Underuse of Catheter Ablation as First-Line Therapy for Supraventricular Tachycardia.
Background Catheter ablation (CA) is a safe, effective, cost-effective technique and may be considered a first-line strategy for the treatment of symptomatic supraventricular tachycardias (SVT). Despite the high prospect of cure and the recommendations of international guidelines in considering CA as a first-line treatment strategy, the average time between diagnosis and the procedure may be long. The present study aims to evaluate predictors related to non-referral for CA as first-line treatment in patients with SVT. Methods and Results The model was derived from a retrospective cohort of patients with SVT or ventricular pre-excitation referred for CA in a tertiary center. Clinical and demographical features were used as independent variables and non-referral for CA as first-line treatment the dependent variable in a stepwise logistic regression analysis. Among 20 clinical-demographic variables from 350 patients, 10 were included in initial logistic regression analysis: age, women, presence of pre-excitation on ECG, palpitation, dyspnea and chest discomfort, number of antiarrhythmic drugs before ablation, number of concomitant symptoms, symptoms' duration and evaluations in the emergency room due to SVT. After multivariable adjusted analysis, age (odds ratio [OR], 1.2; 95% CI 1.01-1.32; P=0.04), chest discomfort during supraventricular tachycardia (OR, 2.7; CI 1.6-4.7; P<0.001) and number of antiarrhythmic drugs before ablation (OR, 1.8; CI 1.4-2.3; P<0.001) showed a positive independent association for non-referral for CA as SVT first-line treatment. Conclusions The independent predictors of non-referral for CA as first-line treatment in our logistic regression analysis indicate the existence of biases in the decision-making process in the referral process of patients who would benefit the most from catheter ablation. They very likely suggest a skewed medical decision-making process leading to catheter ablation underuse.


Prevalence and Predictors of Long-term Opioid Use After Pelvic Fractures.
Opioids are effective in short-term pain treatment; however, their long-term effectiveness is unconfirmed. Many patients are exposed to opioids after pelvic injuries with little known about persistent use afterward. We assessed the prevalence and predictors of long-term opioid use following pelvic fractures. This retrospective study enrolled 277 patients with acute pelvic fractures over five years. Daily and total morphine milligram equivalents (MME) were calculated. The primary outcome was long-term opioid use (LOU) defined as ongoing opioid use 60-90 days post-discharge. The secondary outcome was intermediate-term opioid use (IOU) defined as ongoing opioid use 30-60 days post-discharge. Univariable and logistic regression analyses were performed. Median (interquartile range) total inpatient opioid MME was 422 (157-1667) with a median daily MME of 69 (26-145). Long-term opioid use occurred in 16%, and IOU occurred in 29%. Univariable analysis found that total and daily inpatient opioid use were each significantly associated with LOU (median MME, 1241 vs 371; median MMEs, 127.7 vs 59.2, respectively) and IOU (median MME, 1140 vs 326; median MMEs, 111.8 vs 57.9, respectively). Logistic regression analysis found daily inpatient MME ≥50 (odds ratio [OR] 3.027, 95% confidence interval [CI] 1.059-8.652]) and pelvic fracture type (Tile B/C) (OR 2.992 [CI 1.324-6.763])were independent predictors of LOU. Total and daily inpatient opioid use were significantly associated with LOU and IOU. Patients who received ≥50 MME/inpatient day had a higher likelihood of LOU. This study seeks to inform clinical decisions for pain management to prevent adverse outcomes.


Hyperaminoacidemia in epileptic children treated with valproic acid.
Serum amino acids were determined in 22 epileptic children treated with valproic acid. This treatment caused hypocarnitinemia in all, and hyperammonemia in 16. Regardless of the blood ammonia levels, values for glutamic acid, arginine, glycine, serine and alanine were higher than those of normal controls, while aspartic acid and ornithine were lower. These findings suggest that valproate causes intramitochondrial dysfunction of the urea cycle.


Relief by botulinum toxin of voiding dysfunction due to benign prostatic hyperplasia: results of a randomized, placebo-controlled study.
To evaluate the therapeutic role of botulinum toxin injection in men with benign prostatic hyperplasia. Men with benign prostatic hyperplasia were enrolled in a randomized, placebo-controlled study. After a baseline evaluation, each participant received 4 mL of solution injected into the prostate gland. Patients in the control group received saline solution and patients in the treated group received 200 U of botulinum toxin A. The outcome of each group was evaluated by comparing the symptom scores, serum prostate-specific antigen concentration, prostate volume, postvoid residual urine volume, and peak urinary flow rates. Thirty consecutive patients were enrolled. No local complications or systemic side effects were observed in any patient. After 2 months, 13 patients in the treated group and 3 in the control group had subjective symptomatic relief (P = 0.0007). In patients who received botulinum toxin, the symptom score was reduced by 65% compared with baseline values and the serum prostate-specific antigen concentration by 51% from baseline. In patients who received saline, the symptom score and serum prostate-specific antigen concentration were not significantly changed compared with the baseline values and 1-month values. Follow-up averaged 19.6 +/- 3.8 months. Botulinum toxin injected into the prostate seems to be a promising approach for the treatment of benign prostatic hyperplasia. It is safe, effective, and well-tolerated. Furthermore, it is not related to the patient's willingness to complete treatment.


Amnesic sensitivity to proactive interference: its relationship to priming and the causes of amnesia.
A group of alcoholic amnesics was compared with a group of controls on an A-B, A-C word pairs interference paradigm. With memory instructions the amnesics needed 5 presentation trials to their controls' single trials to match the groups on A-B cued recall. Under these conditions they still showed more proactive interference on the A-C list. When both groups were given five presentation trials for each list and 'free association' instructions, then they both showed this level of interference. This suggested that the amnesic interference effect only occurs because priming is not modulated by conscious memory, i.e. it is an effect of poor conscious memory. This interpretation was further supported by the finding that amnesics forgot the A-B list faster over 2 hr than their controls, when memory instructions were given.


Adult-supervised practice driving for adolescent learners: The current state and directions for interventions.
The aim of this study was to quantify and identify correlates to the amount of parent-supervised behind-the-wheel practice hours by novice teen drivers. A national survey of 945 parents of recently licensed teen drivers was conducted. Multivariate logistic regression was used to identify factors related to the number of practice hours completed. Sixty-one percent of parents reported practicing 50 or more hours with their teen. Two-parent involvement was associated with more practice hours, though use of a professional driving instructor was not. Parents of teens licensed in states mandating 50 or more hours of practice driving were more likely to report at least 50 practice hours than those in states mandating 20-40 hours or in states without mandates. The findings underscore the integral role of parents in the learning to drive process and provide further support for GDL requirements for practice hours.


Identification of a sarcoma virus-coded phosphoprotein in nonproducer cells transformed by Kirsten or Harvey murine sarcoma virus.
A similar protein of 21,000 MW (p21) coded for by Harvey or Kirsten murine sarcoma virus has been identified in nonproducer cells transformed by these two viruses. Antisera prepared from rats bearing tumors induced by syngeneic transplantation of NRK cells transformed by Harvey murine sarcoma virus (Ha-MuSV) specifically precipitated the Ha-MuSV p21 from a nonproducer Balb/c mouse cell and a nonproducer dog cell transformed by Ha-MuSV. The same antisera also precipitated a similar protein, Ki-MuSV p21, from a nonproducer mink cell transformed by Kirsten murine sarcoma virus (Ki-MuSV). Both the p21 of Ha-MuSV and of Ki-MuSV are phosphoproteins. Previous studies have reported a virus-specific p21 polypeptide from translation of Ha-MuSV RNA in cell-free protein synthesis systems (W. P. Parks and E. M. Scolnick, 1977, J. Virol. 22, 711-719; T. Y. Shih, D. R. Williams, M. O. Weeks, J. M. Maryak, W. C. Vass, and E. M. Scolnick, 1978, J. Virol 27, 45-55). This p21 protein was specifically precipitated by the same anti-tumor sera. Similarly, a p21 polypeptide translated from Ki-MuSV RNA was also specifically precipitated by the antitumor sera. Therefore, it is concluded that the p21 of Ha-MuSV and Ki-MuSV are homologous proteins coded for bv homologous sequences found in the recombinant genomes of Ha-MuSV and Ki-MuSV.


Native conformation of human von Willebrand protein. Analysis by electron microscopy and quasi-elastic light scattering.
von Willebrand factor (vWF) was analyzed by electron microscopic and quasi-elastic light scattering techniques in order to evaluate the size and shape of this heterogeneous polymeric plasma glycoprotein. Electron micrographs demonstrated that native vWF molecules are flexible, linear polymers, ranging in contour length from 100 to 1300 nm. In their typical configuration, the polymers were coiled upon themselves with maximal diameters ranging from 60 to 200 nm. Individual repeating protomeric subunits were discernible in occasionally noted, uncoiled polymers and measured 100 nm X 1.5-2.0 nm. Quasi-elastic light scattering analysis confirmed that measurements of the size and shape of purified vWF molecules in solution were similar to those obtained with electron microscopic techniques. In addition, the mean Stokes radius and mean radius of gyration assessed by quasielastic light scattering were directly related over a wide range of values, as were the diameter and contour length measured from electron micrographs, suggesting that the overall shape of polymers does not change with increasing size. This study supports the concept that native vWF molecules are flexible, linear polymers. In addition, this study clearly shows that the polymer configuration assessed from electron micrographs is a valid representation of the configuration of the polymer in solution. The data presented also provide the first evidence for a well-defined, repeating protomeric subunit.


Diffusion-weighted Magnetic Resonance Enterography for Evaluating Bowel Inflammation in Crohn's Disease: A Systematic Review and Meta-analysis.
To systematically determine the performance of diffusion-weighted imaging magnetic resonance enterography (DWI-MRE) for evaluating bowel inflammation in Crohn's disease and sources of heterogeneity between reported results. We identified research studies that investigated DWI-MRE to diagnose bowel inflammation (present versus absent) or to assess bowel inflammatory severity in Crohn's disease by performing a systematic search of PubMed MEDLINE and EMBASE (until March 31, 2015). Study quality was assessed using QUADAS-2. For studies reporting dichotomous diagnosis of bowel inflammation, study heterogeneity and threshold effect were analyzed, summary sensitivity and specificity were estimated, and meta-regression analysis was performed to further explore study heterogeneity. For studies reporting assessment of inflammatory severity, a qualitative summary was performed. Of 159 articles screened, we found 12 studies (1515 bowel segments) reporting a diagnosis of bowel inflammation and 6 studies (1066 bowel segments) reporting assessment of inflammatory severity. The summary sensitivity and specificity were 92.9% (95% CI, 85.8%-96.6%; I = 87.9%) and 91% (95% CI, 79.7%-96.3%; I = 95.1%), respectively. Sensitivity and false-positive rate were inversely correlated (r = -0.650; P = 0.022). Lack of blinding to contrast-enhanced MRE when interpreting DWI-MRE (P = 0.01) and use of contrast-enhanced MRE as a reference standard (P < 0.01) in some studies were significant factors for study heterogeneity and likely caused overestimation of DWI-MRE accuracy. There was rather clear correlation between diffusion-related parameters and bowel inflammation severity, although the strengths were heterogeneous (correlation coefficient, 0.39-0.98). DWI-MRE accuracy was very heterogeneous between studies and was likely overestimated in some studies. Despite rather clear correlation between diffusion-related parameters and bowel inflammatory severity, its strength was variable.


Impaired kidney function at hospital discharge and long-term renal and overall survival in patients who received CRRT.
Critically ill patients with AKI necessitating renal replacement therapy (RRT) have high in-hospital mortality, and survivors are at risk for kidney dysfunction at hospital discharge. The objective was to evaluate the association between impaired kidney function at hospital discharge with long-term renal and overall survival. Degree of kidney dysfunction in relation to long-term effects on renal survival and patient mortality was investigated in a retrospective cohort study of 1220 adults admitted to an intensive care unit who received continuous RRT between 1994 and 2010. After hospital discharge, median follow-up of survivors (n=475) was 8.5 years (range, 1-17 years); overall mortality rate was 75%. Only 170 (35%) patients were discharged with an estimated GFR (eGFR) >60 ml/min per 1.73 m(2). Multivariate proportional hazards regression analysis demonstrated that age, nonsurgical type of admission, preexisting kidney disease, malignancy, and eGFR of 29-15 ml/min per 1.73 m(2) (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.01 to 2.58) and eGFR <15 ml/min per 1.73 m(2) (HR, 1.93; 95% CI, 1.23 to 3.02) at discharge were independent predictors of increased mortality. Renal survival was significantly associated with degree of kidney dysfunction at discharge. An eGFR of 29-15 ml/min per 1.73 m(2) (HR, 26.26; 95% CI, 5.59 to 123.40) and <15 ml/min per 1.73 m(2) (HR, 172.28; 95% CI, 37.72 to 786.75) were independent risk factors for initiation of long-term RRT. Most critically ill patients surviving AKI necessitating RRT have impaired kidney function at hospital discharge. An eGFR <30 ml/min per 1.73 m(2) is a strong risk factor for decreased long-term survival and poor renal survival.


Incidence and duration of incident oropharyngeal gonorrhoea and chlamydia infections among men who have sex with men: prospective cohort study.
This prospective cohort study aimed to determine the natural history and incidence of oropharyngeal gonorrhoea and chlamydia among a cohort of men who have sex with men (MSM) over a 12-week period, and to examine risk factors associated with incident oropharyngeal infections. MSM either aged ≥18 years and had a diagnosis of oropharyngeal gonorrhoea by nucleic acid amplification test (NAAT) in the past 3 months or aged 18-35 years who were HIV-negative taking pre-exposure prophylaxis (PrEP) were eligible for this study. Enrolled men were followed up for 12 weeks. Oropharyngeal swabs were collected at week 0 (baseline) and week 12 (end of study). Between these time points, weekly saliva specimens and the number of tongue kissing, penile-oral and insertive rimming partners were collected by post. Oropharyngeal swabs and saliva specimens were tested by NAAT for Neisseria gonorrhoeae and Chlamydia trachomatis. Poisson regression was performed to examine the risk factors (weekly number of partners) associated with incident oropharyngeal gonorrhoea. A total of 100 MSM were recruited. The incidence of oropharyngeal gonorrhoea and chlamydia was 62 (95% CI 37 to 105) and 9 (95% CI 2 to 35)/100 person-years, respectively. The median duration of incident oropharyngeal infection with gonorrhoea was 28 days (IQR=21-36, n=7). The incidence rate ratio (IRR) for oropharyngeal gonorrhoea increased with an increased number of kissing partners (IRR=1.08; 95% CI 1.03 to 1.12) an increased number of penile-oral sex partners (IRR=1.07, 95% CI 1.01 to 1.14) but not with an increased number of insertive rimming partners (IRR=1.11, 95% CI 0.96 to 1.29) or other demographic factors. The IRR and duration of incident oropharyngeal chlamydia were not calculated due to the small number of cases (n=2). MSM have a high incidence of oropharyngeal gonorrhoea and the median duration of infection was less than 3 months.


[Nonmedical treatment of dementia].
Dementia is a highly prevalent condition. While randomized clinical trials of high quality provide strong evidence for newly developed drugs for dementia, nonpharmacological treatments are investigated mostly in smaller, lower-quality studies although they show promise and are being intensively studied in Europe and the USA. There are indications that programmes based on psychotherapy and neuropsychology can be effective in the early stages of dementia. Ergotherapy during the early and middle stages can delay the loss of abilities for daily living. Validation can ease problems presented by "challenging" behaviour for family members and care personnel. Education of family members has great potential for delaying insitutionalisation and should be integral to every treatment for dementia.


Feeding practices of pre-school children and associated factors in Kathmandu, Nepal.
In developing countries such as Nepal, many children aged below 3 years do not grow at a sufficiently high rate and are vulnerable to micronutrient deficiencies (e.g. vitamin A). Challenges to child nutrition can result from poverty, unhealthy traditional practices, inadequate caring and feeding practices. The present study aimed to assess the feeding practices of pre-school children and their associated factors. A cross-sectional study was carried out in pre-schools located in Kathmandu district between February and March 2018. Three levels in terms of price range (lower, medium and higher level) of pre-schools were selected to reach the mothers of children aged ≤3 years. A structured questionnaire was administered to 145 mothers. Descriptive analyses were conducted to observe the characteristics of the population. Multinomial logistic regression analyses were performed to identify the association for the factors of mothers' perception of their current feeding practices. We found that dal-bhat/jaulo was a common complementary food irrespective of socio-economic background. Interestingly, mothers who had received a higher education were significantly less likely to change their feeding practices (odds ratio = 0.118, confidence interval = 0.01-0.94). The mothers that fed a higher quantity porridge to their children showed a high willingness to change the feeding practices. Poor feeding practices are still an important public health problem in Nepal and were observed to be associated with low socio-economic status, unawareness and a lack of knowledge towards dietary diversity combined with strong beliefs related to social forces and cultures.


PPARα Ligand-Binding Domain Structures with Endogenous Fatty Acids and Fibrates.
Most triacylglycerol-lowering fibrates have been developed in the 1960s-1980s before their molecular target, peroxisome proliferator-activated receptor alpha (PPARα), was identified. Twenty-one ligand-bound PPARα structures have been deposited in the Protein Data Bank since 2001; however, binding modes of fibrates and physiological ligands remain unknown. Here we show thirty-four X-ray crystallographic structures of the PPARα ligand-binding domain, which are composed of a "Center" and four "Arm" regions, in complexes with five endogenous fatty acids, six fibrates in clinical use, and six synthetic PPARα agonists. High-resolution structural analyses, in combination with coactivator recruitment and thermostability assays, demonstrate that stearic and palmitic acids are presumably physiological ligands; coordination to Arm III is important for high PPARα potency/selectivity of pemafibrate and GW7647; and agonistic activities of four fibrates are enhanced by the partial agonist GW9662. These results renew our understanding of PPARα ligand recognition and contribute to the molecular design of next-generation PPAR-targeted drugs.


A nuclear factor-kappaB inhibitor BAY11-7082 inhibits interactions between human endothelial cells, T cells, and monocytes.
Costimulatory molecules play critical roles during cell-mediated immune responses. We undertook this study to determine whether CD154-CD40 interactions induced human endothelial cell (EC) activation via the nuclear factor (NF)-kappaB pathway, and whether the upregulation of monocyte-derived CD40 and CD80 is NF-kappaB pathway dependent. A CD154-expressing D1.1 cell-EC coculture with or without the NF-kappaB inhibitor BAY11-7082 was established to examine EC activation as indicated by CD62E expression. Peripheral blood mononuclear cell (PBMC)-EC cocultures were performed in the presence or absence of BAY11-7082; the expression of CD40 and CD80 on monocytes was analyzed by FACS. Allogeneic mixed lymphocyte-EC reaction (MLER) was performed to determine the inhibitory effects of BAY11-7082 to prevent lymphocyte proliferation. FACS demonstrated upregulation of EC-derived CD62E expression induced by CD154 expressing D1.1 cells. BAY11-7082 pretreated EC failed to upregulate CD62E after interaction with D1.1 cells. Monocytes upregulated CD40 and CD80 expression during PBMC-HEC interaction, and BAY11-7082 suppressed monocyte-derived CD40 and CD80 expression in a dose-dependent manner. The monocyte-derived CD86 expression was downregulated by NF-kappaB inhibitor. BAY11-7082 demonstrated inhibition of lymphocyte proliferation of allogeneic MLER. This study demonstrated that the NF-kappaB inhibitor BAY11-7082 prevented CD154-CD40 interaction-induced EC activation, suggesting that the activation of EC by T-cell-derived CD154 is via NF-kappaB pathway. The NF-kappaB inhibitor suppressed upregulation of monocytederived CD40 and CD80. Additionally, BAY11-7082 suppressed lymphocyte proliferation in response to allogeneic EC. These data indicated that NF-kappaB plays an important role in regulating costimulatory molecules in allogeneic immune responses, and strengthens the rationale for the use of NF-kappaB-directed therapy in allotransplantation.


Discovery of indoline-based derivatives as effective ROCK2 inhibitors for the potential new treatment of idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and devastating lung disease with a median survival of only 3-5 years. Due to the lack of effective therapy, IPF threatens human health. Recently, increasing reports have indicated that Rho-associated coiled-coil protein kinases (ROCKs) play important roles in the development of IPF and might represent a novel target for the treatment of IPF. Herein, a new series of selective ROCK2 inhibitors based on indoline were designed and synthesized. Structural modification resulted in optimized compound 9b with an IC50 value of 6 nM against ROCK2 and the inhibition of collagen gel contraction. Cellular assays demonstrated that 9b could significantly suppress the expression of collagen I and α-SMA, and inhibited ROCK signaling pathway. Oral administration of compound 9b (10 mg/kg) exerted more significant anti-pulmonary fibrosis effects than nintedanib (100 mg/kg) and KD025 (100 mg/kg) in a bleomycin-induced IPF rat model, suggesting that 9b could serve as a potential lead compound for the treatment of IPF.


Glove Changing When Handling Money: Observational and Microbiological Analysis.
The purpose of this study was to determine the rate of glove changing by mobile food vendors after monetary transactions, and the presence of bacterial contamination on a sample of dollar bills obtained from 25 food vendors near five hospitals in Manhattan, New York City. During 495 monetary transactions observed there were only seven glove changes performed by the workers. Eleven of 34 food workers wore no gloves at all while handling money and food. Nineteen of 25 one-dollar bills collected (76 %) had 400 to 42,000 total bacterial colony-forming units. Colonies were of varied morphology and size. Of these 19 samples, 13 were selected (based on level of growth), and tested for the presence of coliform bacteria, which was found in 10 of the 13 samples. Effective strategies to monitor and increase glove wearing and changing habits of mobile food vendors are needed to reduce risk of foodborne illness.


SUITer: An Automated Method for Improving Segmentation of Infratentorial Structures at Ultra-High-Field MRI.
The advent of high and ultra-high-field MRI has significantly improved the investigation of infratentorial structures by providing high-resolution images. However, none of the publicly available methods for cerebellar image analysis has been optimized for high-resolution images yet. We present the implementation of an automated algorithm-SUITer (spatially unbiased infratentorial for enhanced resolution) method for cerebellar lobules parcellation on high-resolution MR images acquired at both 3 and 7T MRI. SUITer was validated on five manually segmented data and compared with SUIT, FreeSurfer, and convolutional neural networks (CNN). SUITer was then applied to 3 and 7T MR images from 10 multiple sclerosis (MS) patients and 10 healthy controls (HCs). The difference in volumes estimation for the cerebellar grey matter (GM), between the manual segmentation (ground truth), SUIT, CNN, and SUITer was reduced when computed by SUITer compared to SUIT (5.56 vs. 29.23 mL) and CNN (5.56 vs. 9.43 mL). FreeSurfer showed low volumes difference (3.56 mL). SUITer segmentations showed a high correlation (R2 = .91) and a high overlap with manual segmentations for cerebellar GM (83.46%). SUITer also showed low volumes difference (7.29 mL), high correlation (R2 = .99), and a high overlap (87.44%) for cerebellar GM segmentations across magnetic fields. SUITer showed similar cerebellar GM volume differences between MS patients and HC at both 3T and 7T (7.69 and 7.76 mL, respectively). SUITer provides accurate segmentations of infratentorial structures across different resolutions and MR fields.


Assessment of major mental disorders in a German peripartum cardiomyopathy cohort.
Peripartum cardiomyopathy (PPCM) is a heart disease affecting women during the last month of pregnancy or in the first months after delivery. The impact of the disease on mental health is largely unknown. Major mental disorders were assessed by a structured clinical interview in 40 patients with a confirmed PPCM diagnosis, and the data were compared with published prevalence in postpartum women. Circulating biomarkers associated with mental health, such as kynurenine, serotonin, and microRNA (miR)-30e, were evaluated in PPCM and compared with matched healthy pregnancy-matched postpartum controls (PP-Ctrl). Major mental disorders were diagnosed in 65% (26/40) of the PPCM cohort. The prevalence for major depressive disorders was 4-fold, for post-traumatic stress disorder 14-fold, and for panic disorder 6-fold higher in PPCM patients compared with postpartum women without a PPCM diagnosis. Compared with PP-Ctrl, PPCM patients displayed elevated levels of serum kynurenine (P < 0.01), reduced levels of serum serotonin (P < 0.05), and elevated levels of plasma miR-30e (P < 0.05). The majority of PPCM patients in the present cohort displayed mental disorders with a higher prevalence of major depressive disorders, post-traumatic stress disorder (PTBS), and panic disorder, compared with postpartum women without a PPCM diagnosis. This higher prevalence was associated with an impaired tryptophan metabolism and elevated levels of the depression-associated miR-30e, suggesting a potential predisposition for mental disorders at the time of PPCM diagnosis. Consequently, physicians should be aware of the increased risk for mental disorders in PPCM patients, and psychiatric assessment should be included in the diagnosis and management of PPCM patients.


A review of size and location of ruptured intracranial aneurysms.
To review our experience and examine the size at which aneurysms ruptured in our patient population. Patient charts and angiograms for all patients admitted with a diagnosis of subarachnoid hemorrhage to the Thomas Jefferson/Wills Eye Hospital between April 1996 and March 2000 were reviewed. Of the 362 cases reviewed, definite measurements of the ruptured aneurysm were obtained in 245. The data clearly showed that most ruptured aneurysms presenting to our institution were less than 10 mm in diameter. We found that, regardless of location on the circle of Willis, 85.6% of all aneurysms presenting with rupture were less than 10 mm. Review by location shows that aneurysms of the anterior communicating artery most often presented with rupture at sizes less than 10 mm (94.4%). A large number of ruptured posterior communicating artery aneurysms also presented at sizes less than 10 mm (87.5%). This trend continued for all aneurysm sites in our review. The incidence of subarachnoid hemorrhage in Western countries is estimated at 10 per 100,000 people per year. Recent reports have indicated that aneurysms less than 10 mm in size are unlikely to rupture. We argue that the risk of small aneurysms rupturing is not insignificant, especially those of the anterior communicating artery. Our findings indicate that surgery on unruptured aneurysms should not be predicated on aneurysm size alone.


Isolation of oral spirochetes from dogs and cats and provisional identification using polymerase chain reaction (PCR) analysis specific for human plaque Treponema spp.
Identification of plaque spirochetes from dogs is rare and no studies to date report cultivation of canine or feline plaque spirochetes. Plaque samples obtained from canine and feline patients were cultured in broth media. Spirochetes cultured were subjected to microscopic evaluation and were cloned on a solid medium. The clones were provisionally identified using species-specific PCR for treponema isolated from human plaque. Canine spirochete clones included Treponema denticola, T. socranskii ssp., T. vincentii, T. maltophilum, T. medium, and T. pectinovorum. Feline clones included T. maltophilum and T. socranskii. Non-amplified clones may represent novel treponemes. Future studies will be aimed at comparison of the spirochetes present in dogs and cats with or without periodontal disease.


Theory of peak capacity in gradient elution.
Peak capacity is the best measure of the performance of a gradient separation. In this paper, the theory of peak capacity for the standard operating conditions of reversed-phase and ion-exchange chromatography is outlined. The influence of the operating conditions on the peak capacity of a separation are discussed. Finally, bandspreading phenomena in gradient chromatography are analyzed.


The Nuclear Transport Factor Kap121 Is Required for Stability of the Dam1 Complex and Mitotic Kinetochore Bi-orientation.
The karyopherin (Kap) family of nuclear transport factors facilitates macromolecular transport through nuclear pore complexes (NPCs). The binding of Kaps to their cargos can also regulate, both temporally and spatially, the interactions of the cargo protein with interacting partners. Here, we show that the essential yeast Kap, Kap121, binds Dam1 and Duo1, components of the microtubule (MT)-associated Dam1 complex required for linking dynamic MT ends with kinetochores (KTs). Like mutations in the Dam1 complex, loss of Kap121 function compromises the formation of normal KT-MT attachments during mitosis. We show that the stability of the Dam1 complex in vivo is dependent on its association with Kap121. Furthermore, we show that the Kap121/Duo1 complex is maintained in the presence of RanGTP but Kap121 is released by the cooperative actions of RanGTP and tubulin. We propose that Kap121 stabilizes the Dam1 complex and participates in escorting it to spindle MTs.


[Diagnosis and treatment of idiopathic hypogonadotropic hypogonadism in men based on a clinical case].
A patient with tertiary hypogonadotropic hypogonadism was followed up for many years. On the basis of this observation the possibilities for a correct diagnosis with the gonadoliberin test are pointed out. A positive effect of the treatment with gonadotropic hormones, especially on the spermatogenesis, is established. Several other new therapeutic means which can be applied in these patients are discussed.


Retinal neovascularization after retinal vaso-obliteration. Frequency--origin--morphology.
Retinal neovascularization (NV) was found microscopically in 76% of 74 eyes with neovascular glaucoma after retinal vaso-obliteration, and in 75% or more of eyes with any type of retinal vascular occlusive disease. Preretinal NV was encountered in 47% and prepapillary NV in 49%. Retinal arterial occlusive disease was more often an underlying condition (81%) than retinal venous occlusive disease (49%). Morphological stages of retinal NV in adults are (1) insudation and/or transudation of vessel walls (100%) with endothelial proliferation (97%) and (2) capillary formation (76%). The latter takes place via intramural capillaries (31%) and endothelial plexuses (24%), and from pre-existent capillaries. New capillaries arise from arterioles, venules and capillaries. Hyalinization can be found in any retinal vessel type. Retinal NV is primarily induced by retinal hypoxia.


The THIP-induced model of bilateral synchronous spike and wave in rodents.
Intraperitoneal administration of 5-10 mg/kg of THIP (4,5,6,7 tetrahydroxyisoxazolo (4,5,c) pyridine 3-ol) induced a transient, reliable model of bilaterally synchronous spikes and waves in rats. The paroxysmal bursts elicited by THIP had similar topographical distribution to the spontaneously-occurring spike and wave discharges often observed in naive rats. The responsiveness to electrical stimulation of subcortical nuclei was different in the two models. Systemic administration of THIP provided a simple, reliable model of bilaterally synchronous spike and wave discharges that may involve the same cerebral structures as those involved in the generation of the spontaneous paroxysms. The administration of the drug increased the yield of paroxysmal responses and provided a stable and predictable 4 hr test situation that may easily be quantified.


Assessment of the effective dose of an experimental intramuscular formulation against immature and adult Fasciola hepatica in sheep.
The effective dose of an injectable prodrug, named compound alpha prodrug, against immature and adult Fasciola hepatica in experimentally infected sheep was determined. In a first experiment, 30 sheep were infected with Fasciola hepatica on day 0 and 50. After microscopic detection of faecal eggs on day 80, groups (n = 6) 1 to 3 were treated with 6, 8 and 10 mg/kg of the experimental water-soluble prodrug compound alpha intramuscularly, respectively. Group 4 was treated with closantel and group 5 remained untreated. Copromicroscopical examinations were made on day 0, 80 and 108. On day 110, trematodes were collected from the bile ducts. Fasciolicide efficacy was assessed as a percentage of fluke-egg and adult-fluke reduction. Fluke length was also recorded. In a second experiment aimed to assess the fasciolicide activity of compound alpha prodrug against four-week-old flukes, 12 sheep were infected on day 0 and allocated into two groups (n = 6). On day 50 post infection, group A was treated with the experimental water-soluble prodrug compound alpha at 6 mg/kg/IM and B remained untreated. Fasciolicide activity was assessed on day 80 after collection, microscopic observation and measurement of flukes present in the parenchyma for immature stages and on day 108 for adults. Egg output decreased 91.2, 96.0, 98.8 and 94.9% for groups 1, 2, 3 and 4, respectively. Compound alpha prodrug cleared 97.6%, 98.51% and 100% of adult stages in a dose-dependent manner. Closantel killed 81.95% flukes. Regarding the second experiment, 81.2% efficacy was achieved. Immature flukes were significantly smaller in the treated group. It is concluded that the intramuscular application of compound alpha prodrug exerted fasciolicide efficacy against adults of Fasciola hepatica.


Lymph node metastases in resected pancreatic ductal adenocarcinoma: predictors of disease recurrence and survival.
Few studies have simultaneously assessed the prognostic value of the multiple classification systems for lymph node (LN) metastases in resected pancreatic ductal adenocarcinoma (PDAC). In 600 patients with resected PDAC, we examined the association of LN parameters (AJCC 7th and 8th editions, LN ratio (LNR), and log odds of metastatic LN (LODDS)) with pattern of recurrence and patient survival using logistic regression and Cox proportional hazards regression, respectively. Regression models adjusted for age, sex, margin status, tumour grade, and perioperative therapy. Lymph node metastases classified by AJCC 7th and 8th editions, LNR, and LODDS were associated with worse disease free-survival (DFS) and overall survival (OS) (all Ptrend<0.01). American Joint Committee on Cancer 8th edition effectively predicted DFS and OS, while minimising model complexity. Lymph node metastases had weaker prognostic value in patients with positive margins and distal resections (both Pinteraction<0.03). Lymph node metastases by AJCC 7th and 8th editions did not predict the likelihood of local disease as the first site of recurrence. American Joint Committee on Cancer 8th edition LN classification is an effective and practical tool to predict outcomes in patients with resected PDAC. However, the prognostic value of LN metastases is attenuated in patients with positive resection margins and distal pancreatectomies.


Note: characterization of Vibrio cholerae O139 Bengal isolated from water in Malaysia.
Four Vibrio cholerae O139 Bengal strains isolated from surface water were characterized by antibiotic resistance, plasmid profile, presence of cholera toxin gene and random amplification of polymorphic DNA (RAPD) analysis. All four strains exhibit multiple resistance towards the antibiotics tested with a multiple antibiotic resistance index of 0.5-0.66, and harboured a 2.0 MDa non-conjugative plasmid. The Vibrio cholerae O139 Bengal were positive for the cholera toxin gene. Antibiotyping and random amplification of polymorphic DNA analysis with four primers proved to be useful in discriminating the isolates. RAPD proved to be more sensitive. These results reveal that there is significant genetic diversity among the Vibrio cholerae O139 Bengal strains studied.


Design and Preparation of Photobodies: Light-Activated Single-Domain Antibody Fragments.
Nanobodies are single-domain antibody fragments that have found widespread use in basic research, therapy, and diagnostics. Like other antibody formats, nanobodies can be developed with high affinity and specificity for desired antigens. A photobody is a light-activatable nanobody, obtained by incorporating a photo-labile caging group into the paratope region. The caging group prevents antigen binding until removed with light (365 nm), thereby rendering the binding controllable with high temporal and spatial resolution. Thus far photocaged tyrosine residues have been used for this purpose, as tyrosine is a frequent residue at critical positions of nanobody paratopes. Nanobodies without a tyrosine residue at the antigen-binding interface may require a different strategy. In this chapter, we describe methods to design and prepare photobodies by recombinant expression in Escherichia coli in combination with genetic code expansion technology to incorporate ortho-nitrobenzyl-tyrosine residues. We use the conversion of the anti-green fluorescent protein enhancer nanobody into a photobody as an example. These protocols should be applicable to many other nanobodies.


An analogue simulation of the luminosity-channel in the vertebrate cone retina. 2. Frequency analysis.
A frequency analysis was performed on an analogue model of the vertebrate cone retina. Bode plots of magnitude and phase angle shifts were obtained from the various stages of the Model. While the cones were non-linear, the rest of the Model was linear and results could be explained by cascading of low-pass filters with linear summation of antagonistic inputs of differing time constants. The cut-off frequency of the Model was determined by the first stage, which was the cone pedicle, while the slope of the db magnitude versus frequency curve increased for each "synaptic delay" in the pathway. An initial increase in the magnitude of the output voltage at any given stage occurred up to the cut-off frequency and was due to the antagonistic input voltages of differing time courses. Physiological data were discussed in terms of the Model.


Plasma levels of activated protein C-protein C inhibitor complex in patients with hypercoagulable states.
Plasma levels of activated protein C (APC)-protein C inhibitor (PCI) were significantly increased in patients with disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), acute myocardial infarction (AMI), pulmonary embolism (PE), or deep vein thrombosis (DVT) and in patients undergoing hemodialysis (HD). Plasma levels of APC-alpha(1)-antitrypsin (AT) complex were significantly increased in patients with DIC and in those with TTP. Plasma levels of PCI were significantly decreased in patients with DIC, non-DIC, or TTP and in those undergoing HD. In the pre-DIC stage, the plasma levels of APC-PCI complex were significantly increased but not those of APC-alpha(1)-AT complex. These data suggest that measurements of APC-PCI complex and APC-alpha(1)-AT complex may be useful for the diagnosis of DIC. After treatment of DIC, the plasma levels of APC-PCI complex and APC-alpha(1)-AT complex were significantly decreased, but not those of PCI. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-alpha(2)-plasmin complex (PPIC), D-dimer, and soluble fibrin monomer (SFM) were markedly increased in patients with DIC or pre-DIC and were moderately increased in patients with non-DIC, TTP, AMI, PE, or DVT and in those undergoing HD. The receiving operating characteristic (ROC) analysis showed that SFM and the APC-PCT complex are useful markers for diagnosis of DIC. The specificity of plasma TAT and PPIC levels was low. The positive rate of APC-PCI complex was higher than 90% with DIC, TTP, AMI, PE, and it was higher than 60% with DVT and HD. Since the APC-PCI complex was elevated not only in patients with venous thrombosis but also in those with arterial thrombosis, components of the protein C pathway might be useful markers for the diagnosis of arterial thrombosis.


ATP-stimulated uptake of S-(2,4-dinitrophenyl)glutathione by plasma membrane vesicles from rat liver.
ATP-stimulated uptake of S-(2,4-dinitrophenyl)glutathione with a high activity of 0.35 nmol/min per mg protein is found in a rat liver plasma membrane vesicle preparation enriched in sinusoidal marker enzymes. Transport takes place into an osmotically active space. Vanadate and S-(azidophenacyl)glutathione inhibit transport, whereas Ca2+, EGTA and ouabain are without effect.


An 18-month survey of infertility treatment by in vitro fertilization, gamete and zygote intrafallopian transfer, and replacement of frozen-thawed embryos.
An 18-month survey of infertility treatment by in vitro fertilization (IVF) and related procedures at the Centre for Reproductive Medicine of the Vrije Universiteit Brussel is described. During this period, 1326 treatment cycles were started in patients with long-standing infertility and 1135 oocyte retrievals were performed in 771 different patients. IVF and embryo transfer (ET) after laparoscopic (N = 793) or ultrasonically guided (N = 342) ovum pickup, gamete intrafallopian transfer (GIFT; N = 284), or zygote intrafallopian transfer (ZIFT; N = 15) combined with IVF as well as the replacement of cryopreserved embryos yielded an overall pregnancy rate of 21.8% per started cycle. Echographic and laparoscopic oocyte retrieval gave similar results except for a higher fertilization rate after echographic-guided retrieval. For in vitro fertilization and embryo transfer an overall pregnancy rate of 26% per transfer was obtained. For GIFT and ZIFT the pregnancy rates were, respectively, 27.8 and 46.7% per replacement. For each procedure one-third of the pregnancies aborted. After the replacement of frozen and thawed embryos, during a natural cycle, a significantly lower fetal loss was observed.


Effect of Helicobacter pylori infection and low-dose aspirin use on iron stores in the elderly.
Helicobacter pylori infection has been associated with lower ferritin levels in some adult populations, but subsets of potentially higher risk subjects, such as the elderly have not been examined. The aim of the present study was to determine the impact of H. pylori infection and low-dose aspirin use on iron stores in a well elderly population. Consecutive subjects aged 65 years or older attending day care facilities were studied. Each subject was assisted in completing a medical questionnaire. Serum ferritin, hemoglobin, mean corpuscular volumes (MCV) and IgG antibodies (ELISA) against H. pylori were measured. In 220 subjects (age 75 +/- 8 years), 42% were H. pylori seropositive (male 41%, female 44%). The median (IQR) ferritin level (ug/L) was higher in men 149 (89-280) than women 94 (54-161), p < 0.002. The ferritin levels were not different in H. pylori positive males 151 (105-283) compared with H. pylori negative males 145 (72-249), or H. pylori positive females 93 (60-142) compared with H. pylori negative females 97 (45-149). This relationship was not altered when controlled for non-steroidal anti-inflammatory agents (NSAID) use (9% of subjects), alcohol or dietary iron intake. Low-dose aspirin use was common (28%), but did not have an independent impact on iron stores: male users 181 (95-248), non-users 145 (86-284); female users 92 (43-162), non-users 95 (62-163). However, in female aspirin users, H. pylori infection was associated with significantly lower ferritin levels: 65 (43-112) compared with uninfected subjects 103 (41-180), p < 0.04. In this well elderly population, the combination of H. pylori infection and low-dose aspirin use was associated with significantly lower serum ferritin concentrations in females. This difference supports the observation that H. pylori, even in asymptomatic subjects, may be a stressor of iron stores.


A report of 918 cases of circumcision with the Shang Ring: comparison between children and adults.
To compare the clinical outcome and surgical complications in circumcision using the Shang Ring between children and adults. Circumcision using the Shang Ring was performed on 702 adults and 216 children. Comparative analysis on indices including operative time, healing time, postoperative edema, postoperative bleeding, postoperative pain, and postoperative infection was conducted. When the ring was removed after surgery, the pain was tolerable in the adult group, but more substantial in the child group. The optimal time for removing the ring was 2 weeks after surgery. Special attention to the pain management is needed when using the Shang Ring to treat redundant foreskin or phimosis in children. The timing of the ring removal is critical to avoiding complications. Surgeons' knowledge in urology is also critical to the clinical outcome.


WITHDRAWN:A Validation Study of the International Consensus Diagnostic Criteria for Neuroleptic Malignant Syndrome.
Ahead of Print article withdrawn by publisher.


Fish oil dietary supplementation reduces Ia expression in rat and mouse peritoneal macrophages.
Preliminary studies suggest that administration of fish oil fatty acids may be beneficial in several immunological diseases; therefore, we studied the effect of fish oil dietary supplementation on the expression of Ia in stimulated murine peritoneal macrophages. Rats (n = 19) and mice (n = 27) on standard rodent feeding were separated in experimental (E) and control (C) groups that received fish oil or saline solution, respectively, daily for 4 weeks by esophageal gavage. Cholesterol serum levels were significantly lowered by fish oil (E vs C, P less than 0.01). E and C groups were injected intraperitoneally with Listeria monocytogenes (LM) and peritoneal cells were harvested 4 and 7 days after infection. Decreased expression of Ia induced by LM was found in rats (C = 49.68 +/- 5.09%, E = 16.95 +/- 4.3%, P less than 0.01) and mice (C = 47.38 +/- 7.63%, E = 26.66 +/- 1.92%, P less than 0.01). Animals with a more pronounced depression of serum cholesterol (reduction of 44.04 +/- 1.52% of baseline levels) had more depression of Ia expression (6.47 +/- 1.22%, P less than 0.001 vs control). Reduction of Ia expression was not related to PGE2 production by peritoneal cells. Reduction of Ia expression by fish oil could induce down-regulation of antigen presentation and alloreactivity.


Association of neurotensin receptors with VIP-containing neurons and serotonin-containing axons in the suprachiasmatic nucleus of the rat.
The aim of the present study was to identify cellular elements bearing high-affinity neurotensin (NT) binding sites in the suprachiasmatic nucleus (SCN) of the rat hypothalamus. Because the distribution of these binding sites had previously been reported to conform to that of both vasoactive intestinal peptide (VIP)-containing nerve cell bodies and serotonin (5-HT)-containing axons, the following experimental approaches were used: (1) the overlap between autoradiographically labeled NT binding sites and immunocytochemically labeled VIP neurons was examined in adjacent 5-microns-thick sections taken across the entire rostrocaudal extent of the SCN; and (2) the density of NT binding sites was examined by quantitative autoradiography following cytotoxic lesioning of 5-HT afferents. Double-labeling studies demonstrated precise overlap between 125I-NT binding and VIP immunostaining throughout the SCN. Moreover, at high magnification intensely VIP-immunoreactive neurons were found in direct register with 125I-NT-labeled cells visualized in adjacent sections. Densitometric autoradiographic studies demonstrated a significant reduction in specific 125I-NT binding within the SCN following intracerebroventricular injection of the neurotoxin, 5,7-dihydroxytryptamine. Taken together, these results indicate that within the SCN, NT receptors are present both presynaptically on serotonin axons and postsynaptically on the perikarya and dendrites of VIP-containing neurons.


[Model of platelet activation as experimental test system for screening kappa-opioid receptor ligands].
A new model is proposed for in vitro testing the efficiency of new chemical substances with kappa-opioid receptor agonist ligand properties.


Evaluation of nonthreshold leukemogenic response to methyl nitrosourea in p53-deficient C3H/He mice.
The classic controversy of whether genotoxic chemicals induce cancers with or without a certain low-dose limit, i.e., the threshold, is revisited because of a number of current publications available addressing the plausibility of "practical" thresholds even for genotoxic carcinogens, the mechanism of which may be hypothesized to be due, in part, to a repair system composed of ordinarily available various defense mechanisms under the steady-state DNA damage. The question of whether an absolute nonthreshold or a relative nonthreshold, i.e., a "practical" threshold specifically in the low-dose level, is present may not be answered even with the use of a prohibitively large number of wild-type mice. Could the excessive incidence of tumorigenesis in p53-deficient mice contribute to our understanding of the threshold vs nonthreshold issue in genotoxic carcinogenesis? This is considered because an exaggeration of tumorigenesis in p53-deficient mice is hypothesized to reduce or eliminate the range of threshold due to the p53-deficiency-mediated reduction of DNA repair and apoptosis. The present study of chemical leukemogenesis in p53-deficient mice by transplantation assay was designed to answer this question. Briefly, 218 C3H/He mice were lethally irradiated and repopulated with bone marrow cells from wild-type, heterozygous p53-deficient, and homozygous p53-deficient C3H/He mice. This was followed by treatment with a single and graded dose of methyl nitrosourea at 6.6, 14.8, 33.3, 50.0, and 75.0 mg/kg body wt, with the vehicle-treated control groups treated with zero dose for each genotype. Whereas mice repopulated with p53-deficient bone marrow cells showed a marked reduction of the threshold for leukemogenicity, mice repopulated with wild-type bone marrow cells did not exhibit leukemia at a dose of 33.3 mg/kg body wt and showed a curve with a high probability for the linear regression model with a positive dose intercept, predicting a threshold by the likelihood ratio test. Thus, the failure of wild-type mice to show an increase in incidence of leukemogenesis at low doses of genotoxic carcinogens may be due not to a statistical rarity, but to various p53-related pharmacophysiological functions, possibly including DNA repair and apoptosis that may account for a threshold.


MECHANOMEDICINE: applications of mechanobiology to medical sciences and next-generation medical technologies.
Mechanical stress underlies most aspects of cell and organismal biology. Mechanomedicine is a field of biology that seeks to understand molecular, cellular, tissue, organ, and individual responses to mechanical stimuli and aims to apply the gained knowledge to improve health. Combining biology and engineering, we explore research areas including mechanosensitive ion channels, heart failure, and regenerative medicine.This review will describe our findings in mechanobiology, our establishment of a joint venture business as we developed devices responding to medical needs, and our alliance with other companies.


An epidemiological survey of vector-borne pathogens infecting cattle in Kyrgyzstan.
Cattle production is a major contributor to the national economy of Kyrgyzstan. Most cattle in Kyrgyzstan are managed via extensive systems and graze in communal pastures. As a result, infestations with ectoparasites are widespread, implying that various vector-borne diseases might be common in cattle. However, methods to control such infectious diseases are not available in Kyrgyzstan because the epidemiology of vector-borne pathogens (VBPs) infecting cattle remains unclear. The present study was therefore designed to survey Kyrgyz cattle for VBPs. We prepared blood DNA samples from 319 cattle in Kyrgyzstan and screened them with specific PCR assays for detecting Babesia bovis, Babesia bigemina, Babesia naoakii, Theileria annulata, Theileria orientalis, Trypanosoma evansi, Trypanosoma theileri, and Anaplasma marginale infections. Our findings indicated that the surveyed cattle were infected with six of the eight pathogens targeted, with the exceptions being B. naoakii and Try. evansi. The most common pathogen was T. orientalis (84.3%), followed by B. bigemina (47.6%), T. annulata (16.6%), A. marginale (11.6%), Try. theileri (7.2%), and B. bovis (2.5%). Additional screening of the B. bovis- and B. bigemina-negative samples with a Babesia genus-specific 18S rRNA PCR identified two positive samples, and sequencing analysis confirmed that each of them was infected with either Babesia major or Babesia occultans. To the best of our knowledge, this is the first report of B. bovis, B. bigemina, B. occultans, Try. theileri, and A. marginale infections in cattle in Kyrgyzstan. Our findings suggest that cattle in Kyrgyzstan are at high risk of infectious diseases caused by VBPs.


Recurrent giant cell tumor of long bones: analysis of surgical management.
Treatment of giant cell tumor of bone (GCT) often is complicated by local recurrence. Intralesional curettage is the standard of care for primary GCTs. However, there is controversy whether intralesional curettage should be preferred over wide resection in recurrent GCTs. We investigated the rerecurrence-free survival after surgical treatment of recurrent GCTs to determine the influence of the surgical approach, adjuvant treatment, local tumor presentation, and demographic factors on the risk of further recurrence. We retrospectively reviewed the medical records of 46 patients with recurrent GCTs of long bones treated with wide resection or intralesional curettage and compared these cohorts. Recurrence rates, risk factors for recurrence, and the development of pulmonary metastases were determined. The minimum followup was 37 months (mean, 134 months; range, 37-337 months). The rate of rerecurrence after wide resection was 6%. Intralesional curettage showed an overall rerecurrence rate of 32%. Implantation of polymethylmethacrylate (PMMA) instead of bone grafting was associated with a lower risk of subsequent recurrence in intralesional procedures (14% versus 50%). Extracompartmental disease did not increase the risk of rerecurrence. Pulmonary metastases occurred in seven patients and appeared independent of the surgical treatment modality chosen. Intralesional curettage with methylmethacrylate for recurrent GCT provided equivalent tumor control compared with resection in this retrospective study. If joint salvage is possible, we advocate this treatment over resection in recurrent GCTs to preserve the native joint articulation. Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Editorial: Autoimmune Pancreatitis in Children: Is This a New Subtype of Disease or Early-Onset Idiopathic Duct-Centric Chronic Pancreatitis?
The term autoimmune pancreatitis (AIP) encompasses two distinct steroid-responsive pancreatitides, type 1 AIP and idiopathic duct-centric pancreatitis (IDCP) (or type 2 AIP). The current study describes cases of both AIP subtypes in a pediatric population. A comparison of the clinical profile of the described cohort with published data strongly suggests the majority of patients in the current cohort had IDCP. Since relapse rates in IDCP are low and long-term maintenance therapy is not required for IDCP, this has implications for prognosis and therapy. However, longer follow-up is needed to more accurately determine if onset during childhood leads to a different disease course.


A ligand-receptor interactome atlas of the zebrafish.
Studies in zebrafish can unravel the functions of cellular communication and thus identify novel bench-to-bedside drugs targeting cellular communication signaling molecules. Due to the incomplete annotation of zebrafish proteome, the knowledge of zebrafish receptors, ligands, and tools to explore their interactome is limited. To address this gap, we de novo predicted the cellular localization of zebrafish reference proteome using deep learning algorithm. We combined the predicted and existing annotations on cellular localization of zebrafish proteins and created repositories of zebrafish ligands, membrane receptome, and interactome as well as associated diseases and targeting drugs. Unlike other tools, our interactome atlas is based on both the physical interaction data of zebrafish proteome and existing human ligand-receptor pair databases. The resources are available as R and Python scripts. DanioTalk provides a novel resource for researchers interested in targeting cellular communication in zebrafish, as we demonstrate in applications studying synapse and axo-glial interactome. DanioTalk methodology can be applied to build and explore the ligand-receptor atlas of other non-mammalian model organisms.


The antivascular action of physiotherapy ultrasound on a murine tumor: role of a microbubble contrast agent.
This study investigated whether a microbubble-containing ultrasound contrast agent had a role in the antivascular action of physiotherapy ultrasound on tumor neovasculature. Ultrasound images (B-mode and contrast-enhanced power Doppler [0.02 mL Definity]) were made of 22 murine melanomas (K1735(22)). The tumor was insonated (I(SATA) = 1.7 W cm(-2), 1 MHz, continuous output) for 3 min and the power Doppler observations of the pre- and postinsonation tumor vascularities were analyzed. Significant reductions (p = 0.005 for analyses of color-weighted fractional area) in vascularity occurred when a contrast-enhanced power Doppler study occurred before insonation. Vascularity was unchanged in tumors without a pretherapy Doppler study. Histologic studies revealed tissue structural changes that correlated with the ultrasound findings. The underlying etiology of the interaction between the physiotherapy ultrasound beam, the microbubble-containing contrast agent and the tumor neovasculature is unknown. It was concluded that contrast agents play an important role in the antivascular effects induced by physiotherapy ultrasound.


Effect of portal hypertension on in vivo bile acid-mediated small intestinal mucosal injury in the rat.
This study's purpose was to determine whether portal hypertension adversely affects small intestinal mucosal injury. Portal hypertension was produced in male Sprague-Dawley rats by two-stage ligation of the portal vein. Sham-operated rats were used as controls. Two weeks later, intestinal injury was produced by in vivo perfusion with 5 mM chenodeoxycholic acid for 30 min. Intestinal injury was assessed by quantitative morphometry and by measuring intestinal water and mannitol absorption. Portal hypertension resulted in more injury in the distal perfused intestine as manifested by increased villus tip denudation [portal hypertensive 52.5 +/- 9.6 (SEM) vs controls 28.1 +/- 5.7 microns, P = 0.05). Additionally there was a significant decrease in the unperfused duodenal villus height in portal hypertensive rats (portal hypertensive 755 +/- 22 vs controls 848 +/- 28 microns, P less than 0.02). Portal hypertension had no significant effect on the increase in mannitol absorption or water secretion caused by chenodeoxycholic acid perfusion. This study suggests that portal hypertension alters small intestinal mucosa and increases susceptibility to injury.


Simian virus 40 cRNA is processed into functional mRNA in microinjected monkey cells.
Monkey cells, microinjected with simian virus 40 (SV40) in vitro synthesized cRNA produce full-size tumor (T)-antigen. This was verified by analyzing immunoprecipitates of microinjected cells by polyacrylamide gel electrophoresis. Early SV40 DNA contains an intron within the large T-antigen coding sequences. Therefore, cRNA copied in vitro from the early DNA strand requires removal of the intron in order to become a functional mRNA. Polyadenylation of the cRNA in vitro by Escherichia coli poly(A)-polymerase increased the biological activity of the RNA. Detection of T-antigen by gel electrophoresis required as little as 50 poly(A)-cRNA injected cells. Splicing of the microinjected cRNA appears to be a nuclear process. Cells enucleated by cytochalasin B prior to injection do not synthesize large T-antigen. However, small t-antigen, a protein with a continuous sequence, is synthesized in these cells. Finally, it is shown that the process of splicing is not required for the transport of mRNA from the nucleus into the cytoplasm. Authentic T-antigen mRNA, isolated from virus infected cells, induced T-antigen synthesis with similar efficiency after either nuclear or cytoplasmic injection.


Primary Renal Synovial Sarcoma: An Oncologic Surprise.
Primary renal synovial sarcoma is a rare tumor having a specific chromosomal translocation t(X; 18) (p11.2; q11.2). The clinical features of this tumor and radiologic appearances are quite similar to those of renal cell carcinoma. Confirmatory diagnosis requires fluorescent in situ hybridization or reverse transcriptase polymerase chain reaction validation for differentiating the tumors from sarcomatoid renal cell carcinoma. We present a case of primary renal synovial sarcoma that was diagnosed in a middle-aged man.


Student Preparation to Care for Dying Patients: Assessing Outcomes Across a Curriculum.
Most nurses are called on to care for dying patients in their professional practice. Yet, ineffective educational preparation to provide this care is consistently reported. An assessment of the preparation of nursing students and associated outcomes is needed to identify the effectiveness of various components of nursing education programs. A study design involving cross-sectional surveys of five cohorts of nursing students in a baccalaureate nursing program was implemented. End-of-life education outcomes assessed included perceived competence, attitudes, and knowledge. Mixed analysis of variance analyses supported significant cohort differences for attitudes and knowledge outcomes; perceived competence outcomes lacked significance. The pattern of between cohort differences identified suggests that students experience positive changes in knowledge and attitudes associated with academic progression. However, deficiencies persist that need to be addressed with targeted educational interventions. [J Nurs Educ. 2017;56(10):633-637.].


Peritubular capillaries of the renal cortex in experimental diabetes mellitus in the rat.
Microangiopathy affects the peritubular capillaries in experimental diabetes. Five to six months after streptozotocin administration to induce experimental diabetes in rats, a progressive increase of lymph flow and of the entry of albumin from the renal peritubular capillaries into the interstitium was seen. Under these conditions, owing to the alteration of peritubular physical forces, the uptake of tubular reabsorbate into the capillaries can be impaired with potentially severe consequences in diabetic nephropathy.


Case report: Diverticulitis complicating a giant Meckel's divertuculum.
In this paper, we discuss a unique case of diverticulitis in which the patient presented a giant Meckel's diverticulum. The patient was a 44 year old male whose medical history included a laparoscopic gastric bypass four years before the finding, and chronical high blood pressure. The patient came to the emergency department with an abdominal pain and elevated acute-phase reactants. An abdominal CT revealed a 17 cm long Meckel's diverticulum with signs of severe inflammation. The patient was then taken to the operating room, and subjected to a 4 cm ileum resection, including the entire diverticulum, with a manual end-to-end anastomosis. Although Meckel's diverticulum is the most common congenital abnormality of the intestinal tract, it is unusual for it to cause symptoms in adults. However, when a patient arrives at the emergency department with a complicated Meckel's diverticulum, an early diagnosis is essential to prevent serious complications, such as perforation of the diverticulum and subsequent peritonitis. The presence of a giant diverticulum is an extremely rare condition. There are few publications to date, but these diverticula are associated with more complications, presenting a higher risk of torsion, volvulus or intestinal obstruction. This paper include a bibliographic review of existing studies on etiopathogenesis, and the diagnosis and treatment of complicated Meckel's diverticulum, particularly in its giant variant. Although Meckel's diverticulitis is a rare entity, it can appear as an acute abdomen. An early diagnosis and treatment to prevent subsequent complications is essential to ensure an optimal recovery.


A Simple Method for the Detection of Wybutosine-Modified tRNAPheGAA as a Readout of Retrograde tRNA Nuclear Import and Re-export: HCl/Aniline Cleavage and Nonradioactive Northern Hybridization.
tRNAs are highly mobile molecules that are trafficked back and forth between the nucleus and cytoplasm by several proteins. However, characterization of the movement of tRNAs and the proteins mediating these movements can be difficult. Here, we describe an easy and cost-effective assay to discover genes that are involved in two specific tRNA trafficking events, retrograde nuclear import and nuclear re-export for yeast, Saccharomyces cerevisiae. This assay, referred to as the hydrochloric acid (HCl)/aniline assay, identifies the presence or absence of a unique modification on tRNAPheGAA called wybutosine (yW) that requires mature, spliced tRNAPheGAA to undergo retrograde nuclear import and subsequent nuclear re-export for its addition. Therefore, the presence/absence of yW-modified tRNAPheGAA serves as a readout of retrograde nuclear import and nuclear re-export. This simple assay can be used to determine the role of any gene product in these previously elusive tRNA trafficking events.


Ceiling art in a radiation therapy department: its effect on patient treatment experience.
A new initiative has been implemented at the Sunshine Hospital Radiation Therapy Centre, to provide a calming and comforting environment for patients attending radiation therapy treatment. As part of this initiative, the department's computed tomography (CT) room and radiation therapy bunkers were designed to incorporate ceiling art that replicates a number of different visual scenes. The study was undertaken to determine if ceiling art in the radiation therapy treatment CT and treatment bunkers had an effect on a patient's experience during treatment at the department. Additionally, the study aimed to identify which of the visuals in the ceiling art were most preferred by patients. Patients were requested to complete a 12-question survey. The survey solicited a patient's opinion/perception on the unit's unique ceiling display with emphasis on aesthetic appeal, patient treatment experience and the patient's engagement due to the ceiling display. The responses were dichotomised to 'positive' or 'negative'. Every sixth patient who completed the survey was invited to have a general face-to-face discussion to provide further information about their thoughts on the displays. The results demonstrate that the ceiling artwork solicited a positive reaction in 89.8% of patients surveyed. This score indicates that ceiling artwork contributed positively to patients' experiences during radiation therapy treatment. The study suggests that ceiling artwork in the department has a positive effect on patient experience during their radiation therapy treatment at the department.


Revision Rhinoplasty.
Revision rhinoplasty is one of the most challenging operations the facial plastic surgeon performs given the complex 3-dimensional anatomy of the nose and the psychological impact it has on patients. The intricate interplay of cartilages, bone, and soft tissue in the nose gives it its aesthetic and function. Facial harmony and attractiveness depends greatly on the nose given its central position in the face. In the following article, the authors review common motivations and anatomic findings for patients seeking revision rhinoplasty based on the senior author's 30-year experience with rhinoplasty and a review of the literature.


Co-creating sensible care plans using shared decision making: Patients' reflections and observations of encounters.
To evaluate how the use of a within-encounter SDM tool (compared to usual care in a randomized trial) contributes to care plans that make sense to patients with atrial fibrillation considering anticoagulation. In a planned subgroup of the trial, 123 patients rated post-encounter how much sense their decided-upon care plan made to them and explained why. We explored how sense ratings related to observed patient involvement (OPTION12), patient's decisional conflict, and adherence to their plan based on pharmacy records. We analyzed patient motives using Burke's pentad. Plan sensibility was similarly high in both arms (Usual care n = 62: mean 9.4/10 (SD 1.0) vs SDM tool n = 61: 9.2/10 (SD 1.5); p = .8), significantly and weakly correlated to decisional conflict (rho=-0.28, p = .002), but not to OPTION12 or adherence. Plans made sense to most patients given their known efficacy, safety and what is involved in implementing them. Adding an effective intervention to promote SDM did not affect how much, or why, care plans made sense to patients receiving usual care, nor patient adherence to them. Evaluating the extent to which care plans make sense can improve SDM assessments, particularly when SDM extends beyond selecting from a menu of options.


[Expert consensus statement on blood pressure measurement from the French Society of Hypertension, an affiliate of the French Society of Cardiology].
Since 2016, the French Society of Hypertension has warned about the decline in the management of high blood pressure in France: stagnation, or even decreased number of people who know their blood pressure level, take a treatment and are controlled. These results are lower than those observed in many other countries. Blood pressure is measured with an old method in the doctor's office. Accepted, simple and cost-effective, this method is currently unavoidable for reasons of feasibility and social habit. It has been used in observational and intervention studies that are the basis of the medical reasoning for screening, treatment and drug control of hypertension. In practice, it is too often poorly applied and unpredictable. It is now necessary to measure blood pressure in mmHg using a validated oscillometric automatic device coupled to a specific upper arm cuff adapted to the arm circumferences for the diagnosis and monitoring of high blood pressure in the doctor's office and at home. The auscultatoric measurement is only recommended if any doubt about the reliability of the electronic measurement. Blood pressure measurement is basically performed on both arms to detect asymmetry and then on the arm with the highest blood pressure. It is performed in sitting or lying position after a few minutes of rest without speaking and without having smoked and then in standing position to diagnose orthostatic hypotension, especially in elderly, diabetic and multi-medicated subjects. The blood pressure measurement during the consultation must be repeated and include at least 3 consecutive measurements at one minute intervals. The average of the last 2 measurements determines the blood pressure level. It is recommended to perform BP measurements outside the medical environment for the diagnosis and monitoring of hypertension; Home BP measurement is preferred to ambulatory blood pressure measurement for practical reasons unless otherwise specified. The home blood pressure measurement should include three measurements in the morning at breakfast and three measurements in the evening before bedtime at one minute intervals for at least three days. Prior training must be provided. In treated hypertensive patients, a masked hypertension should be considered as an uncontrolled hypertension and antihypertensive therapy adapted accordingly. The measurement of central BP pressure (aorta) should be limited to clinical research.


An analysis of the histomorphometric and clinical significance of mucosal biofilm in tonsil tissue of the children with a history of recurrent/chronic tonsillitis in both the mother and father.
The aim of this study is to analyse the histomorphometric and clinical features of the mucosal biofilm in tonsil tissue of children with a history of recurrent/chronic tonsillitis in both the mother and father. This study enrolled 82 children (between 3 and 14 years of age). These children were divided into two main groups according to the present of recurrent/chronic tonsillitis. Patients in group 1 were divided into four subgroups (A, B, C, D) according to the history of recurrent/chronic tonsillitis in mother and/or father. 30 patients in group 1 were underwent tonsillectomy and the 52 patients in control group (2) have not had history of recurrent/chronic tonsillitis. To that end, among children with a history of recurrent/chronic tonsillitis certain changes in the volume and thickness of mucosal biofilm in tonsil tissue have been exhibited with respect to it is histomorphometric and clinical significance. The children with a parental history of recurrent/chronic tonsillitis in group A, an increase in the thickness and volume of mucosal biofilm samples was detected according to the other subgroups (B, C, D). Parents history of group A patients statistically significant differences were detected with respect to halitosis symptoms, attack age of the first tonsillitis and resistant fever despite antibiotic treatment for children under the age of 3 years. This study showed that children under the age of 3 years of age with a history of recurrent/chronic tonsillitis in both the mother and father, halitosis symptoms, attack age of the first tonsillitis and resistant fever despite antibiotic treatment are collectively linked.


Organosulphur Compounds Induce Apoptosis and Cell Cycle Arrest in Cervical Cancer Cells via Downregulation of HPV E6 and E7 Oncogenes.
The quest for strong, safe and cost-effective natural antiproliferative agents that could reduce cancer has been the focus now a days. In this regard, the organosulfur compounds from garlic (Allium sativum L.), like Diallyl Sulfide (DAS) and Diallyl Disulfide (DADS), have been shown to exhibit potent antiproliferative and anticancer properties in many studies. However, the potential of these compounds against viral oncoproteins in cervical cancer has not been fully elucidated yet. The objective of this study was to analyze the antiproliferative and apoptotic properties of DADS and DAS in HPV16+ human cervical cancer Caski cell line. Caski (cervical cancer cells) were cultured and followed by the treatment of various concentrations of organosulphur compounds (DADS and DAS), cell viability was measured by MTT assay. The apoptotic assay was performed by DAPI and Hoechst3342 staining. Reactive Oxygen Species (ROS) was estimated by DCFDA staining protocol. The distributions of cell cycle and apoptosis (FITC-Annexin V assay) were analyzed by flow cytometry. Finally, gene expression analysis was performed via quantitative real time PCR. Our results showed that DAS and DADS exerted a significant antiproliferative effect on Caski cells by reducing the cell viability and inducing a dose-related increment in intracellular ROS production along with apoptosis in Caski cells. DAS and DADS also induced cell cycle arrest in G0/G1 phase, which was supported by the downregulation of cyclin D1 and CDK4 and upregulation of CDK inhibitors p21WAF1/CIP1 and p27KIP1 in Caski cells. Additionally, DAS and DADS lead to the downregulation of viral oncogene E6 and E7 and restoration of p53 function. Thus, this study confirms the efficacy of both the organosulfur compounds DADS and DAS against cervical cancer cells.


An audit of 50 bitemporal flaps in primary facial trauma.
The bitemporal (bicoronal) flap is a well recognised technique for exposing the skull and upper face. Prospectively collected data over a 5-year period in which this technique was used for access in primary craniomaxillofacial trauma was analysed. Emphasis was placed on indications, complications and outcome. A total of 50 cases were audited. 84% were male. 74% had sustained midface or frontal bone trauma, 24% had lateral upper face injuries. Only 1 patient had a penetrating missile injury. Consistent complications of the procedure were altered sensation at the vertex in the early postoperative period and a small area of wound breakdown over the suture knot in the galea. In all cases the altered sensation greatly improved or resolved, 12% developed a wound infection, however, 83% of these were trivial requiring no active treatment. There was an isolated case of pressure necrosis over a drain site. 12% had a demonstrable transient deficit of the temporal branch of the facial nerve, all of which improved.


Why Wolbachia-induced cytoplasmic incompatibility is so common.
Cytoplasmic incompatibility (CI) is the most common reproductive manipulation produced by Wolbachia, obligately intracellular alphaproteobacteria that infect approximately half of all insect species. Once infection frequencies within host populations approach 10%, intense CI can drive Wolbachia to near fixation within 10 generations. However, natural selection among Wolbachia variants within individual host populations does not favor enhanced CI. Indeed, variants that do not cause CI but increase host fitness or are more reliably maternally transmitted are expected to spread if infected females remain protected from CI. Nevertheless, approximately half of analyzed Wolbachia infections cause detectable CI. Why? The frequency and persistence of CI are more plausibly explained by preferential spread to new host species (clade selection) rather than by natural selection among variants within host populations. CI-causing Wolbachia lineages preferentially spread into new host species because 1) CI increases equilibrium Wolbachia frequencies within host populations, and 2) CI-causing variants can remain at high frequencies within populations even when conditions change so that initially beneficial Wolbachia infections become harmful. An epidemiological model describing Wolbachia acquisition and loss by host species and the loss of CI-induction within Wolbachia lineages yields simple expressions for the incidence of Wolbachia infections and the fraction of those infections causing CI. Supporting a determinative role for differential interspecific spread in maintaining CI, many Wolbachia infections were recently acquired by their host species, many show evidence for contemporary spatial spread or retreat, and rapid evolution of CI-inducing loci, especially degradation, is common.


A Case Of Neuroendocrine Carcinoma Expressing Myeloid Markers By Flow Cytometry And Review Of the Literature.
Flow cytometric data is often analyzed in isolation, without the benefit of clinical and morphologic context, and the findings must be interpreted with caution when unexpected results are obtained. A bone marrow aspirate from a 69-year-old female with incidentally discovered pancytopenia was initially analyzed by flow cytometry alone. The results were subsequently correlated with clinical, morphologic, immunohistochemical, and cytogenetic findings. Morphology and immunohistochemistry confirmed metastatic small cell carcinoma; by flow cytometric analysis, the neoplastic cells were positive for CD56 and showed unexpected expression of CD13 and CD117, raising the possibility of a myeloid neoplasm. Flow cytometric markers are not entirely sensitive or specific, and aberrant expression or lack of expression of certain markers can complicate interpretation, particularly when this is done in isolation (i.e., in reference laboratories). Whenever possible, clinical and morphologic correlation is strongly recommended. © 2016 International Clinical Cytometry Society.


Stereocontrolled synthesis of the sterically encumbered F ring of lancifodilactone G.
A stereochemically linear strategy has been developed to prepare the heavily congested F-ring sector of lancifodilactone G (1) from commercially inexpensive (R)-carvone. Prominent operations in our synthesis include Negishi-type sp2-sp3 cross-coupling and intramolecular free-radical cyclization for the purpose of appending the sidearm links of the D and H rings onto the F platform.


Healthcare Providers' Advice About Gestational Weight Gain, Diet, and Exercise: a Cross-Sectional Study with Brazilian Immigrant Women in the USA.
This study sought to quantify healthcare providers' advice about gestational weight gain (GWG), diet, and exercise among first-time pregnant Brazilian women living in the USA. This is a cross-sectional study of first-time pregnant Brazilian women living in selected cities in Massachusetts. The study sample included 86 women, nearly all (97%; n = 83) immigrants. Participants' mean age was 28.3 years and mean gestation was 27.5 weeks. Approximately 25.6% (n = 22) reported being overweight, and 1.2% (n = 1) being underweight. Only about 62% (n = 53) reported receiving advice from their healthcare provider on recommended GWG. In addition, about 83% (n = 71) and 81% (n = 70) reported receiving healthcare providers' advice on exercise and diet, respectively. Women who self-reported being overweight pre-pregnancy (OR 0.15; 95% confidence interval [CI] 0.03-0.73; p = 0.02) and women who were classified low acculturation levels (OR 0.12; 95% CI 0.02-0.08; p = 0.03) were less likely to report receiving healthcare providers' advice on GWG compared to women who self-reported being normal weight pre-pregnancy and those classified having high acculturation level, respectively. Furthermore, women who self-reported being overweight pre-pregnancy were less likely to report receiving diet-related advice (OR 0.32; 95% CI 0.10-1.02; p = 0.05) than women who self-reported being normal weight pre-pregnancy. Findings indicate the need for increased communication and counseling between healthcare providers and Brazilian immigrant women about GWG, in particular for women with low acculturation levels and language barriers suggesting the need for linguistic and culturally relevant interventions designed to improve Brazilian immigrant women's access to evidence-based information about GWG, diet, and exercise.


Temporal infectivity and specificity of vesicular-arbuscular mycorrhizas in co-existing grassland species.
Specificity in vesicular-arbuscular mycorrhizas (VAM), arising from selection favouring host plant/mycorrhizal fungus associations in which both organisms receive benefit, might have a significant influence on interactions between co-existing plant species. In an attempt to detect such specificity root inoculum of four tempt to detect such specificity root inoculum of four plant species, harvested from a species-rich grassland on three dates during the plant growth season, was used to infect the same plant species grown in pots. The rate and overall level of infection was different according to inoculum source and the time of year in which the inoculum was harvested, i.e. temporal variation in VAM infectivity occurs. However, there was no evidence for either specificity or mycorrhizal benefit. Inoculum produced during this experiment was used to infect "bait" Trifolium pratense plants and protein patterns of these roots indicated that a number of biochemically different endophytes were present, both within the inoculum of the four plant species but also within inoculum from one plant species. Temporal variation in mycorrhizal infectivity could be important for mycorrhizal propagation in the field. However, the lack of evidence, in this study, for specificity of VAM or an obvious nutritional benefit to plants with mycorrhizas make the role of mycorrhizas in this community difficult to interpret.


Hemiface rhytidectomy.
In the current study, skin flaps raised in the subcutaneous plane were applied for 22 patients who underwent reconstruction for unilateral upper facial skin defects after skin tumor surgery. The defect was reconstructed with flaps designed via procedures similar to classic rhytidectomy techniques using periauricular and temporal skin incisions. Objective assessment of the aesthetic result was possible by comparison with the healthy contralateral side of the face. Immediate postoperative evaluation confirmed facial asymmetry due to unilateral skin tension. High patient acceptance of the procedure, uneventful flap healing, and good aesthetic results were achieved, with almost complete restoration of facial symmetry 1 year postoperatively. In conclusion, unilateral rhytidectomy without plication or resection of the subcutaneous musculoaponeurotic system (SMAS) is an ideal application of aesthetic surgical techniques for the reconstruction of unilateral skin defects.


Modulation of erlotinib pharmacokinetics in mice by a novel cytochrome P450 3A4 inhibitor, BAS 100.
Administration of BAS 100, a novel mechanism-based CYP3A4 inhibitor isolated from grapefruit juice, resulted in a 2.1-fold increase in erlotinib exposure following oral administration to wild-type and humanized CYP3A4 transgenic mice. This study illustrates the potential of BAS 100 to increase the low and variable oral bioavailability of erlotinib in cancer patients.


Five cases of rhinocerebral mucormycosis.
Rhinocerebral mucormycosis is a rare and often fatal fungal infection in immunocompromised patients. We encountered three women and two men with diabetes and mucormycosis in a period of 4 years. Two of the patients died.


Calculation of the geometrical three-point parameter constant appearing in the second order accurate effective medium theory expression for the B-term diffusion coefficient in fully porous and porous-shell random sphere packings.
Using computational fluid dynamics (CFD), the effective B-term diffusion constant γ(eff) has been calculated for four different random sphere packings with different particle size distributions and packing geometries. Both fully porous and porous-shell sphere packings are considered. The obtained γ(eff)-values have subsequently been used to determine the value of the three-point geometrical constant (ζ₂) appearing in the 2nd-order accurate effective medium theory expression for γ(eff). It was found that, whereas the 1st-order accurate effective medium theory expression is accurate to within 5% over most part of the retention factor range, the 2nd-order accurate expression is accurate to within 1% when calculated with the best-fit ζ₂-value. Depending on the exact microscopic geometry, the best-fit ζ₂-values typically lie in the range of 0.20-0.30, holding over the entire range of intra-particle diffusion coefficients typically encountered for small molecules (0.1 ≤ D(pz)/D(m) ≤ 0.5). These values are in agreement with the ζ₂-value proposed by Thovert et al. for the random packing they considered.


The pericholecystic hepatic activity sign in a normal DISIDA study. Case report.
A patient with a normal DISIDA study underwent a laparotomy that revealed acute cholecystitis. Retrospective review of the DISIDA study showed pericholecystic hepatic activity.


[The study of Balantidium Helenae Bezzenberger, 1904 (Litostomatea, Trichostomatia) inhabiting the intestines of the frog Rana temporaria Linnaeus, 1758, in optical and electron microscopes].
The structure of the ciliate Balantidium helenae Bezzenberger, 1904 was investigated with the use of optical and electron microscopy. It was demonstrated that, together with the basic dimensional characteristics, main distinguishing features of the studied species include the following characters: the presence of a pointed prominence on the posterior margin of the cell; the presence of elongated cilia on the left margin of the vestibulum; and different shape and size of cortical ridges. Two morphologically different types of electron-dense bodies (supposedly hydrogenosoms) and also endobiotic bacteria were also found in the cytoplasm of B. helenae.


Biofilm formation and antibiotic resistance among Coagulase Negative Staphylococcus species isolated from central venous catheters of intensive care unit patients.
This study was conducted to determine the biofilm formation of coagulase negative Staphylococcus species (CoNS) isolated from patients with catheter related blood stream infection (CRBSI) and colonized central venous catheters (CVC) and their antibiotic susceptibility patterns and in situ biofilm formation of CVC tips. Eighty-two CoNS isolated from intensive care unit (ICU) patients with CRBSI (n = 8) or colonized CVC (n = 74) were included. Species identification and antibiotic susceptibility test were done. All isolates were screened for biofilm formation using crystal violet and 3-(4,5-dimethylthiazole-2-yl)-2-5-diphenyl-2H-tetrazolium bromide (MTT) assays and categorized as strong or moderate biofilm formers. CVC tips were subjected to crystal violet stain and scanning electron microscopy (SEM) to detect in-situ biofilm formation. Staphylococcus haemolyticus (n = 34; 41%) was the commonest to cause both CRBSI and CVC colonization. All 82 CoNS produced biofilms. Among them 77 (93.90%) were strong biofilm formers including all from CRBSI patients and 05 (6.10%) were moderate biofilm formers as detected by both methods. SEM showed bacteria adhered to surfaces of CVC tips with microbial-aggregates embedded in extracellular matrix. Mean crystal violet absorbance of CVC from CRBSI patients (0.6628) was significantly higher than colonized CVC (mean value 0.5592) (p = 0.030). S. haemolyticus showed higher resistance to cloxacillin compared to other CoNS (p = 0.039). Majority of CoNS isolated were strong biofilm formers. In-situ biofilm formation on CVC tips were significantly evident in CRBSI patients compared to CVC colonized patients. S. haemolyticus is the commonest to cause both CRBSI and CVC colonization and shows significantly higher cloxacillin resistance rate.


Decreasing tendency of seasonality in suicide may indicate lowering rate of depressive suicides in the population.
The seasonality of suicide is well known and a repeatedly demonstrated phenomenon. The authors analyzed the seasonality of 148 suicide events on Gotland between 1981 and 1996. A marked and significant seasonality with a spring and summer peak was found between 1981 and 1989, when the prescription of antidepressants was relatively low and stable. However, this seasonality disappeared in the period between 1990 and 1996, when prescription of antidepressants increased dramatically, indicating that more and more depressed patients were pharmacologically treated. As the seasonality of suicide in the population is the reflection of the seasonal nature of depressive suicides, the result suggests that a decreasing tendency of seasonality in suicide may indicate the lowering rate of depressive suicides in the given population.


Copper-induced immunotoxicity involves cell cycle arrest and cell death in the spleen and thymus.
Copper is an essential trace element for human physiological processes. To evaluate the potential adverse health impact/immunotoxicological effects of this metal in situ due to over exposure, Swiss albino mice were treated (via intraperitoneal injections) with copper (II) chloride (copper chloride) at doses of 0, 5, or 7.5 mg copper chloride/kg body weight (b.w.) twice a week for 4 wk; these values were derived from LD₅₀ studies using copper chloride doses that ranged from 0 to 40 mg/kg BW (2×/wk, for 4 wk). Copper treated mice evidenced immunotoxicity as indicated by dose-related decreases and increases, respectively, in thymic and splenic weights. Histomorphological changes evidenced in these organs were thymic atrophy, white pulp shrinkage in the spleen, and apoptosis of splenocytes and thymocytes; these observations were confirmed by microscopic analyses. Cell count analyses indicated that the proliferative functions of the splenocytes and thymocytes were also altered because of the copper exposures. Among both cell types from the copper treated hosts, flow cytometric analyses revealed a dose related increase in the percentages of cells in the Sub-G₀/G₁ state, indicative of apoptosis which was further confirmed by Annexin V binding assay. In addition, the copper treatments altered the expression of selected cell death related genes such as EndoG and Bax in a dose related manner. Immunohistochemical analyses revealed that there was also increased ubiquitin expression in both the cell types. In conclusion, these studies show that sublethal exposure to copper (as copper chloride) induces toxicity in the thymus and spleen, and increased Sub G₀/G₁ population among splenocytes and thymocytes that is mediated, in part, by the EndoG-Bax-ubiquitin pathway. This latter damage to these cells that reside in critical immune system organs are likely to be important contributing factors underlying the immunosuppression that has been documented by other investigators following acute high dose/chronic low-medium dose exposures to copper agents.


A chemometric study of ageing in lead-based paints.
The development of non-invasive analytical methods is of widespread interest to the field of conservation science, providing chemical insight into the materials used to create painted works of art, which can, for example, inform decisions about their restoration and preservation, or help discern original works from forgeries. A key undertaking in this area is to develop practical methods for identifying and understanding the chemical processes that occur in paint films under ageing. Furthermore, whereas a number of scientific studies have focussed on model systems in which natural ageing processes are simulated in a short time by irradiation under ultraviolet (UV) light, it remains to be established to what extent natural and accelerated ageing induce similar chemical changes. In this work, we employ FT-Raman spectroscopy, together with a simple spectral-deconvolution algorithm, to study in detail the spectral changes accompanying the natural and UV-accelerated ageing of lead-based paint films. We find that the two processes differ significantly, and that spectroscopic signatures, principally in the fluorescence background, can thus be used to differentiate the two modes of ageing and hence possibly to identify attempted forgeries. Our studies also suggest that paints based on proteinaceous binders are more stable to ageing than lipid-bound ones. Finally, we investigate the possibility of using our chemometric deconvolution technique, in conjunction with multivariate analysis, for the semi-automated characterisation of the degree or extent of ageing in unknown samples.


Systemic sclerosis with subcutaneous nodules.
A case of systemic sclerosis with subcutaneous nodules is described. The nodules consisted of fibrinoid degeneration with surrounding fibrosis, but lacked the typical histiocytic palisade of the rheumatoid nodule. The patient had neither coexistent rheumatoid arthritis nor circulating rheumatoid factor.