Roles of α‑synuclein in gastrointestinal microbiome dysbiosis‑related Parkinson's disease progression (Review).
Parkinson's disease (PD) is the second most common neurodegenerative disease amongst the middle‑aged and elderly populations. Several studies have confirmed that the microbiota‑gut‑brain axis (MGBA) serves a key role in the pathogenesis of PD. Changes to the gastrointestinal microbiome (GM) cause misfolding and abnormal aggregation of α‑synuclein (α‑syn) in the intestine. Abnormal α‑syn is not eliminated via physiological mechanisms and is transported into the central nervous system (CNS) via the vagus nerve. The abnormal levels of α‑syn aggregate in the substantia nigra pars compacta, not only leading to the formation of eosinophilic Lewis Bodies in the cytoplasm and mitochondrial dysfunction in dopaminergic (DA) neurons, but also leading to the stimulation of an inflammatory response in the microglia. These pathological changes result in an increase in oxidative stress (OS), which triggers nerve cell apoptosis, a characteristic of PD. This increase in OS further oxidizes and intensifies abnormal aggregation of α‑syn, eventually forming a positive feedback loop. The present review discusses the abnormal accumulation of α‑syn in the intestine caused by the GM changes and the increased levels of α‑syn transport to the CNS via the MGBA, resulting in the loss of DA neurons and an increase in the inflammatory response of microglial cells in the brain of patients with PD. In addition, relevant clinical therapeutic strategies for improving the GM and reducing α‑syn accumulation to relieve the symptoms and progression of PD are described.


Kingpin approaches to fighting crime and community violence: Evidence from Mexico's drug war.
This study considers the effects of the kingpin strategy, an approach to fighting organized crime in which law-enforcement efforts focus on capturing the leaders of criminal organizations, on community violence in the context of Mexico's drug war. Newly constructed historical data on drug-trafficking organizations' areas of operation at the municipality level and monthly homicide data allow us to control for a rich set of fixed effects and to leverage variation in the timing of kingpin captures to estimate their effects. This analysis indicates that kingpin captures cause large and sustained increases to the homicide rate in the municipality of capture and smaller but significant effects on other municipalities where the kingpin's organization has a presence, supporting the notion that removing kingpins can have destabilizing effects throughout an organization that are accompanied by escalations in violence. We also find reductions in homicides in municipalities surrounding the municipality where kingpins are captured.


A 60-Year-Old Woman with Primary Biliary Cholangitis and Crohn's Ileitis Following the Suspension of Ursodeoxycholic Acid.
BACKGROUND There is a recognized association between inflammatory bowel disease (IBD) and hepatobiliary autoimmune disease, particularly primary sclerosing cholangitis (PSC). There have been fewer reported cases of IBD and primary biliary cholangitis (PBC), which is treated with ursodeoxycholic acid (UDCA). This report presents the case of a 60-year-old woman with PBC who was diagnosed with Crohn's ileitis after suspension of UDCA treatment. CASE REPORT A 66-year-old female patient with PBC was admitted to our department for irrepressible chronic diarrhea and recurrent abdominal pain. PBC was diagnosed on the basis of serological data: chronic (>6 months) increase in alkaline phosphatase (ALP) associated with positivity for specific anti-nuclear antibodies (sp100 and gp210), without requiring a liver biopsy and a magnetic resonance cholangiopancreatography to rule out PSC. Given the intolerance and non-responsiveness according to the Toronto criteria (ALP <1.67 times the normal limit after 2 years) to UDCA at 15 mg/kg/day, an oral monotherapy treatment using obeticholic acid at 5 mg/day was prescribed. The patient complained of abdominal pain and upper gastrointestinal symptoms. The endoscopic/histologic and radiologic examinations supported the diagnosis of Crohn's ileitis. Given the potential benefits to PBC patients of what is described as off-label therapy, budesonide at a dosage of 9 mg/day p.o. was also administered. One month after discharge, an improvement was observed both in the cholestasis indices and in gastrointestinal symptoms. CONCLUSIONS This report presents a case of PBC in which the patient was diagnosed with Crohn's ileitis after cessation of treatment with UDCA, and highlights the importance of recognizing the association between autoimmune hepatobiliary disease and IBD.


Nuclear proteasomal degradation and cytoplasmic retention underlie early nuclear exclusion of transcription factor Max upon axon damage.
The behavior of the transcription factor Max in axon-damaged retinal ganglion cells (RGC) was investigated in explants from the rat retina, used as a tissue culture model of the central nervous system (CNS). Axon damage leads to an apparent rapid shift in the localization of Max from the nucleus to the cytoplasm, in advance of markers of apoptosis. This nuclear exclusion resisted treatments with calpeptin or the CRM1 exportin inhibitor leptomycin B, but was prevented by low temperature. Inhibition of either transcription or translation prevented RGC death, but only the latter robustly prevented nuclear exclusion. The proteasome inhibitor lactacystin prevented nuclear exclusion, whereas newly synthesized Max still accumulated in the cytoplasm of the axon-damaged RGC. The results show that proteosomal degradation of nuclear Max coupled with continued expression and cytoplasmic accumulation of Max, with blockade of nucleocytoplasmic transport of the newly synthesized protein, is an early event after CNS axonal damage.


Interferon-alpha-2b/ribavirin-induced vestibulocochlear toxicity with dysautonomia in a chronic hepatitis C patient.
A 57-year-old man developed vertigo, tinnitus, bilateral hearing loss and postural intolerance temporally related to the administration of pegylated interferon-alpha-2b/ribavirin for chronic hepatitis C viral infection. Clinical examination showed bilateral sensorineural hearing loss, subjective vertigo with saccadic intrusions during fixation and smooth visual pursuit, and supine hypertension followed by orthostatic hypotension with inadequate reflexive compensatory cardiovascular responses. Laboratory assessment showed marked hemolytic anemia. Formal audiometry revealed high-frequency sensorineural hearing loss with abnormal high-frequency distortion product otoacoustic emissions, indicative of damage to the cochlear outer hair cells. Cessation of therapy resulted in rapid clinical resolution with mild residual hearing loss and tinnitus. This case report illustrates vestibulocochlear and autonomic nervous system adverse effects of pegylated interferon-alpha-2b/ribavirin, emphasizing the importance of early recognition and cessation of therapy to prevent permanent neurootologic injury.


Clinicopathologic features and endoscopic resection of early primary nonampullary duodenal carcinoma.
Early primary nonampullary duodenal carcinoma is an extremely rare disease with poorly defined clinicopathologic features; early detection of this carcinoma is not common. To clarify the clinicopathologic characteristics of early primary nonampullary duodenal carcinoma and retrospectively analyze methods of treatment. Seventeen early duodenal carcinomas identified between 1994 and 2001 in 15 patients were studied. Lesions were divided into 2 groups: sporadic carcinoma (10 cases in 10 patients) and familial adenomatous polyposis associated carcinoma (7 cases in 5 patients). Clinicopathologic features and methods of treatment were compared between groups. The mean age of patients with sporadic carcinoma (63.8 years) was significantly higher than that of patients with FAP-associated carcinoma (34.9 years). The incidence of sporadic carcinoma was significantly higher in men that in women (M:F ratio 9:1); the difference between sexes in the incidence of FAP-associated carcinoma (1:4) was not significant. There was no significant difference between both groups in relation to tumor size, location, gross appearance, or histopathology. Thirteen of the duodenal tumors were treated by endoscopic mucosal resection (EMR), two by polypectomy, and two by open surgery. Complications were encountered in 1 of 15 cases (6%); local bleeding occurred after one EMR, but hemostasis was achieved endoscopically. The mean follow-up period for all patients was 51.7 months. No patients experienced recurrence after resection. The significant differences between patients with sporadic and those with early FAP-associated duodenal carcinoma were in age and sex. Endoscopic resection appears to be a safe and efficient treatment of carefully selected patients with early primary nonampullary duodenal carcinoma.


Mediating role of splitting in relation to attachment styles and shopping addiction.
Shopping can provide a sense of satisfaction and pleasure; however, if a person's excessive involvement in this behavior starts to negatively impact other aspects of their life, similar to other addictive behaviors like excessive internet use, gaming, and gambling, it may be classified as pathological. Given the lack of agreement regarding the classification of excessive shopping tendencies as a separate mental health condition or addictive behavior, taking a socio-emotional approach to explore the psychological factors that precede this behavior, may offer a better comprehension of it. The purpose of this study was to examine the relationship between attachment styles and excessive shopping behavior, as well as to investigate the potential mediating effect of defense mechanisms like splitting on this relationship. Using convenience sampling, a group of 457 stock market employees (116 female, 341 male) between the ages of 24 and 60 were recruited. The researchers utilized a set of validated psychological questionnaires to assess the employees attachment styles, shopping addiction, and splitting tendencies. The results obtained from both the mediation model and path analysis suggest that attachment styles do not have a direct relationship with shopping addiction. Nonetheless, the study supports the impact of insecure anxious and avoidan attachment styles on splitting. Furthermore, the findings confirm that splitting has a mediating effect on the relationship between attachment styles and splitting. The present study enhanced our comprehension of the subconscious mechanisms underlying shopping tendencies. Specifically, the findings suggest that excessive tendencies towards shopping can be considered a maladaptive response resulting from insecure attachment styles and the unconscious utilization of the splitting defense mechanism.


Proliferating cell nuclear antigen (PCNA) in high-grade malignant fibrous histiocytoma: prognostic value in 48 patients.
Grading based on histopathologic features is used to predict survival in soft-tissue sarcoma. However, variations in clinical behavior between tumors of the same grade motivate a search for additional factors that correlate with prognosis. Proliferating cell nuclear antigen (PCNA) is expressed in proliferating cells during the G1, S and G2-phases. To evaluate a prognostic implication of PCNA, the tumors of 48 patients with malignant fibrous histiocytomas (13 grade III, 35 grade IV) with a minimum follow-up of 2 years were immunohistochemically studied. We used PC10, a monoclonal antibody (MAb) directed against PCNA, which allows cell proliferation in formalin-fixed, paraffin-embedded tumor tissue to be evaluated. We applied a semiquantitative PCNA grading scheme to all stained nuclei of an entire slide. The 3-year metastasis-free survival rate was 0.87 for patients in grade A (low PLNA rate), and 0.14 for patients in grade C (high PLNA). Our findings show that immunohistochemical evaluation of cell kinetics in soft-tissue sarcomas by PCNA might be a useful adjunct to conventional tumor grading.


Exploration of Caregiver Interrater Agreement and Test-Retest Reliability on the Infant Cleft Observer Outcomes (iCOO).
Caregiver and observer-reported measures are frequently used as outcomes for research on infants and young children who are unable to report on their own health. Our team developed the Infant with Clefts Observation Outcomes Instrument (iCOO) for infants with cleft lip with or without cleft palate. This exploratory study compared test-retest and interrater reliabilities to inform whether differences in caregiver perspective might affect the iCOO. This study is a secondary analysis comparing caregiver interrater agreement to test-retest reliability. Twenty-five pairs of caregivers completed the iCOO before surgery, 1 week later for test-retest reliability, 2 days after surgery, and 2 months after surgery. Reliability was assessed using intraclass correlations (ICCs) and t-tests were used to compare ratings between caregivers. Infants had cleft lip (28%) or cleft lip and palate (72%). Primary caregivers were predominantly mothers (92%) and secondary caregivers were predominantly fathers (80%). Test-retest reliability met psychometric standards for most items on the iCOO (81%-86% of items). Caregiver agreement on the iCOO items was lower than test-retest reliability (33%-46% of items met psychometric standards). Caregivers did not systematically differ in whether they rated infants as healthier or less healthy than the other caregiver (5%-16% of items had statistically significant differences). Caregivers used the measure consistently, but had different experiences and perceptions of their infant's health and functioning. Future studies are needed to explore mechanisms for the differences in test-retest and interrater reliability. Whenever possible, the same caregiver should provide ratings of the infant, including on the iCOO.


[Favorable effects of epsilon-aminocaproic acid on the children with nephrotic syndrome and Schonlein-Henoch syndrome treated with corticosteroids].
An effect of EACA given in the daily dose of 85-230 mg/kg for 1-1-days on the activity of certain plasma protease inhibitors in 7 children with steroid-sensitive and steroid-dependent nephrotic syndrome (age between 3.5 and 18 years), and in 6 children with Schönlein-Henoch syndrome (aged between 3.5 and 6 years). Additionally, an effect of EACA on clinical status, dynamics of improvement, proteinuria and/or erythrocyturia, and incidence of adverse reactions was studied. It was found that EACA significantly increased antithrombin III activity by approximately 68.8% proteinase alpha 1-inhibitor by 41.8% alpha 2-antiplasmin by 55% in patients with nephrotic syndrome, and increased an activity of protease alpha 1-inhibitor by 75% in patients with Schönlein-Henoch syndrome. EACA given together with corticosteroids enhanced their efficiency manifested--especially in children with Schönlein-Henoch syndrome--by a rapid diminishment of skin changes, proteinuria and erythrocyturia. A drop in blood pressure, loose stools, upper respiratory inflammation, and fever were most frequent adverse reactions. EACA given alone produced rapidly increasing edema in patients with hephrotic syndrome. It seems that EACA may be used as an adjuvant therapy in some cases of nephrotic and Schönlein-Henoch syndromse.


A comparison of the donor-site morbidity after using the prelaminated fasciomucosal flap and the fasciocutaneous radial forearm flap for intraoral reconstruction.
Since 1996 we have performed mucosal prelamination of the distal radial forearm flap for functional reconstruction of defects of the intraoral lining. This study was undertaken to demonstrate that the prelaminated fasciomucosal radial forearm flap can provide physiological oropharyngeal reconstruction with mucus-producing tissue, while avoiding the donor-site complications of the fasciocutaneous radial forearm flap. We examined the donor hand at least 6 months postoperatively in 20 patients after using a prelaminated fasciomucosal radial forearm flap and in 15 patients after harvesting a classical fasciocutaneous radial forearm flap. The evaluation of hand function included range of motion, grip power, pinch power, sensibility and vascular analysis in both hands. The patients were asked about cold intolerance, pain and any restrictions in daily life, and the cosmetic appearance of the donor hand was noted. In the prelaminated-flap group (n 20), two patients had decreased wrist extension, and one of these patients also had reduced strength and mild hypaesthesia in the donor hand. In the classical-fasciocutaneous-flap group (n 15), six patients had decreased wrist extension, five patients had reduced strength and four patients had diminished sensibility in the donor hand. Painful neuromas were found only after fasciocutaneous flaps (three cases). Subjective assessment revealed restricted hand function in one patient in the prelaminated-flap group, and in five patients who had undergone fasciocutaneous flap transfer. The results of this study show that using the prelaminated fasciomucosal radial forearm flap minimises the donor-site morbidity. Furthermore, we were able to improve the cosmetic appearance of this very exposed region.


Workers with Occupational Contact Dermatitis: Work Outcomes and Return to Work Process in the First Six Months following Diagnosis.
Workers with occupational contact dermatitis may have poor outcomes that impact their health, work, and quality of life. While there is information available on overall return to work, little is known about the actual return to work process. The objectives of the study were to describe the return to work experience and work outcome in workers with contact dermatitis following diagnosis. 78 workers with occupational contact dermatitis were followed for 6 months after assessment. Information collected included clinical presentation and status, the return to work process and work outcomes. Six months after assessment, 38% were not working, almost all because of their skin problem. Of the 62% working 32% had changed job, most because of their skin problem. Limited advice to enable return to work and communication were reported. These findings suggest that there are gaps in return to work programs for occupational contact dermatitis and further research is needed.


[Behavioral risk factors for cardiovascular diseases in adolescents from the rural area of a municipality in Southern Brazil].
The study aimed to estimate the prevalence of behavioral risk factors for cardiovascular diseases (CVDs) and factors associated with their accumulation in adolescents from the rural area of a municipality in Pelotas, Rio Grande do Sul State, Brazil. This was a cross-sectional school-based census-type study with a sample of 515 sixth to nineth-grade schoolchildren in 21 rural public schools in Pelotas. The target behavioral risk factors were: physical inactivity; irregular consumption of fruits, vegetables, and greens; initiation to alcohol consumption and smoking; and addition of salt to foods. The study outcome was the cluster score of behavioral risk factors, varying from 0 to 3: no behavioral risk factors for CVD or exposure to 1, 2, or ≥ 3 behavioral risk factors. Ordinal logistic regression was performed to assess the effect adjusted for individual characteristics on the accumulation of behavioral risk factors, using as the reference category individuals without any risk factor. Physical inactivity was the most prevalent risk factor (74.8%), followed by irregular consumption of fruits, vegetables, and greens (56.2%). Approximately 42% of the adolescents presented two behavioral risk factors, the most prevalent combination of which was physical inactivity and irregular consumption of fruits, vegetables, and greens (23%). The odds of accumulating two or more behavioral risk factors increased with age. The presence and simultaneity of behavioral risk factors is quite high among adolescents from the rural area of Pelotas, showing that they are exposed to the development of CVD. Interventions are needed to prevent the simultaneous occurrence of these risk factors.


Recurrent Pindborg tumor of the maxilla: a case report and review of the literature.
We report a case of recurrent Pindborg tumor (calcifying epithelial odontogenic tumor) of the maxilla. The patient was a 34-year-old woman who had been previously diagnosed with Pindborg tumor and treated with curettage. She was subsequently referred to us for evaluation of nasal obstruction. Examination revealed the presence of a mass lesion in the right nasal cavity and right maxilla, which was identified as a recurrence of her earlier Pindborg tumor. The patient was treated with maxillectomy with orbital preservation. Pindborg tumor is a rare odontogenic tumor; when it does occur, it is more often seen in the mandible than in the maxilla. While this tumor is often treated with curettage alone, the aggressive nature of the recurrence in our patient necessitated radical surgery. We report this case to highlight the need to be suitably aggressive in treating these types of tumors in order to avoid recurrence.


Result of school-based intervention on cardiovascular risk factors.
To assess the effectiveness of a two-year school-based intervention, consisting of integrated and replicable physical activity and nutritional education on weight, fat percentage, cardiovascular risk factors, and blood pressure. Six elementary schools in Reykjavik were randomly assigned to be either intervention (n = 3) or control (n = 3) schools. Seven-year-old children in the second grade in these schools were invited to participate (n = 321); 268 (83%) underwent some or all of the measurements. These 286 children were followed up for two years. Children in intervention schools participated in an integrated and replicable physical activity programme, increasing to approximately 60 minutes of physical activity during school in the second year of intervention. Furthermore, they received special information about nutrition, and parents, teachers, and school food service staff were all involved in the intervention. Subjects. 321seven-year-old schoolchildren. Blood pressure, obesity, percentage of body fat, lipid profile, fasting insulin. Children in the intervention group had a 2.3 mmHg increase in systolic blood pressure (SBP) and a 2.9 mmHg increase in diastolic blood pressure (DBP) over the two-year intervention period, while children in the control group increased SBP by 6.7 mmHg and DPB by 8.4 mmHg. These changes were not statistically significant. Furthermore there were no significant changes in percentage body fat, lipid profile, or fasting insulin between the intervention and control schools. A two-year school-based intervention with increased physical activity and healthy diet did not have a significant effect on common cardiovascular risk factors.


Nucleotide sequence of Lactobacillus viridescens 5S RNA.
The nucleotide sequence of Lactobacillus viridescens ATCC 12706 5S RNA was determined to be pU-G-U-U-G-U-G-A-U-G-A-U-G-G-C-A-U-U-G-A-G-G-U-C-A-C-A-C C-U-G-U-U-C-C-C-A-U-A-C-C-G-A-A-C-A-C-A-G-A-A-G-U-U-A-A-G-C-U-C-A-A-U-A-G-C-G C-C-G-A-A-A-G-U-A-G-U-U-G-G-A-G-G-A-U-C-U-C-U-U-C-C-U-G-C-G-A-G-G-A-U-A-G-G-A C-G-U-C-G-C-A-A-U-G-COH. When compared with other published sequences of prokaryotic 5S RNA species, this sequence shows as much homology with that from B. substilis (80% homology when all variations included) and B. megaterium (77% homology) as with the 5S RNA from another member of Lactobacillaceae family (L. brevis, 79% homology). The sequence contains the proposed tRNA binding site (CGAAC, positions 41-45) and can accomodate most, but not all, of the more recently proposed helical regions of secondary structure.


The meaning of dignified care: an exploration of health and social care professionals' perspectives working with older people.
Despite well established national and local policies championing the need to provide dignity in care for older people, there continues to be a wealth of empirical evidence documenting how we are failing to deliver this. While we have evidence as to what older people and their relatives understand by the term 'dignified care' we have less insight into the perspectives of staff regarding their understanding of this key policy objective. This paper aimed to explore the meaning of dignified care from the perspective of health and social care professionals' working with older people. In-depth interviews and focus groups with health and social care professionals were carried out across four NHS Trusts in England, as part of a larger study, to investigate how dignified care for older people is understood and delivered. A total of 48 health professionals took part in in-depth interviews and 33 health and social care professionals participated in one of eight focus groups. Health and social care professionals defined the meaning of dignified care as: 'dignity is the backbone of care', 'it's the "little things"', 'feeling safe and secure', 'treat as you want to be treated', 'treat as an individual' and 'Dignity encompasses multiple factors'. 'Hands on' aspects of care were rarely mentioned when defining dignity. This suggests that policies around providing dignified care are being interpreted as an approach towards care and not with direct care provision. This limited interpretation of dignity may be one factor contributing to the continued neglect of older people in acute settings. These findings highlight that proactive measures are required to ensure that both relational and 'hands on' aspects of care are met for all older people receiving care in NHS trusts.


Herpes simplex virus virion stimulatory protein mRNA leader contains sequence elements which increase both virus-induced transcription and mRNA stability.
To investigate the role of 5' noncoding leader sequence of herpes simplex virus type 1 (HSV-1) mRNA in infected cells, the promoter for the 65,000-dalton virion stimulatory protein (VSP), a beta-gamma polypeptide, was introduced into plasmids bearing the chloramphenicol acetyltransferase (cat) gene together with various lengths of adjacent viral leader sequences. Plasmids containing longer lengths of leader sequence gave rise to significantly higher levels of CAT enzyme in transfected cells superinfected with HSV-1. RNase T2 protection assays of CAT mRNA showed that transcription was initiated from an authentic viral cap site in all VSP-CAT constructs and that CAT mRNA levels corresponded to CAT enzyme levels. Use of cis-linked simian virus 40 enhancer sequences demonstrated that the effect was virus specific. Constructs containing 12 and 48 base pairs of the VSP mRNA leader gave HSV infection-induced CAT activities intermediate between those of the leaderless construct and the VSP-(+77)-CAT construct. Actinomycin D chase experiments demonstrated that the longest leader sequences increased hybrid CAT mRNA stability at least twofold in infected cells. Cotransfection experiments with a cosmid bearing four virus-specified transcription factors (ICP4, ICP0, ICP27, and VSP-65K) showed that sequences from -3 to +77, with respect to the viral mRNA cap site, also contained signals responsive to transcriptional activation.


Promoter/origin structure of the complementary strand of hepatitis C virus genome.
Hepatitis C virus (HCV) NS5B protein encodes an RNA-dependent RNA polymerase (RdRp). Sequences in the 3' termini of both the plus and minus strand of HCV genomic RNA harbor the activity of a replication origin and a transcription promoter. There are unique stem-loop structures in both termini of the viral RNA. We found that the complementary strand of the internal ribosome-binding site (IRES) showed strong template activity in vitro. The complementary strand RNA of the HCV genome works as a template for mRNA and viral genomic RNA. We analyzed the promoter/origin structure of the complementary sequence of IRES and found that the first and second stem-loops worked as negative and positive elements in RNA synthesis, respectively. The complementary strand of the second stem-loop of IRES was an important element also for binding to HCV RdRp.


Video-based skill assessment of endoscopic suturing in a pediatric chest model and a box trainer.
Pediatric endoscopic surgery requires special surgical skills because of the small working space and tissue fragility. This article presents a video-based skill assessment method for endoscopic suturing using a pediatric chest model. A commercial suture pad was placed in a rapid-prototyped pediatric chest model of a 1-year-old patient to simulate the thoracoscopic repair of esophageal atresia type C. Twenty-eight pediatric surgeons (9 experts, 9 intermediates, and 10 trainees) performed an endoscopic intracorporeal suturing and knot-tying task both in the pediatric chest model and in a box trainer. The tasks were video-recorded and rated by two blinded observers using the 29-point checklist method and a suturing errors score sheet method. The task completion time and the number of needle manipulations were measured. The expert group showed better performance than the intermediate and trainee groups in the pediatric chest model, and the differences were larger than those in the box trainer. Significant differences between the expert and the trainee groups were observed in the items related to safety such as the skills for keeping the needle in view at all times. Significant differences between the expert and intermediate groups were observed in the items related to task quality and efficiency such as the smoothness of knot tying and the number of needle manipulations. Video-based skill assessment of endoscopic suturing using the pediatric chest model and a box trainer distinguished pediatric endoscopic surgeons according to their clinical experience, and pediatric-specific skills were identified.


The type of relationship in marriages of patients with neurosis disorders.
Conjugal relationships are an integral part of spouses' bonds. The only pattern of relationships in the marriages of patients with neurosis disorders was a type based on a dependence mechanism, i.e. subordinating one partner to another, whereas in the control group the pattern is based on a sense of mutual confidence, self-control, and the need to understand oneself and other people as well.


Advances in treating bronchopulmonary dysplasia.
Introduction: Bronchopulmonary dysplasia (BPD) is a common long-term adverse complication of very premature delivery. Affected infants can suffer chronic respiratory morbidities including lung function abnormalities and reduced exercise capacity even as young adults. Many studies have investigated possible preventative strategies; however, it is equally important to identify optimum management strategies for infants with evolving or established BPD. Areas covered: Respiratory support modalities and established and novel pharmacological treatments. Expert opinion: Respiratory support modalities including proportional assist ventilation and neurally adjusted ventilatory assist are associated with short term improvements in oxygenation indices. Such modalities need to be investigated in appropriate RCTs. Many pharmacological treatments are routinely used with a limited evidence base, for example diuretics. Stem cell therapies in small case series are associated with promising results. More research is required before it is possible to determine if such therapies should be investigated in large RCTs with long-term outcomes.


The synaptonemal complexes of the nematode Caenorhabditis elegans: gametic response to retinol.
Retinol (RO) is essential for normal gene expression and progression of gametogenesis. Excessive amounts of RO in the diet results in the condition termed 'hypervitaminosis A' which severely affects gametogenesis. In the present work, the nematode Caenorhabditis elegans was grown in different concentrations of RO for up to seven generations. Decreased fecundity was positively correlated with increasing concentrations of RO with successive generations. Decreased nuclear volume was positively correlated with increasing RO concentration for each generation. Abnormal chromatin condensation was present along the bivalent and the lengths of the synaptonemal complexes (SC) were consistently longer than in the wild-type. Increasing RO concentration was also negatively correlated with the presence of SCs. The presence of disjunction regulator regions (DRR), which are decondensed regions of chromatin along the bivalent which occur in specific numbers, was negatively correlated with increasing RO concentration. By the third generation, DRRs were no longer observed in any of the organisms. This study shows that high levels of retinol in the diet affect gene expression, via changes in chromosome structure, and interferes with gamete production by inhibiting the pairing of homologous chromosomes during meiotic prophase.


Long-lasting effects of cyclophosphamide on lymphocytes in peripheral blood and spinal fluid.
Moderate doses of cyclophosphamide can cause effects on lymphocytes that may last for some time after discontinuation of the treatment. Since cyclophosphamide is also often used at high doses, we studied the short- and long-term effects of such a high dose (8 grams in 20 days) in 50 patients with chronic progressive multiple sclerosis with the use of monoclonal antibodies. The treatment caused a depletion of lymphocytes, especially CD4+ cells resulting in a significant decrease of the CD4/CD8 ratio. These changes can still be found up to 13.5 years after treatment. Although there was some recovery in the first few years after treatment this was only partial. Therefore, some of the effects of high dose cyclophosphamide on cellular immunity may be permanent. These changes should be taken into account when studying immune parameters or considering new treatments in these patients.


Design and Synthesis of Energetic Melt-Castable Materials by Substituent-Specific Modification.
With the increase in the demand for high-performance composite explosives, the search for advanced energetic melt-castable compounds has attracted increasing attention in the field of energetic materials. Herein, two new energetic materials with nitromethyl and azidomethyl substituents (1-(nitromethyl)-3,4-dinitro-1H-pyrazole (NMDNP) and 1-(azidomethyl)-3,4-dinitro-1H-pyrazole (AMDNP) were prepared by the substituent modification of a potential melt-castable molecule ((3,4-dinitro-1H-pyrazol-1-yl) methyl nitrate, MC-4), respectively. NMDNP exhibited a suitable melting point (90 °C), good thermal stability (Td : 185 °C) and excellent detonation performance (8484 m s-1 ) and impact sensitivity (25 J), thereby demonstrating promise as an energetic melt-castable material. Simultaneously, compared with the nitrato-methyl and azidomethyl substituents, the nitromethyl substituent exhibited greater advantages in regulating performance.


DNA repair after X-irradiation: lessons from plants.
The effects of low-dose radiation causing DNA damage continue to be subjects of interest. Problems with existing approaches to low-dose DNA damage are that single-strand breaks (the predominant radiation-induced lesion) are very rapidly repaired and that results using current methods for measuring DNA damage can be difficult to interpret. As a novel approach, we conducted studies using plants (rye grass and the model plant Arabidopsis) exposed to X-rays and used the alkaline comet assay to measure DNA damage and repair after exposures. Consistent with previous studies, we detected so-called 'rapid' and 'slow' phases of DNA repair after acute exposures of 5 and 15 Gy. After exposures corresponding to 2 Gy and lower, 'rapid' repair was so fast that it was difficult to detect. We also found that the so-called 'slow' phase in both plants actually consisted of two components; an initial period of negligible repair lasting 80-120 min followed by a period of rapid repair lasting <30 min. Using Arabidopsis mutants homozygous for both ATM and BRCA1, we found that both of these genes are required for DNA repair during the 3-h period of our experiments, indicating that the 'slow' phase involves a homologous repair (HR) of double-strand breaks and clustered single-strand breaks. The lag of repair in the 'slow' phase presumably involves induction of expression of genes involved in HR repair such as BRCA1 and RAD51.


Determination of diarrheic shellfish toxins in mussels by microliquid chromatography-tandem mass spectrometry.
A fast, sensitive, and specific procedure for determining toxins that cause diarrheic shellfish poisoning (DSP) using microliquid chromatography coupled with tandem mass spectrometry (micro-LC-MS-MS) is reported. The lipophylic polyether acidic toxins okadaic acid (OA), its isomer dinophysistoxin-2 (DTX-2), the 35-methylokadaic acid dinophysistoxin-1 (DTX-1), and the novel toxin dinophysistoxin-1B (DTX-2B; recently isolated from Irish mussels) were extracted from shellfish tissues with acetone and chromatographed by isocratic elution at 10 microL/min with CH3 CN-H2O, 80 + 20 (v/v), containing 0.1% trifluoroacetic acid, through a C18 reversed-phase column (1.0 mm id). The chromatograph is coupled via an ion spray interface to an atmospheric pressure ionization source. Collision-induced-dissociation (CID) ion mass spectra of the protonated molecule, [M + H]+, at m/z 805 for OA, DTX-2, and DTX-2B and at m/z 819 for DTX-1, were obtained in MS-MS experiments to identify 2 diagnostic fragment ions for each analyte that could be used for selected-reaction-monitoring (SRM) micro-LC-MS-MS analysis. The CID spectrum of DTX-2B confirmed it to be a new OA isomer, like DTX-2. Standard curves obtained by SRM micro-LC-MS-MS were linear (r2 > or = 0.9992) over the range 0.05-1.00 micrograms/mL (i.e., 0.10-2.00 micrograms toxin/g hepatopancreas), and a detection limit of 15 pg/injection was obtained for each DSP toxin. Average recoveries ranged from 95 to 101%, and coefficients of variation ranged from 1.8 to 3.4%. This novel SRM micro-LC-MS-MS method was used to confirm acidic DSP toxins in Irish and Italian toxic mussels. It offers a high degree of specificity because analyte confirmation is based on retention time, molecular weight, structural information obtained from the presence of 2 diagnostic fragments for each analyte, and ion ratios. OA was found in both Irish (< or = 0.7 micrograms/g hepatopancreas) and Italian (< or = 1.5 micrograms/g hepatopancreas) mussels. DTX-1 was found only in Italian mussels (< or = 0.3 micrograms/g hepatopancreas). DTX-2 (< or = 6.1 micrograms/g hepatopancreas) and DTX-2B (< or = 0.08 micrograms/hepatopancreas) were unique to Irish shellfish.


Pharmacokinetic analysis of cefquinome in healthy chickens.
1. The pharmacokinetics of cefquinome (CEQ) in chickens was determined after intravenous (IV) and intramuscular (IM) administration of 2 mg/kg body weight. Plasma concentrations were measured by high performance liquid chromatography assay with an ultraviolet detector at 265 nm wavelength. 2. Plasma concentration-time data after IV administration were best fitted by a two-compartment model. The pharmacokinetic parameters following IV injection were distribution half-life 0·43 ± 0·19 h, elimination half-life 1·29 ± 0·10 h, total body clearance 0·35 ± 0·04 l/kg/h, area under curve 5·33 ± 0·55 µg/h/ml and volume of distribution at steady state 0·49 ± 0·05 l/kg. 3. Plasma concentration-time data after IM administration were best described by a two-compartment model. The pharmacokinetic parameters after IM administration were absorption half-life 0·07 ± 0·02 h, distribution half-life 0·58 ± 0·27 h, elimination half-life 1·35 ± 0·20 h, peak concentration 3·04 ± 0·71 µg/ml and bioavailability 95·81 ± 5·81%. 4. Cefquinome kinetics in chicken and data from other species were summarised and analysed to provide a comprehensive understanding of CEQ pharmacokinetics.


Prognostic neurodevelopmental testing of preterm infants: do we need to change the paradigm?
Longitudinal follow-up with assessment of developmental status at about 2 years of age is routine for high-risk newborns. The results of these assessments can be used for many purposes, including helping physicians, parents, and teachers plan educational or developmental interventions. These assessments also provide outcome measures for clinical research studies. Outcome results may also serve as a source of information for clinicians when counseling parents regarding provision of care for extreme preterm infants. Consideration should be given to use of different outcome metrics based on the purpose for testing. Categorization of composite cognitive, motor and neurosensory findings to define levels of impairment should be limited to research. Planning for individual interventions is better guided by descriptive findings. Current tools for assessing neurodevelopmental status at 2 years of age have important limitations. First, outcomes at early ages do not always predict function later in life. They are, at best, an estimate of longer-term outcomes, with important individual variation. For infants without severe neurologic injury, postnatal environmental factors play a predominant role in determining long-term cognitive and academic outcomes. Further investigations should assess quality of life and other considerations that are important for parents when making decisions about neonatal intensive care unit care for their infant.


Structural and computational depth of diffusion-limited aggregation.
Diffusion-limited aggregation (DLA) is studied from the perspective of computational complexity. A parallel algorithm is exhibited that requires a number of steps that scales as the depth of the tree defined by the cluster. The existence of this algorithm suggests a connection between a fundamental computational and structural property of DLA.


Pharmacokinetics of cycloalliin, an organosulfur compound found in garlic and onion, in rats.
Cycloalliin, an organosulfur compound found in garlic and onion, has been reported to exert several biological activities and also to remain stable during storage and processing. In this study, we investigated the pharmacokinetics of cycloalliin in rats after intravenous or oral administration. Cycloalliin and its metabolite, (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid, in plasma, urine, feces, and organs was determined by a validated liquid chromatography-mass spectrometry method. When administered intravenously at 50 mg/kg, cycloalliin was rapidly eliminated from blood and excreted into urine, and its total recovery in urine was 97.8% +/- 1.3% in 48 h. After oral administration, cycloalliin appeared rapidly in plasma, with a tmax of 0.47 +/- 0.03 h at 25 mg/kg and 0.67 +/- 0.14 h at 50 mg/kg. Orally administered cycloalliin was distributed in heart, lung, liver, spleen, and especially kidney. The Cmax and AUC0-inf values of cycloalliin at 50 mg/kg were approximately 5 times those at 25 mg/kg. When administered orally at 50 mg/kg, cycloalliin was excreted into urine (17.6% +/- 4.2%) but not feces. However, the total fecal excretion of (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid was 67.3% +/- 5.9% (value corrected for cycloalliin equivalents). In addition, no (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid was detected in plasma (<0.1 microg/mL), and negligible amounts (1.0% +/- 0.3%) were excreted into urine. In in vitro experiments, cycloalliin was reduced to (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid during anaerobic incubation with cecal contents of rats. These data indicated that the low bioavailability (3.73% and 9.65% at 25 and 50 mg/kg, respectively) of cycloalliin was due mainly to reduction to (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid by the intestinal flora and also poor absorption in the upper gastrointestinal tract. These findings are helpful for understanding the biological effects of cycloalliin.


Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1.
PON1 (paraoxonase-1) is an HDL (high-density lipoprotein)-associated enzyme capable of hydrolysing diverse substrates from OP (organophosphate) toxins to oxidized phospholipids. As such, it has been linked with both the prevention of OP poisoning and inhibition of atherosclerosis initiated by oxidatively modified LDL (low-density lipoprotein). Mice deficient in PON1 are more susceptible to OP poisoning and oxidative stress and more prone to develop atherosclerosis than their wild-type siblings. There are a number of polymorphisms in the PON1 gene which affect serum PON1 activity and concentration. Many (but not all) studies in human populations have suggested that these polymorphisms may be a risk factor for atherosclerosis. The serum concentration of PON1 across the general population is highly variable and there is some debate as to whether genotype or phenotype (i.e. the quantity or quality of the enzyme) is most accurately associated with risk of disease development. What is clear is that factors influencing serum levels of PON1, be they genetic or environmental, will, in turn, affect the capacity of HDL to protect LDL from oxidation and, consequently, may be linked to atherosclerosis. This review will focus on mechanisms which determine the serum concentration of PON1, including gene expression and genetic polymorphisms, protein secretion and association with HDL, pharmacological and environmental factors.


Case-control, exploratory study of cerebrospinal fluid chemokines/cytokines and lymphocyte subsets in childhood Tourette syndrome with positive streptococcal markers.
A longstanding question is whether neuroinflammation is present in children symptomatic for Tourette syndrome (TS) with positive streptococcal serology and throat cultures. The objective was to directly test for it using modern hypothesis-driven approaches. Profiling studies for 14 immune cell types (flow cytometry), 7 chemokines/cytokines (ELISA), oligoclonal bands, and other immunoglobulins were performed in this IRB-approved study of 5 children with TS and streptococcal markers compared to data from 26 non-inflammatory pediatric neurological controls. Subjects were well-characterized clinically and with standardized scales for tics and obsessions/compulsions. Three subjects with TS (60%) had positive throat cultures for Group A beta-hemolytic strep, five had elevated anti-deoxyribonuclease-B titers (mean=444), and 4 (80%) had elevated anti-streptolysin O titers (981). There were no significant differences between groups in the frequency of CSF B and T cell subsets or NK cells; the proportion of intracellularly-stained T helper type 1 (IFN-γ) or type 2 (IL-4) cells; the concentrations of B cell chemoattractants CXCL13, CXCL10; the B cell proliferation/survival cytokines BAFF and APRIL, or other chemokines (CCL19, CCL21, CCL22). None of the patients had positive CSF oligoclonal bands or an abnormal IgG index/synthesis rate. Parallel blood studies were negative. This novel study found no group CSF lymphocyte phenotypic abnormalities or elevated inflammatory mediators in childhood TS despite positive serology and throat cultures for Group A beta-hemolytic streptococci. It demonstrates feasibility of the methodology, and should serve as the basis for a larger study of putative streptococcal-associated neuroimmunological disorders.


Pharmacokinetic Interactions Between Isavuconazole and the Drug Transporter Substrates Atorvastatin, Digoxin, Metformin, and Methotrexate in Healthy Subjects.
This article summarizes 4 phase 1 trials that explored interactions between the novel, triazole antifungal isavuconazole and substrates of the drug transporters breast cancer resistance protein (BCRP), multidrug and toxin extrusion protein-1 (MATE1), organic anion transporters 1/3 (OAT1/OAT3), organic anion-transporting polypeptide 1B1 (OATP1B1), organic cation transporters 1/2 (OCT1/OCT2), and P-glycoprotein (P-gp). Healthy subjects received single doses of atorvastatin (20 mg; OATP1B1 and P-gp substrate), digoxin (0.5 mg; P-gp substrate), metformin (850 mg; OCT1, OCT2, and MATE1 substrate), or methotrexate (7.5 mg; BCRP, OAT1, and OAT3 substrate) in the presence and absence of clinical doses of isavuconazole (200 mg 3 times a day for 2 days; 200 mg once daily thereafter). Coadministration with isavuconazole increased mean area under the plasma concentration-time curves (90% confidence interval) of atorvastatin, digoxin, and metformin to 137% (129, 145), 125% (117, 134), and 152% (138, 168) and increased mean maximum plasma concentrations to 103% (88, 121), 133% (119, 149), and 123% (109, 140), respectively. Methotrexate parameters were unaffected by isavuconazole. There were no serious adverse events. These findings indicate that isavuconazole is a weak inhibitor of P-gp, as well as OCT1, OCT2, MATE1, or a combination thereof but not of BCRP, OATP1B1, OAT1, or OAT3.


Report of the national survey of Urology Program Directors: attitudes and actions regarding the accreditation council for graduate medical education regulations.
Residency programs in the United States are held accountable for achieving outcomes based on the new Accreditation Council for Graduate Medical Education (ACGME) regulations for improving resident fatigue and education. A national survey of Urology Program Directors was conducted to determine the attitudes toward the new regulations and the actions taken to implement them. A national survey was developed by an ad hoc committee and distributed electronically. A total of 24 multiple-choice customized Likert scale questions were used to obtain opinions from Urology Program Directors across the country. The data were evaluated using statistical analysis. There was an 88% response rate to the survey. Of the respondents 53% demonstrated a statistically significant association between the size of the program and the degree to which the program was involved in addressing the duty hours standard (p = 0.015). A majority of program directors reported involvement in educating residents and faculty about the ACGME competencies. According to program directors, faculty members were negative about training residents in an 80-hour workweek and residents seemed to be apathetic. The national survey of Urology Program Directors has demonstrated that most programs have started to attend to the cultural change occurring in GME. Although there are some pockets of resistance to the ACGME regulations, the duty hours have been folded into most programs with little apprehension. Barriers to implementation of the Core Competencies discovered in this survey included inadequate validated instrumentation, inadequate staffing, and insufficient financial support.


Optimization of the methods for introduction of amine groups onto the silica nanoparticle surface.
The luminescent silica nanoparticle has attracted the researchers' concentration in bioanalysis recently. Its extensive application is based on the immobilization of various biomolecules such as deoxyribonucleic acid, antibody, and so forth onto the surface. By comparing different introduction methods of amine groups, it was confirmed that the "two-step" route is more preferable by adding tetraethyl orthosilicate and 3-aminopropyl-(triethoxyl)silane in sequence, to attain ideal amine-modified silica nanoparticles. On this basis, carboxyl groups were derived from amine groups on the nanoparticle surface and then were activated by 1-ethyl-3-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxy-succinimide. Finally, mouse monoclonal antihuman CD71 antibody (McAb CD71) and transferrin were effectively linked with the carboxyl groups and successfully labeled the receptors in the membrane of fibroblast cells, respectively.


Spectrophotometric assay for total peroxyl radical-trapping antioxidant potential in human serum.
Antioxidants prevent modification of low density lipoprotein (LDL) by free radicals and possibly also atheroma formation. The capacity of human serum to resist attacks by free radicals is measured by the total peroxyl radical-trapping potential (TRAP). Its measurement has thus far required equipment not available in many clinical laboratories such as a thermostated oxygen electrode cell or a luminometer. To develop a simpler method we used a free radical probe, dichlorofluorescin-diacetate (DCFH-DA), described before in studies of respiratory burst in inflammatory cells. Its oxidation by radicals from thermal decomposition of 2,2'-diazobis(2-amidinopropane)dihydrochloride (AAPH) converts this compound to highly fluorescent dichlorofluorescein (DCF). The DCF also has absorbance at 504 nm thus enabling the determination of TRAP either fluorometrically or spectrophotometrically. Increasing the concentration of AAPH enables the measurement of DCF formation and its inhibition by serum samples at room temperature. The intra- and interassay coefficients of variation of this assay are 3.4% and 4.6%, respectively. The mean value for serum TRAP of healthy subjects is 1155 mumol/l (n = 38). The TRAP in human serum can be increased by adding various antioxidant substances to the assay in vitro or by dietary supplementation of healthy subjects with vitamin E in vivo (P < 0.025). An increase was also found in serum vitamin E levels (P < 0.0001) and in the length of the time human LDL is able to resist oxidation (P < 0.05). Thus the determination of TRAP by this method, which requires only commercially available chemicals, can be used for the evaluation of phenomena associated with lipid accumulation in human artery wall.


Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy.
B cells are not limited to producing protective antibodies; they also perform additional functions relevant to both health and disease. However, the relative contribution of functionally distinct B cell subsets in human disease, the signals that regulate the balance between such subsets, and which of these subsets underlie the benefits of B cell depletion therapy (BCDT) are only partially elucidated. We describe a proinflammatory, granulocyte macrophage-colony stimulating factor (GM-CSF)-expressing human memory B cell subset that is increased in frequency and more readily induced in multiple sclerosis (MS) patients compared to healthy controls. In vitro, GM-CSF-expressing B cells efficiently activated myeloid cells in a GM-CSF-dependent manner, and in vivo, BCDT resulted in a GM-CSF-dependent decrease in proinflammatory myeloid responses of MS patients. A signal transducer and activator of transcription 5 (STAT5)- and STAT6-dependent mechanism was required for B cell GM-CSF production and reciprocally regulated the generation of regulatory IL-10-expressing B cells. STAT5/6 signaling was enhanced in B cells of untreated MS patients compared with healthy controls, and B cells reemerging in patients after BCDT normalized their STAT5/6 signaling as well as their GM-CSF/IL-10 cytokine secretion ratios. The diminished proinflammatory myeloid cell responses observed after BCDT persisted even as new B cells reconstituted. These data implicate a proinflammatory B cell/myeloid cell axis in disease and underscore the rationale for selective targeting of distinct B cell populations in MS and other human autoimmune diseases.


Temporal Envelope Coding by Inferior Colliculus Neurons with Cochlear Implant Stimulation.
Modulations in temporal envelopes are a ubiquitous property of natural sounds and are especially important for hearing with cochlear implants (CIs) because these devices typically discard temporal fine structure information. With few exceptions, neural temporal envelope processing has been studied in both normal hearing (NH) and CI animals using only pure sinusoidal amplitude modulation (SAM) which poorly represents the diversity of envelope shapes contained in natural sounds because it confounds repetition rate and the width of each modulation cycle. Here, we used stimuli that allow independent manipulation of the two parameters to characterize envelope processing by inferior colliculus (IC) neurons in barbiturate-anesthetized cats with CIs. Specifically, the stimuli were amplitude modulated, high rate pulse trains, where the envelope waveform interleaved single cycles ("bursts") of a sinusoid with silent intervals. We found that IC neurons vary widely with respect to the envelope parameters that maximize their firing rates. In general, pure SAM was a relatively ineffective stimulus. The majority of neurons (60 %) preferred a combination of short bursts and low repetition rates (long silent intervals). Others preferred low repetition rates with minimal dependence on envelope width (17 %), while the remainder responded most strongly to brief bursts with lesser sensitivity to repetition rate (23 %). A simple phenomenological model suggests that a combination of inhibitory and intrinsic cellular mechanisms suffices to account for the wide variation in optimal envelope shapes. In contrast to the strong dependence of firing rate on envelope shape, neurons tended to phase lock precisely to the envelope regardless of shape. Most neurons tended to fire specifically near the peak of the modulation cycle, with little phase dispersion within or across neurons. Such consistently precise timing degrades envelope coding compared to NH processing of real-world sounds, because it effectively eliminates spike timing as a cue to envelope shape.


Diabetic gastroparesis from autonomic neuropathy: surgical considerations and changes in vagus nerve morphology.
Two cases with intractable vomiting due to gastroparesis, a rare feature of diabetic autonomic neuropathy, are described. Both required surgical treatment. In the first a gastroenterostomy was complicated by reflux gastritis requiring a revision operation; in the second a gastrojejunostomy was successful. Electron microscopic studies of the vagus nerve in one of the cases showed a severe reduction in the density of unmyelinated axons, the surviving axons tending to be of small calibre. The severity of the abnormalities supports the view that diabetic gastroparesis is related to vagal denervation.


Are hypertensive disorders in pregnancy associated with congenital malformations in offspring? Evidence from the WHO Multicountry cross sectional survey on maternal and newborn health.
Annually, around 7.9 million children are born with birth defects and the contribution of congenital malformations to neonatal mortality is generally high. Congenital malformations in children born to mothers with hypertensive disorders during pregnancy has marginally been explored. Country incidence of congenital malformations was estimated using data on the 310 401 livebirths of the WHO Multicountry Survey which reported information from 359 facilities across 29 countries. A random-effect logistic regression model was utilized to explore the associations between six broad categories of congenital malformations and the four maternal hypertensive disorders "Chronic Hypertension", "Preeclampsia" and "Eclampsia" and "Chronic hypertension with superimposed preeclampsia". The occupied territories of Palestine presented the highest rates in all groups of malformation except for the "Lip/Cleft/Palate" category. Newborns of women with chronic maternal hypertension were associated with a 3.7 (95 % CI 1.3-10.7), 3.9 (95 % CI 1.7-9.0) and 4.2 (95 % CI 1.5-11.6) times increase in odds of renal, limb and lip/cleft/palate malformations respectively. Chronic hypertension with superimposed preeclampsia was associated with a 4.3 (95 % CI 1.3-14.4), 8.7 (95 % CI 2.5-30.2), 7.1 (95 % CI 2.1-23.5) and 8.2 (95 % CI 2.0-34.3) times increase in odds of neural tube/central nervous system, renal, limb and Lip/Cleft/Palate malformations. This study shows that chronic hypertension in the maternal period exposes newborns to a significant risk of developing renal, limb and lip/cleft/palate congenital malformations, and the risk is further exacerbate by superimposing eclampsia. Additional research is needed to identify shared pathways of maternal hypertensive disorders and congenital malformations.


Location of Tessellations in Ocular Fundus and Their Associations with Optic Disc Tilt, Optic Disc Area, and Axial Length in Young Healthy Eyes.
Tessellated fundus is found as common and early-phase characteristic of myopic eyes and their locations are varied among patients. However, the relationship between their locations and morphological parameters of the eyes is still unknown. The purpose is this study is to determine the locations of the tessellations in the ocular fundus of young healthy eyes, and to determine relationships between their locations and morphological parameters of the eyes. This is a prospective observational cross sectional study of 126 eyes of 126 healthy volunteers (mean age 26.0±4.1 years). The eyes were classified into eight groups based on the location of the tessellations; no tessellation, temporal, infra-temporal, inferior, nasal, peripapillary, whole retina, and unclassified tessellations. The degree of optic disc tilt was quantified using a sine curve fitting program on the optical coherence tomographic circle scan images. The correlations between each tessellation location and the axial length, area of the optic disc plus conus (AOC), and optic disc tilt were determined. Forty-four eyes were place in the no tessellation group, 12 eyes in the temporal, 21 eyes in the infra-temporal, 9 eyes in the inferior, 8 eyes in the nasal, 15 eyes in the peripapillary, 11 eyes in the whole, and 6 eyes in the unclassified groups. The differences in the axial lengths between the no tessellation group and the infra-temporal groups were significant. A significant difference was found in the AOC between the no tessellation and the inferior, infra-temporal, and peripapilalry groups. A significant difference was found in the optic disc tilt between the no tessellation and infra-temporal groups (P<0.05). The tessellations are located at specific sites in the fundus of young healthy eyes with the infra-temporal location most frequent. It was correlated with some parameters associated with myopia.


An active acoustic tripwire for simultaneous detection and localization of multiple underwater intruders.
An algorithm allowing simultaneous detection and localization of multiple submerged targets crossing an acoustic tripwire based on forward scattering is described and then evaluated based upon data collected at sea. This paper quantifies the agreement between the theoretical performance and the results obtained from processing data gathered at sea for crossings at several depths and ranges. Targets crossing the acoustic field produce shadows on each side of the barrier, for specific sensors and for specific acoustic paths. In post-processing, a model is invoked to associate expected paths with the observed shadows. This process allows triangulation of the target's position inside the acoustic field. Precise localization is achieved by taking advantage of the multipath propagation structure of the received signal, together with the diversity of the source and receiver locations. Environmental robustness is demonstrated using simulations and can be explained by the use of an array of sources spatially distributed through the water column.


Prehabilitation for kidney transplant candidates: Is it time?
Many patients become frail with diminished cardiorespiratory fitness while awaiting kidney transplantation. Frailty and poor fitness powerfully predict mortality, transplant graft survival, and healthcare utilization after kidney transplantation. Efforts to intervene with post-transplant physical therapy have been met with limited success, in large part due to high study dropout. We reviewed the literature on chronic kidney disease and exercise to propose a clinical framework for physical therapy interventions to improve fitness, scheduled for before the transplant. This framework may lead to better patient retention and compliance, and thus demonstrate better efficacy in mitigating the effects of frailty and poor fitness after kidney transplantation.


Evaluation of bovine and human teeth exposed to thermocycling for microleakage under bonded metal brackets.
Bovine teeth are commonly used as substitutes for human teeth in scientific investigations. The present study was performed in vitro with the objective of comparing bovine and human enamel subjected to thermocycling for microleakage beneath metal brackets. A total of 50 bovine and human teeth (25 per group) void of defects or carious decay were extracted and stored in chloramine B (0.5%). A light-curing adhesive (Transbond™ XT) was used as instructed by the manufacturer (3M Unitek, Monrovia, CA, USA) to bond a metal bracket (discovery®; Dentaurum, Ispringen, Germany) to the surface of each tooth following 30 s of enamel etching (phosphoric acid 35%). After 24 h of dye penetration in methylene blue (0.5%), the cervical and incisal bracket surfaces were analyzed by light microscopy for excess bonding material, dye penetration, and microleakage at the bracket-adhesive and adhesive-enamel interfaces. Staining and evaluation was repeated after thermocycling (5000 cycles at 5/55 °C). Before thermocycling, the number of human teeth showing marginal gaps was one-third the number of bovine teeth (p<0.001). After thermocycling, the distribution of gaps was similar (p=0.180). The adhesive-enamel interface was most frequently affected (on 74% of human and 64% of bovine teeth). No dye penetration in either group after examining a horizontal slice through the bracket basis was observed. Immediately after bonding, less microleakage was observed around the base of metal brackets on human than bovine teeth. These marginal gaps were, however, superficial in both groups, none of them involving deep penetration of dye under the bracket base.


The scapular dyskinesis test: Reliability, agreement, and predictive value in patients with subacromial impingement syndrome.
Prospective cohort. Assessment of scapular dysfunction is considered important in the clinical evaluation and treatment of patients with symptoms of subacromial impingement. However, sparse research has been conducted into the reliability and predictive value of clinical tests with which to identify scapular dyskinesis. To evaluate intrarater and interrater reliability and predictive value of the Scapular Dyskinesis Test (SDT) in patients with subacromial impingement syndrome. Forty-five patients with subacromial impingement syndrome were included. The presence of scapular dyskinesis was classified by 2 raters using the SDT. Intrarater and interrater reliabilities were examined and compared. Patients with and without scapular dyskinesis were compared in terms of Oxford Shoulder Score and EQ-5D-5L scores at baseline and 3 months, as well rating of overall improvement in shoulder condition. SDT could not be performed in 5 patients, leaving 40 patients for further analysis. Kappa with squared weights was 0.64 for rater A and 0.86 for rater B; the intrarater agreement was 88% for A and 96% for B. For interrater comparison, the Kappa value was 0.59 and agreement 86%. No statically significant differences in Oxford Shoulder Score and EQ-5D-5L baseline and change scores or overall improvement in shoulder condition at 3 months were observed between patients with or without scapular dyskinesis. Intrarater and interrater reliability and agreement of the SDT were determined. The findings that functional impairment and outcomes did not differ between patients with or without the presences of scapular dyskinesis may question the clinical value of the SDT in patients with subacromial impingement syndrome. 1b.


Clinical Response and Pattern of B cell Suppression with Single Low Dose Rituximab in Nephrology.
There is no consensus regarding dose and frequency of rituximab in nephrology with extrapolation of doses used in treating lymphoproliferative disorders. There are no guidelines on targeting initial and subsequent doses on the basis of CD19+ B cells. Initially, 100 mg rituximab was given to 42 adults with steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS), idiopathic membranous nephropathy (MN), and high-immunologic-risk kidney transplantation. Absolute and percentage levels of CD19 B cells and clinical status were assessed at baseline, days 30, 90, and 180, and at 1 year. Subsequent doses of rituximab were on the basis of CD19 B cell reconstitution and clinical response. CD19 B cell percentage decreased from 16.3 ± 7.6 to 0.3 ± 0.3 (P≤0.001), 1.9 ± 1.7 (P≤0.001), and 4.0 ± 4.5 (P=0.005) by 30, 90, and 180 days, respectively. Suppression of CD19 B cell count below 1% at days 30, 90, and 180 was seen in 40 of 42 (95.2%), 18 of 42 (42.9%), and 7 of 42 (16.7%) patients, respectively. Of 30 with SDNS and FRNS followed up for 1 year, 29 (96.7%) went into remission at day 30. Remission was sustained in 23 (76.6%) at day 180 and 21 (70%) at 1 year. There was a significant decrease (P<0.001) in the dose of steroids needed to maintain remission at 180 days after rituximab (0.27 ± 0.02 mg/kg to 0.02 ± 0.00 mg/kg). CD19 B cell percentage at 90 days correlated with relapse (P=0.001; odds ratio 1.42; 95% confidence interval, 1.25 to 2.57). Eighteen (60%) required an additional dose. Of five with MN, four achieved remission by 6 months, which was sustained in three by 1 year. Of the seven kidney transplant recipients, two had antibody-mediated rejections, although CD19 B cells were suppressed even at 1 year. Low-dose rituximab induces sustained depletion of CD19 B cells for up to 90 days. Its role in preventing relapses in SDNS, FRNS, MN, and rejection needs further study.


MRI-Detected Knee Ligament Sprains and Associated Internal Derangement in Athletes Competing at the Rio de Janeiro 2016 Summer Olympics.
Describe the frequency and severity of knee ligament sprains diagnosed by MRI in athletes participating at the 2016 Summer Olympic Games, their association with certain sports and assess correlations with additional knee structural injury. All knee MRIs performed in the Olympic Village and polyclinics during the 2016 Olympics were retrospectively, blindly reviewed for ligament sprains and associated knee injuries. In addition to the absence or presence of these abnormalities, athletes were stratified by age, gender and sport. 11,274 athletes participated in the 2016 Olympic Games: 113 athletes received at least one knee MRI with some having bilateral or repeat MRI on the same knee. Anterior cruciate and medial collateral ligament (ACL/MCL) sprains were most common, accounting for 32 of the 43 sprains (74.4%). Wrestling (10), hockey (7), athletics (7), and judo (5) accounted for over half of ligament sprains. ACL sprains showed a significant positive correlation with medial, lateral meniscal tears and bone contusions. The positive correlation between posterior cruciate ligament (PCL) sprains with MCL/lateral collateral ligament sprain, and popliteus tendon tear was statistically significant with 50% of total PCL sprains occurring in hockey. When athletes were stratified by gender, ligament sprains had a similar occurrence and distribution between men and women. Knee ligament sprains, at the Rio 2016 Games, were most common in wrestling, hockey, athletics and judo with ACL and MCL sprains most frequent. Meniscal tears and bone contusions occurred often with ACL sprains. PCL sprains tended to be multi-ligamentous injuries. Sustained ligament sprains had similar occurrence between genders, while men had a peak incidence of sprains at a younger age and women at an older age.


Epizootiology of canine distemper in New Jersey raccoons.
Seventeen epizootics of canine distemper (CD) involving at least 615 raccoons (Procyon lotor) were identified between 1 September 1977 and 25 March 1991 in New Jersey (USA). Epizootics occurred three times at four year intervals in three areas. Based on this cycling, the wide distribution of CD cases, and their occurrence between epizootics, I propose an enzootic status for CD in New Jersey raccoons. The peak period prevalence of raccoon canine distemper cases occurred at the end of the mating season in March. Another period of CD activity began with increased movements of the young in September. Epizootics were associated with river drainages and other wetlands. Age and sex distribution of raccoons with CD was not significantly different (P > 0.05) from that of an asymptomatic composite sample of four northern New Jersey raccoon populations. Lethargy was the most commonly reported clinical sign in raccoons with alert or aggressive behavior rarely observed.


APOBEC3B High Expression in Gastroenteropancreatic Neuroendocrine Neoplasms and Association With Lymph Metastasis.
Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B (APOBEC3B) is known as a source of mutations in multiple cancers. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a group of heterogeneous tumors. However, the expression and significance of APOBEC3B in GEP-NENs remains unclear. A total of 158 cases of GEP-NENs, including 78 cases of biopsy or endoscopic submucosal dissection resection specimens and 83 cases of surgical resection specimens were collected in this study. The cases were grouped according to tumor classification grade, including 42 cases of neuroendocrine tumors G1 (NET G1), 36 cases of NET G2, 36 cases of NET G3, 44 cases of neuroendocrine carcinoma (NEC). All of the 158 tumors were immunohistochemically studied using a polyclonal antibody against APOBEC3B. We evaluated APOBEC3B expression in GEP-NENs and investigated the relationships among the immunoreactivity of APOBEC3B, clinical and pathologic features, such as age, sex, tumor site, Ki67 cell proliferation index, and lymph metastasis. A total of 33 cases (78.6%) of NET G1 showed high expression of APOBEC3B. A total of 28 cases (77.8%) of NET G2 demonstrated high expression of APOBEC3B. In NET G3 and NEC cases, the positive rates were 52.8% and 2.3%, respectively. The expression of APOBEC3B in NETs was significantly higher than that in NECs, NET G1 and NET G2 were higher than NET G3, and the difference was statistically significant. APOBEC3B high expression cases have lower lymph node metastasis rate, lower Ki67 cell proliferation index. In this study, APOBEC3B is highly expressed in GEP-NETs and is a predictor of lymph node metastasis in NET G3 and NEC cases. These findings might provide new insights into the biological mechanisms of GEP-NENs tumorigenesis and progression.


Age and treatment of kidney failure.
This review discusses issues related to treatment of chronic kidney disease, and kidney failure in particular, among older adults. A substantial proportion of older adults have chronic kidney disease and progress to kidney failure. There is considerable variability in treatment practices for advanced kidney disease among older adults, and evidence that treatment decisions such as dialysis initiation may be made without adequate preparation. When initiated, survival among older adults on chronic dialysis remains poor, and is associated with a significant decline in functional status. There is also evidence to suggest that dialysis initiation may not reflect overall treatment goals of elderly patients, but rather a lack of clear communication between patients and health practitioners, and underdeveloped conservative care programs in many centers. Kidney failure is common among older adults. When considering treatment options for kidney failure, patient priorities, preferences, and symptoms should be taken into account, using a shared decision-making approach.


Factors influencing on retro-odontoid soft-tissue thickness: analysis by magnetic resonance imaging.
A retrospective, consecutive case series. To analyze the relationship between retro-odontoid soft-tissue thickness and patients' age, sex, and degenerative changes of cervical spine and to investigate the effect these factors have on retro-odontoid soft-tissue thickness. Thickening of the soft tissue posterior to the odontoid process can form a retro-odontoid pseudotumor causing symptoms of spinal cord compression. Rheumatoid arthritis and long-term dialysis have been reported as possible causes for this. However, there have been reports of retro-odontoid pseudotumors without coexisting diseases. Findings from a total of 503 cases of cervical spine magnetic resonance images were reviewed, and retro-odontoid soft-tissue thickness was measured. The values were matched for age, sex, presence of degenerative changes, rheumatoid arthritis, and dialysis and were analyzed for significance. Retro-odontoid soft tissue thickened with age, and this was also seen in male patients and patients with degenerative changes. Significant increase in thickness was also observed in patients undergoing dialysis and further increased with prolonged dialysis. There was no significant association with presence of rheumatoid arthritis. There is association between age, sex, degenerative cervical spine changes, and dialysis with retro-odontoid soft-tissue thickness. With dialysis, retro-odontoid soft-tissue thickness increases with increasing duration. Thus, reviewing magnetic resonance image from daily practice indicates that cervical spine degeneration is associated with the development of retro-odontoid pseudotumors.


Neuronal glutamate transporters vary in substrate transport rate but not in unitary anion channel conductance.
Excitatory amino acid transporters (EAATs) not only sustain a secondary active glutamate transport but also function as anion-selective ion channels. The relative proportion of currents generated by glutamate transport or by the chloride conductance varies for each cloned EAAT subtype. For EAAT1, EAAT2, and EAAT3, the anion current is only a small component of the total transporter-associated current amplitude, whereas EAAT4 and EAAT5 transporters mediate predominantly anion currents. We here demonstrate that the distinct current proportions are entirely due to differences in glutamate transport rates. EAAT3 and EAAT4 differ in unitary glutamate transport rates as well as in the voltage and substrate dependence of anion channel opening, but ion conduction properties are very similar. Noise analysis revealed identical unitary current amplitudes and similar absolute open probabilities for the two anion channels. The low glutamate transport rate of EAAT4 allows regulation of cellular excitability without interfering with extracellular glutamate homeostasis and makes this EAAT isoform ideally suited to regulate excitability in dendritic spines of Purkinje neurons.


Higher levels of physical activity are independently associated with a lower incidence of diabetic retinopathy in Japanese patients with type 2 diabetes: A prospective cohort study, Diabetes Distress and Care Registry at Tenri (DDCRT15).
We assessed the prospective association between baseline levels of physical activity (PA) and the incidence of newly developed diabetic retinopathy (DR) in patients with type 2 diabetes. Data from 1,814 patients with type 2 diabetes without DR were obtained from a Japanese diabetes registry at Tenri Hospital, Nara, Japan. To assess the independent correlations between baseline PA levels and newly developed DR, the participants were divided into five categories based on their PA levels. A Cox proportional hazards model with time-varying exposure information was used and adjusted for potential confounders to assess the independent correlations. At baseline, the mean age, BMI, and hemoglobin A1c levels of the patients were 65.5 years, 24.5 kg/m2, and 7.2% (54 mmol/mol), respectively. After 2 years, newly developed DR was confirmed in 184 patients (10.1%). Patients with newly developed DR had longer duration of type 2 diabetes (14.7 versus 11.0 years, p < 0.0001), higher systolic blood pressure (139.2 versus 135.1 mmHg, p = 0.0012), lower estimated glomerular filtration rate (74.0 versus 77.1 mL/min/1.73 m2, p = 0.0382), greater urinary albumin-creatinine ratio (4.00 versus 2.45 mg/mmol, p < 0.0039), and higher HbA1c levels (7.5 versus 7.2%, p = 0.0006) than those without newly developed DR. The multivariable-adjusted hazard ratios for DR development were 0.87 (95% CI, 0.53-1.40; p = 0.557), 0.83 (95% CI, 0.52-1.31; p = 0.421), 0.58 (95% CI, 0.35-0.94; p = 0.027), and 0.63 (95% CI, 0.42-0.94; p = 0.025)for the second, third, fourth, and fifth PA categories, respectively, compared with the reference category of patients with a mean PA of 0 metabolic equivalent of task-hours/week). Higher PA levels are independently associated with a lower incidence of DR in Japanese patients with type 2 diabetes.


Current options for the treatment of Helicobacter pylori.
Treatment of Helicobacter pylori (H. pylori) infection is crucial for prevalent disease's management, including gastritis, peptic ulcer and gastric cancer, whereas novel extradigestive causal associations are increasingly being recognized. Despite long-standing efforts, there is not as yet an optimal empirical therapy to eradicate H. pylori. In the present article the authors review current options for H. pylori eradication. Advantages and disadvantages of each of the recommended regimens, and the perspectives for their rational use in clinical practice, are critically discussed. The continuous rising of antimicrobial resistance has accounted for the declined efficiency of standard triple therapies, yielding < 70% eradication in most countries. Alternative first-line strategies have been proposed and largely validated and are now replacing standard-of-care therapies in areas with a high incidence of clarithromycin-resistance (> 20%). Such treatments include the bismuth-containing quadruple therapy, concomitant, sequential and levofloxacin-based regimens, the later mainly designated, together with rifabutin-based therapies as second-line/rescue options. Clinicians should be aware of the local resistance pattern and maintain first-line eradication to levels > 90% (per-protocol efficacy). This will prevent both exposing the patient to repeated treatments and spreading of secondary antimicrobial resistance. In the future, perspectives of tailored therapy and a prophylactic vaccine will obviate any treatment concern.


Proteolytic activity of cosmetic enzyme peel products.
Our goal was to verify the proteolytic mode of action and activity levels among several commercial cosmetic facial peels advertised by manufacturers as "enzymatic". Eleven enzyme peels were analyzed for their proteolytic activity against casein as a generic substrate and compared to the activity found in pineapple and papaya fruits. The highest specific protease activity was observed in the flesh of a pineapple (5.88 U/g). Only two products demonstrated sufficient activity (0.924 and 0.238 U/g) to be called "enzyme peels". Three products showed trace activity (0.023-0.125 U/g), albeit too low to exert a significant exfoliating effect. Six preparations had no detectable enzyme activity.


Review article: management of cyanide poisoning.
Cyanide poisoning is uncommon, but generates interest because of the presumed utility of an antidote immediately available in those areas with a high risk of cyanide exposure. As part of its regular review of guidelines, the Australian Resuscitation Council conducted a systematic review of the human evidence for the use of various proposed cyanide antidotes, and a narrative review of the relevant pharmacological and animal studies. There have been no relevant comparative or placebo-controlled human trials. Nine case series were identified. Treatment with hydroxocobalamin was reported in a total of 361 cases. No serious adverse effects of hydroxocobalamin were reported, and many patients with otherwise presumably fatal poisoning survived. Sodium thiosulphate use was reported in two case series, similarly with no adverse effects. Treatment with a combination of sodium nitrite, amyl nitrite and sodium thiosulphate was reported in 74 patients, with results indistinguishable from those of hydroxocobalamin and sodium thiosulphate. No case series using dicobalt edetate or 4-dimethylaminophenol were identified, but successful use in single cases has been reported. Hydroxocobalamin and sodium thiosulphate differ from alternatives in having negligible adverse effects, and on the basis of current evidence are the antidotes of choice. The indications for the use of an antidote, the requirements for supportive care and a recommended approach for workplaces where there is a risk of cyanide poisoning are presented.


Clinical and anorectal motility features in chronically constipated children.
Constipation is a common problem in children. It can be a symptom of functional disorder in majority of cases, but sometimes a serious organic disease is a cause of constipation. Anorectal manometry plays an important role in the diagnostic procedure. It can be presumed that some values of manometric parameters could be very useful in treatment plan. The aim of this study was to confirm or exclude such limits in manometric finding, to make a plan of the therapy more accurate. Therefore the group of 81 constipated children was investigated. There were 58 patients suffering from functional constipation and 23 with organic disorders. The age of the patients was 3 to 15 years. Scoring system was applied to estimate severity of constipation and anorectal manometry was performed. Our results did not show significant correlation between clinical symptoms and signs and the values that we obtained using anorectal manometry. But, we recommend anorectal manometry because it is a safe method and contributes to clarify the diagnosis, which is very important for treatment plan.


[Epidemiological characteristics of the pediatric population of cochlear implant users in St. Petersburg].
An epidemiological analysis of the pediatric population of cochlear implant (CI) users in St. Petersburg, the second largest metropolis of Russian Federation, was carried out. CI users are 14% of the total number of hearing impaired children, and 26% of children with hearing devices. Only 43% of children who are candidates for cochlear implantation in according to audiological criteria use CI. Since 2012, unilateral cochlear implantation has been carried out for all children in need - their annual number ranges from 25 to 45. Bilateral implantation, mostly sequential with an interval of 1-3 years, was performed in 21% of children The average age at the time of the surgery was 3 years, more than 50% of children were implanted between 1 and 3 years. In recent years, the number of children implanted before 2 years has increased, as well as the number of children implanted at school age. 27% of children with CI continue wearing a hearing aid on the opposite ear. 23% of implanted children have additional disabilities. It has been established that the proportion of children attending mainstream educational institutions is significantly higher among children with CI, compared with children using hearing aids. Some directions have been developed to improve care for CI children and to increase the effectiveness of cochlear implantation as a medical-technical-pedagogical technology for hearing restoration in a regional centre for hearing impaired children.


[Physical properties of the agar of Gracilariopsis tenuifrons (Gracilariacea) from Sucre, Venezuela].
The yield, gel strength, gelling and melting temperatures of Gracilariopsis tenuifrons agar from Guayacán, Araya Peninsula, Sucre State, Venezuela were determined. Yield values with and without alkali treatment ranged from 23.22 to 39.57% and from 16.29 to 22.42% respectively, while gel strength with alkali treatment fluctuated betwen 699.31 and 1231.69 g/cm2 and without treatment varied from 278.0 to 691.06 g/cm2. Gelling and melting temperatures were in the range reported for other agarophytes. Considering gel strength, the agar quality of G. tenuifrons was higher than in other species and its exploitation in economically feasible.


In vitro evaluation of endodontic debris removal as obtained by rotary instrumentation coupled with ultrasonic irrigation.
The cleaning capacity of rotary Ni-Ti instrumentation using Profile GT files, coupled with irrigation energised by ultrasound, was evaluated. Thirty-six human mandibular incisors were instrumented in vitro using the crown-down technique with the Profile GT system to 1 mm from the anatomical apex to a size 30.04 taper file. The instrumented teeth were then divided randomly into four groups where various final irrigations were used: Group I: 100 ml of 1% NaOCl with a Luer-Lok syringe (control group); Group II, Group III and Group IV: final irrigation with 100 ml of 1% NaOCl energised by ultrasound for 1, 3 and 5 min, respectively. After biomechanical preparation, the apical thirds of the roots were submitted to histological processing and examination. The specimens were analysed at 40x magnification and the images submitted to morphometric analysis with an integration grid. anova showed a statistically significant difference (P < 0.01) between the irrigation techniques. Group I (Luer-Lok syringe) showed the highest percentage of debris (35.81 +/- 4.49) and was statistically different from the other groups energised by ultrasound: Group II (27.28 +/- 4.49), Group III (24.39 +/- 5.72) and Group IV (18.46 +/- 5.25). It was concluded that rotary instrumentation using Ni-Ti files associated with final irrigation of 1% NaOCl energised by ultrasound leads to better debris removal from the apical third of mesio-distally flattened root canal.


Network Analysis of Publications on Topological Indices from the Web of Science.
In this paper we analyze a collection of bibliographic networks, constructed from the data from the Web of Science on works (papers, books, etc.) on the topic of topological indices and on relating scientific fields. We present the general outlook and more specific findings about authors, works and journals, subtopics and keywords and also important relations between them based on scientometric approaches like the strongest and main citation paths, the main themes on citation path based on keywords, results of co-authorship analysis in form of the most prominent islands of citing authors, groups of collaborating authors, two-mode cores of authors and works. We investigate the nature of citing of authors, important journals and citing of works between them, journals preferred by authors and expose hierarchy of similar collaborating authors, based on keywords they use. We perform temporal analysis on one important journal as well. We give a comprehensive scientometric insight into the field of topological indices.


Effects of hemoperfusion and continuous renal replacement therapy on patient survival following paraquat poisoning.
Mortality in patients with paraquat (PQ) poisoning is related to plasma PQ levels. Concentrations lower than 5,000 ng/mL are considered critical but curable. This study assessed the effects of hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the survival of PQ-poisoned patients with plasma PQ levels below 5,000ng/mL. We analyzed the records of 164 patients with PQ poisoning who were treated at the First Affiliated Hospital of Wenzhou Medical University in China between January 2011 and May 2015. We divided these patients into six sub-groups based on baseline plasma PQ levels and treatment, compared their clinical characteristics, and analyzed their survival rates. Patient sub-groups did not differ in terms of age, sex, time between poisoning and hospital admission, or time to first gavage. Biochemical indicators improved over time in all sub-groups following treatment, and the combined HP and CRRT treatment yielded better results than HP or CRRT alone. Fatality rates in the three treatment sub-groups did not differ among patients with baseline plasma PQ levels of 50-1,000 ng/mL, but in patients with 1,000-5,000 ng/mL levels, the mortality rate was 59.2% (HP treatment group), 48% (CRRT treatment group), and 37.9% (combined treatment group). Mortality rates were higher 10-30 days after hospitalization than in the first 10 days after admission. In the early stages of PQ poisoning, CRRT is effective in reducing patient fatality rates, particularly when combined with HP. Our data could be useful in increasing survival in acute PQ poisoning patients.


Automatic approach-avoidance tendencies as a candidate intermediate phenotype for depression: Associations with childhood trauma and the 5-HTTLPR transporter polymorphism.
Depression risk genes in combination with childhood events have been associated with biased processing as an intermediate phenotype for depression. The aim of the present conceptual replication study was to investigate the role of biased automatic approach-avoidance tendencies as a candidate intermediate phenotype for depression, in the context of genes (5-HTTLPR polymorphism) and childhood trauma. A naturalistic remitted depressed patients sample (N = 209) performed an Approach-Avoidance Task (AAT) with facial expressions (angry, sad, happy and neutral). Childhood trauma was assessed with a questionnaire. Genotype groups were created based on allele frequency: LaLa versus S/Lg-carriers. The latter is associated with depression risk. We found that remitted S/Lg-carriers who experienced childhood trauma automatically avoided sad facial expressions relatively more than LaLa homozygotes with childhood trauma. Remitted LaLa-carriers who had not experienced childhood trauma, avoided sad faces relatively more than LaLa homozygotes with childhood trauma. We did not find a main effect of childhood trauma, nor differential avoidance of any of the other facial expressions. Although tentative, the results suggest that automatic approach-avoidance tendencies for disorder-congruent materials may be a fitting intermediate phenotype for depression. The specific pattern of tendencies, and the relation to depression, may depend on the genetic risk profile and childhood trauma, but replication is needed before firm conclusions can be drawn.


[Psychotherapy of personality disorders in adolescence].
By the current state of knowledge adolescent personality disorders should be taken seriously due to their high prevalence and severe symptomatology. Personality disorders are characterized by a stable pattern of deviation concerning cognition, affectivity, impulse control, and interpersonal relationships and have negative repercussions in psychosocial functioning and subsequent development. There is emerging evidence that personality disorder diagnosis is reliable and valid during adolescence. It is essential to detect youth with personality pathology in order to refer them to specific psychotherapeutic interventions and consequently avoid further chronification and life-long functional impairment. This selective review will give an overview over personality disorders in adolescents as well as according psychotherapeutic interventions.


Theodor Benzinger, German pioneer in high altitude physiology research and altitude protection.
Theodore Benzinger was a pilot-physician who performed pioneering research-often involving self-experimentation-in areas related to flight at high altitude during World War II. Of greatest historical interest to those of us in aerospace medicine is his work on the effects of rapid decompression and related oxygen equipment. Benzinger was born in Stuttgart, Germany, on 28th August 1905. He studied medicine and natural sciences at the universities of Tuebingen, Munich, and Berlin. From 1934 to 1944, Benzinger headed the aeromedical laboratory "EMed" in Rechlin, where he was instrumental in conducting studies related to stratospheric flight, including self-experimentation with rapid decompression up to 19,000 m (62,320 ft). His Rechlin experiments made an important contribution to understanding the physiology and life-support requirements for high-altitude aviation and later work under space-equivalent conditions. Following World War II, Benzinger joined the staff of the U.S. Army Air Force Aeromedical Center in Heidelberg. In 1947 he was recruited by "Operation Paperclip" to work at the U.S. Naval Medical Research Institute (NMRI) in Bethesda, MD, where he worked on various aspects of human physiology. He died as a U.S. citizen in Bethesda, MD, on 26th October 1999.


Responsible use of computed tomography in the evaluation of coronary artery disease and chest pain.
Many options are available to clinicians for the noninvasive evaluation of the cardiovascular system and patient concerns about chest discomfort. Cardiac computed tomography (CT) is a rapidly advancing field of noninvasive imaging. Computed tomography incorporates coronary artery calcium scoring, coronary angiography, ventricular functional analysis, and information about noncardiac thoracic anatomy. We searched the PubMed database and Google from inception to September 2009 for resources on the accuracy, risk, and predictive capacity of coronary artery calcium scoring and CT coronary angiography and have reviewed them herein. Cardiac CT provides diagnostic information comparable to echocardiography, nuclear myocardial perfusion imaging, positron emission tomography, and magnetic resonance imaging. A cardiac CT study can be completed in minutes. In patients with a nondiagnostic stress test result, cardiac CT can preclude the need for invasive angiography. Prognostic information portends excellent outcomes in patients with normal study results. Use of cardiac CT can reduce health care costs and length of emergency department stays for patients with chest pain. Cardiac CT examination provides clinically relevant information at a radiation dose similar to well-established technologies, such as nuclear myocardial perfusion imaging. Advances in technique can reduce radiation dose by 90%. With appropriate patient selection, cardiac CT can accurately diagnose heart disease, markedly decrease health care costs, and reliably predict clinical outcomes.