Protease-activated receptor-2 activating peptide SLIGRL inhibits bacterial lipopolysaccharide-induced recruitment of polymorphonuclear leukocytes into the airways of mice.
Protease-activated receptor-2 (PAR2) acts as a receptor for trypsin and trypsin-like enzymes. The role of this receptor in airway inflammation is uncertain. In this study we assessed the effect of activation of PAR2 following intranasal administration of the peptide activator of PAR2, SLIGRL, over 72 h in mice. The extent of immune cell infiltration into the airways and activities of matrix metalloprotease-2 (MMP-2) and MMP-9 were assessed in bronchoalveolar lavage (BAL) by differential cell counts and gelatin zymography, respectively. SLIGRL did not cause a change in the number or types of cells retrieved in BAL at any time point and did not alter the levels of MMP-2 and MMP-9 present in BAL. In contrast, similar intranasal administration of bacterial lipopolysaccharide (LPS) caused a large influx of neutrophilic polymorphonuclear leukocytes, which was associated with increased MMP-2 at 3 h only and MMP-9 activity from 3-72 h. Simultaneous administration of SLIGRL and LPS transiently potentiated increased MMP-9 activity at 3 h but markedly inhibited neutrophil influx and elevated MMP-2 activity at 3 h. These findings suggest that PAR2 agonists may be useful therapeutic molecules in pulmonary inflammatory diseases.


Pathogenesis of Woronoff ring in psoriasis.
As a result of ultraviolet light and coal tar therapy, a white ring (Woronoff) may develop in the normal skin adjacent to psoriatic plaques. Injection of prostaglandin E2 (PGE2) 1 cm outside of Woronoff ring produced redness in the ring, demonstrating that vessels within the ring were not unresponsive to PGE2. Whole skin homogenates from Woronoff ring contained an inhibitor of prostaglandin synthesis that was not found in uninvolved skin that was obtained from either psoriatics or normal controls. Prostaglandin E2 levels in the ring were one third of those in uninvolved skin from either psoriatics or normal controls. These findings suggest that the white ring that surrounds ultraviolet-light-treated psoriatic plaques is produced by a local inability to synthesize PGE2 in response to an ultraviolet light stimulus, resulting from the presence of an inhibitor of prostaglandin synthesis.


Effect of Axonal Trauma on Nerve Regeneration in Side-to-side Neurorrhaphy: An Experimental Study.
Side-to-side (STS) neurorrhaphy can be performed distally to ensure timely end-organ innervation. It leaves the distal end of the injured nerve intact for further reconstruction. Despite encouraging clinical results, only few experimental studies have been published to enhance the regeneration results of the procedure. We examined the influence of different size epineural windows and degree of axonal injury of STS repair on nerve regeneration and donor nerve morbidity. Three clinically relevant repair techniques of the transected common peroneal nerve (CPN) were compared. Group A: 10-mm long epineural STS windows; group B: 2-mm long windows and partial axotomy to the donor tibial nerve; and group C: 2-mm long windows with axotomies to both nerves. Regeneration was followed by the walk track analysis, nerve morphometry, histology, and wet muscle mass calculations. The results of the walk track analysis were significantly better in groups B and C compared with group A. The nerve fiber count, total fiber area, fiber density, and percentage of the fiber area values of CPN of the group C were significantly higher when compared with group A. The wet mass ratio of the CPN-innervated anterior tibial muscle was significantly higher in group C compared with group A. The wet mass ratio of the tibial nerve-innervated gastrocnemial muscle was higher in group A compared with the other groups. All three variations of the STS repair technique showed nerve regeneration. Deliberate donor nerve axotomy enhanced nerve regeneration. A larger epineural window did not compensate the effect of axonal trauma on nerve regeneration.


An article on "letter to the editor".
A 'Letter to the Editor' is an abbreviated form of communication where 'readers' can express their carefully considered scientific opinion about a recently published article in a journal. It is considered as 'post-publication peer review'. There are certain things that a letter writer and the 'editor' need to keep in mind while writing a 'Letter' for a journal. The 'editor' needs to curate the contents of the 'Letter' and make sure that there are no misinformation shared. The formatting, type, scope and the scientific quality of the 'Letter' depend on the journal that publishes them, and hence, different publications may require their 'letter writers' to present the information that they want in a certain way. The following article reflects an overview of the role of editors and writers, guidelines, scope, and format of the 'Letter to the Editor'.


Dynamic light scattering from colloidal fractal monolayers.
We address experimentally the problem of how the structure of a surface monolayer determines the viscoelasticity of the interface. Optical microscopy and surface quasielastic light scattering have been used to characterize aggregation of CaCO3 particles at the air-water interface. The structures formed by cluster-cluster aggregation are two-dimensional fractals that grow to eventually form a percolating network. This process is measured through image analysis. On the same system we measure the dynamics of interfacial thermal fluctuations (surface ripplons), and we discuss how the relaxation process is affected by the growing clusters. We show that the structures start damping the ripplons strongly when the two length scales are comparable. No macroscopic surface pressure is measured and this is in contrast to lipid, surfactant, or polymer monolayers at concentrations corresponding to surface coverage. This observation and the difficulty in fitting the ripplon spectrum with traditional models suggest that a different physical mechanism might be responsible for the observed damping of ripplons in this system.


Stromal invasion by carcinoma of the cervix: assessment with dynamic MR imaging.
The purpose of this study was to evaluate dynamic MR imaging in assessing the depth of stromal invasion by carcinoma of the cervix and to compare dynamic MR imaging with T2-weighted and contrast-enhanced T1-weighted MR imaging. Forty-one patients with carcinoma that was clinically considered to be confined to the cervix were examined with T2-weighted, dynamic, and contrast-enhanced T1-weighted MR imaging before surgery. We evaluated enhancement patterns of the cervix and tumor and assessed the degree of stromal invasion with MR imaging. The degree of stromal invasion was divided into two groups: superficial disease (no stromal invasion or invasion of < or = 3 mm) and deep invasion (> 3 mm of stromal invasion). Then we compared these MR findings with histologic results for the depth of stromal invasion. With dynamic MR imaging, cervical carcinoma with deep invasion was seen as a focal enhanced area in the early dynamic phase. The cervical epithelium and stroma enhanced less vividly. In distinguishing deep invasion from superficial disease, we found the accuracy of T2-weighted MR images, dynamic MR images, and contrast-enhanced T1-weighted MR images to be 76%, 98%, and 63%, respectively. In particular, the detectability of 3.1-5.0 mm of stromal invasion with dynamic MR images was significantly higher than that with the other techniques: with T2-weighted MR images, we saw 3.1-5.0 mm of stromal invasion in 23% of patients; with dynamic MR images, in 92%; and with contrast-enhanced T1-weighted MR images, in none. Superficial disease was not revealed with any of the three MR techniques. We believe that dynamic MR imaging is superior to T2-weighted MR imaging and contrast-enhanced T1-weighted MR imaging when assessing the depth of invasion of cervical carcinoma.


Nerve growth factor promotes human sperm motility in vitro by increasing the movement distance and the number of A grade spermatozoa.
Nerve growth factor (NGF) was first found in the central nervous system and is now well known for its multiple pivotal roles in the nervous system and immune system. However, more and more evidences showed that NGF and its receptors TrkA and p75 were also found in the head and tail of spermatozoa, which indicate the possible effect of NGF on the sperm motility. Nevertheless, the exact role of NGF in the human sperm motility remains unclear until now. In this study, we investigated the effect of NGF on human sperm motility, and the results showed that NGF could promote human sperm motility in vitro by increasing the movement distance and the number of A grade spermatozoa. Further analysis demonstrated that NGF promoted the sperm motility in a dose-dependent manner in vitro. These results may facilitate the further studies on human fertility and assisted reproduction techniques.


Cholangiohepatitis in Dairy Cattle: 13 Cases.
The signalment, clinicopathologic, bacteriological, histopathological, ultrasonographic characteristics, and the treatment and outcomes of adult cattle with cholangiohepatitis are poorly defined. Thirteen Holstein cows with cholangiohepatitis. Retrospective study of medical records of cattle admitted to the CHUV and the AVC between 1992 and 2012 and 2000 and 2012, respectively, for cattle older than 3 months of age with a histopathological diagnosis of cholangiohepatitis. Cholangiohepatitis was defined as the presence of portal inflammation surrounding or infiltrating bile ducts, with or without epithelial damage, and extending into the adjacent lobules. At the time of diagnosis of cholangiohepatitis, cows had decreased appetite (n = 7) or were anorectic (n = 6), had fever (n = 5), and had tachycardia (n = 8). Icterus was detected in 5 cows. Yellow discoloration was identified on the skin of the udder (n = 3), conjunctiva (n = 2), and vulva (n = 1). There was leukocytosis (n = 6), neutrophilia (n = 9), and hyperfibrinogenemia (n = 8). Alteration in the serum biochemistry profile included hyperglobulinemia (n = 8), hypoalbuminemia (n = 10), increased activity of GGT (n = 12), AST (n = 8), and ALP (n = 10), and hyperbilirubinemia (n = 10). Histopathological diagnosis included mild, subacute, nonsuppurative cholangiohepatitis (n = 4), mild suppurative cholangiohepatitis (n = 4), mild mixed (neutrophilic and lymphocytic) cholangiohepatitis (n = 3), and moderate, chronic, nonsuppurative cholangiohepatitis (n = 1). Six cows were discharged from the hospital, and 7 were euthanized. Cholangiohepatitis is a rare condition in adult cattle. Antemortem diagnosis can be challenging because clinical signs are unspecific.


Psychological distress and social factors in patients with asthma and chronic obstructive lung disease.
Chronic respiratory diseases which embrace asthma and chronic obstructive pulmonary disease (COPD) are common in the population. In a large number of cases they are diagnosed very late. Statistics of deaths, especially in the case of COPD, are underestimated because morbidity and mortality can be affected by other comorbid conditions, for example cardiovascular disease. Asthma and COPD impair not only physical functioning of patients but also affect their psychological state. Mood disorders and cognitive function impairment are more often observed in this group than in the general population. It has been proven that the coexistence of psychological dysfunction significantly worsens the functioning of patients (affects, among others, their work, family and social lives) and has an impact on the course of the treatment of the somatic illness. First of all, patients with cognitive deficits have greater problems in applying treatment recommendations. Accordingly, it seems to be important to pay more attention to the problem of mental disorders in patients with obstructive lung diseases. There is a clear need for a multidisciplinary approach that will enable prevention, early detection and effective treatment of the psychological disorders in that group of patients.


[Coronary arteriography in severe aortic valve disease].
Three hundred and twelve patients with severe aortic valve disease underwent a pre-operative haemodynamic study including coronary arteriography either as routine (age more than 50 years) or because of chest pains, previous myocardial infarction or for patients with risk factors of coronary atherosclerosis. Significant coronary artery disease was present in 9% of all cases. Coronary artery disease was more frequent in patients with angina and in patients with previous myocardial infarction but none of these factors was specific. We conclude that except young patients < 40 years old, with no chest pain and no coronary risk factors, coronary arteriography is recommended in patients with severe aortic valve disease before aortic valve replacement.


Repression of miR156 by miR159 Regulates the Timing of the Juvenile-to-Adult Transition in Arabidopsis.
Temporally regulated microRNAs have been identified as master regulators of developmental timing in both animals and plants. In plants, vegetative development is regulated by a temporal decrease in miR156 level, but how this decreased expression is initiated and then maintained during shoot development remains elusive. Here, we show that miR159 is required for the correct timing of vegetative development in Arabidopsis thaliana Loss of miR159 increases miR156 level throughout shoot development and delays vegetative development, whereas overexpression of miR159 slightly accelerated vegetative development. The repression of miR156 by miR159 is predominantly mediated by MYB33, an R2R3 MYB domain transcription factor targeted by miR159. Loss of MYB33 led to subtle precocious vegetative phase change phenotypes in spite of the significant downregulation of miR156. MYB33 simultaneously promotes the transcription of MIR156A and MIR156C, as well as their target, SPL9, by directly binding to the promoters of these three genes. Rather than acting as major players in vegetative phase change in Arabidopsis, our results suggest that miR159 and MYB33 function as modifiers of vegetative phase change; i.e., miR159 facilitates vegetative phase change by repressing MYB33 expression, thus preventing MYB33 from hyperactivating miR156 expression throughout shoot development to ensure correct timing of the juvenile-to-adult transition in Arabidopsis.


The management of clinical laboratories in Europe: a FESCC survey. Forum of the European Societies of Clinical Chemistry and Laboratory Medicine.
The professional duties of the specialists in clinical chemistry differ from country to country in Europe. One of the main goals of the Strategic Plan of the Forum of the European Societies of Clinical Chemistry and Laboratory Medicine (FESCC; IFCC-Europe) is to promote a high scientific and professional standard in the field of clinical chemistry and laboratory medicine in Europe. This can be stimulated by the knowledge of the local conditions in each country and by striving towards a strong and harmonised position in all the European countries. In order to enhance the knowledge of the managerial situation of the specialists in clinical chemistry in Europe, FESCC launched a survey in September 2000. This survey provides information about the position of the specialists in clinical chemistry in the various disciplines in the medical laboratories and in hospitals, and about the advisory tasks and the managerial education during the post-graduate training in clinical chemistry. Of the 35 FESCC member countries 33 have participated in the survey (94%). The results show a rather heterogeneous situation in Europe caused by the local historical developments, the differences in academic background and the relative numbers of private and physicians' office laboratories. Large differences exist between the European countries in the disciplines of laboratory medicine that are headed by a specialist in clinical chemistry. In the different countries the clinical chemistry laboratories are headed by specialists in clinical chemistry in between 20% and 100% of the laboratories. The haematology, immunology, microbiology, therapeutic drug monitoring, molecular biology and haemostasis laboratories and departments of blood banking are headed by specialists in clinical chemistry in between 0% and 100% of the laboratories. The responsibilities for the various managerial tasks of the specialists in clinical chemistry show no uniformity in Europe. In the majority of the countries the general management, the purchase of equipment and reagents and the education of technicians are in >90% the responsibility of the specialists in clinical chemistry. In most countries the majority of the specialists in clinical chemistry are members of the medical staff of the hospitals and have a position equivalent to the position of specialists in other medical disciplines. In some countries, however, it only holds true for the specialists with a medical background. In 79% of the countries the law regulates the profession of the specialists in clinical chemistry and in 60% of the countries the law regulates their position in the medical staff of the hospital. The advisory tasks to physicians, general practitioners and other users of laboratory tests are practised by >90% of the laboratories in 64% of the countries. Information is given directly to the patients by >90% of the laboratories in 30% of the countries. Only in a few countries laboratories give information to the public. The post-graduate training in clinical chemistry includes a managerial training in 58% of the countries, the study of information technology in 61% of the countries and an economy and/or a business administration study in 15% of the countries. In 27% of the countries no managerial education forms part of the post-graduate study in clinical chemistry. Harmonisation of the managerial aspects of the profession is one of the challenges for the European specialists in clinical chemistry. A European syllabus for post-graduate training could be helpful.


[Resection of navicular bone for severe midfoot deformity in children].
The navicular bone lies at the apex of the deformity in severe talipes planovalgus with forefoot abductus, in the residual cavus of congenital talipes equinovarus, in certain cases of congenital convexity, and in certain types of neurological equinovarus. Resection of the navicular bone can be proposed to correct certain deformities. This series included 15 feet operated on in 13 children from 1980 to 2003. The deformity to be corrected was a residual cavus after surgery for congenital talipes equinovarus (five feet), plantar and medial dislocation of the navicular bone on an acquired equinovarus in non-walking children (three feet), planovalgus with major forefoot abductus in non-walking children (four feet). Among the 13 children in this series, five did not walk (seven feet) and underwent surgery because of skin wounds caused by protrusion of the head of the talus and serious mechanical problems (shoes, ortheses). Mean age at operation was 8.5 years (range 2-16 years). The surgical procedure was part of an overall strategy combining use of ortheses, physiotherapy, and medical management. For congenital equinovarus with residual cavus, naviculectomy was performed after the usual technique for equinovarus when the navicular bone was dislocated above the medial tarsal and prevented reduction of the cavus. After extraperiosteal release, resection of the navicular bone enabled correction of the cavus. The lateral column had to be shortened in order to avoid adductus subsequent to medial-lateral length discrepancy. The same surgical technique was used for acquired equinovarus except that the navicular bone was displaced medially and above the talus. The lateral column had to be shortened. Standard procedures were applied for congenital convex feet before naviculectomy when there was major forefoot abductus after medial tarsal release and tendon lengthenings. The lateral column was not shortened since it was already too short. For planovalgus with forefoot abductus, naviculectomy was combined with release of the calcaneocuboid joint. Fibular tendons were lengthened. Mean follow-up was two years five months (range 5 months-12 years 6 months). For the talipes equinovarus feet, the Méary Toméno angle was 24.4 degrees on average preoperatively and 5 degrees at last follow-up, giving a mean gain of 19.4 degrees . For congenital convex feet, the M5-lateral calcaneal border angle was 29.7 degrees on average preoperatively and 11.7 degrees at last follow-up for a mean gain of 18 degrees . For the planovalgus feet with forefoot abductus, the M5-lateral calcaneal border angle was 32.7 degrees on average preoperatively and 12.2 degrees at last follow-up, for a gain of 20.5 degrees on average; the mean Méary Toméno angle was -30 degrees preoperatively and -3 degrees at last follow-up, for a mean gain of 27 degrees . For carefully selected patients, naviculectomy performed in combination with other procedures can provide appropriate correction of severe midfoot deformities in children.


The presence of a methylation fingerprint of Helicobacter pylori infection in human gastric mucosae.
Aberrant DNA methylation is deeply involved in human cancers, but its inducers and targets are still mostly unclear. Helicobacter pylori infection was recently shown to induce aberrant methylation in gastric mucosae, and produce a predisposed field for cancerization. Here, we analyzed the presence of target genes in methylation induction by H. pylori and the mechanism for the gene specificity. Noncancerous gastric mucosae were collected from 4 groups of individuals (with and without a gastric cancer, and with and without current H. pylori infection; N = 11 for each group), and methylation of promoter CpG islands of 48 genes that can be methylated in gastric cancer cell lines was analyzed by methylation-specific PCR. In total, 26 genes were consistently methylated in individuals with current or past infection by H. pylori, whereas 7 genes were not methylated at all. In addition, 14 genes were randomly or intermediately methylated in individuals with gastric cancers and the remaining 1 gene was methylated in all the cases. The methylation-susceptible genes had significantly lower mRNA expression levels than the methylation-resistant genes. H. pylori infection did not induce mRNA and protein expression of DNA methyltransferases; DNMT1, DNMT3A or DNMT3B. Gene specificity was present in the induction of aberrant DNA methylation by H. pylori infection, and low mRNA expression, which could precede methylation, was one of the mechanisms for the gene specificity. These findings open up the possibility that a methylation fingerprint can be used as a novel marker for past exposure to a specific carcinogenic factor.


Crystal structure of 2'-deoxycytidine hemidihydrogenphosphate reveals C+.C base pairs and tight, hydrogen-bonded (H2PO4-)infinity columns (1).
2'-Deoxycytidine hemidihydrogenphosphate has been crystallized in the hexagonal space group P6(2) with a = 25.839(3), c = 12.529(1) A. The structure has been solved using the Patterson search method. The asymmetric unit contains two protonated, base-paired 2'-deoxycytidine dimers and two H2PO4- anions. The C+.C base pairs are composed of a protonated and a neutral species each and are triple H-bonded, the central N(3) ... N(3) bonds being 2.850(7) and 2.884(5) A. The conformations of the four nucleosides fall in the same category (sugar puckers 2'-endo, glycosidic links anti) but in one of them the glycosidic torsion angle is quite low with consequences in other geometrical parameters. The H2PO4- anions are located on twofold axes and form two types of tight columns with P ... P separations about 4.18 A. The neighboring units along a column are linked via two very short O ... H ... O hydrogen bonds (O ... O about 2.49 A) leading to effective equalization of the P-O bonds. The base pairs of the two dC+.dC cations are coplanar and form layers perpendicular to the phosphate columns repeating every c/3. Within the layers, the dimers form a network through O(5') ... O(2) hydrogen bonds but their primary intermolecular interactions have the form of H-bond anchors [N(4)-H ... O-P and O(3')-H ... O-P] to the phosphate groups.


Recurrences of thyroid well differentiated cancer: ultrasonography-guided surgical treatment.
Differentiated thyroid carcinomas (DTC) have a favourable outlook overall. Cornerstone of treatment is total thyroidectomy (TT), followed, if needed, by radiometabolic therapy. Such lesions however show a definite tendency to recur (about 35% of cases), generally in the first decade of follow-up: in 70% of patients such recurrence is local. Surgical resection is the only curative treatment option for local recurrence of well-differentiated thyroid cancer. Intraoperative ultrasonography (US) can be of significant help in facilitating localization and complete resection of lesions. The aim of the study was to review the authors' own experience with the use of such diagnostic method in the clinical setting of thyroid neoplasm recurrence. Between January 2005 and March 2008 31 patients with DTC recurrences underwent intraoperative US exploration. Recurrences were easily identified and resected in all patients. Postoperative tireoglobuline (TG) was undetectable. In all 31 patients preoperative US confirmed the presence of the lesion. In 26 patients digital exploration of the surgical field did not yield a definitively positive finding, whereas in 5 the lesion was easily palpable. Intraoperative US revealed the presence of pathologic tissue in all cases, with examination time ranging from 4 to 14 minutes (median 8 minutes). In all cases surgical resection was complete, with pathologic confirmation of the sample, and no necessity to extend ablation. Intraoperative US can be of significant help in the identification of DTC recurrences, in particular when lesion dimensions are smaller than 10 mm in diameter and can facilitate a more radical excision of the tumor in a surgical field were anatomical landmarks can be altered by previous surgery and/or radiometabolic therapy.


Model-Based Tool for Personalized Adjustment of Basal Insulin Supply in Patients With Intensified Conventional Insulin Therapy.
The decisive factor in successful intensive insulin therapy is the ability to deliver need-based-adjusted nutrition-independent insulin dosages at the closest possible approximation to the physiological insulin level. Because this basal insulin requirement is strongly influenced by the patient's lifestyle, its subtlety is of great importance. This challenge is very different between patients with type 1 diabetes and those with insulin-dependent type 2 diabetes. Furthermore, it is more difficult to finetune a basal insulin dosage with intensified conventional insulin therapy (ICT), due to delayed insulin delivery, compared to insulin pump therapy, which provides continuous delivery of small doses of exclusively short-acting insulin. In all cases, the goal is to achieve an optimal basal delivery rate. We hypothesized that this goal could be achieved with a modeling tool that determined the optimal basal insulin supply based on the patient's anamnestic data and monitored glucose values. This type of modeling tool has been used in health insurance programs in Germany to improve insulin control in patients that receive ICT. Our retrospective data analysis showed that this modeling tool provided a significant improvement in metabolic control, significant reductions in HbA1c and Q scores, and improved time-in-range values, with reduced daily insulin levels. The model-based basal rate test could provide additional data of the actual effect of the basal insulin adjustment in intensified insulin treated diabetes to the physician or treatment team.


A Negative Element Located in the Upstream Flanking Region of the Gene Encoding Arginyl-tRNA Synthetase (argS) from Escherichia coli.
The gene, argS, encoding the arginyl-tRNA synthetase (ArgRS) from Escherichia coli ( E.coli ) was overexpressed 1 000 fold in the transformant when E. coli TG1 was transformed with the recombinant plasmid containing argS and pUC18. In order to investigate the regulation of expression of E. coli argS, a series of deletion mutations was constructed. The results of SDS-PAGE showed that deletions of the whole 5' flanking region (argSdelta1) or the region in front of Shine-Dalgarno Sequence (argSdelta2) or the -10 region of promoter (argSdelta3), caused no overexpression of argS. If argS was deleted from 3' end of the flanking region (-189 nt) to the upstream of -10 region of promoter (argSdelta4), the -35 region (argSdelta5), -52 nt (argSdelta6), -70 nt (argSdelta7) and -122 nt (argSdelta8), respectively, the mutant gene was overexpressed to a level similar to that of argS bringing the full length 5' flanking region. However, in the expression of argSdelta4, argSdelta5, argSdelta6, some of ArgRS formed an inclusion body. By determination of RNA dot hybridization, the amount of mRNA produced in the transcription of argSdelta4, argSdelta5 and argSdelta6 was about 2--3 times than that of the wild type argS, argS delta7 and argS delta8. This indicated that the deletion of a 19 nt sequence (AATAGTGAAAACGGCAATA) located between -52 nt and -70 nt of the gene increased the transcription of argS. The 19 nt sequence is a negative region that represses transcription of argS. Deletion of the negative element may result in a faster production of ArgRS and the accumulation of some unfolding protein intermediates aggregating to form the inclusion body. The result by analysis of gel retardation shows that a factor binds to the negative element. Arginine induced specifically the transcription of argS and its effect correlated with the above negative element.


Pupillometric analysis for assessment of gene therapy in Leber Congenital Amaurosis patients.
Objective techniques to assess the amelioration of vision in patients with impaired visual function are needed to standardize efficacy assessment in gene therapy trials for ocular diseases. Pupillometry has been investigated in several diseases in order to provide objective information about the visual reflex pathway and has been adopted to quantify visual impairment in patients with Leber Congenital Amaurosis (LCA). In this paper, we describe detailed methods of pupillometric analysis and a case study on three Italian patients affected by Leber Congenital Amaurosis (LCA) involved in a gene therapy clinical trial at two follow-up time-points: 1 year and 3 years after therapy administration. Pupillary light reflexes (PLR) were measured in patients who had received a unilateral subretinal injection in a clinical gene therapy trial. Pupil images were recorded simultaneously in both eyes with a commercial pupillometer and related software. A program was generated with MATLAB software in order to enable enhanced pupil detection with revision of the acquired images (correcting aberrations due to the inability of these severely visually impaired patients to fixate), and computation of the pupillometric parameters for each stimulus. Pupil detection was performed through Hough Transform and a non-parametric paired statistical test was adopted for comparison. The developed program provided correct pupil detection also for frames in which the pupil is not totally visible. Moreover, it provided an automatic computation of the pupillometric parameters for each stimulus and enabled semi-automatic revision of computerized detection, eliminating the need for the user to manually check frame by frame. With reference to the case study, the amplitude of pupillary constriction and the constriction velocity were increased in the right (treated eye) compared to the left (untreated) eye at both follow-up time-points, showing stability of the improved PLR in the treated eye. Our method streamlined the pupillometric analyses and allowed rapid statistical analysis of a range of parameters associated with PLR. The results confirm that pupillometry is a useful objective measure for the assessment of therapeutic effect of gene therapy in patients with LCA. ClinicalTrials.gov NCT00516477.


17 beta-(cyclopropylamino)-androst-5-en-3 beta-ol, a selective mechanism-based inhibitor of cytochrome P450(17 alpha) (steroid 17 alpha-hydroxylase/C17-20 lyase).
A new compound, 17 beta-(cyclopropylamino)-androst-5-en-3 beta-ol, MDL 27,302, has been designed and synthesized as a mechanism-based inhibitor of cytochrome P450(17 alpha). The time-dependent inactivation of human testicular P450(17 alpha) is irreversible by dialysis and requires the cofactor, NADPH; Kiapp. 90 nM (determined on cynomolgous monkey testis enzyme). Inactivation was not affected by the nucleophile DTT, suggesting retention of the inhibitor in the enzyme active site during the inactivation process. Inhibition is specific to the cyclopropylamino compound, since the isopropylamino- and cyclobutylamino-analogs were not inhibitory. Enzymatic specificity of MDL 27,302 for P450(17 alpha) was demonstrated by its failure to inhibit steroid 21-hydroxylase and the cholesterol side chain cleavage enzyme (P450scc). Both the 17 alpha-hydroxylase and C17-20 lyase activities of cytochrome P450(17 alpha) of human testis microsomes were inhibited by MDL 27,302.


EROL scale: a new behavioural olfactory measure and its relationship with anxiety and depression symptoms.
The main objective of this study was to develop and validate a new olfactory measure that assesses the influence of olfaction on several emotional, behavioural, and cognitive issues: The Relational Scale of Olfaction (EROL). A secondary objective was to explore the relationship between the olfactory function and the anxiety and depression symptoms by means of EROL and the Hospital Anxiety and Depression Scale (HADS). A positive relationship between anxiety symptoms and the olfactory function was hypothesized. Regarding depressive symptoms, a significant relationship with the olfactory scores was not expected. Psychometric properties of EROL scale and correlations between HADS and EROL were tested in a sample from the general population. EROL showed an adequate level of test-retest reliability (ICC=.748) and good internal consistency (Cronbach's alpha=.761). Convergent validity with other olfactory measures was satisfactory. A one-factor solution was found for the scale. HADS showed a significant relationship with EROL (r=.280, p<.01), but the analysis through dimensions revealed that only the anxiety subscale correlated significantly and moderately with the olfactory measure (r=.325, p<.001), whereas the correlation with the depression subscale was non-significant (r=.146, p>.05). Given that EROL displayed good psychometrical properties, it appears as a suitable tool to assess the olfactory function in general population. The relationship between this olfactory scale and anxiety symptoms found in this study is an interesting issue that requires further research.


From Dispersed Microspheres to Interconnected Nanospheres: Carbon-Sandwiched Monolayered MoS2 as High-Performance Anode of Li-Ion Batteries.
Hierarchical structured carbon@MoS2 (C@MoS2) microspheres and nanospheres composed of carbon-sandwiched monolayered MoS2 building blocks are synthesized through a facile one-pot polyvinylpyrrolidone (PVP) micelle-assisted hydrothermal route. The dimension and carbon content of C@MoS2 spheres are effectively controlled by singly adjusting the concentration of PVP, which plays the dual functions of soft-template and carbon source. As the anode materials of Li-ion batteries, C@MoS2 nanospheres present considerably higher capacity, better rate behavior and cycling stability than C@MoS2 microspheres. The reasons are attributed to the unique interconnected nanospherical morphology and the internal hierarchical construction of C@MoS2 nanospheres with expanded MoS2/carbon interlayer spacing.


Automated axon tracking of 3D confocal laser scanning microscopy images using guided probabilistic region merging.
This paper presents a new algorithm for extracting the centerlines of the axons from a 3D data stack collected by a confocal laser scanning microscope. Recovery of neuronal structures from such datasets is critical for quantitatively addressing a range of neurobiological questions such as the manner in which the branching pattern of motor neurons change during synapse elimination. Unfortunately, the data acquired using fluorescence microscopy contains many imaging artifacts, such as blurry boundaries and non-uniform intensities of fluorescent radiation. This makes the centerline extraction difficult. We propose a robust segmentation method based on probabilistic region merging to extract the centerlines of individual axons with minimal user interaction. The 3D model of the extracted axon centerlines in three datasets is presented in this paper. The results are validated with the manual tracking results while the robustness of the algorithm is compared with the published repulsive snake algorithm.


An adolescent with asthma presenting with worsening cough.
The diagnosis of systemic histoplasmosis may be delayed due to underlying pulmonary conditions in patients from an endemic area. An adolescent White male from the Midwestern United States with a history of moderate persistent asthma presented to the pulmonary clinic with a 10-day's history of cough. The patient had no response to modifications of his asthma treatment regimen and proceeded to experience worsening symptoms, including pleuritic chest pain and dysphagia. Chest imaging revealed multiple pulmonary nodules, right mainstem bronchus narrowing, bilateral hilar adenopathy, and esophageal thickening. Ophthalmologic examination revealed an ocular "histo spot", but the patient denied any ocular symptoms. Despite negative initial histoplasmosis antibody testing, the patient began oral itraconazole therapy for presumed histoplasmosis infection. Follow-up histoplasmosis antibody titers were positive, and the patient responded well to itraconazole. Disseminated histoplasmosis can have a wide range of presenting symptoms, which may delay its diagnosis among patients with pre-existing asthma.


Is it morally justifiable not to sedate this patient before ventilator withdrawal?
In their case description and analysis, Barbara Springer Edwards and Winston M. Ueno provide a nice opportunity to examine the intersection of theory and practice in medical ethics, as well as to discuss the fine tuning of treatment decisions in the clinical setting. They raise the question: Is it morally justifiable to sedate an alert patient before his life-supporting ventilator is disconnected? Clearly they have a thorough understanding of their patient's legal and ethical entitlement to have his request for discontinuation of life-supporting treatment honored. They also recognize the principle of double effect in allowing large doses of medication to control pain even at the risk of accelerating death. My doubts lie in their specific application of the notion of beneficence, a principle that involves mainly two objectives: preservation of life and alleviation of suffering....


Anatomy of the Pain Centre waiting list at the Centre hospitalier de l'Université de Montréal (CHUM).
Waiting list management at chronic pain clinics has become a serious problem throughout Canada. We analyzed the waiting list at the Centre hospitalier de l'Université de Montréal (CHUM) Pain Centre. The present study is an observational, prospective study. We used a specifically designed survey questionnaire. Survey findings were analyzed with descriptive statistical methods. A total of 270 patients were contacted; only 146 were included. Of these, 93 were women and 53 men. The average age was 55.9 years. Fifty-two percent of the patients were referred by a medical specialist; 34% by family physicians; 3% for emergency; and 11% unknown. The mean for pain score was 6.7/10. Seventy-three percent were taking pain killers with an average improvement on their pain score of 52%. Ten percent of respondents were not taking any type of analgesic medication, while 17% were taking over-the-counter drugs. Fifty-three percent of the patients had been suffering from chronic pain for 5 years or less, while 10% had been suffering and awaiting specialized pain treatment for more than 20 years. Our data suggests that accessibility to specialized health care is not the sole obstacle to the timely and effective management of chronic pain. Seventy-three percent of the patients were taking some form of pharmaceutical treatment for pain and reported an average improvement rate of 52% on their pain score under medication. Such inconsistency may be attributable to patients' lack of compliance with their treatment. The World Health Organization Working Group recommended in chronic patients a novel approach to health care, based on patient therapeutic education. Our results show that patients need to acquire self-management skills regarding their chronic conditions.


Effector T lymphocyte subsets in human pancreatic cancer: detection of CD8+CD18+ cells and CD8+CD103+ cells by multi-epitope imaging.
Pancreatic cancer is characterized by an increasing incidence and an extremely poor prognosis. It is resistant to most of the conventional treatment modalities. Histomorphologically, it presents with a strong desmoplastic reaction around cancer cells, and lymphocytes are typically localized as aggregates in the fibrotic interstitial tissue. Using the method of multi-epitope imaging with fluorochrome-tagged specific MoAbs which allows the simultaneous localization and characterization of T cells in tissues, we studied phenotypes and distribution of tumour-infiltrating lymphocytes (TIL) in pancreatic cancer. CD3+ T cells comprised up to 90% of the tumour-infiltrating cells which were either CD4+ or CD8+, most of them being memory cells (CD45RO+). In decreasing order of frequency, T lymphocytes carried the markers for CD45RO, CD18, CD103 and TCR gammadelta. Very few natural killer cells (CD56+) were observed. Twenty percent of CD8+ were labelled with CD103. These CD8+CD103+ T cells, analogous to the gut intraepithelial lymphocytes (IEL), were found in the fibrous interstitial tissue. Furthermore, an inverse correlation was found between the expression of CD18, the beta2-integrin, which mediates adhesion of activated lymphocytes, and CD45RO in the CD8+ subset of TIL (P = 0.046). In conclusion, phenotyping of T lymphocytes in pancreatic cancer raises the possibility that pancreatic cancer cells develop several strategies to escape the T cell-induced cytolysis by (i) the aggregation of cytotoxic CD8+CD103+ T cells in the fibrous tissue distant from the tumour cells, and (ii) the presence of CD18-bearing cells which lack the expression of the activation marker CD45RO.


[Carbon emission from forest fires in Daxing' anling region in 2005-2007].
Based on field investigation, the burned areas and consumed fuel loadings in Daxing' anling region caused by forest fires in 2005-2007 were estimated by comparing the normalized difference vegetation index (NDVI) before and after burning. The burned areas were classified with fire intensity, and the carbon emission from the fires was estimated by the fuel consumption and the average carbon content of plants. It was estimated that the total burned area was 436512. 5 hm2, of which, the severe, moderate, and light burned areas occupied 207178.4, 150159.2, and 79159.4 hm2, respectively. The consumed fuel loadings were 3.9 x 10(6) t in total, and the emitted carbon was 1.76 x 10(6) t, with 0.34 x 10(6), 0.83 x 10(6), 0.27 x 10(6), and 0.32 x 10(6) t from larch (Larix gmelini) forest, conifer and broadleaves mixed forest, broad-leaved forest, and grassland, respectively.


In vivo effect of insulin on the hormone production of immune cells in mice - gender differences.
The immune cells of rat and man synthesize, store and secrete hormones, characteristic to the endocrine glands. In the present experiments female and male CD1 mice were treated with 10 IU/kg insulin sc. (the controls with normal saline) and after 30 min peritoneal fluid was gained. The cells of the peritoneal fluid (lymphocytes and the monocyte-granulocyte group) were studied by immunocytochemical flow-cytometry to adrenocorticotropic hormone (ACTH), triiodothyronine (T3), histamine and serotonin content. In the female mice each hormone level was significantly lower in the insulin-treated animals, except histamine in the monocyte-granulocyte group. In the insulin-treated male animals, the hormone levels were similar to the control. The results 1) support the previously hypothesized hormonal network in the immune system, 2) justify that the insulin effect is not species dependent and 3) call attention to the sex, species and organ differences in the response.


Matrix Gla protein T-138C polymorphism is associated with carotid intima media thickness and predicts mortality in patients with diabetic nephropathy.
We sought to determine the predictive value of Matrix Gla Protein MGP T-138C polymorphism in relation to all-cause mortality, cardiovascular mortality and cardiovascular events in patients with diabetic nephropathy (DN). MGP T-138C polymorphism was assessed in 40 diabetic patients without nephropathy and 118 patients at different stages of DN, including patients on hemodialysis. Measurement of carotid intima-media thickness (cIMT) was performed using real-time B-mode ultrasonography. Plasma levels of dephoshorylated uncarboxylated Matrix Gla Protein (dp-ucMGP) were determined in a subgroup of 67 patients by ELISA. Mortality and cardiovascular events were assessed during a 7year follow-up. TT homozygotes for the MGP T-138C polymorphism had higher values of cIMT compared to combined TC and CC genotypes (P=0.006) whereas no association was observed between cIMT and dp-ucMGP levels. MGP T-138C polymorphism was a strong independent predictor of cIMT (P<0.0001), after adjustment for several well-known atherosclerosis risk factors. Patients with TT genotype presented a significantly higher all-cause and cardiovascular mortality risk compared to patients with TC and CC genotypes (P=0.01 and P=0.04 respectively), after adjustment for several traditional risk factors. MGP T-138C polymorphism is a strong and independent predictor of increased cIMT as well as all-cause and cardiovascular mortality in DN patients.


Inherited duplication of the pseudoautosomal region Xq28 in a subject with Gilles de la Tourette syndrome and intellectual disability: a case report.
Tourette syndrome (TS) is a complex neurodevelopmental disorder (NDD) characterized by multiple chronic involuntary motor and vocal tics with onset during childhood or adolescence. Most TS patients present with additional comorbidities, typically attention deficit hyperactivity disorder (ADHD), obsessive- compulsive disorder (OCD), autism spectrum disorder (ASD) and intellectual disability (ID). Both TS and ID are genetically complex disorders that likely occur as a result of the effects of multiple genes interacting with other environmental factors. In addition to single gene mutations and chromosomal disorders, copy number variations (CNVs) are implicated across many NDDs and ID and contribute to their shared genetic etiology. Screening of CNVs using microarray-based Comparative Genomic Hybridization (aCGH) is now routinely performed in all subjects with NDD and ID. We report a case of a 12-year-old girl diagnosed with Gilles de la Tourette Syndrome associated to behavior disorders and intellectual disability in particular with regard to language. Array-CGH analysis showed a CNV of a subtelomeric region Xq28 (gain of 260 kb) inherited from the healthy father. The duplication contains two genes, VAMP7 and SPRY3 of the PAR2 pseudoautosomal region. FISH analysis revealed that the duplicated segment is located on the short arm of a chromosome 13, resulting in a trisomy of the region. In the proband the expression levels of the genes evaluated in the peripheral blood sample are comparable both those of the mother and to those of female control subjects. Although the trisomy of the 260 kb region from Xq28 identified in proband is also shared by the healthy father, it is tantalizing to speculate that, together with genetic risk factors inherited from the mother, it may play a role in the development of a form of Tourette syndrome with intellectual disability. This hypothesis is also supported by the fact that both genes present in the duplicated region (VAMP7 and SPRY3) are expressed in the CNS and are implicated in neurotransmission and neurite growth and branching. In addition, similar CNVs have been identified in individuals whose phenotype is associated with autism spectrum disorders or intellectual disability.


Characterization of a novel micro-pressure double-cycle reactor for low temperature municipal wastewater treatment.
To solve the deterioration of effluent caused by low temperature in urban sewage treatment plant in cold areas, a new type of reactor was proposed, the biochemical environmental and low-temperature operating characteristics of the reactor were studied. Through analysis of flow simulation and dissolved oxygen (DO) distribution when the aeration rate was 0.6 m3/h, it showed that there were many different DO environments in the reactor at the same time, which provided favourable conditions for various biochemical reactions. The operation test showed that the average effluent removal rate of COD, TN, NH4+-N and TP was 92.53%, 74.57%, 89.61% and 96.04%, respectively. And there were a variety of functional bacteria related to nitrogen and phosphorus removal in the system, most of them with strong adaptability at low temperatures. Among the dominant microorganisms, Flavobacterium and Rhodobacter were related to denitrification, Aeromonas and Thiothrix were related to phosphorous removal. Denitrifying phosphorus removal was the main way of phosphorus removal. Picrust2 results showed that the reactor operated well at low temperature, and the regional difference distribution of nitrification genes further confirmed the existence of functional zones in the reactor. The results showed that the Micro-pressure Double-cycle reactor worked well at low temperature, which provided a new idea and way for the upgrading of urban sewage treatment plants in cold areas.


Development of an Everyday Spatial Behavioral Questionnaire.
The authors developed a 12-category, 116-item critical incident questionnaire of spatial behavior. The authors administered the Everyday Spatial Behavioral Questionnaire (ESBQ) to volunteer undergraduates (114 women, and 31 men) and tests of spatial ability to establish both the reliability and construct validity of the instrument. The authors found that Cronbach's alpha across the subscale scores was .92, and that 8 of the 12 subscales had alphas of .70 or greater. The authors found validity of the ESBQ through canonical correlation analysis. Specifically, spatial tests, gender, and age variables, jointly with the ESBQ subscales, identified 2 apparent continua of spatial skills. The authors labeled the first continuum movement through space (from moving a vehicle at one end of the continuum, to moving one's own body through space at the other end of the continuum). The authors labeled the second identified continuum drawing/perceiving perspective/path finding, and it appeared to represent a continuum of 3-dimensional visualization or redirection. Another suggested label was dimensional discernment. Thus, the ESBQ is a first step toward identifying new ways to think about and quantify people's spatial experience.


Influence of male gonadal hormones and familiarity on pregnancy interruption in prairie voles.
Pregnancy interruption (PI) was examined in female prairie voles, Microtus ochrogaster, exposed to stimuli from males 7 to 12 days after pairing. Urine from unfamiliar males interrupted pregnancy when placed directly on the external nares of newly mated females, but urine from familiar stud males was without effect. Castration of males did not reduce the efficacy of unfamiliar male urine in interrupting pregnancy. The neuroendocrine system of female prairie voles responded selectively to male urine as a function of its familiarity; the efficacy of male stimuli leading to PI was not dependent on gonadal hormones.


INTERPROFESSIONAL ROLES AND COLLABORATIONS TO ADDRESS COVID-19 PANDEMIC CHALLENGES IN NURSING HOMES.
Nursing home experts and informatics nurses collaborated to develop guidelines for nursing homes that revealed partnership principles in action during the COVID-19 pandemic. This article describes efforts to define interprofessional nursing home staff roles within the partnership-based COVID-19 Response Guideline, and to examine changes in nursing practice compared to the pre-pandemic practice of nurses. The qualitative process of identification of nursing home staff roles revealed the extensive scope of interprofessional partnership needed to respond to the pandemic. Using the Omaha System structure, we compared these collective COVID-19 response interventions of Nursing Service roles with nursing interventions of RNs and LPN/LVNs defined in previous nursing home studies. This comparison showed the necessary transformation and collaboration among nurses needed for the pandemic response in nursing homes. The Omaha System Pandemic Guideline is available online and in the Omaha System Guidelines app for immediate use as COVID-19 response practice guidelines and references for interprofessional roles in nursing homes, as well as for multidisciplinary roles across diverse care settings. The guideline is an exemplar of how informatics can facilitate interprofessional and multidisciplinary partnership for nursing homes and other care settings. Future use of the guidelines for decision making and documentation related to infection prevention and control in nursing homes may improve care quality and health outcomes of residents and population.


Changes in Clotting Time, Plasma Fibrinogen Levels, and Blood Viscosity After Administration of Ranibizumab for Treatment of Choroidal Neovascularization.
To observe changes in clotting time, plasma fibrinogen levels, and blood viscosity after intravitreal ranibizumab (IVR) injection in patients with macular choroidal neovascularization (CNV). A total of 77 patients were enrolled in the study. Patients were divided into a study group (n = 42 CNV patients) and a control group (n = 35 age- and gender-matched healthy subjects). Study group patients received IVR injections; control group patients received none. Clotting times, plasma fibrinogen levels and blood viscosity were evaluated before, and 1 week and 1 month after the first IVR injection, and again 1 month after the second injection in the study group, but only once in the control group. A paired-sample t-test was used to analyze data at four time points in the study group. Study group patients were further categorized as those with neovascular age-related macular degeneration (AMD subgroup) or CNV secondary to pathological myopia (PM subgroup). Indicators were also analyzed for each subgroup. There were no significant differences between study and control group patients in baseline values. Results showed that 1 week after the first IVR injection, the mean activated partial thromboplastin time (APTT) of study group patients was significantly reduced compared with baseline values (27.88 ± 4.00 versus 30.70 ± 5.56 s), respectively. Low-, median- and high-shear viscosity rates were increased significantly compared with baseline values. No statistically significant changes in tested indicators were found at other time points. In AMD subgroup patients, changes in all indicators were similar to those found overall. In contrast, only changes in median- and high-shear viscosity rates were statistically significant in PM subgroup patients. IVR injection may cause short-term fluctuations in APTT and blood viscosity in AMD patients. Further studies are needed to establish the long-term safety of IVR treatment.


[X protein variations of genotype B and C hepatitis B virus isolated from the patients with hepatocellular carcinoma].
X protein was one of the most important pathogens of hepatitis B virus (HBV), and was crucial in the carcinogenesis of HBV related hepatocellular carcinoma (HCC). It was demonstrated that the infection of genotype B or C HBV would result in different clinical manifestations and pathological characteristics in HCC patients, however, it was under elucidation whether these differences related to different genotypes of HBV X protein. This study was designed to investigate the amino acid differentiations of X proteins in standard genotype B or C HBV strains and the variations in HBV isolated from the HCC patients, and elucidate preliminarily the relationship between the genotype of HBV and carcinogenesis of HCC. HBV X genes from the serum of twenty-two HBsAg positive HCC patients were amplified, cloned and sequenced. Genotyping of the X gene was carried out by Vector NTI6.0 software and the amino acid alignment among the standard and HCC originated X protein were done by DNAMAN software. Twenty-two HBV X genes were obtained and all of them could be categorized into genotype B or C. Besides of 14 amino acid differentiations within X protein between standard B and C HBV strains, HCC originated X protein of B and C genotype showed 4 consensus amino acid variations, and genotype C X protein showed additional 6 genotype-specific variations. All these differentiated and varied amino acids were located in the B, T cell epitopes and transactive or related regulatory regions. In addition to amino acid differentiations, X protein of genotype B or C HBV also showed genotype-specific variations in HCC patients. Amino acid differentiations and variations may result in the different immunocompetence and transactivation capacity between X proteins of genotype B and C.


Role of the simultaneous sequential strategy for failed acute sinus restoration after modified left maze procedure for persistent atrial fibrillation with concomitant mitral surgery.
We assessed whether the simultaneous sequential strategy could (1) achieve additional sinus restoration for those patients who were not in sinus rhythm while coming off bypass after modified left maze procedure and (2) attain the same long-term success rates as the bi-atrial maze procedure in patients with persistent atrial fibrillation (AF) and mitral valve disease. Twenty-seven consecutive patients - ten men and 17 women with a mean age of 52 +/- 13 years, all with persistent AF and mitral valve disease - underwent the modified maze procedure with the simultaneous sequential strategy. In the first phase, the modified left atrial maze operation was carried out with concomitant valvular surgery; the right side maze operation was subsequently carried out as a second phase of the sequential strategy only if AF re-appeared following the spontaneous restoration of heart beats during the operation. Twenty patients (74.1%) underwent the left atrial maze procedure only, and seven patients (25.9%) required the subsequent right atrial maze procedure as part of the sequential strategy. At a mean follow-up of 15.1 +/- 7.7 months, six of the 27 patients (22.2%) who underwent additional right atrial maze procedure had restored sinus rhythm. At a mean follow-up of 17.8 +/- 7.3 months, 24 of the 27 patients (88.9%) had restored sinus rhythm and 22 patients (81.5%) had restored bi-atrial transport function (right atrial filling fraction: 40.8 +/- 11.7%; left atrial filling fraction: 22.9 +/- 8.1%) after application of the sequential strategy. Compared with modified left atrial maze procedure, the application of the simultaneous sequential strategy successfully restored sinus rhythm in an additional 22.2% of patients with persistent AF. The overall sinus conversion rate of 88.9% was comparable with that of the standard bi-atrial maze procedure.


Characterization of a unique defective type C virus associated with a Moloney leukemia virus-induced splenic T-cell lymphoma cell line.
Moloney leukemia virus (MoLV) induces lymphomas in BALB/c mice which either involve an immature thymic T-cell subpopulation or a splenic mature T-cell subpopulation. To investigate further the possible virological and immunological differences in these lymphomas, several lymphoma cell lines were derived. Although the majority of these cell lines expressed only the parental MoLV, one lymphoma cell line (5F4) was found which expressed only a defective virus. 5F4 virions lacked detectable reverse transcriptase activity and by immunoprecipitation lacked a serologically detectable reverse transcriptase. The lack of reverse transcriptase did not appear to be due to a deletion in the viral genome. Intracellularly 5F4 cells synthesized normal gag gene precursors but had little, if any, detectable Pr180gag-pol or an altered precursor. These results suggest that the defect of the 5F4 virus is associated with the inability to translate the appropriate precursor for reverse transcriptase. The possible origin of the detective 5F4 virus was also examined by competition radioimmunoassays. These results demonstrate that the type-specific proteins, gp71 and p12, are serologically identical to those of the endogenous ecotropic virus and distinct from the MoLV proteins. Competition assays of 5F4 cell extracts further demonstrated the lack of any detectable MoLV type-specific proteins, although the tumor was presumably induced by MoLV. The significance of these observations to leukemogenesis is discussed.


Post-Marketing Surveillance of Quality of Artemether Injection Marketed in Southwest Nigeria.
Access to good-quality medicines remains a contentious issue in developing countries. This development is worrisome, particularly in a setting with a high incidence of malaria. Monitoring of antimalarial drugs in the commercial domain becomes necessary; thus, we evaluated the quality of artemether injection marketed in Southwest Nigeria. A cross-sectional survey was conducted to obtain 22 different brands of artemether injections within Southwest Nigeria. The samples were examined for their sources, lot numbers, containers for injection, oil base used for preparation, and dates of expiration. Further analysis involved visual inspection, assessment of extractable volume, identity tests, and an assay of active pharmaceutical ingredient. The pharmaceutical quality of each sample was determined according to the criteria set in the International Pharmacopoeia 2019. None of the products had any particulate matter, but there were certain irregularities in their presentation. Eighteen of the 22 products (81.7%) were packaged in plain instead of amber-colored ampoules, and 77.3% (17/22) did not indicate the oil base used as the vehicle on the label as against the pharmacopoeial standard. Sixteen products (72.7%) passed the extractable volume test, although the remaining 22.3% did not conform to the extractable volume per unit dose. Artemether was present in all the samples, although only 40.9% (9/22) met the recommended percentage content of 90-110% of artemether. The study revealed the presence of a high percentage of substandard artemether injection products marketed in Nigeria. Further surveillance is warranted to confirm the quality of artemether injection circulated in other regions within Nigeria.


Optimizing lung cancer radiation treatment worldwide in COVID-19 outbreak.
COVID-19 has spread around the planet, sending billions of people into lockdown as health services struggle to cope. Meanwhile in Asia, where the disease began, the spread continues, in China it seems for now to have passed its peak. Italy, Spain, France, UK, and the US have been the countries more affected in terms of deaths. The coronavirus is more dangerous to the elderly and those with certain pre-existing medical conditions which is precisely the profile of lung cancer patients. Essential cancer services should be delivered but all steps should be taken to protect patients and the health workforce from infection with COVID-19. This presents a major challenge to radiotherapy (RT) departments worldwide. An international panel with expertise in the management of lung cancer in high-volume comprehensive centres has come together to share its experience on COVID-19 preparedness to deliver optimal care in such exceptional circumstances. A comprehensive systematic review of the literature through a PubMed search was undertaken. Twelve recommendations including, among others, the consideration of shorter courses, delays, and the omission of RT for lung cancer are proposed by the panel. In summary, we recommend the screening of every single person accessing the treatment room, the consideration of hypofractionation and to delay postoperative RT for non-small cell lung cancer, to avoid twice-daily treatments and delay or deliver prophylactic cranial irradiation during radio(chemo)therapy for limited-stage small cell lung cancer, review image guided RT images for suspicious image findings, and the use of single-fraction RT for the palliative treatment of stage IV lung cancer patients. Given that lung cancer is one of the most common and severe pathologies in radiation oncology departments, the following recommendations require particularly urgent consideration. The decision-making paths strongly depend on locally available resources, and a tailored approach should be used to attend lung cancer patients during this pandemic.


Growth hormone but not insulin-like growth factor-I improves wound strength in pigs.
Systemic growth hormone and locally administered insulin-like growth factor-I have been shown in a number of studies to improve the breaking strength of incisional wounds, especially in compromised animals. The objective of the present study was to compare these two agents when administered subcutaneously distant from an incisional wound site in pigs, as well as to examine effects of a combination growth hormone/insulin-like growth factor treatment. Growth hormone was shown to increase wound breaking strength in two experiments, whereas insulin-like growth factor-I or a more potent analog had no effect. Moreover, breaking strength was only minimally improved above the vehicle groups by the combination of growth hormone and insulin-like growth factor-I. These effects could not be explained by changes in plasma insulin-like growth factor-I concentrations which were highest in the combination groups, nor by plasma insulin-like growth factor binding protein-3 which was raised equally whenever growth hormone was administered. We conclude that systemic growth hormone but not insulin-like growth factor-I improves wound strength in normal pigs, whereas insulin-like growth factor-I reduces the magnitude of the growth hormone effect by an unknown mechanism.


Evolving Rapid Methicillin-resistant Staphylococcus aureus Detection: Cover All the Bases.
The dissemination of methicillin-resistant (MR) Staphylococcus aureus (SA) in community and health-care settings is of great concern and associated with high mortality and morbidity. Rapid detection of MRSA with short turnaround time can minimize the time to initiate appropriate therapy and further promote infection control. Early detection of MRSA directly from clinical samples is complicated by the frequent association of MRSA with methicillin-susceptible SA (MSSA) and coagulase-negative Staphylococcus (CoNS) species. Infection associated with true MRSA or MSSA is differentiated from CoNS, requires target specific primers for the presence of SA and mec A or nuc or fem A gene for confirmation of MR. Recently, livestock-associated MRSA carrying mec C variant complicates the epidemiology of MRSA further. Several commercial rapid molecular kits are available with a different combination of these targets for the detection of MRSA or MSSA. The claimed sensitivity and specificity of the currently available commercial kits is varying, because of the different target combination used for detection of SA and MR.


The use of acuity and frailty measures for district nursing workforce plans.
This article discusses the use of Quest acuity and frailty measures for community nursing interventions to quantify and qualify the contributions of district nursing teams. It describes the use of a suite of acuity and frailty tools tested in 8 UK community service trusts over the past 5years. In addition, a competency assessment tool was used to gauge both capacity and capability of individual nurses. The consistency of the results obtained from the Quest audits offer significant evidence and potential for realigning community nursing services to offer improvements in efficiency and cost-effectiveness. The National Quality Board (NQB) improvement resource for the district nursing services ( NQB, 2017 ) recommends a robust method for classifying patient acuity/frailty/dependency. It is contended the Quest tools and their usage articulated here offer a suitable methodology.


Coordination of olfactory receptor choice with guidance receptor expression and function in olfactory sensory neurons.
Olfactory sensory neurons choose to express a single odorant receptor (OR) from a large gene repertoire and extend axons to reproducible, OR-specific locations within the olfactory bulb. This developmental process produces a topographically organized map of odorant experience in the brain. The axon guidance mechanisms that generate this pattern of connectivity, as well as those that coordinate OR choice and axonal guidance receptor expression, are incompletely understood. We applied the powerful approach of single-cell RNA-seq on newly born olfactory sensory neurons (OSNs) in young zebrafish larvae to address these issues. Expression profiles were generated for 56 individual Olfactory Marker Protein (OMP) positive sensory neurons by single-cell (SC) RNA-seq. We show that just as in mouse OSNs, mature zebrafish OSNs typically express a single predominant OR transcript. Our previous work suggests that OSN targeting is related to the OR clade from which a sensory neuron chooses to express its odorant receptor. We categorized each of the mature cells based on the clade of their predominantly expressed OR. Transcripts expressed at higher levels in each of three clade-related categories were identified using Penalized Linear Discriminant Analysis (PLDA). A genome-wide approach was used to identify membrane-associated proteins that are most likely to have guidance-related activity. We found that OSNs that choose to express an OR from a particular clade also express specific subsets of potential axon guidance genes and transcription factors. We validated our identification of candidate axon guidance genes for one clade of OSNs using bulk RNA-seq from a subset of transgene-labeled neurons that project to a single protoglomerulus. The differential expression patterns of selected candidate guidance genes were confirmed using fluorescent in situ hybridization. Most importantly, we observed axonal mistargeting in knockouts of three candidate axonal guidance genes identified in this analysis: nrp1a, nrp1b, and robo2. In each case, targeting errors were detected in the subset of axons that normally express these transcripts at high levels, and not in the axons that express them at low levels. Our findings demonstrate that specific, functional, axonal guidance related genes are expressed in subsets of OSNs that that can be categorized by their patterns of OR expression.


Emotional Intelligence and Emotional State Effects on Simulated Flight Performance.
BACKGROUND: Flight cadets' emotion is a factor of great importance to flight training. So it is of profound significance to address how emotional factors affect flight training performance. The present study aimed to investigate the relationship between emotional intelligence (EI) and simulated flight performance (SFP), and explore the mechanism of emotional state as a mediator in the effect of EI on SFP.METHODS: Ninety undergraduates took part in the study. EI (Wong and Law Emotional Intelligence Scale), neuroticism (Eysenck Personality Questionnaire Revised), anxiety (State Anxiety Inventory), and tension (Profile of Mood States) were collected. Conducted were 9 h of simulated flight training in a simulator of the Type 6 Primary Trainer. The Delphi Experts Grading Method was used to assess students' SFP. Mediation effect of emotional state was explored using regression analysis.RESULTS: EI was significantly correlated with neuroticism (r = -0.31), tension (r = -0.31), and anxiety (r = -0.31), respectively. Multiple mediation effects showed that emotional state mediated the association between EI and SFP. Tension especially mediated the associations between the Self Emotion Appraisals and Regulation of Emotion dimensions of EI and SFP. However, the Use of Emotion dimension of EI had a direct negative effect on SFP without the mediating role of emotional state.DISCUSSION: The findings indicated that EI was significantly correlated with emotional state (neuroticism, tension, and anxiety). EI may directly or indirectly affect SFP and tension played an important mediating role. Implications for the promotion of EI and emotional state to enhance performance in real flight training are discussed.Dai J, Wang H, Yang L, Wen Z. Emotional intelligence and emotional state effects on simulated flight performance. Aerosp Med Hum Perform. 2019; 90(2):101-108.


Inter-individual variability in the dynamics of natural accommodation in humans: relation to age and refractive errors.
1. To study the relationship between accommodation under natural viewing conditions, age and refractive errors, we have measured time courses of accommodation in thirty-nine human subjects aged 5-49 years using a newly developed technique. The technique is based on infrared photoretinoscopy and involves fully automated on-line image processing of digitized video images of the eyes with a sampling rate of 5.3 Hz. 2. The distance between the subject and the video camera was about 1.3 m. Head movements of the subject required little restriction because the eyes were automatically tracked in the video image by the computer program. All subjects were tested under binocular viewing conditions. 3. Both refraction of the right eye and pupil diameter were measured with a precision of 0.2-0.4 dioptres (D) and 0.1 mm, respectively, and were plotted on-line. The data were subsequently automatically analysed. 4. Automated infrared photoretinoscopy proved to be very convenient and easy to handle in both children and adults. 5. The maximal speed of accommodation for a target at a distance of 5 D declined in the subjects with age (from up to 21.7 D s-1 for accommodation and 32.7 D s-1 for subsequent accommodation to a distant target ('near to far accommodation') in children down to 2-18 D s-1 in adults). There was a striking inter-individual variability in the maximum possible speed of accommodation and near to far accommodation. 6. Speed of accommodation and of near to far accommodation was correlated for each subject. However, in most of the subjects, the process of near to far accommodation was faster than accommodation (P < 0.005, if averaged over all subjects). This correlation was independent of age. 7. The accommodation-induced pupillary constriction (pupillary near response) was absent in children for a 4 D target; even at 10 D, there was no reliable pupillary response. The pupillary near response increased to about 1.6 mm D-1 of accommodation at the age of 47. Since a pupillary near response could still be elicited in presbyopic subjects unable to accommodate, the ratio of pupillary constriction per dioptre of accommodation approached infinity. 8. The magnitude of the pupillary near response was highly variable even among subjects of the same age but was typical for each subject. There was a correlation (P < 0.01) to refractive error: corrected myopes had weaker pupillary near responses than emmetropes or hyperopes.(ABSTRACT TRUNCATED AT 400 WORDS)


Prevalence and variations of the median maxillary labial frenum in children, adolescents, and adults in a diverse population.
The median maxillary labial frenum (MMLF) is a normal anatomic structure with inherent morphologic variations. This study sought to evaluate the prevalence of those variations in a diverse ethnic population and to educate practitioners about the prevalence of MMLF variations to prevent unnecessary biopsies. This study included adult, adolescent, and child patients at the Louisiana State University Health Science Center School of Dentistry. Among the 284 subjects examined, frenum normale was the most common frenum classification, followed by frenum with nodule and frenum with appendix. Most nodules were found in the intermediate third of the MMLF, while appendices were mainly found in the labial third. The prevalence of an appendix was significantly higher (P < 0.001) in Caucasians compared to African-Americans. The prevalence of nodules was marginally higher (P = 0.096) in Caucasians than in African-Americans. No other statistically significant differences were found with regard to ethnicity. Additionally, nodules and appendices on the MMLF were identified in all age groups, and may become more common with increasing age. The authors determined that variations of the MMLF are inherent and do not represent a pathologic condition, nor do they require biopsy for diagnostic purposes.


[Structure of the dermo-epidemic junction].
The basement membranes are extracellular proteic matrixes involved mainly in cell-substrate interactions. The dermo-epidermal junction (DEJ) is defined as the region formed by the dermal pole of the basal cell layer, the intercellular spaces, the lamina densa or basal lamina and the acellular fibrous components of the papillary dermis. The functions of the DEJ are to bind the epithelia to the connective tissue, and to preserve the viability of the epidermis by means of connecting it to the dermis. which is in charge of providing the necessary nutrients for its normal proliferation. The purpose of the present communication is to provide a concise review of the recent knowledges about the ultrastructure of the DEJ, with special emphasis on its antigenic components.


Small molecule inhibitors promote efficient generation of induced pluripotent stem cells from human skeletal myoblasts.
Human somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by ectopic expression of key transcription factors. iPSCs have been generated from a variety of cell types. However, iPSC induction from human myoblasts has not yet been reported. Human primary skeletal myoblasts can be cultured from diagnostic muscle biopsy specimens, and thousands of lines are frozen and stored in biobanks, and are a valuable source for iPSC-based etiological and pathogenic studies. Our aim was to generate iPSCs from human skeletal myoblasts enriched from muscle biopsy samples. We used retro- or Sendai virus vector-mediated reprogramming of enriched human myoblasts from 7 donors. We show that stable iPSC lines can be generated from human myoblasts at efficiency similar to that of fibroblasts when appropriate media is used, and the efficiency of the feeder-free iPSC generation can be significantly improved by inhibitors of histone deacetylase (sodium butyrate) and TGF-β signaling (SB431542).


DbyDeep: Exploration of MS-Detectable Peptides via Deep Learning.
Predicting peptide detectability is useful in a variety of mass spectrometry (MS)-based proteomics applications, particularly targeted proteomics. However, most machine learning-based computational methods have relied solely on information from the peptide itself, such as its amino acid sequences or physicochemical properties, despite the fact that peptides detected by MS are dependent on many factors, including protein sample preparation, digestion, separation, ionization, and precursor selection during MS experiments. DbyDeep (Detectability by Deep learning) is an innovative end-to-end LSTM network model for peptide detectability prediction that incorporates sequence contexts of peptides and their cleavage sites (by protease). Utilizing the cleavage site contexts could improve the performance of prediction, and DbyDeep outperformed existing methods in predicting peptides recognizable from multiple MS/MS data sets with diverse species and MS instruments. We argue for the necessity of a learning model that encompasses several contexts associated with peptide detection, as opposed to depending just on peptide sequences. There is a Python implementation of DbyDeep at https://github.com/BISCodeRepo/DbyDeep.


Amphoterin induction in prostatic stromal cells by androgen deprivation is associated with metastatic prostate cancer.
Amphoterin, the major product of the high mobility group-1 gene, is a ligand associated with cancer invasion and metastasis through activation of the receptor for advanced glycation end products (RAGE). Expression of amphoterin and RAGE was examined in prostatectomy specimens from 40 patients with pT3 prostate cancer (18 non-metastatic and 22 metastatic) preoperatively treated with lutenizing hormone-releasing hormone (LH-RH) agonist. Amphoterin expression was detected in tumor cells of 6 (27%) metastatic and 0 non-metastatic cases (p<0.0001). Amphoterin was also detected in prostatic stromal cells of 14 (63%) metastatic cases and 2 (11%) non-metastatic cases (p=0.0010). RAGE production was detected in cancer cells of 16 (73%) metastatic and 6 (33%) non-metastatic cases (p=0.0244). A total of 2 (22%) non-metastatic and 16 (73%) metastatic cases showed co-expression of amphoterin and RAGE in tumor cells or in tumor cells and stromal cells (p=0.0001). The in vitro invasive capacity of PC-3, a prostatic cancer cell line that co-expressed amphoterin and RAGE, was suppressed by treatment with amphoterin antisense S-oligodeoxynucleotide (ODN). Primary cultured human prostatic stromal cells secreted no amphoterin; however, amphoterin secretion was induced by androgen deprivation. The conditioned medium of human prostatic stromal cells deprived of androgen recovered the in vitro invasive capacity of PC-3 cells suppressed by amphoterin antisense S-ODN. These results suggest that androgen deprivation provides a paracrine interaction between cancer and stromal cells through the RAGE-amphoterin system in advanced prostate cancer.


Safety and efficacy of neratinib in combination with capecitabine in patients with metastatic human epidermal growth factor receptor 2-positive breast cancer.
Neratinib is a potent irreversible pan-tyrosine kinase inhibitor with antitumor activity and acceptable tolerability in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer. A multinational, open-label, phase I/II trial was conducted to determine the maximum-tolerated dose (MTD) of neratinib plus capecitabine in patients with solid tumors (part one) and to evaluate the safety and efficacy of neratinib plus capecitabine in patients with HER2-positive metastatic breast cancer (part two). Part one was a 3 + 3 dose-escalation study in which patients with advanced solid tumors received oral neratinib once per day continuously plus capecitabine twice per day on days 1 to 14 of a 21-day cycle at predefined dose levels. In part two, patients with trastuzumab-pretreated HER2-positive metastatic breast cancer received neratinib plus capecitabine at the MTD. The primary end point in part two was objective response rate (ORR). In part one (n = 33), the combination of neratinib 240 mg per day plus capecitabine 1,500 mg/m(2) per day was defined as the MTD, which was further evaluated in part 2 (n = 72). The most common drug-related adverse events were diarrhea (88%) and palmar-plantar erythrodysesthesia syndrome (48%). In part two, the ORR was 64% (n = 39 of 61) in patients with no prior lapatinib exposure and 57% (n = 4 of 7) in patients previously treated with lapatinib. Median progression-free survival was 40.3 and 35.9 weeks, respectively. Neratinib in combination with capecitabine had a manageable toxicity profile and showed promising antitumor activity in patients with HER2-positive metastatic breast cancer pretreated with trastuzumab and lapatinib.


Dissecting Aneurysm of the Internal Carotid Artery as a Complication of Facial Bone Trauma.
The involvement of the internal carotid artery in dissecting aneurysm is rarely reported in the literature and may occur as a complication of trauma, surgery, and other medical conditions. We report a case of a 22-year-old male who was involved in a motor vehicle accident with associated multiple orthopedic and maxillofacial fractures. During surgical management, the patient was incidentally diagnosed with a dissecting aneurysm involving the right internal carotid artery.


Young individuals with stroke in rehabilitation: a cohort study.
Stroke in younger populations is a public health crisis and the prevalence is rising. Little is known about the progress of younger individuals with stroke in rehabilitation. Characterization of the course and speed of recovery is needed so that rehabilitation professionals can set goals and make decisions. This was a cohort study with data extracted from electronic medical records. Participants were 408 individuals diagnosed with stroke who participated in inpatient rehabilitation in an urban, academic medical center in the USA. The main predictor was age which was categorized as (18-44, 45-64, 65-74 and 75+). Outcomes included baseline-adjusted discharge functional independence measure (FIM) scores and FIM efficiency. In linear regression models for FIM scores, the reference category was the youngest age group. The oldest group was discharged with significantly lower FIM total (B = -8.84), mobility (B = -4.13), self-care (B = -4.07) and cognitive (B = -1.57) scores than the youngest group after controlling for covariates. The 45-64 group also finished with significantly lower FIM total (B = -6.17), mobility (B = -2.61) and self-care (B = -3.01) scores than youngest group. FIM efficiencies were similar for all ages in each of the FIM scales. Younger individuals with stroke make slightly greater functional gains compared to older individuals with stroke, but other factors, such as admission scores, are more important and the rates of recovery may be similar.


Biology of the fibroblast growth factor gene family.
The biology of the fibroblast growth factor (FGF) gene family is reviewed. The structure, expression and known and putative functions of the seven members of this family characterized to date are discussed. These genes include: acidic and basic FGF, the INT.2 and HST proto-oncogenes and the recently characterized FGF.5, FGF.6 and KGF genes. These genes play a role in various processes such as cell proliferation, angiogenesis and embryogenesis, and possibly carcinogenesis.


Avoidance and cognitive fusion--central components in pain related disability? Development and preliminary validation of the Psychological Inflexibility in Pain Scale (PIPS).
Acceptance of pain and other associated negative private experiences has received increasing attention in recent years. This approach is in stark contrast to the traditional approach of reducing or controlling symptoms of pain. The empirical support for treatments emphasizing exposure and acceptance, such as Acceptance and Commitment Therapy, is growing. However, to date, few instruments exist to assess the core processes in these types of treatments. This study describes the development and preliminary validation of the Psychological Inflexibility in Pain Scale. Principal components analysis (PCA) suggests a 2-factor solution with a total of 16 items measuring avoidance of pain and cognitive fusion with pain. Results also indicate adequate reliability and validity for the scale. Implications of these findings for clinical assessment, as well as for research on pain related disability, are discussed along with suggestions for further research in this area.


Locally Advanced Scalp Tumors: Clinical and Survival Outcomes of a Tertiary Unit.
Locally advanced nonmelanoma skin cancers of the head and neck are well described in the current literature. However, data about clinical and survival outcomes are lacking. We present survival data from a tertiary head and neck cancer unit in London. A retrospective analysis of data collected from a single institution was conducted. All patients with locally advanced cutaneous scalp carcinomas invading the skull between 2011 and 2019 were included. Data included patient demographics, tumor, comorbidities, interventions, flap survival, and metal work exposure. Survival outcomes were examined using Kaplan-Meier analysis. Twenty-three patients were identified. The mean age was 72 years. Eighteen patients were male, and 5 were female. Five patients were immunosuppressed. Nineteen patients underwent outer cortex drill-down/full-thickness calvarial resection, followed by reconstruction with free tissue transfer. Six patients had titanium mesh reconstruction after segmental skull resections. Three patients underwent further surgery because of exposed metalwork. Disease-free survival at 3 years after surgery was 60%. Locally advanced nonmelanoma skin cancers invading the bone are sporadic. There are little published data on clinical and survival outcomes in this group. Despite the nature of these skin lesions, a high degree of local control can be obtained by extensive surgical resection, outer table drill-down, and calvarial resection. We conclude that aggressive management of the bony invasion improves disease-free survival and improves local control.


Non-Tuberculous Mycobacterial Infections Related to Peritoneal Dialysis.
Most infections related to peritoneal dialysis (PD) are caused by common bacteria, and non-tuberculous mycobacteria are rare. The clinical characteristics and prognosis of PD patients with non-tuberculous mycobacterial infections were investigated at our hospital. Non-tuberculous mycobacteria were detected in 11 patients (exit-site infection, tunnel infection, and peritonitis in 3, 5, and 3 patients, respectively). Mycobacterium fortuitum, Mycobacterium chelonae, and Mycobacterium abscessus were identified in 4, 2, and 2 patients, respectively. Most patients with peritonitis or tunnel infection required catheter removal. During the study period (2007 - 2017), peritonitis occurred in 44 patients, including 3 patients (6.8%) with non-tuberculous mycobacterial peritonitis. When non-tuberculous mycobacterial infection occurs, multi-agent antibiotic therapy, unroofing surgery, and/or catheter replacement should be performed to prevent peritonitis.


Relationships between soft tissues in a posed smile and vertical cephalometric skeletal measurements.
The purposes of this study were to measure the 3-dimensional parameters of the posed smile and to see whether there are any correlations with vertical cephalometric skeletal measurements. Pretreatment records from a sample of 110 white girls between the ages of 12 and 18 years were gathered. The measurements of SN-GoGn, anterior facial height, and lower and upper facial height percentages were obtained from tracing lateral cephalograms. Superimposing the repose and the posed smile facial scans allowed for measurements to be obtained showing the movements in the x, y, and z dimensions of the upper and lower lips, the commissures, and the Cupid's bows. Correlations and multiple linear regression analyses were run to check for associations and predictive relationships between the cephalometric skeletal measurements and soft tissue changes. We found significant moderate correlations and weak correlations. Significant multiple regression models were found for intercommissural width, smile index, and lower lip in the y and z dimensions. There were moderate correlations showing that as SN-GoGn and anterior facial height increased, the interlabial gap increased as the smile index decreased. Significant relationships were found between certain hard tissue cephalometric measurements and the width of the smile as well as the movements of the lower lip.


The refinement of ipsilateral eye retinotopic maps is increased by removing the dominant contralateral eye in adult mice.
Shortly after eye opening, initially disorganized visual cortex circuitry is rapidly refined to form smooth retinotopic maps. This process asymptotes long before adulthood, but it is unknown whether further refinement is possible. Prior work from our lab has shown that the retinotopic map of the non-dominant ipsilateral eye develops faster when the dominant contralateral eye is removed. We examined whether input from the contralateral eye might also limit the ultimate refinement of the ipsilateral eye retinotopic map in adults. In addition, we examined whether the increased refinement involved the recruitment of adjacent cortical area. By surgically implanting a chronic optical window over visual cortex in mice, we repeatedly measured the degree of retinotopic map refinement using quantitative intrinsic signal optical imaging over four weeks. We removed the contralateral eye and observed that the retinotopic map for the ipsilateral eye was further refined and the maximum magnitude of response increased. However, these changes were not accompanied by an increase in the area of responsive cortex. Since the retinotopic map was functionally refined to a greater degree without taking over adjacent cortical area, we conclude that input from the contralateral eye limits the normal refinement of visual cortical circuitry in mice. These findings suggest that the refinement capacity of cortical circuitry is normally saturated.


Prediction of advanced ovarian cancer recurrence by plasma metabolic profiling.
Epithelial ovarian cancer (EOC) is the most lethal of gynecologic malignancies due to the high rate of recurrence and poor prognosis. Predicting the prognosis in patients with EOC is clinically challenging, partly because appropriate biomarkers of recurrence have yet to be explored. In this prospective study, pre-treatment plasma samples were collected from 38 patients with stage III or IV EOC who were subsequently followed up. Ultra-performance liquid chromatography mass spectrometry was used to perform metabolic profiling, which yielded five metabolites that were potential biomarkers for EOC recurrence: l-tryptophan, kynurenine, bilirubin, LysoPC (14 : 0) and LysoPE (18 : 2). A combination of these five potential biomarkers strongly predicted recurrence, the area under the curve being 0.91. In summary, the candidate biomarkers identified in this study may both facilitate clinical prediction of EOC recurrence and prognosis and serve as potential therapeutic targets in patients with EOC.


Insensitivity to the bitter taste of chloramphenicol: an autosomal recessive trait.
Sensitivity to the bitter taste of chloramphenicol was studied in 860 students, 620 males and 240 females. About 8.6% of them were insensitive to this bitter taste. Familial lineage studies were carried out on a subset of these students, and the results suggested that the sensitivity or insensitivity was controlled by a pair of autosomal Mendelian genes, with the sensitive gene being dominant over the insensitive.


The spectrum of clinical sequelae associated with alpha-1 antitrypsin deficiency.
Alpha-1 antitrypsin (AAT) deficiency (AATD) is an autosomal co-dominant condition that predisposes to the development of lung disease, primarily emphysema. Emphysema results from the breakdown of lung matrix elastin by proteases, including neutrophil elastase, a protease normally inhibited by AAT. AATD also predisposes to liver (cirrhosis) and skin (panniculitis) disease, and to vasculitis. The prevalence of AATD is estimated to be approximately 1 in 3,500 individuals in the United States. However, lack of awareness of AATD among some physicians, misperceptions regarding the absence of effective therapy, and the close overlap in symptoms with asthma and non-AATD chronic obstructive pulmonary disease are thought to contribute to under-recognition of the disease. In patients with AATD, treatment with intravenous AAT augmentation therapy is the only currently available treatment known to slow the progression of emphysema. Moreover, smoking cessation and other lifestyle interventions also help improve outcomes. Early diagnosis and intervention are of key importance due to the irreversible nature of the resultant emphysema. Liver disease is the second leading cause of death among patients with AATD and a minority of patients present with panniculitis or antineutrophil cytoplasmic antibody-associated vasculitis, thought to be directly related to AATD. Though no randomized trial has assessed the effectiveness of augmentation therapy for AATD-associated panniculitis, clinical experience and case series suggest there is a benefit. Other diseases putatively linked to AATD include aneurysmal disease and multiple neurological conditions, although these associations remain speculative in nature.


Flow cytometry analysis of T cell subsets in skin of patients with specific cutaneous manifestation of B non-Hodgkin lymphoma.
Cutaneous lesions may be the atypical initial manifestation of blood disorder. Monoclonal antibodies identify surface phenotype of lymphocytes present in specific cutaneous lesions. We studied cutaneous infiltrates with flow cytometry in 10 cases of non-Hodgkin lymphoma. We characterized T cell subset in skin immune system. The percentage of T cells was compared to percentage observed in healthy specimens from same patient. T4 cells predominate in cutaneous infiltrates, with an increase in T4/T8 ratio. There was also an increase in T6+ cells, Langerhans cell markers in the skin. HLA-Dr+, T6 cells increased in all cases tested, indicative of dendritic cells. These data showed a modification of T lymphocytes only in skin infiltrate of lymphoma.