the Lipo + COX-2 AS-ODN group, the density of newly generated vessels in the Lipo + COX-2 AS-ODN + PGE2 group was between those of the other 2 groups. COX-2 AS-ODN significantly inhibits the angiogenesis in the pancreatic carcinoma. Endogenous COX-2 AS-ODN may play an important role in such a process and PGE2 may play an intermediate role therein.


The stability of 5-aminolevulinic acid and its ester derivatives.
Application of 5-aminolevulinic acid (ALA) and its esters for treatment of cancer and other disorders became a rapidly developing branch of photodynamic diagnosis and therapy. For clinical use, solutions of ALA (must be buffered to physiological pH. Unfortunately, in such conditions they are unstable. Two molecules of ALA condense and 2.5-(beta-carboxyethyl)-dihydropyrazine and 2.5-(beta-carboxyethyl)-pyrazine are formed. Although, numerous eleborations relate to stability of ALA alone very little or none is known about the stability of ester derivatives of ALA. The present investigations have comprised the stability of ALA and its esters at 37 degrees C in respect of pH. concentration and time of reaction. The studies showed that ALA esters alike ALA undergo dimerisation at pH near 5. Moreover, it is possible that at pH>5.5 hydrolysis of the esters occurs, but this elaboration do not comprise explanation of this phenomenon.


Epidemiology of pertussis in a West African community before and after introduction of a widespread vaccination program.
The control of pertussis remains a worldwide concern. Little has been documented about its epidemiology in Africa. The authors have studied pertussis in a prospective cohort of children in a rural West African community over a 13-year period comprising time before and after introduction of a vaccination program. Children under age 15 years who were residents of the Niakhar study area in Senegal were followed prospectively between January 1984 and December 1996 for the occurrence of pertussis. Morbidity and mortality rates were extremely high before the launch of immunization. Crude incidence was 183 per 1,000 child-years at risk under age 5 years, with a 2.8% case-fatality rate. After the introduction of the vaccination program, overall incidence dropped rapidly and dramatically-by 27% after 3 years and 46% after 6 years. The decline in incidence involved all age groups but was most substantial in the group under age 5 years and was particularly pronounced in unvaccinated infants. The median age of acquisition of the disease rose steadily with population vaccine coverage. This study shows the tremendous magnitude of the disease burden in children and the rapid decline after vaccination, and it suggests a strong herd-immunity effect.


Milk production and blood metabolites of dairy cattle as influenced by thermal-humidity index.
The effects of high thermal stress on serum protein metabolites, milk production of transition dairy cows in semi-arid areas in South Africa were evaluated. Forty, ± 8 months pregnant, Jersey heifers (± 26 months) in zero grazing management were selected during summer from two semi-arid communal areas. Summer thermal-humidity index (THI) of the areas were THI-1 (72-83: extreme caution) and THI-2 (75-87: danger). Blood samples were collected (21 days pre-partum, and 21 and 75 days post-partum) and analysed for serum protein metabolites. Milk yield was recorded daily and samples collected for milk fat, protein, lactose and urea nitrogen analysis. Heifers in THI-2 had lower (P < 0.05) total serum proteins, albumin and blood urea nitrogen than THI-1. Post-calving, cows in THI-1 had higher (P < 0.05) TP (73.4 vs 67.9 g/l) and BUN (4.61 vs 3.77 mmol/l) at 21 DIM, and lower (P creatinine at 21 and 75 DIM than THI-2 group. Milk yield, fat and protein in THI-2 were all lower (P < 0.05) than THI-1 21DIM. The results confirm that heat stress affects utilisation of nutrients in transition dairy cows.


Self-Reported Allergic Occupational Contact Dermatitis among Dental Healthcare Professionals in United Arab Emirates -A Cross Sectional Study.
In dentistry, occupational contact dermatitis may affect dental professionals along with technicians, nurses, and patients. Changes to dental practice in recent years have altered the reported frequencies of allergens causing contact dermatitis in both dental professionals and dental patients. In the current cross-sectional study, we used a structured questionnaire and clinical examinations to examine the prevalence of self-reported hand eczema among United Arab Emirates (UAE). The relationship between subjective skin discomfort and latex, composite/bonding, or other dental materials also was explored. A structured questionnaire was designed to analyze the prevalence of skin conditions among dental professionals and study its implication in gender, occupation, and age groups. The questionnaire included information about skin symptoms, atopy, occupational experience, and other background factors like respiratory symptoms, work history and methods, and exposure at work. It was distributed to 550 randomly selected dental healthcare professionals. Out of 550 dental healthcare workers contacted, 434 responded giving a response rate of 79%. The prevalence of dry and rough skin on the hands was highest (45%). There was a total of 29 cases of allergic contact dermatitis, 15 cases of contact urticaria, 12 cases of irritating contact dermatitis, and 1 incidence of onychomycosis among the 100 dental healthcare professionals who reported having dermatitis on their hands, forearms, or faces due to their daily dental chores. Rubber chemicals and natural rubber latex (NRL) in protective gloves used by dentists, as well as dental-restorative plastic materials (methylacrylates), were the most common causes of allergy. Dry skin and hand eczema were more common among dental healthcare professionals. Plastic gloves or NRL gloves with a low protein content are recommended for dental work. Skin exposure to methylacrylates or latex should be avoided.


Child serum metabolome and traffic-related air pollution exposure in pregnancy.
Maternal exposure to traffic-related air pollution during pregnancy has been shown to increase the risk of adverse birth outcomes and childhood disorders. High-resolution metabolomics (HRM) has previously been employed to identify metabolic responses to traffic-related air pollution in adults, including pregnant women. Thus far, no studies have examined metabolic effects of air pollution exposure in utero on neonates. We retrieved stored neonatal blood spots for 241 children born in California between 1998 and 2007. These children were randomly selected from all California birth rolls to serve as birth-year matched controls for children with retinoblastoma identified from the California cancer registry for a case control study of childhood cancer. We estimated prenatal traffic-related air pollution exposure (particulate matter less than 2.5 μm (PM2.5)) during the third-trimester using the California Line Source Dispersion Model, version 4 (CALINE4) based on residential addresses recorded at birth. We employed untargeted HRM to obtain metabolic profiles, and metabolites associated with air pollution exposure were identified using partial least squares (PLS) regression and linear regressions. Biological effects were characterized using pathway enrichment analyses adjusting for potential confounders including maternal age, race/ethnicity, and education. In total we extracted 4038 and 4957 metabolite features from neonatal blood spots in hydrophilic interaction (HILIC) chromatography (positive ion mode) and C18 reverse phase columns (negative ion mode), respectively. After controlling for confounding factors, partial least square regression (Variable Importance in Projection (VIP) ≥ 2) selected 402 HILIC positive and 182 C18 negative features as statistically significantly associated with increasing third trimester PM2.5 exposure. Using pathway enrichment analysis, we identified metabolites in oxidative stress and inflammation pathways as being altered, primarily involving lipid metabolism. The metabolite features and pathways associated with air pollution exposure in neonates suggest that maternal exposure during late pregnancy contributes to oxidative stress and inflammation in newborn children.


Outcomes of DATA 2000 certification trainings for the provision of buprenorphine treatment in the Veterans Health Administration.
Despite the high numbers of veterans with opioid dependence, few receive pharmacologic treatment for this disorder. The adoption of buprenorphine treatment within the Veterans Health Administration (VHA) has been slow. To expand capacity for buprenorphine treatment, the VHA sponsored two eight-hour credentialing courses for the Drug Addiction Treatment Act of 2000. We sought to describe the outcomes of such training. Following the training sessions, 29 participants (18 physicians) were highly satisfied with course content and affirmed their intention to prescribe buprenorphine; after nine-month follow-up, two physicians were prescribing. We conclude that providing credentialing courses, while popular, did not markedly promote the prescription of buprenorphine.


[Factors associated with mortality in cryptococcal meningitis].
To investigate factors associated with mortality in non-AIDS patients with cryptococcal meningitis. We retrospectively reviewed 154 cases of non-HIV cryptococcal meningitis in a tertiary care hospital in China, from 1997 through 2007. The 1-year attributable mortality was 19.6% (28/143), and overall mortality was 28.7% (41/143). Advanced age (> or = 60 years), delay in diagnosis (> 4 months), hematologic malignancy, solid malignancy, altered mental status (coma, seizure, herniation), and CSF drainage or shunting were factors associated with increased death; factors associated with increased survival were amphotericin B based initial therapy and flucytosine containing therapy. In multivariate analysis, age > or = 60 years, the time from symptom onset to diagnosis > 4 months, coma, cerebral herniation, and non-amphotericin B based initial therapy were independently associated with increased overall mortality; factors independently associated with cause-specific mortality were time from symptom onset to diagnosis > 4 months, cerebral herniation and non-amphotericin B based initial therapy. A variety of factors were associated with mortality in non-AIDS cryptococcal meningitis. Amphotericin B based initial treatment was independently correlated to improved 1-year survival.


Werner's syndrome--chromosome analyses of cultured fibroblasts and mitogen-stimulated lymphocytes.
Two cases of Werner's syndrome are reported. Fibroblasts derived from both patients revealed reduced population doubling numbers. Chromosomal analyses for fibroblasts from both patients and lymphocytes from one patient revealed that chromosomal aberrations occur frequently and randomly. Although some of the chromosomal aberrations involved sites where tumour suppressor genes have been mapped, neither of our patients demonstrated malignancy. Chromosomal aberration at one critical site may not be sufficient to induce cancer or additional factors may be necessary.


The Application of Human Spinal Cord Magnetic Resonance Spectroscopy to Clinical Studies: A Review.
This article reviews the current state of magnetic resonance spectroscopy applied in the human spinal cord with respect to its clinical applications and challenges in comparison to investigations in the human brain. Results from several disease processes affecting the spinal cord are presented, and potential advantages of applying clinical MRS in their investigation are emphasized.


1,4-Bis[2-(prop-1-en-yl)phen-oxy]butane.
The mol-ecule of the title compound, C(22)H(26)O(2), exhibits C(i) mol-ecular symmetry with a crystallographic inversion centre at the mid-point of the central C-C bond. A kink in the mol-ecule is defined by the torsion angle of 66.7 (2)° about this central bond of the alkyl bridge.


[Osteoplastic flap: our experience].
Despite the advances of endoscopic surgical techniques, the frontal sinus obliteration via the osteoplastic flap (OPF) remains the treatment option for frontal sinus pathologies. The aim of this study is to evaluate indications, procedures and results of this technique. Retrospective study of thirty one patients that underwent OPF procedure between 1986 and 1999. The average patient's age was 42 years. The treated pathologies were: 12 mucoceles, 8 fractures, 4 osteomas, 4 sinutisis, 1 frontal abscess, 1 frontal osteomielitis and 1 orbital celullitis. The main clinical symptoms were headache (32%) and nasal obstruction (29%). The surgical approaches es used were: brow incision in 24 patients (78%), bicoronal in 5 (16%) and through the frontal wound in 2 traumatic cases (6%). Endonasal surgical procedures were associated in 8 patients (25%). Frontal sinus obliteration was performed in 23 patients (74%). Surgical revision was necessary in two cases. The were no serious complications. The overall esthetic and functional outcome was good. OPF with fat obliteration is an useful technique in patients who had frontal sinus disease refractary to other methods.


Central pontine myelinolysis complicating treatment of the hyperglycaemic hyperosmolar state.
Central pontine myelinolysis (CPM) is well recognized to occur in a variety of clinical settings, but particularly following rapid correction of severe hyponatraemia. The development of CPM as a result of rapid shifts in plasma osmolality during the treatment of the hyperglycaemic hyperosmolar state (HHS) has hitherto been described in only one case. We report a second case in which this complication occurred in association with treatment of the HHS. The patient was a 49-year-old woman who presented to another hospital with drowsiness and a plasma glucose of 106 mmol/L. Her admission plasma sodium was 135 mmol/L. She received treatment with intravenous insulin and 0.9% normal saline, and there was a rapid drop in plasma glucose by 60 mmol/L within 6 h, which was associated with a rebound rise of plasma sodium to 159 mmol/L. Her plasma glucose and sodium were later stabilized. When the patient was transferred to our hospital a few days later, she was noted to have flaccid quadraparesis and pseudobulbar palsy. A magnetic resonance imaging scan revealed a pontine lesion consistent with CPM. She made a gradual recovery over several months with intensive rehabilitation and eventually returned to near normal functional capacity. This is the second case report in the literature of CPM complicating the management of HHS and highlights the importance of the judicious and measured correction of hyperglycaemia and the appropriate management of fluid replacement and electrolyte balance when treating this condition.


Genetic Background and Clinical Characters of Pediatric Chronic Pancreatitis: Data and Implications from the East.
Background. The clinical pattern and genetic background of juvenile idiopathic chronic pancreatitis (ICP) are yet unclear. Methods. A retrospective study of 73 Chinese juvenile ICP patients was performed, and genetic tests were carried out to detect relevant mutations using direct sequencing technique and high-resolution melting technique. Subjects without pancreatitis served as controls. Results. The SPINK1 c.194+2T>C variant was present in 56.16% and 42.00% of juvenile and adult ICP patients, respectively (p = 0.020), but was not present in any of the control subjects. Thirty-four (46.58%) of the 73 juvenile ICP patients were male, and a significantly higher ratio of male patients in the adult group was identified (46.58% versus 64.00%, p = 0.022). Although most of the juvenile patients presented with abdominal pain (70/73, 95.89%), the patterns of pain attack are significantly different in patients with or without SPINK1 c.194+2T>C mutation. Patients carrying the mutation are more likely to present with recurrent acute pancreatitis (70.70%). Conclusions. The main symptom of pediatric ICP was abdominal pain. SPINK1 c.194+2T>C mutation had a higher occurrence in juvenile ICP patients than in adult group and typically presented with recurrent acute pancreatitis. There may be unidentified factors that lead to a greater incidence rate of ICP in adult male population.


Is the degree of sensitivity to nondepolarizing muscle relaxants related to requirements for postoperative ventilation in patients with myasthenia gravis?
The purpose of this study was to examine whether the degree of sensitivity to nondepolarizing muscle relaxants is related to the requirement for postoperative ventilatory support in patients with myasthenia gravis. Thirty-six patients with myasthenia gravis undergoing trans-sternal thymectomy were monitored by electromyography in order to assess the neuromuscular response to vecuronium. After calibration to 100% of baseline electromyographic response values using an EMG monitor, incremental doses of 5, 10 and 20 microg/kg of vecuronium were administrated to produce 95% neuromuscular blockade and to obtain a cumulative dose-response curve for each patient. A univariable logistic regression with odds ratio was used to examine the predictive variables of prolonged postoperative ventilation. Depending on their postoperative ventilatory needs, patients were divided into an early extubation group and a prolonged ventilatory group. There were no significant differences between the two groups in terms of vecuronium ED95 (prolonged ventilation group: 23.2 +/- 18 microg/kg; early extubation group: 23.2 +/- 18 microg/kg P=0.129) and vecuronium requirement to maintain less than 25% neuromuscular blockade (prolonged ventilation group: 24 +/- 1.7 mg/kg; early extubation group: 3.8 +/- 4.5 mg/kg P=0.249). There were, however, significant differences in the incidence of a history of previous respiratory crises and the presence of bulbar palsy between the early extubation and prolonged ventilation groups. History of previous respiratory crisis (odds ratio (OR), 3.5; 95% confidence interval (CI), 1.0-13; P=0.03) and presence of bulbar palsy (OR, 3.7; 95%CI, 0.9-15; P=0.049) were associated with the need for prolonged postoperative ventilation. However, we failed to demonstrate that the degree of sensitivity to nondepolarizing muscle relaxants was related to an increased requirement for postoperative ventilation in patients with myasthenia gravis.


Desiderata for representing anatomical knowledge.
The general problem of knowledge representation for gross anatomy supporting both computers and human is rarely globally solved. Partial solutions are flourishing, but the actual and potential users are left with a lack of satisfaction and uncomfortable feeling of incompleteness. Moreover, these solutions are not ready for a sound evolution and are at risk to disappear at any moment by default of adequate maintenance. In addition, the problem is complicated by the fact that any solutions should be relevant for Natural Language Processing applications in a multilingual environment.This paper tackles with this problem and defines the basic steps for a proper knowledge representation scheme. Taking the subdomain of gross anatomy, it shows how each step has been solved and what performances and benefits are expected by such a solution. A discussion is done on the way to interface from a common source for both computers and humans.


Incidental detection of colonic inflammation on PET/CT using 18F-FDG-labeled autologous leukocytes.
Labeled leukocyte scintigraphy and (18)F-FDG PET are well-documented techniques for the assessment of inflammatory bowel disease. In this study, a 28-year-old man with abdominal pain, vomiting, and raised serum amylase and lipase levels underwent PET/CT imaging using FDG-labeled autologous leukocytes to assess for pancreatic infection. While the pancreas showed no abnormal tracer uptake, colonic inflammation was incidentally detected, and a diagnosis of pseudomembranous colitis was subsequently confirmed on colonoscopy and biopsy.


Prevention of metabolic syndrome from atypical antipsychotic medications: applying Rogers' diffusion of innovations model in clinical practice.
Patients who are taking atypical antipsychotic medications have a high incidence of metabolic complications, including increased weight, waist circumference, blood sugar, lipid levels, and blood pressure. In 2004, the American Diabetic Association and three other associations, including the American Psychiatric Association, developed guidelines to screen for metabolic syndrome, but in practice, adherence to the guidelines varies. This article describes a process to implement the guidelines in a suburban psychiatric day treatment hospital using Rogers' Diffusion of Innovations model. Measurement of waist circumference was identified as an opportunity to improve the current metabolic screening protocol. Post-intervention evaluation revealed increased adherence to the guidelines (0% pre versus 95% post). Adherence to the guidelines demonstrates the effect of the systematic application of Rogers' model on acceptance of practice change. Fully implementing the guidelines meets recommendations for the standard of practice and can improve the health and quality of life of patients prescribed atypical antipsychotic medications.


Carbohydrate metabolism and plasma levels of insulin and glucagon in patients with atherosclerotic vascular disease.
In non-obese, non-diabetic patients suffering acute myocardial infarction, angina pectoris, previous myocardial infarction and peripheral vascular disease, the plasma levels of glucose, insulin, C-peptide and glucagon were determined in basal condition and during an intravenous glucose tolerance test. In the four groups there was a high frequency of glucose intolerance. Basal hyperinsulinism was present in all groups; in groups; in those which maintained normal glucose tolerance there was a high B-cell response to the sugar. Basal hyperglucagonemia was found in the early stage of acute ischemic heart disease, in patients with previous myocardial infarction and in those with peripheral vascular disease. The elevated plasma glucagon levels may play a role in the complex disturbance of carbohydrate metabolism present in patients with atherosclerotic vascular disease.


Chromatin accessibility and guide sequence secondary structure affect CRISPR-Cas9 gene editing efficiency.
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (CRISPR-Cas9) systems have emerged as the method of choice for genome editing, but large variations in on-target efficiencies continue to limit their applicability. Here, we investigate the effect of chromatin accessibility on Cas9-mediated gene editing efficiency for 20 gRNAs targeting 10 genomic loci in HEK293T cells using both SpCas9 and the eSpCas9(1.1) variant. Our study indicates that gene editing is more efficient in euchromatin than in heterochromatin, and we validate this finding in HeLa cells and in human fibroblasts. Furthermore, we investigate the gRNA sequence determinants of CRISPR-Cas9 activity using a surrogate reporter system and find that the efficiency of Cas9-mediated gene editing is dependent on guide sequence secondary structure formation. This knowledge can aid in the further improvement of tools for gRNA design.


Dietary versus postmortem supplementation of vitamin E on pigment and lipid stability in ground beef.
Effects of dietary supplementation and postmortem addition of vitamin E on pigment and lipid stability in raw ground beef were examined in this study. Six Holstein steers were fed a control diet for 232 or 252 d and six Holstein steers were supplemented with 1,500 IU of vitamin E per animal daily for 232 or 252 d. Three aliquots of ground beef from each longissimus lumborum were allotted to the following postmortem treatments: no addition (NO), white mineral oil (OIL), and white mineral oil containing sufficient D-alpha-tocopherol to equal the mean difference of alpha-tocopherol concentration between beef from supplemented and control steers (OIL + E). Metmyoglobin percentages and 2-thiobarbituric acid reactive substances values were determined at d 1, 3, 5, 7, and 9 after postmortem treatment. Dietary vitamin E supplementation delayed metmyoglobin increase and highly suppressed lipid oxidation in ground beef during 9 d of display compared with the control. The postmortem addition of vitamin E (OIL + E) was slightly effective in retarding the oxidation of pigment and lipid, especially compared with the OIL treatments. Endogenous vitamin E improved pigment and lipid stability much better than exogenous vitamin E.


On Rhinella gildae Vaz-Silva, Maciel, Bastos Pombal 2015 (Anura: Bufonidae): Phylogenetic relationship, morphological variation, advertisement and release calls and geographic distribution.
Anurans in the Rhinella margaritifera group have a long history of taxonomic confusion, mainly by morphological similarity between species and lack of acoustic and genetic data for many of the 19 described species. Herein, we presented data for Rhinella gildae based on recently collected specimens from its type locality. We provide patterns of morphological variation, measurements, advertisement and release calls and infer the phylogenetic position of R. gildae. The species geographical distribution was updated, occurring in two Amazonian localities in Maranhão state, and Cerrado areas in Maranhão and Tocantins states and also in a rainforest enclave inside Caatinga domain in Ceará state.