TCR beta-independent development of CD4+ CD8+ thymocytes observed in a strain of scid mice.
Mice homozygous for severe combined immunodeficiency (scid) mutation usually halt their thymocyte development at the CD4-CD8- double negative (DN) stage due to their inability of TCR gene rearrangement. In this study, we report that SCID-bg mice, which were originally generated by mating CB-17-scid mice with KSN-bg mice, spontaneously develop dominant CD4+ CD8+ double positive (DP) thymocytes. Their thymi were mainly composed of DN, CD4-CD8+ and DP cells, and the majority of them did not present CD3. Similarly, they lacked TCR beta expression both on cell surface and in cytoplasm, which suggests that the thymocyte development to the DP stage observed in SCID-bg mice, was independent of CD3 and TCR beta expression. In spite of significant DP thymocytes in SCID-bg mice, the histology of their thymi was not so different from those of CB-17-scid mice. Analysis of bone marrow cells in SCID-bg mice showed that the development of B lineage cells was not altered when compared with CB-17-scid mice. These findings point out the fact that thymocytes in SCID-bg mice have a peculiar characteristic compared to CB-17-scid mice, and provide evidence of TCR beta-independent development of thymocytes to the DP stage.


Magnesium trisilicate mixture BP. Its physical characteristics and effectiveness as a prophylactic.
Study of samples of magnesium trisilicate mixture BP obtained commercially has shown that redistribution of the mixture into a reasonably well-dispersed suspension becomes increasingly difficult the longer the mixture is stored. This process of compacting is hastened in response to an increase of environmental temperature. It is possibly for this reason that to administer the mixture at some time later than shortly after it has been prepared contravenes the recommendation of the British National Formulary, that 'it should be recently prepared.' These findings were reflected in the contrast between gastric aspirates obtained from anaesthetised patients who had received the commercially-obtained antacids and those whose antacid had been prepared by the hospital pharmacy. There was a higher incidence of patients 'at risk' because of aspirates with pH value less than 3.0 in the former group. Among the latter group of 131 patients, only one was found to have been 'at risk'. The importance of administering a final dose of antacid within the 15-minute period before induction of anaesthesia is emphasised. The results of assays of the magnesium concentration in the gastric aspirates varied widely, and bore no systematic relationship to the total dose of antacid administered, the time elapsing since the last dose was given, or the pH value of the same aspirate.


Discovery of novel fatty acid synthase (FAS) inhibitors based on the structure of ketoaceyl synthase (KS) domain.
Development of fatty acid synthase (FAS) inhibitors has increasingly attracted much attention in recent years due to their potential therapeutic use in obesity and cancers. In this investigation, pharmacophore modeling based on the first crystal structure of human KS domain of FAS was carried out. The established pharmacophore model was taken as a 3D query for retrieving potent FAS inhibitors from the chemical database Specs. Docking study was further carried out to refine the obtained hit compounds. Finally, a total of 28 compounds were selected based on the ranking order and visual examination, which were first evaluated by a cell line-based assay. Seven compounds that have good inhibition activity against two FAS overexpressing cancer cell lines were further evaluated by an enzyme-based assay. One compound with a new chemical scaffold was found to have low micromolar inhibition potency against FAS, which has been subjected to further chemical structural modification.


Prospective study of human metapneumovirus infection: diagnosis, typing and virus quantification in nasopharyngeal secretions from pediatric patients.
During the winter-spring seasons 2004-2005 and 2005-2006, 965 nasopharyngeal aspirates from 871 patients were examined for human metapneumovirus (hMPV) by both monoclonal antibodies (MAbs) and reverse transcription (RT)-PCR. Overall, 46 samples (4.8%) from 37 patients were positive for hMPV. Of these, 39 were positive by RT-PCR, and 35 by MAbs. Thus, using RT-PCR as a reference assay, the sensitivity, specificity, positive and negative predictive values of MAbs were 71.8%, 99.2%, 80.0% and 98.8%, respectively. Typing showed that concordant results were obtained in 32/46 (69.6%) strains (five untyped), whereas three strains were typed by MAbs only, and 11 by RT-PCR only. Finally, quantification of hMPV RNA allowed to correlate high viral load in nasopharyngeal secretions with acute respiratory symptoms in a group of 11 infants with acute lower respiratory tract infection examined upon admission and discharge from hospital, and a group of nine infants examined upon admission only. Conversely, hMPV etiology was questioned in a group of 14 infants with low viral load. MAbs may represent an alternative to or a complement to RT-PCR for detection and typing of hMPV strains, while hMPV RNA quantification may help in associating viral load with clinical symptoms.


Endogenous opiates: 1982.
This article is the fifth installment in an annual series of reviews of successive year's research dealing with the endogenous opiate peptides. Due to the continuing massive increase in the number of studies in this field, it has become impossible to continue comprehensive reviews of all aspects of this work. As a result we have decided that beginning this year the coverage will be abbreviated to emphasize non-analgesic and behavioral work. The specific areas discussed include stress, tolerance and dependence, consummatory responses, alcohol consumption, schizophrenia and emotional disorders, learning and memory, cardiovascular responses, respiratory effects, thermoregulatory effects, neurological deficits and other disorders, activity, and other, miscellaneous behaviors. As in previous years, we have attempted a relatively comprehensive review of the subjects covered only for the previous year and have not made an attempt to evaluate their contributions relative to those of past years.


Potential of endogenous formation of volatile nitrosamines from Nigerian vegetables and spices.
Nitrosatability of dried Nigerian vegetables and spices was investigated under simulated gastric conditions. N-Nitroso-dimethylamine (NDMA) was the only volatile nitrosamine found above the preformed level except in ugwu where N-nitroso-piperidine (2.3 ppb) was also detected. The lowest NDMA value of 0.4 ppb was found in bitterleaf while onions had the highest level (14.7 ppb) of nitrosation. The results suggest that, under endogenous conditions, nitrosation of these foodstuffs could be an important contributory factor in cancer aetiology.


A prospective randomized study of three types of platelet concentrates in patients with haematological malignancy: corrected platelet count increments and frequency of nonhaemolytic febrile transfusion reactions.
We prospectively randomized 51 patients with haematological malignancy requiring platelet concentrates (PCs) to receive either single donor platelet-pheresis products (SD-PC), PCs made from pooled buffy coats (BC-PC) or pooled units of platelets made by the platelet-rich plasma method (PRP-PC). The leucocyte content of each type of PC was 0.33 (0.03-13.5), 5.68 (0.19-99.0) and 365 (65-910) x 10(6); median (range), respectively; P < 0.0001. All red cell transfusions were leucodepleted by filtration. Statistical comparison of the probability of the occurrence of a nonhaemolytic febrile transfusion reaction (NHFTR) following transfusion of PCs in patients in each group showed a significant decrease for the SD-PC and BC-PC groups (0.031 and 0.038, respectively) when compared with PRP-PC (0.171); P = 0.0001. The actual corrected platelet count increments (CCI) at 1-6 and 18-24 h post-transfusion for all three types of PC did not differ significantly. We conclude that transfusion of PRP-PC is associated with a significant increase in NHFTR.


Anorectal motility in children with complete rectal prolapse.
Anorectal manometry, defecography, and ultrasonographic study were performed in 36 children with complete rectal prolapse and 45 age- and sex-matched controls. Anorectal manometry disclosed that there was no significant difference in Pr, Pac, or length of HPZ between patients and controls. The rate of BRC of the smooth muscle of the anal canal and RC were significantly lower in patients. Rectoanal reflex was present in all patients and controls. Defecography and ultrasonographic examination confirmed the hypothesis that rectal prolapse starts initially as an intussusception of the rectum, then fully develops. In 29 cases patients were cured by conservative treatment, but seven patients required surgical treatment. Results of modified Sudeck's operation were, in general, satisfactory.


Investigation of the relationship between disease severity and development of amyloidosis and genetic mutation in FMF disease.
Familial Mediterranean fever (FMF) is an autosomal recessive genetic disease. Amyloidosis is the most important complication of FMF that determines the prognosis of the disease. In our study, we have investigated the relationship between the genetic mutations with the disease severity and the frequency of development of amyloidosis inpatients with FMF. A total of 148 patients with FMF were included this study. The relationship between disease activity score, clinical findings, response to treatment, and presence of amyloid and genetic mutations were evaluated. One hundred forty-eight patients (80 women (54%), 68 men (46%)) were enrolled over 18 years of age. The mean age of the patients was 30.98 ± 11.18 (18-67) years. In our study, the most frequently seen mutations are M694V, M680I, R202Q, and E148Q, respectively. The most common genotype is M694V/M694V mutation and this mutation has been found in 37 patients (25%). In 25 patients, M694V heterozygous have been found (16.8%). The third frequent mutationis M694V/M680I/R202Q has been found in13 patients (8.7%). In 23 patients, amyloidosis has been developed. Ten patients with amyloidosis have M694V homozygous mutations (27%) and 5 patients with amyloidosis M694V heterozygous (20%) mutations. The both of the two patients who carry the homozygous E148Q mutations have developed amyloidosis. In our study, the distribution of the frequency of mutations is consistent with other similar studies performed in Turkey. We found that patients with M694V mutation had a significantly higher rate of exacerbation, higher drug doses for treatment, and a close relationship with amyloidosis, as compared to patients with other mutations.


Human papillomavirus as an independent risk factor of invasive cervical and endometrial carcinomas in Jordan.
Endometrial and cervical carcinomas are the most common gynecologic malignancies in Western world and many countries. The human papillomavirus (HPV) high-risk genotypes are associated with cervical carcinoma (CC). Chlamydia trachomatis (C. trachomatis), the most common sexually transmitted bacterial infection worldwide, considered a cofactor for HPV infection and CC. Information on HPV infection rate and type distribution among Jordanian women having CC is currently limited and unavailable among those with endometrial carcinoma. Therefore, the present study aimed to provide an updated estimate on HPV infection rate and its high-risk genotypes' distribution among Jordanian women by comparing data from invasive cervical carcinoma (ICC) to normal cervical tissues. Similarly, assessment of HPV infection rate was extended to the endometrial tissues. C. trachomatis infection was investigated as well to explore its possibility as HPV cofactor for induction of such carcinomas. Total DNA was extracted from 144 formaldehyde-fixed paraffin-embedded cervical and endometrial tissue, equally divided between age-matched control and carcinoma cases. Polymerase chain reaction (PCR) was used for general detection of HPV-DNA, high risk HPV-16 and 18 genotypes and C. trachomatis DNA using specific primers. HPV infection was detected in 91.7% and 61.1% of cervical cancer patients and controls, respectively. Likewise, it was higher among cases (47.2%) than controls (13.8%) in endometrial biopsies. Significantly higher HPV infection rates were found among ICC and endometrial control biopsies of women >50 years. Out of 33 HPV positive ICC cases, single HPV-16 infections were detected in 69.7% compared to HPV-18 (15.2%), while HPV-16/18 co-infections were only found in three (9%) samples. C. trachomatis was not detected in all studied groups. The present study has successfully provided an updated estimate on HPV infection rate among Jordanian women with and without ICC and endometrial carcinoma. In addition, a lack of co-infection was observed between HPV and C. trachomatis in both cancer types.


Design and Analysis of a Sample-and-Hold CMOS Electrochemical Sensor for Aptamer-based Therapeutic Drug Monitoring.
In this paper, we present the design and the analysis of an electrochemical circuit for measuring the concentrations of therapeutic drugs using structure-switching aptamers. Aptamers are single-stranded nucleic acids, whose sequence is selected to exhibit high affinity and specificity toward a molecular target, and change its conformation upon binding. This property, when coupled with a redox reporter and electrochemical detection, enables reagent-free biosensing with a sub-minute temporal resolution for in vivo therapeutic drug monitoring. Specifically, we design a chronoamperometry-based electrochemical circuit that measures the direct changes in the electron transfer (ET) kinetics of a methylene blue reporter conjugated at the distal-end of the aptamer. To overcome the high-frequency noise amplification issue when interfacing with a large-size (> 0.25 mm2) implantable electrode, we present a sample-and-hold (S/H) circuit technique in which the desired electrode potentials are held onto noiseless capacitors during the recording of the redox currents. This allows disconnecting the feedback amplifiers to avoid its noise injection while reducing the total power consumption. A prototype circuit implemented in 65-nm CMOS demonstrates a cell-capacitance-insensitive input-referred noise (IRN) current of 15.2 pArms at a 2.5-kHz filtering bandwidth. We tested our system in human whole blood samples and measured the changes in the ET kinetics from the redox-labeled aptamers at different kanamycin concentrations. By employing principal component analysis (PCA) to compensate for the sampling errors, we report a molecular noise floor (at SNR = 1) of 3.1 µM with sub 1-sec acquisition time at 0.22-mW power consumption.


Acoustical and electrical biasing of the cochlea partition. Effects on the acoustic two tone distortions f2-f1 and 2f1-f2.
Low frequency acoustical biasing of the cochlear partition with 5 Hz tones produces phase correlated changes of the acoustic two-tone distortions 2f1-f2 and f2-f1. Pronounced changes of f2-f1 and only small changes of 2f1-f2 for lower bias tone levels indicate that there is a close relation between changes in the difference tone f2-f1 and changes in the operating point of the cochlear amplifier (Frank and Kössl, 1996). To further investigate this relationship, the cochlear partition was additionally biased by current injection into the scala media of the gerbil. The injection of low frequency (5 Hz) AC currents (max. 1.3 microA) has a similar effect to that caused by low frequency tones in that both produce phase correlated changes of the two distortions (so-called biasing patterns), with stronger effects on f2-f1. For bias tone levels of about 105 dB SPL and current values of 1.3 microA, the effects are approximately of the same size. A change in the f2-f1 biasing pattern that can be found for increasing bias tone levels can also be seen for increasing primary levels. Changing the setpoint of the cochlear amplifier through the injection of DC current into the scala media during acoustical biasing of the cochlear partition produces the same changes of f2-f1 biasing patterns as increasing the primary levels. This indicates that the operating point of the outer hair cells that respond to the primary tones is not only influenced by low frequency biasing stimuli but also by shifts with increasing primary levels.


Pulse oximetry measures a lower heart rate at birth compared with electrocardiography.
To examine the effect of time after birth on heart rate (HR) measured by pulse oximetry (PO) (HRPO) and electrocardiography (ECG) (HRECG). HRECG and HRPO (collected at maximum sensitivity) were assessed in 53 term and preterm infants at birth. ECG electrodes and a PO sensor were attached as soon as possible and HRECG and HRPO were compared every 30 seconds from 1-10 minutes after birth. Data were compared using a Wilkinson signed-rank test. Clinical relevance (eg, HR <100 beats per minute [bpm] was tested using a McNemar test). Seven hundred fifty-five data pairs were analyzed. Median (IQR) gestational age was 37 (31-39) weeks. Mean (SD) starting time of PO and ECG data collection was 99 (33) vs 82 (26) seconds after birth (P = .001). In the first 2 minutes after birth, HRPO was significantly lower compared with HRECG (94 (67-144) vs 150 (91-153) bpm at 60 seconds (P < .05), 81 (60-109) vs 148 (83-170) bpm at 90 seconds (P < .001) and 83 (67-145) vs 158 (119-176) at 120 seconds (P < .001). A HR <100 bpm was more frequently observed with a PO than ECG in the first 2 minutes (64% vs 27% at 60 seconds (P = .05), 56% vs 26% at 90 seconds (P < .05) and 53% vs 21% at 120 seconds (P < .05). HR by ECG was verified by ultrasound for outflow from a subset of infants. In infants at birth, HRPO is significantly lower compared with ECG with clinically important differences in the first minutes.


Reconstructing host range evolution of bacterial plant pathogens using Pseudomonas syringae pv. tomato and its close relatives as a model.
Several lines of evidence suggest that highly virulent bacterial human pathogens evolved from less virulent wider host range animal pathogens since human migration out of Africa. To investigate evolution of host specificity of bacterial plant pathogens, here we report a molecular evolutionary analysis of the model plant pathogen Pseudomonas syringae pv. tomato DC3000 and of close relatives that are pathogens of a diverse set of crop plants. Extensive host range tests on five different plant species were performed. Combining phylogenetic data with host range data, a reconstruction of host range of all putative ancestors was performed. In particular, the hypothesis was tested that highly virulent narrow host range pathogens of today's crops grown in monoculture evolved from ancestors with wider host range that were adapted to natural mixed plant communities of pre-agricultural times. We found support for this hypothesis in individual clades. However, reconstruction of host range of the most recent common ancestor of all analyzed strains was not conclusive. Based on the obtained results we stress the importance of including pathogens from wild plants when reconstructing the evolution of plant pathogenic bacteria.


Energy requirements of infants.
To estimate the energy requirements of infants from total energy expenditure and energy deposition during growth. Energy requirements during infancy were estimated from total energy expenditure measured by the doubly labelled water method and energy deposition based on measured protein and fat gains. Database on the total energy expenditure and energy deposition of infants was compiled from available studies conducted in China, Chile, Gambia, Mexico, The Netherlands, UK, and USA. Healthy, term infants. Total energy requirements (kJ day(-1)) increased with age and were higher in boys than girls due to differences in weight. Energy requirements decreased from 473 kJ kg(-1) per day for boys and 447 kJ kg(-1) per day for girls at 1 month of age to 337 kJ kg(-1) per day for boys and 341 kJ kg(-1) per day for girls at 6 months of age, and thereafter tended to plateau. Energy deposition as a percentage of total energy requirements decreased from 40% at 1 month to 3% at 12 months of age. These estimates are 10-32% lower than the 1985 FAO/WHO/UNU recommendations which were based on observed energy intakes of infants. Recommendations for the energy intake of infants should be revised based on new estimates of total energy expenditure and energy deposition.


Androgens and Androgen Receptors as Determinants of Vascular Sex Differences Across the Lifespan.
Androgens, including testosterone and its more potent metabolite dihydrotestosterone, exert multiple actions in the body. Physiologically, they play a critical role in male sex development. In addition, they influence vascular function, including arterial vasodilation and mediation of myogenic tone. Androgens are produced from 9 weeks' gestation in the human fetal testis, as well as in small amounts by the adrenal glands. Serum concentrations vary according to age and sex. The vasculature is a target for direct actions of androgens, which bind to various sex hormone receptors expressed in endothelial and vascular smooth muscle cells. Androgens exert both vasoprotective and vasoinjurious effects, depending on multiple factors including sex-specific effects of androgens, heterogeneity of the vascular endothelium, differential expression of androgen and sex hormone receptors in endothelial and vascular smooth muscle cells, and the chronicity of androgen administration. Long-term administration of androgens induces vasoconstriction and influences endothelial permeability, whereas acute administration may have opposite effects. At the cellular level, androgens stimulate endothelial cell production of nitric oxide and inhibit proinflammatory signalling pathways, inducing vasorelaxation and vasoprotection. However, androgens also activate endothelial production of vasoconstrictors and stimulate recruitment of endothelial progenitor cells. In humans, both androgen deficiency and androgen excess are associated with increased cardiovascular morbidity and mortality. This review discusses how androgens modulate vascular sex differences across the lifespan by considering the actions and production of androgens in both sexes and describes how cardiovascular risk is altered as levels of androgens change with aging.


Plasma contact system activation drives anaphylaxis in severe mast cell-mediated allergic reactions.
Anaphylaxis is an acute, potentially lethal, multisystem syndrome resulting from the sudden release of mast cell-derived mediators into the circulation. We report here that a plasma protease cascade, the factor XII-driven contact system, critically contributes to the pathogenesis of anaphylaxis in both murine models and human subjects. Deficiency in or pharmacologic inhibition of factor XII, plasma kallikrein, high-molecular-weight kininogen, or the bradykinin B2 receptor, but not the B1 receptor, largely attenuated allergen/IgE-mediated mast cell hyperresponsiveness in mice. Reconstitutions of factor XII null mice with human factor XII restored susceptibility for allergen/IgE-mediated hypotension. Activated mast cells systemically released heparin, which provided a negatively charged surface for factor XII autoactivation. Activated factor XII generates plasma kallikrein, which proteolyzes kininogen, leading to the liberation of bradykinin. We evaluated the contact system in patients with anaphylaxis. In all 10 plasma samples immunoblotting revealed activation of factor XII, plasma kallikrein, and kininogen during the acute phase of anaphylaxis but not at basal conditions or in healthy control subjects. The severity of anaphylaxis was associated with mast cell degranulation, increased plasma heparin levels, the intensity of contact system activation, and bradykinin formation. In summary, the data collectively show a role of the contact system in patients with anaphylaxis and support the hypothesis that targeting bradykinin generation and signaling provides a novel and alternative treatment strategy for anaphylactic attacks.


Green tea extract (AR25) inhibits lipolysis of triglycerides in gastric and duodenal medium in vitro.
In this study, we aimed to evaluate in vitro the inhibitory activity of a green tea extract (AR25 standardized at 25% catechins) on gastric and pancreatic lipase activities. We first used tributyrin as a substrate to evaluate the capability of AR25 to induce digestive lipase inhibition. Gastric lipase was totally inhibited by 40 mg AR25/g tributyrin whereas pancreatic lipase inhibition was maximum (78.8 +/- 0.7%) with 80 mg AR25/g tributyrin. We then used triolein, a long-chain triglyceride, to check whether AR25 could alter lipase activities on a physiologic substrate. AR25 60 mg/g triolein induced a dramatic inhibition of gastric lipase (96.8 +/- 0.4%) whereas pancreatic lipase activity was partially reduced (66.50 +/- 0.92%). Finally, the concerted action of gastric and pancreatic lipases was studied with an excess of enzymes to mimic the physiologic conditions observed in vivo. Incubation of AR25 with an excess of digestive lipases resulted in a drastic decrease in gastric lipolysis but the inhibitory effect on pancreatic lipase was less marked. On the whole, as compared to the control, lipolysis of triolein under the successive action of the two digestive lipases was reduced by 37 +/- 0.6% in the presence of AR25. Because a lipid/water interface is necessary for lipolysis to occur, lipid emulsification and emulsion droplet size were measured in gastric and duodenal media in the presence of AR25. In gastric and duodenal conditions, AR25 inhibited the lipid emulsification process. From these data we conclude that (1) in vitro, fat digestion is significantly inhibited by 60 mg AR25/g triolein, and (2) gastric as well as pancreatic lipase inhibition could be related to altered lipid emulsification in gastric or duodenal media. The green tea extract AR25 exhibiting marked inhibition of digestive lipases in vitro is likely to reduce fat digestion in humans.


Intrinsic fluorescence studies of the kinetic mechanism of unfolding of alpha-lactalbumin on weakly hydrophobic chromatographic surfaces.
The kinetic mechanism of unfolding of calcium depleted bovine alpha-lactalbumin adsorbed on two weakly hydrophobic chromatographic surfaces, methyl- and ethyl-polyether phases bonded to porous silica, with a solution phase of 3 M ammonium sulfate at pH 6.3, has been determined using intrinsic fluorescence and liquid chromatography (LC). The adsorbent has been packed into quartz flow cells which are used for both fluorescence measurements and as a microcolumn for LC. The LC measurements revealed two peaks for alpha-lactalbumin on both phases, the first being folded and the second unfolded. The rate of unfolding was measured to be 1.75.10(-3) min-1 on the Cl-ether and 7.42.10(-3) min-1 on the C2-ether phase. Fluorescence studies revealed a slow change in emission maximum from ca. 330 nm to 350 nm and a 4-fold increase in intensity for the protein adsorbed on the two supports. Variation of fluorescence intensity at a given wavelength revealed biphasic kinetics in which the rate law on the surface was deduced as F in equilibrium X----U, where F is the folded form, U an unfolded form and X an intermediate. The normalized emission spectra of the three species were calculated and it was found that there was approximately a 20-nm-red shift in the position of the maximum from F to U. The emission maximum for X was close to U on both columns; however, the normalized intensity for X was between F and U. Activation enthalpies and entropies were determined from the temperature dependence of the microscopic rate constants. The formation of the intermediate on the C1-ether phase was entropy driven whereas on the C2-ether phase it was enthalpy driven. Finally, the solution refolding rates of U desorbed from the two supports were found to be identical. The differences observed in the surface kinetics of unfolding on the two supports are related to the hydrophobic differences of the adsorbents.


Authors' reply to: Letter to the Editor in response to 'Parental attachment and depressive symptoms in pregnancies complicated by twin-twin transfusion syndrome: a cohort study'.
In this correspondence we thank the authors for highlighting the importance of our work, and agree with the limitations they have raised regarding performing this study.


Post-transplantation encapsulating peritoneal sclerosis in a pediatric patient.
Encapsulating peritoneal sclerosis (EPS) is a serious complication of long-term peritoneal dialysis (PD), but only a few cases have been described in the pediatric patient population. There is no established medical treatment, and surgery has been reported with variable success. The number of reports of EPS being successfully treated with tamoxifen, based on its anti-fibrotic effects, are increasing. The role of sirolimus, an mTOR inhibitor with immunomodulatory and anti-proliferative properties, has been less well-defined. A 17-year-old kidney transplant recipient, with a previous cumulative time on PD of 8 years and 3 months, developed severe bowel obstruction 8 months after undergoing a second kidney graft. Her immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil, and prednisolone. The patient underwent laparotomy, which revealed multiple thick leathery adhesions with an encapsulated small bowel. Enterolysis was performed, and total parenteral nutrition was commenced after surgery to provide an adequate food intake. Treatment with tamoxifen was initiated, but the patient developed significant liver toxicity 2 weeks later, and the drug was withdrawn. The immunosuppressive regimen was changed to an increased dose of prednisolone, and tacrolimus was replaced with sirolimos. At 20 months of follow-up, the patient remains symptom-free, with a functioning kidney transplant. Although EPS is a very rare condition in the pediatric population, it should be considered when a child or adolescent with a long-term history of PD presents with nonspecific gastrointestinal symptoms or with signs of bowel obstruction. There is an urgent need for alternative immunosuppressive protocols. The use of sirolimus in this group of patients remains controversial.


Dentinogenic potential of human adult dental pulp cells during the extended primary culture.
Despite the frequent use of primary dental pulp cells in dental regenerative research, few systematic studies of stemness for osteogenic and dentinogenic differentiation of human adult pulp cells have been reported. To investigate the stemness of human adult dental pulp cells, pulp tissues were obtained from extracted third molars and used as a source of pulp cells. In FACS analysis and immunophenotyping, the general mesenchymal stem cell markers CD44, CD90, and CD146 were highly expressed in early passages of the pulp cell culture. The stem cell population was dramatically decreased in an expansion culture of human dental pulp cells. When pulp cells were treated with additives such as β-glycerophosphate, ascorbic acid, and dexamethasone, nodule formation was facilitated and mineralization occurred within 2 weeks. Expression of osteogenic markers such as alkaline phosphatase, osteocalcin, and osteonectin was relatively low in undifferentiated cells, but increased significantly under differentiation conditions in whole passages. Dentinogenic markers such as dentin sialophosphoprotein and dentin matrix protein-1 appeared to decrease in their expression with increasing passage number; however, peak levels of expression occurred at around passage 5. These data suggested that stem cells with differentiation potential might exist in the dental pulp primary culture, and that their phenotypes were changed during expansion culture over 8-9 passages. Under these conditions, a dentinogenic population of pulp cells occurred in limited early passages, whereas osteogenic cells occurred throughout the whole passage range.


Patient characteristics and the effect of three physician-delivered smoking interventions.
This paper investigates individual patient characteristics predicting differential response to each of three physician-delivered smoking interventions after 6 months. Participants were 1,286 currently smoking patients seen by 196 medical and family practice residents in five primary care clinics affiliated with the University of Massachusetts Medical School. Of the participants, 57% were female, 92% were white, their average age was 35 years, and they smoked an average of 23 cigarettes per day. Physicians were trained to provide the following interventions: advice only (AO), a brief (< 10 min) patient-centered counseling intervention (CI), and counseling plus prescription of the nicotine-containing gum Nicorette (CI+NCG). The CI+NCG condition included NCG only when appropriate and if acceptable to the patient. Patients were randomized to one of these three physician-delivered intervention conditions. Overall, stratified univariate analyses revealed that AO produced consistently lower cessation rates across most subgroups (generally 9-13%) but was somewhat more effective for certain groups of lighter smokers. Relative to AO, CI was somewhat more effective (about 20-24%) for less addicted smokers, for those with more previous quit attempts, and for those with fewer close associates who smoke, but generally failed to produce higher quit rates for harder core smokers or for women. CI+NCG had an overall pattern of greater effectiveness for both more addicted and less addicted smokers, with the highest absolute levels of cessation (about 27-30%) among less dependent smokers. Women in this group had cessation rates (20.6%) comparable to those of men (23.6%). Condition-stratified logistic regression analyses, controlling for a wide range of covariates, revealed associations similar to those observed in the univariate analyses: An overall logistic model in which intervention conditions were fitted as dummy variables produced the following significant main effects: sex, years smoked, contact with other smokers, symptoms, and CI+NCG condition. Significant interactions were observed for both CI and CI+NCG and smoking when feeling too ill to continue normal activities and CI+NCG and amount smoked. We observed significant main effects on cessation of variables related to addiction, sex, social factors, and physician counseling interventions. Specific interactions were observed between reported smoking when feeling ill and each of the counseling interventions as well as by amount smoked in the CI+NCG condition.


Observations of the action of limit dextrinases on amylopectin-like polysaccharides.
The rate of hydrolysis of amylopectin by three different limit dextrinase preparations is only about 15-23% of that of amylopectin beta-limit dextrin under similar conditions. On dilution of the enzymes there was no change in specificity. The factors controlling the specificity of the enzyme and the possible significance in vivo of the results are discussed.


Effects of dietary intervention on vitamin B12 status and cognitive level of 18-month-old toddlers in high-poverty areas: a cluster-randomized controlled trial.
The local diet in high-poverty areas in China is mainly vegetarian, and children may be more vulnerable to vitamin B12 deficiency. The aims of this study were to explore the vitamin B12 status of toddlers living in high-poverty areas of China and to observe the effects of different complementary foods on the vitamin B12 status and cognitive level of these toddlers. The study was nested within a cluster-randomized controlled trial implemented in 60 administrative villages (clusters) of Xichou County in which infants aged 6 months old were randomized to receive 50 g/d of pork (meat group), an equi-caloric fortified cereal supplement (fortified cereal group) or local cereal supplement (local cereal group) for one year. At 18 months, a subsample of the 180 toddlers (60 from each group) was randomly tested for serum vitamin B12 and total homocysteine (tHcy) levels, and their neurodevelopment was evaluated. The median serum concentrations of vitamin B12 and tHcy were 360.0 pg/mL and 8.2 μmol/L, respectively, in children aged 18 months. Serum vitamin B12 concentrations less than 300 pg/mL were found in 62 (34.4%) children, and concentrations less than 200 pg/mL were found in 30 (16.7%) children. The median vitamin B12 concentration was significantly different among the three groups (P < 0.001). The highest vitamin B12 level was demonstrated in the fortified cereal group (509.5 pg/mL), followed by the meat group (338.0 pg/mL) and the local cereal group (241.0 pg/mL). Vitamin B12 concentration was positively correlated with the cognitive score (P < 0.001) and the fine motor score (P = 0.023) of the Bayley Scales of Infant Development, 3rd Edition (BSID III) screening test. Compared to the local cereal group, children in the meat group had higher cognitive scores (P < 0.05). In poor rural areas of China, vitamin B12 deficiency in toddlers was common due to low dietary vitamin B12 intake. Fortified cereal and meat could help improve the vitamin B12 status of children and might improve their cognitive levels. The larger trial in which this study was nested was registered at clinical trials.gov as NCT00726102 . It was registered on July 31, 2008.


Computed tomography demonstration of acute thrombosis of a portal vein aneurysm.
The author presents a case of surgically proven acute thrombosis of a portal vein aneurysm, a rare occurrence, demonstrated by computed tomography.


Ascorbic acid in the 21st century - more than a simple antioxidant.
Ascorbic acid (AA) is an essential micronutrient for man, with many biological roles. It is a powerful antioxidant both directly via scavenging of reactive oxygen species and indirectly through regeneration of other antioxidant systems. Paradoxically, under certain conditions (low concentration in vitro, presence of metal ions) it can exert a pro-oxidant effect, increasing oxidative damage to lipids, DNA and protein. Herein, the effects of vitamin C both in vitro and in vivo are addressed in terms of modulation of oxidative DNA damage, gene expression and protein oxidation. The view of AA as a simple scavenger is outdated, where the arrival of new bioinformatic techniques, heralds a new dawning in our understanding of ascorbate as a potential direct or indirect modulator of gene expression.


Investigation of binding interaction behavior between antiemetic drugs and Trypsin by spectroscopy and molecular docking.
Antiemetic drugs are used to control excessive vomiting and nausea and generally absorbed through gastrointestinal tract. In present study, the in-vitro binding interactions two of the antiemetic drugs (dimenhydrinate and ondansetron) between Trypsin (Tsn) secreted from pancreas to small intestine for protein digestion were investigated by fluorescence emission spectroscopy (FES), UV-VIS spectroscopy, synchronous fluorescence spectroscopy (SFS), FT-IR spectroscopy and molecular modeling methods. Also, the effect of these drugs on the catalytic activity of Tsn was determined. The fluorescence quenching experiments indicated that each drugs quenched the intrinsic fluorescence of Tsn with their increased concentrations. The results of SFS and UV-VIS spectra proved the interaction of dimenhydrinate and ondansetron with Tsn. FT-IR spectra showed that the secondary structure of enzyme was altered in the presence of the drugs. All these spectroscopy results were validated and explained by molecular docking studies. Both drugs have inhibition effect on the catalytic activity of Tsn and the IC50 values were determined as 2.6 × 10-4 M and 6.4 × 10-4 M for dimenhydrinate and ondansetron, respectively. Docking results revealed that the hydrogen bond interaction of dimenhydrinate with active-site residue Ser195 and ondansetron with active-site residues His57 and Ser195 hydrogen bonds might be cause the inhibition of enzyme activity. The results of this study can provide valuable information in the field of pharmacokinetics and pharmacodynamics.


The metropolitanization and suburbanization of the U.S. elderly population: 1970-1988.
This paper analyzes U.S. Census, Current Population Survey data from 1970 to 1988. It establishes that the young-old (age 65-74) and old-old (75 plus) populations are now more likely to live in metropolitan areas, especially within suburban areas, and are occupying residential locations that are less segregated from other age groups. As early as 1977 the majority of metropolitan elderly people lived in suburban areas, and by 1988 only just over one-quarter of the U.S. elderly population lived in nonmetropolitan areas.


Experimental design and husbandry.
Rodent gerontology experiments should be carefully designed and correctly analyzed so as to provide the maximum amount of information for the minimum amount of work. There are five criteria for a "good" experimental design. These are applicable both to in vivo and in vitro experiments: (1) The experiment should be unbiased so that it is possible to make a true comparison between treatment groups in the knowledge that no one group has a more favorable "environment." (2) The experiment should have high precision so that if there is a true treatment effect there will be a good chance of detecting it. This is obtained by selecting uniform material such as isogenic strains, which are free of pathogenic microorganisms, and by using randomized block experimental designs. It can also be increased by increasing the number of observations. However, increasing the size of the experiment beyond a certain point will only marginally increase precision. (3) The experiment should have a wide range of applicability so it should be designed to explore the sensitivity of the observed experimental treatment effect to other variables such as the strain, sex, diet, husbandry, and age of the animals. With in vitro data, variables such as media composition and incubation times may also be important. The importance of such variables can often be evaluated efficiently using "factorial" experimental designs, without any substantial increase in the overall number of animals. (4) The experiment should be simple so that there is little chance of groups becoming muddled. Generally, formal experimental designs that are planned before the work starts should be used. (5) The experiment should provide the ability to calculate uncertainty. In other words, it should be capable of being statistically analyzed so that the level of confidence in the results can be quantified.


[Characteristics of ocular involvement in Behçet disease in Tunisia: Monocentric study and review of literature].
Behçet's disease is a multisystemic inflammatory disease characterized by recurrent oral and genital ulcers, skin lesions and uveitis. The diagnosis of Behçet's disease is based on clinical criteria. The etiology of the disease is unknown but the wide variations of ethnic prevalence and of the prevalence in the same ethnic group in different geographic areas indicate environmental triggering of a genetically determined disorder. A retrospective analysis of the medical charts of 150 Behçet's disease patients seen in our internal medicine department between 1995 and 2010 was undertaken. Patients with confirmed ocular involvement were analyzed and compared with those without ocular involvement. Among the 150 medical charts studied, 85 patients were included in the study. Thirty-three patients (38.5%) had ocular involvement. Mean age at ocular BD diagnosis onset were 35.3. Male to female ratio was 5.6. Ocular involvement was bilateral in 26 patients (78.8%). Uveitis was the most common ocular lesion (n=31 patients, 93.9%). Panuveitis was the most common anatomical location (n=21, 63.6%). The comparison of patients treated for BD with or without ocular involvement showed a statistically significant association between ocular and neurological manifestations (p=0.03). All patients with ocular involvement were treated with corticosteroids. Immunosuppressive (IS) treatments were used in 28 patients (84.8%). Cyclophosphamide was the most used as first-line treatment (71.4%). Cyclophosphamide relayed by azathioprine was the most adopted protocol (28.5%). In case of resistance or relapse and depending on the other manifestations of the BD, the IS used in first intention was replaced by another one. Seven of the 33 patients had received treatment with infliximab (IFX) after failure of other therapeutic lines. Ocular prognosis in the BD can be improved by early treatment and regular monitoring. It is important to adjust the therapeutic protocol to the anatomic form, to the severity of uveitis and to the extra-ocular manifestations associated.


Production of polyhydroxyalkanoates (PHA) by a thermophilic strain of Schlegelella thermodepolymerans from xylose rich substrates.
The aim of this work was to investigate the thermophilic bacterium Schelegelella thermodepolymerans DSM 15344 in terms of its polyhydroxyalkanoates (PHA) biosynthesis capacity. The bacterium is capable of converting various sugars into PHA with the optimal growth temperature of 55 °C; therefore, the process of PHA biosynthesis could be robust against contamination. Surprisingly, the highest yield was gained on xylose. Results suggested that S. thermodepolymerans possess unique xylose metabolism since xylose is utilized preferentially with the highest consumption rate as compared to other sugars. In the genome of S. thermodepolymerans DSM 15344, a unique putative xyl operon consisting of genes responsible for xylose utilization and also for its transport was identified, which is a unique feature among PHA producers. The bacterium is capable of biosynthesis of copolymers containing 3-hydroxybutyrate and also 3-hydroxyvalerate subunits. Hence, S.thermodepolymerans seems to be promising candidate for PHA production from xylose rich substrates.


Binding a Meridional Ligand in a Facial Geometry: A Square Peg in a Round Hole.
The bis(pyridylimino)isoindoline (BPI) ligand is a tridentate chelate that binds to metals via a meridional coordination mode. However, when this ligand forms a complex with Re(CO)3, an almost exclusively facial moiety, the BPI ligand deforms to coordinate in a facial mode. We have in-vestigated this deformation via structural and theoretical means, and the non-planar binding mode of the ligand bathochromically shifts the metal to ligand charge transfer (MLCT) transition.


Chemical reactivity and mutagenicity of some dihalomethanes.
Four dihalomethanes; dichloromethane, bromochloromethane, dibromomethane and diiodomethane, have been studied with respect to their reactivities towards nucleophilic compounds of different strengths in water solution and with respect to their toxicities and mutagenic effectiveness in bacterial test systems. The correlation between biological activity (toxicity and mutagenic effectiveness in Salmonella TA100) and reactivity towards strong nucleophiles indicates that reactions with nucleophilic groups of high reactivity in the biological material, possibly SH or amino groups in proteins, are involved in their mechanism of action.


Discriminating between deleterious and neutral non-frameshifting indels based on protein interaction networks and hybrid properties.
More than ten thousand coding variants are contained in each human genome; however, our knowledge of the way genetic variants underlie phenotypic differences is far from complete. Small insertions and deletions (indels) are one of the most common types of human genetic variants, and indels play a significant role in human inherited disease. To date, we still lack a comprehensive understanding of how indels cause diseases. Therefore, identification and analysis of such deleterious variants is a key challenge and has been of great interest in the current research in genome biology. Increasing numbers of computational methods have been developed for discriminating between deleterious indels and neutral indels. However, most of the existing methods are based on traditional sequential or structural features, which cannot completely explain the association between indels and the resulting induced inherited disease. In this study, we establish a novel method to predict deleterious non-frameshifting indels based on features extracted from both protein interaction networks and traditional hybrid properties. Each indel was coded by 1,246 features. Using the maximum relevance minimum redundancy method and the incremental feature selection method, we obtained an optimal feature set containing 42 features, of which 21 features were derived from protein interaction networks. Based on the optimal feature set, an 88 % accuracy and a 0.76 MCC value were achieved by a Random Forest as evaluated by the Jackknife cross-validation test. This method outperformed existing methods of predicting deleterious indels, and can be applied in practice for deleterious non-frameshifting indel predictions in genome research. The analysis of the optimal features selected in the model revealed that network interactions play more important roles and could be informative for better illustrating an indel's function and disease associations than traditional sequential or structural features. These results could shed some light on the genetic basis of human genetic variations and human inherited diseases.


Wave-like behaviour in (0,1) binary sequences.
A comprehensive study of the properties of finite (0,1) binary systems from the mathematical viewpoint of quantum theory is presented. This is a quantum-inspired extension of the GenomeBits model to characterize observed genome sequences, where a complex wavefunction [Formula: see text] is considered as an analogous probability measure and it is related to an alternating (0,1) binary series having independent distributed terms. The real and imaginary spectrum of [Formula: see text] vs. the nucleotide base positions display characteristic features of sound waves. This approach represents a novel perspective for identifying and "observing" emergent properties of genome sequences in the form of wavefunctions via superposition states. The motivation is to develop a simple algorithm to perform wave calculations from binary sequences and to apply these wave functions to sonification.


Immunocytochemistry of a novel GABA receptor subunit Rdl in Drosophila melanogaster.
Following our recent cloning of a novel gamma-aminobutyric acid (GABA) receptor subunit gene Resistance to dieldrin or Rdl form cyclodiene resistance locus in Drosophila melanogaster, we were interested in defining its pattern of expression during development. Here we report the raising of an anti-Rdl polyclonal antibody that recognizes a single protein of the expected 65 kDa size in immunoblots of Drosophila head homogenates. In situ hybridization using Rdl cDNA probes and the anti-Rdl antibody shows that Rdl message and protein are highly expressed in the developing central nervous system (CNS) of 15-17 h embryos. Interestingly, despite the use of GABA in both the peripheral and CNS of insects, Rdl GABA receptor subunits appear to be confined to the CNS. Detailed immunocytochemistry of Drosophila brain sections showed particularly strong anti-Rdl antibody staining in the optic lobes, ellipsoid body, fan shaped body, ventrolateral protocerebrum and the glomeruli of the antennal lobes. Results are compared with the distribution of staining observed in the insect CNS with antibodies against GABA itself and synaptotagmin, a synaptic vesicle protein.


Improvement of biological time-of-flight-secondary ion mass spectrometry imaging with a bismuth cluster ion source.
A new liquid metal ion gun (LMIG) filled with bismuth has been fitted to a time-of-flight-secondary ion mass spectrometer (TOF-SIMS). This source provides beams of Bi(n)q+ clusters with n = 1-7 and q = 1 and 2. The appropriate clusters have much better intensities and efficiencies than the Au3+ gold clusters recently used in TOF-SIMS imaging, and allow better lateral and mass resolution. The different beams delivered by this ion source have been tested for biological imaging of rat brain sections. The results show a great improvement of the imaging capabilities in terms of accessible mass range and useful lateral resolution. Secondary ion yields Y, disappearance cross sections sigma, efficiencies E = Y/sigma , and useful lateral resolutions deltaL have been compared using the different bismuth clusters, directly onto the surface of rat brain sections and for several positive and negative secondary ions with m/z ranging from 23 up to more than 750. The efficiency and the imaging capabilities of the different primary ions are compared by taking into account the primary ion current for reasonable acquisition times. The two best primary ions are Bi3+ and Bi5(2+). The Bi3+ ion beam has a current at least five times larger than Au3+ and therefore is an excellent beam for large-area imaging. Bi5(2+) ions exhibit large secondary ions yields and a reasonable intensity making them suitable for small-area images with an excellent sensitivity and a possible useful lateral resolution <400 nm.


International facilitators and barriers to family engagement in the ICU: Results of a qualitative analysis.
Patient and family engagement in the intensive care unit (ICU) is beneficial for patient recovery from critical illness. Yet limited information exists on facilitators and barriers from an international perspective. As part of ongoing work from a task force of the World Federation of Intensive and Critical Care (WFICC) exploring international practices of family engagement from a survey of 345 healthcare clinicians from 43 countries, qualitative analysis was conducted for two open ended questions: 1) What are strategies that you and your colleagues have found helpful to promote patient and family-centered care/engagement in the ICU? and 2) What are potential barriers have you encountered in implementing patient and family-centered care/engagement in the ICU? Thematic content analysis was used to code data to identify major themes of facilitators and barriers of family engagement. A total of 257 comments were provided from intensivist physicians (n = 107, 31.4%), ICU directors (n = 74, 21.7%), ICU nurse managers (n = 33, 9.7%), and others including fellows, nurse specialists and consultant anesthesiologists. Major themes that emerged related to team engagement, family engagement, communication, leadership, relationships, and structured process. Highlighting strategies can assist ICU clinicians globally to adopt and promote best practices for family engagement.


Distribution and trends of mercury in deciduous tree cores.
The distribution of total mercury (THg) within common deciduous trees and the applicability of tree cores as biomonitors of historical environmental THg trends were assessed for both contaminated and reference sites around Kingston, Ontario. Samples were collected from Acer spp., Quercus spp. Populus spp. and Salix spp. Bark and wood THg concentrations were found to be highly correlated whereas soil and wood THg concentrations were not. There were no temporal relationships for THg in dated tree rings corresponding with any other known environmental Hg trends. The shoreline species, Populus and Salix spp., had the greatest bark and wood Hg concentrations reaching 18 ng/g, significantly higher than for inland trees Quercus and Acer spp. with maximum values of 7 and 1.2 ng/g for bark and wood respectively. While tree cores cannot be reliably used as temporal THg biomonitors, there is promise for tree species such as Populus spp and Salix spp as spatial indicators of local long-term Hg contamination.


Evaluating driver eye glance behavior and secondary task engagement while using driving automation systems.
Partial driving automation systems are designed to assist drivers in some vehicle operation demands. However, modifications to the driving task that change the driver's role from that of an active participant to a passive supervisor could result in insufficient monitoring of the driving automation system and the surrounding environment. A reduced subset of driving data for 19 drivers from the Virginia Connected Corridors 50 Elite Naturalistic Driving Study was used to assess whether driver eye glance behavior and secondary task engagement were different when driver assistance systems were active compared to when they were available but inactive (n = 148). The results of this study demonstrate that drivers spent more time looking away from the road while driving automation systems were active and that drivers were more likely to be observed browsing on their cell phones while using driving automation systems. Current driving automation features require human monitoring of automation, yet the drivers of these automation-equipped vehicles are inclined to engage in secondary tasks and take longer and more frequent glances away from the roadway. It is possible that performance effects, such as omission errors or delayed reactions, may occur as a result of drivers' substandard monitoring of the driving scene.


Interpreting device diagnostics for lead failure.
Implantable cardioverter-defibrillators (ICDs) incorporate automated, lead-monitoring alerts (alerts) and other diagnostics to detect defibrillation lead failure (LF) and minimize its adverse clinical consequences. Partial conductor fractures cause oversensing, but pacing or high-voltage alerts for high impedance detect only complete conductor fracture. In both pacing and high-voltage insulation breaches, low-impedance alerts require complete breach with metal-to-metal contact. Oversensing alerts for pace-sense LF also require complete breach, but not metal-to metal contact. Electrograms (EGMs) from leads with confirmed fractures have characteristics findings. In insulation breach, however, oversensed EGMs reflect characteristics of the source signal. Oversensing alerts that operate on the sensing channel analyze R-R intervals for 2 patterns typical of LF but uncommon in other conditions: a rapidly increasing count of "nonphysiological" short intervals and rapid "nonsustained tachycardias." These alerts are sensitive but nonspecific. Alerts that compare sensing and shock channels define oversensing as sensed events that do not correlate temporally with EGMs on the shock channel. Their performance depends on implementation. Specific advantages and limitations are reviewed. Most ICDs measure impedance using subthreshold pulses. Patterns in impedance trends provide diagnostic information, whether or not an alert is triggered. Gradual increases in impedance do not indicate structural LF, but they may cause failed defibrillation if shock impedance is high enough. Because impedance-threshold alerts are insensitive, normal impedance trends never exclude LF, but an abrupt increase that triggers an alert almost always indicates a header connection issue or LF. Methods for discriminating connection issues from LF are reviewed.


Microbiological findings in prepubertal and pubertal girls with vulvovaginitis.
Vulvovaginitis is a common and challenging gynaecological problem in prepubertal and pubertal girls. Such an infection, owing to a wide range of aetiologies, if not responding to hygienic measures, needs further investigation through vaginal cultures, since treatment should be tailored accordingly. This study aimed to investigate the pathogens isolated in prepubertal and pubertal girls with signs and symptoms of vulvovaginitis. A total of 2314 symptomatic girls, 1094 prepubertal and 1220 pubertal, aged 2 to 16 years, were included. Vaginal samples were inoculated on specific culture plates followed by incubation in aerobic, anaerobic or CO2 atmosphere at 37 °C for 24 or 48 h, as appropriate. The identification of the isolated pathogens was carried out using Gram stain, conventional methods and the automated system VITEK 2 (BioMerieux, Marcy l'Etoile, France). Positive cultures were obtained from 587 (53.7%) of prepubertal girls and 926 (75.9%) of pubertal girls. A total of 613 and 984 pathogens were detected in prepubertal and pubertal subjects, respectively. Isolated bacteria included 40.1% and 22.8% Gram-positive cocci, 35.6% and 24.8% Gram-negative rods in the prepubertal and pubertal groups, respectively, with faecal pathogens being the most prevalent. Bacterial vaginosis was diagnosed in 22.8% of prepubertal and 37.9% of pubertal girls. Candida species were isolated mostly in the pubertal girls (14.5%). Culture results should be evaluated with caution in children with vulvovaginitis. In the prepubertal girls, the most common isolated pathogens were opportunistic bacteria of faecal origin while girls in late puberty were more susceptible to bacterial vaginosis and vulvovaginal candidiasis. • Vulvovaginitis is the most frequent and challenging reason for referral to paediatric and adolescent gynaecology services. • Microbiological examination can prove to be a significant tool to help diagnosis although results should be evaluated with caution in children. • Significantly more positive vaginal cultures and pathogens were recorded in symptomatic pubertal girls compared to prepubertal children. • The prevalence of bacterial vaginosis was increased in both prepubertal and pubertal girls with vulvovaginitis although significantly more in girls at puberty.


Increasing Safe Sleep Practices in the Neonatal Intensive Care Unit.
The American Academy of Pediatrics (AAP) encourages healthcare providers to practice and model safe sleep practices (SSPs) in the neonatal intensive care unit (NICU) when it is developmentally and medically appropriate for the infant. Preintervention data were collected as a baseline prior to the quality improvement (QI) initiative and revealed that 87% of eligible infants were in unsafe sleep environments (n = 331/379). This data revealed the need for an improvement project to help increase the percentage of infants placed in safe sleep in this NICU. The purpose of this QI initiative was to increase the percentage of eligible infants being placed in safe sleep environments by registered nurses in a NICU. The development of an evidence-based safe sleep bundle was implemented in a level IV NICU at an academic medical center in the Southeastern United States. Data were subsequently collected for 5 months via bi weekly crib audits. Of the 744 infants audited in the QI period, 604 were observed in a safe sleep environment. From the pre- to postintervention period, SSPs increased by 68% (preintervention: 13%, postintervention: 81%, P value < .001). Adherence to the varying components of SSPs also reflected statistically significant improvements. SSPs should be endorsed and modeled in all NICUs. Introducing proper SSPs in the hospital setting may lead to better compliance at home by the infants' caregivers.


Sphingosine kinase 1 (SK1) allosteric inhibitors that target the dimerization site.
The sphingosine kinase 1 (SK1)/sphingosine-1-phosphate (S1P) signaling pathway is a crucial target for numerous human diseases from cancer to cardiovascular diseases. However, available SK1 inhibitors that target the active site suffer from poor potency, selectivity and pharmacokinetic properties. The selectivity issue of the kinases, which share a highly-conserved ATP-pocket, can be overcome by targeting the less-conserved allosteric sites. SK1 is known to function minimally as a dimer; however, the crystal structure of the SK1 dimer has not been determined. In this study, a template-based algorithm implemented in PRISM was used to predict the SK1 dimer structure and then the possible allosteric sites at the dimer interface were determined via SiteMap. These sites were used in a virtual screening campaign that includes an integrated workflow of structure-based pharmacophore modeling, virtual screening, molecular docking, re-screening of common scaffolds to propose a series of compounds with different scaffolds as potential allosteric SK1 inhibitors. Finally, the stability of the SK1-ligand complexes was analyzed by molecular dynamics simulations. As a final outcome, ligand 7 having a 4,9-dihydro-1H-purine scaffold and ligand 12 having a 2,3,4,9-tetrahydro-1H-β-carboline scaffold were found to be potential selective inhibitors for SK1.


Synergistic effect of tumor chemo-immunotherapy induced by leukocyte-hitchhiking thermal-sensitive micelles.
Some specific chemotherapeutic drugs are able to enhance tumor immunogenicity and facilitate antitumor immunity by inducing immunogenic cell death (ICD). However, tumor immunosuppression induced by the adenosine pathway hampers this effect. In this study, E-selectin-modified thermal-sensitive micelles are designed to co-deliver a chemotherapeutic drug (doxorubicin, DOX) and an A2A adenosine receptor antagonist (SCH 58261), which simultaneously exhibit chemo-immunotherapeutic effects when applied with microwave irradiation. After intravenous injection, the fabricated micelles effectively adhere to the surface of leukocytes in peripheral blood mediated by E-selectin, and thereby hitchhiking with leukocytes to achieve a higher accumulation at the tumor site. Further, local microwave irradiation is applied to induce hyperthermia and accelerates the release rate of drugs from micelles. Rapidly released DOX induces tumor ICD and elicits tumor-specific immunity, while SCH 58261 alleviates immunosuppression caused by the adenosine pathway, further enhancing DOX-induced antitumor immunity. In conclusion, this study presents a strategy to increase the tumor accumulation of drugs by hitchhiking with leukocytes, and the synergistic strategy of chemo-immunotherapy not only effectively arrested primary tumor growth, but also exhibited superior effects in terms of antimetastasis, antirecurrence and antirechallenge.


Evidence that Nectin-3 is the soybean agglutinin binding protein on rat corneal endothelium cell surfaces.
The means by which the lectin soybean agglutinin (SBA) binds to the corneal endothelium cell surface following explantation into organ culture was investigated using Sprague-Dawley rats. SBA binding does not occur in freshly isolated and fixed rat corneal endothelium. However, after 48 h in organ culture, SBA binding occurs in a punctate pattern that clearly outlines all endothelial cells of the tissue monolayer. To determine what cell surface component was responsible for this binding, a series of experiments were employed that focused on the possibility that SBA bound to a nectin molecule(s). To this extent we performed a series of immunocytochemical localizations using antibodies against either nectin-2, nectin-3 or nectin-4. Of these, only nectin-3 bound to the endothelium in a manner that mimicked SBA binding. To further verify that nectin-3 bound SBA, displacement experiments employing non-labeled SBA were undertaken. Following a 48 h organ culture, tissues were fixed and incubated with SBA followed by exposure to nectin-3 antibody. No subsequent immunofluorescence could be detected, indicating that anti-nectin-3 binding was prevented. Likewise, when organ-cultured tissues were fixed and incubated in anti-nectin-3 antibody, followed by SBA exposure, no SBA binding could be detected. These results suggest that stresses accompanying explantation of the tissue into organ culture promote the appearance of nectin-3 around the cell periphery. The emergence of nectin-3 along the peripheral endothelial cell membrane in organ culture may imply a necessary role for this molecule in maintaining monolayer integrity and barrier function during either a pathologic condition, wound repair, or in organ storage.


Forelimb regeneration in thyroidectomized adult newts following organ culture and autografting of the thyroid glands.
Thyroidectomy and organ culture of adult newt thyroid glands three days prior to forelimb amputation was followed by autografting the glands subcutaneously into the animal's lower jaw region 9, 18 or 25 days postamputation (GC9, 18, 25 day series). This was an attempt, utilizing 515 animals, to elucidate further the role of the thyroids in regeneration. Amputated limbs of the thyroidectomized (Thx) and autografted muscle explant (MC = sham) cases underwent stumping or were significantly delayed in their regeneration rate and displayed abnormal morphogenesis compared with control regenerates. In the GC9 series newts, regenerates were identical to controls 45 days postamputation. However, regenerates of the GC18 series cases exhibited delayed and abnormal development at 45 days; but they were not as delayed and had fewer abnormalities than those cases in the Thx and MC groups. Results of the GC25 series newts were similar to those of the Thx group. Within 5 days of autografting the thyroids, epidermal moulting resumed and long-term survival ensued. We conclude that normal limb regeneration in the adult newt is thyroid hormone(s) dependent, specifically the later stages of growth, differentiation and morphogenesis.


Implementation and evaluation of pharmaly houses as learning communities to promote community, wellness, and advising.
Although medical education has demonstrated learning communities promote wellness and community while supporting advising and mentoring, its application in pharmacy is limited. This study explored faculty and student perceptions of pharmacy learning communities (PLC), including structure, member interactions, and curriculum topics. PLCs involving first-year (PY1) student advisees, third-year (PY3) peer mentors, and faculty coaches were implemented. The PLC model included Pharmaly Houses, which were compromised of multiple Pharmalies, with each Pharmaly consisting of one faculty coach, two PY3 peer mentors, and approximately 10 PY1 advisees. PLC members were invited to participate in semi-structured focus groups, and transcripts were analyzed using inductive coding. Three major themes and related subthemes emerged: strengths of the PLC structure (e.g., multiple perspectives, community, networking); interactions of Pharmaly members (i.e. faculty coaches, PY3 peer mentors, PY1 advisees); and feedback on PLC curriculum topics (e.g., topic consultation, continued learning). Participants indicated the multiple perspectives provided by Pharmaly members was a strength and highlighted the PLC structure facilitated a sense of community and belonging among Pharmaly members while promoting expanded networking within the House. While the PLC expanded networks, faculty and PY1 advisees desired more one-to-one interactions. Further, students reflected on how current PLC curriculum topics (e.g., wellness) prompted continued learning, reflection, and discussion outside the House or Pharmaly meeting. Participants indicated PLCs can support student access to mentoring and advising, promote wellness, and foster a sense of community and belonging. The unique peer mentoring model further promoted community.


MDCT evaluation of pancreatic contour variations in head, neck, body and tail: surgical and radiological significance.
The purpose of the study was to investigate the incidence of pancreatic contour variations on multidetector CT (MDCT) for abdominal examinations. A retrospective analysis of 700 MDCT scans was performed in patients who underwent triple phase CT abdomen between October 2018 and January 2021. After excluding 176 patients, finally total of 524 patients were included in the study. For simplification, we classified the pancreatic contour variations as classified by Ross et al. and Omeri et al. Pancreatic head-neck variations was classified into Type I-anterior, Type II-posterior and Type III-horizontal variety. Pancreatic body-tail variation was divided into Type Ia-anterior projection; Ib-posterior projection and Type IIa-globular, IIb-lobulated, IIc-tapered, and IId-bifid pancreatic tail. The most common type of variation in the head was Type II (n = 112, 21.3%) followed by Type III (n = 37, 7%) and Type I (n = 21, 4%). The most common type of variation in the body of pancreas was Type Ia (n = 33, 6.2%) followed by Type Ib (n = 13, 2.4%). In the tail region of pancreas, the most common variation was Type IIb (n = 21, 4%) followed by Type IIa (n = 19, 3.6%). Pancreatic contour variations are not very uncommon in daily practice. Knowledge of these variations is important for surgeons, radiologists and avoids misjudgement of normal pancreatic tissue as tumor or lymph node especially on unenhanced or single phase MDCT.


Post-earthquake outbreak of insecticide-associated conjunctivitis in a primary school of Lixian district, China: An epidemiological investigation.
To describe the time course and characteristics of an insecticide-associated incident and highlight potential risks from similar outbreaks that may occur in other areas to enhance the preparedness of emergency physicians and other healthcare providers to deal with the sequelae of these events. Outbreak investigation From 5 to 8 August 2008, an outbreak investigation was carried out among the affected primary school located in the refugee camp area of Lixian district, Sichuan, China. Affected pupils, parents, teachers and doctors working in the local medical stations were visited. Clinical checking, clinical treatment, epidemiological investigation and environmental investigation were undertaken. In total, 138 individuals were diagnosed with acute conjunctivitis, characterized by inflammation of the conjunctiva and intense ocular symptoms such as redness, itching and mucus discharge. According to the results, all risk factors (i.e. drinking water, indoor air and the materials used in camp classrooms) were excluded except insecticide exposure. The characteristics of symptoms, distribution of cases and records of irregular insecticide spraying support the assumption that the conjunctivitis outbreak was associated with synthetic pyrethroid alphacypermethrin exposure. The results suggest that non-standard operating procedures in pest control could lead to disease incidents. Medical rescue teams should receive training and education in preventive techniques.


Changes in basic nuclear proteins during sperm maturation in Palaemon serratus (Crustacea Natantia).
The spermatozoa from the shrimp Palaemon serratus have been studied with respect to their morphological and biochemical characters. At the ultrastructural level the acrosomal vesicle of the nail-shaped spermatozoon displays a periodically striated bundle. This appearance seems to be characteristic for the Palaemonidae. The biochemical parameters of the chromatin, extracted from the spermatozoa, have been compared with those obtained from the testes and the hepatopancreas. The basic proteins of testes and sperm have been characterized by polyacrylamide gel electrophoresis. Protamines appear to be absent in the sperm of P. serratus. On the contrary, histones with a somatic character remain present. Moreover, supplementary histone fractions have been identified. These proteins have been further studied after purification on Biogel P-100. Their amino acid composition shows similarities to that of the H2A and H2B histone and has a molecular weight of 15,500 +/- 300.


Cervicovaginal microbiome in patients with recurrent pregnancy loss.
There have been few studies concerning an association between unexplained recurrent pregnancy loss (RPL) and the microbiome. A recent study including 67 patients demonstrated that an increase in Ureaplasma species in the endometrium raised the risk of miscarriage with an euploid karyotype. While endometrial sampling is invasive, cervicovaginal sampling is not. We compared vaginal and cervical microbiomes with a 16 S ribosomal RNA sequence between 88 patients with unexplained RPL and 17 healthy women with no history of miscarriage. We prospectively assessed risk factors for maternal colonization at a subsequent miscarriage without an aneuploid karyotype in patients. Cervicovaginal bacteria were dominated by Lactobacillus iners, Gardnerella vaginalis, Atopobium vaginae and Bifidobacterium breve in Japanese population. The proportions of Delftia and unknown bacteria in the cervix were significantly higher in patients with RPL than in controls. Streptococcus, Microbacterium, Delftia, Anaerobacillus and Chloroplast in the cervix were significantly higher in patients with a history of chorioamnionitis compared to the controls. The abundance of Cutibacterium and Anaerobacillus in the cervix was significantly higher in patients who had subsequently miscarried compared to those who gave birth. The miscarriage rate in patients with higher proportions of both Cutibacterium and Anaerobacillus (66.7%, 2/3) was significantly greater than that of patients who lacked these bacteria (9.2%, 6/65, adjusted odds ratio 16.90, 95% confidence interval 1.27-225.47, p = 0.032). The presence of certain bacteria could be a predictor of subsequent miscarriage without an aneuploid karyotype. The cervicovaginal microbiome might be useful for investigating a possible cause of RPL.


Unfractionated Heparin TID Dosing Regimen Is Associated With a Lower Rate of Pulmonary Embolism When Compared With BID Dosing in Patients Undergoing Craniotomy.
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), and intracranial hemorrhage (ICH) may complicate the post-operative course of patients undergoing craniotomy. While prophylaxis with unfractionated heparin (UFH) has been shown to reduce VTE rates, twice-daily (BID) and three-times-daily (TID) UFH dosing regimens have not been compared in neurosurgical procedures. The objective of this study was to explore the association between UFH dosing regimen and rates of VTE and ICH in craniotomy patients. A retrospective chart review was conducted for 159 patients at Northwestern University receiving 5000 units/0.5 mL UFH injections either BID (n = 132) or TID (n = 27). General linear regression models were run to predict rates of DVT, PE, and reoperation due to bleeding from UFH dosing regimen while controlling for age at surgery, sex, VTE history, craniotomy for tumor resection, surgery duration, length of stay, reoperation, infections, and IDH/MGMT mutations. Receiving UFH TID was significantly associated with a lower rate of PE when compared with receiving UFH BID (β = -0.121, P = 0.044; TID rate = 0%, BID rate = 10.6%). UFH TID also showed a trend toward lower rates of DVT (β = -0.0893, P = 0.295; TID rate = 18.5%, BID rate = 21.2%) when compared with UFH BID. UFH TID showed no significant difference in rate of reoperation for bleeding when compared to UFH BID (β = -0.00623, P = 0.725; TID rate = 0%, BID rate = 0.8%). UFH TID dosing is associated with lower rates of PE when compared with BID dosing in patients undergoing craniotomy.


The secrets of keeping fit: exercising and healthy eating.
Physical fitness not only requires exercising, but also healthy eating habits. Herein, a cartoon and a related text on physical fitness are submitted.


[Clinical and microbiological studies on the effect of locally applied aminofluorides on bacterial plaque and gingiva condition of Soviet school children].
In a short-term (over 4 weeks) clinico-microbiological study on 18 Soviet school children, 12 years of age, it was found that a supervised oral hygiene action with the amine fluoride-containing caries-preventing agents Silca and Elmex fluid (produced in the GDR) had resulted in a marked reduction in plaque formation, an improvement in gingival conditions and a reduction of the germ content in the plaques.


"Personal recovery depends on NA unity": an exploratory study on recovery-supportive elements in Narcotics Anonymous Flanders.
Mutual aid organizations, such as Narcotics Anonymous (NA), can provide support in substance use disorder (SUD) recovery processes. However, research on NA and its recovery-supportive elements is scarce and perspectives of NA-members remain understudied, in particular outside the US. Therefore, this study aims to gain insight into recovery-supportive elements of NA, as experienced by its members. To explore the perspectives on and experiences with recovery-supportive elements in NA, 11 in-depth interviews with NA-members were conducted in Flanders (Belgium). Interviews were audio-taped, transcribed verbatim and analyzed by using CHIME-D, a personal recovery framework (Connectedness, Hope, Identity, Meaning in life, Empowerment, Difficulties) developed by Leamy and colleagues in 2011. Various recovery-supportive elements of NA were highlighted, with Connectedness as a key component including opportunities for building up a social network and for providing a safety net or sounding board. Elements that enabled Connectedness were 1) a non-judgemental approach, and 2) mutual understanding through sharing in NA. Other elements of the CHIME-D framework were less frequently mentioned, although these were inextricably linked to Connectedness. Connectedness appeared to be the crucial recovery-supportive element in NA, emphasizing the relational character of SUD recovery. Although other elements of the CHIME-D framework were identified, these were closely related to and intertwined with the concept of connectedness.


Is the academic physician-scientist an oxymoron in contemporary obstetrics and gynecology?
Because of changes in health care reimbursement and decreasing federal funding, academic obstetrics and gynecology is at a pivotal point. Either the discipline can regress to the past, when the field and its practitioners were viewed negatively and failed to attract the academic upper echelons of medical students, or it can build on the immense gains it has made in recent years and develop a critical cadre of well-trained clinician-scientists who maintain the discipline at the leading edge of medicine and biology. Data from two programs in which extensive contemporary training in biomedical research is provided, the Reproductive Scientist Development Program and the American Association of Obstetricians and Gynecologists Foundation fellowship program, indicate that the superb physician-scientists in these programs are obtaining peer-reviewed funding in excess of 70%. Thus the risk of recruiting such individuals to academic faculties is small. More important, these individuals are the linchpins for an even more exciting future. The alternatives are unthinkable.


Some histological aspects of amyloid polyneuropathy.
Two sporadic cases of amyloid polyneuropathy with clinical features corresponding to the Portuguese type of this disease were studied. Histological examination of sural nerve demonstrated a marked loss of myelinated and unmyelinated fibres in the case 1 due to axonal degeneration, high content of fibers with segmental demyelination and the occurrence of several enlarged axons filled with the 10 nm filaments (so-called giant axons). In the case 2 there was total loss of unmyelinated axons and myelinated fibers were nearly completely lacking. In the development of changes in the myelinated fibers their direct compression by amyloid deposits seems to play an important role. It leads to the appearance of both axonal degeneration and segmental demyelination. The latter seems to be due to local compression and it may involved many fibers. In the light of observations reported by other authors the mechanism of changes developing in unmuelinated fibers is explained by the presence of changes in the cells of posterior root ganglia, however the question whether some abnormalities seen in unmyelinated axons could not be related to the pressure exerted by amyloid deposits directly to these fibers, remains open.


Numerical simulation of red blood cell distributions in three-dimensional microvascular bifurcations.
We constructed three-dimensional microvascular bifurcation models using a parent vessel of diameter 10μm and investigated the flow behavior of the red blood cells (RBCs) through bifurcations. We considered symmetric and asymmetric model types. Two cases of equal daughter vessel diameter were employed for the asymmetric models, where the first was 10μm, which is the same as the parent vessel and the second was 7.94μm, which satisfies Murray's law. Simulated blood flow was computed using the lattice Boltzmann method in conjunction with the immersed boundary method for incorporating fluid-membrane interactions between the flow field and deformable RBCs. First, we investigated the flow behavior of a single RBC through microvascular bifurcations. In the case of the symmetric bifurcation, the turning point of the fractional plasma flow wherein the RBC flow changed from one daughter vessel to the other was 0.50. This turning point was however different for asymmetric bifurcations. Additionally, we varied the initial offset of RBCs from the centerline of the parent vessel. The simulation results indicated that the RBCs preferentially flow through the branch of a larger flow ratio. Next, we investigated the distribution characteristics of multiple RBCs. Simulations indicated that the results of the symmetric model were similar to those predicted by a previously published empirical model. On the other hand, results of asymmetric models deviated from those of the symmetric and empirical models. These results suggest that the distribution of RBCs varies according to the bifurcation angle and daughter vessel diameter in a microvascular bifurcation of the size considered.


Replacing paper with digital recording.
Addressing the needs to achieve the highest standards at multidisciplinary team meetings at the Stroke Unit of Broomfield Hospital, an electronic version is applied instead of the traditional paper model. This is to ensure that patients within the unit are receiving appropriate care and their progress is monitored throughout their entire journey. This also enables the stroke team to retrieve old information anywhere in the hospital, electronically, from previous documentations to compare progress of rehabilitation. The electronic model also helps when assessing readmission or those who attend the stroke clinics to clarify new onset changes from residual weakness. The tool kit estimates Barthel Index score for activities of daily living and Rivermead Mobility Index for physical capacity assessment weekly as the team attending the meetings. The goals from all disciplines, physiotherapists, occupational therapists, speech and language therapists, and nurses are clearly documented along with patient cognition, emotion, and perception. This initiative commenced in late April 2013 and the first clinical outcome assessments performed at the beginning of September 2013, enabling the stroke team to assess rehabilitation activities and achievements. Front-line staff expressed satisfaction with the initiative model, which successfully managed to monitor and analyze the rehabilitation activities within the stroke unit.


The influence of childhood trauma on the treatment outcomes of pharmacological and/or psychological interventions for adolescents and adults with bipolar disorder: A systematic review and meta-analysis.
The influence of childhood trauma on the treatment outcomes of pharmacological and/or psychological interventions for adolescents and adults with bipolar disorder was systematically reviewed. Randomised and non-randomised studies of interventions for bipolar disorder that included an assessment of childhood trauma were eligible. MEDLINE Complete, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials were searched. Two independent reviewers completed the screening and extraction process. Two independent reviewers assessed the risk of bias in the included studies using the Cochrane Collaboration's Risk of Bias tool and the Newcastle-Ottawa Scale. Alongside a narrative synthesis, random-effects meta-analyses were performed. Twelve studies (1175 participants) were included. The narrative review highlighted differential treatment outcomes among individuals with a history of childhood trauma. The meta-analyses suggested that childhood trauma was unrelated to treatment response (five studies, 426 participants; odds ratio 0.58, 95% CI 0.27-1.25, p = .164) but may be associated with greater improvement in global functioning (three studies, 210 participants; Hedge's g 0.65, 95% CI 0.04-1.26, p = .037). The impact of childhood trauma on the effectiveness of specific pharmacological/psychological interventions could not be explored due to the small body of research identified. The overall quality of the extant evidence is low, which precludes definitive comment on the role of childhood trauma in the treatment of bipolar disorder. Additional research that uses large and representative samples is required to ascertain whether a history of childhood trauma affects the treatment outcomes of interventions for individuals with bipolar disorder.


Transarterial chemoembolisation: effect of selectivity on tolerance, tumour response and survival.
To compare selective and non-selective TACE techniques in the treatment of HCC with a special emphasis on clinical and liver tolerance, tumour response and survival. 184 patients with advanced HCC were retrospectively included. Three different TACE techniques were compared: non selective lipiodol-chemotherapy + non selective embolisation (TACE-technique group 1), non selective lipiodol-chemotherapy + selective embolisation (group 2), and selective lipiodol-chemotherapy + selective embolisation (group 3). In multivariate analysis TACE-technique group is an independently significant prognostic factor for poor clinical tolerance, poor liver tolerance and tumour response. The rate of patients with poor clinical tolerance was lower in group 3 (27.0%) than in groups 1 (64.1%, p < 10(-3)) or 2 (66.7%, p < 10(-3)). The rate of patients with poor liver tolerance was higher in group 2 (34.0%) than in groups 1 (17.6%, p = 0.050) or 3 (6.9%, p = 0.011). The rate of patients with tumour response was higher when embolisation was selective versus non-selective, i.e., group 2 + 3 (78.7%) versus group 1 (62.5%, p = 0.054). Overall survival was not significantly different between the three groups (p = 0.383). Both selective techniques resulted in better tumour response. As for improving tolerance, our study suggests that the main technical factor is the use of selective lipiodol-chemotherapy injection.


Bioactive glass S53P4 to fill-up large cavitary bone defect after acute and chronic osteomyelitis treated with antibiotic-loaded cement beads: A prospective case series with a minimum 2-year follow-up.
Bioactive glass S53P4 (BAG-S53P4) has been used in the treatment of osteomyelitis with excellent results. The aim of this study was to evaluate the clinical and radiographic results of patients treated with use of antibiotic-loaded cement beads, followed by bone defects filling using bioglass. We treated a prospective series of patients presenting with acute or chronic osteomyelitis of a long bone of the upper or lower limb. The first-stage procedure involved debridement and filling of cavitary defects with antibiotic-loaded polymethylmethacrylate (PMMA) beads. When signs of infection subsided, the defects were filled with BAG-S53P4. The main outcomes assessed were the reinfection rate, need for reoperation, radiographic and functional evaluations (DASH and Lysholm scores). Ten patients were included, aged between 4 and 66 years (mean 25.4 years). The source of infection was hematogenic in five cases and post-traumatic in the other five. Hematogenic infections required two debridements before filling with bioglass, whereas post-traumatic cases required only one. The time between the first debridement and the application of bioglass varied from 1 to 63 weeks (average of 17 weeks). All patients showed a favorable evolution after bioglass procedure, with no need for reoperation or relevant wound problems. The radiographic evaluation showed partial incorporation of the material and adequate bone formation, and functional scores were satisfactory in all cases. The treatment of osteomyelitis with surgical debridement and PMMA beads, followed by filling of bone defect with BAG-S53P4, was effective in all patients evaluated, with adequate infectious control and bone regeneration. No cases required reoperation after bioglass implantation. Patients with hematogenous osteomyelitis required a greater number of debridements before filling with bioglass.


Sterols and sphingolipids: dynamic duo or partners in crime?
One manner in which eukaryotic cells respond to their environments is by optimizing the composition and proportions of sterols and sphingolipids in membranes. The physical association of the planar ring of sterols with the acyl chains of phospholipids, particularly sphingolipids, produces membrane micro-heterogeneity that is exploited to coordinate several crucial pathways. We hypothesize that these lipid molecules play an integrated role in human disease; when one of the partners is mis-regulated, pathology frequently ensues. Sterols and sphingolipid levels are not coordinated by the action of a single master regulator, however the cross-talk between their metabolic pathways is considerable. We describe our perspectives on the key components of synthesis, catabolism and transport of these lipid partners with an emphasis on evolutionarily conserved reactions that produce disease states when defective.


Linoleic acid increases monocyte deformation and adhesion to endothelium.
Fatty acids have been implicated in having both anti- or pro-inflammatory actions, which may contribute to the progression and severity of atherosclerosis. Linoleic acid has been shown by others to decrease CD18 expression and leukocyte adhesion under static conditions. We investigated the effect of steric acid (18:0), oleic acid (18:1), and linoleic acid (18:2) on the cortical tension (a measure of cell membrane deformability) and adhesion characteristics of the monocytic cell line Mono Mac 6 (MM6) cells to TNF-alpha activated HUVEC under fluid flow. Linoleic acid concentrations up to 23 microM decreased cortical tension and increased adhesion frequencies. Increased adhesion was not due to altered cell morphology or adhesion kinetics and occurred despite decreases in receptor expression (CD18 and CD11a). At higher levels of linoleic acid (> or = 46 microM), cell dissociation constants significantly increased. Results show that decreasing cortical tension increased the probability that contact between MM6 cells and endothelium would produce an adhesive interaction, possibly due to increased deformation of the microvilli and the cell membrane cortex. However, more deformable cells rolled more erratically at low shear rates. The different behavior during initial contact and rolling suggest that adhesion is influenced by two force-dependent mechanisms, deformation of microvilli and a steric barrier. Incubation of MM6 with 23 microM steric or oleic acid did not significantly affect cortical tension. However, cells incubated with steric acid greatly increased their adherence to HUVEC and cells incubated with oleic acid showed no significant effect, indicating factors other than deformability may dominate.


The Effect of an Evaluative Label on Consumer Perception of Cheeses in Hungary.
Traditional strategies (such as education, economic incentives or prohibitions) targeted at altering dietary habits only influence health-conscious consumers. Less health-conscious consumers are less capable of self-regulatory behavior, therefore they are more likely to be influenced through perception. The present study aimed to examine how external cues such as labeling affect the consumer's perception of foods. The paper includes a case study based on an experiment. In the experiment the same cheese was tested with four different types of labeling (labeled "conventional", "low salt", "low fat" and "low salt and low fat"). It was found that the health halo effect worked in the case of cheese testing. In spite of all the samples being identical, the healthy samples were associated with considerably less sensory pleasure. The use of labels by the producers resulted in exactly the opposite effect to that intended. The experiment confirmed the efficiency of the application of this type of behavior-oriented nudge.


Occurrence, transport and environmental risk assessment of pharmaceuticals and personal care products (PPCPs) at the mouth of Jiaozhou Bay, China based on stir bar sorptive extraction.
In recent years, research on pharmaceuticals and personal care products (PPCPs) in the marine environment has attracted increasing attention worldwide. However, more work is needed to improve PPCPs detection methods, specifically for seawater environments. An analytical method based on stir bar sorptive extraction (SBSE) had been developed and fully optimized for the pretreatment and detection of ten widely used PPCPs that are commonly found in seawater samples. By optimizing several variables including the material of the stir bars, extraction temperature, extraction time, ionic strength, desorption solvent, and desorption time, the optimized method has achieved excellent results in the detection and quantification of target PPCPs with detection limits ranging from 0.03 to 1 ng/L. The distribution of target PPCPs at the mouth of Jiaozhou Bay was successfully determined by this method, and the concentrations and detection frequencies of PPCPs varied greatly from N.D. to 449.36 ng/L and from 9.1 % to 100 %, respectively. Moreover, the distributions of PPCPs were explained by the Lagrangian particle-tracking model, and the results showed that the Tuandao sewage treatment plant had the most significant impact on the study area. The environmental risk assessment results showed that several target PPCPs might pose risks to aquatic organisms. In particular, triclocarban should receive more attention and the risk quotients of the mixtures (MRQ) should not be ignored.


Genetic control of maltase formation in yeast. III. Isolation and characterization of temperature-sensitive mutants affecting maltase induction and maltose utilization.
Temperature-sensitive mutants affecting maltose utilization in the yeast Saccharomyces cerevisiae have been isolated. Two such mutants although failing to ferment maltose at the restrictive temperature, have normal induced level of maltase. The third mutant (UNT-37) not only failed to ferment maltose but has 5-6 fold less induced level of maltase at the restrictive temperature than the parental strain. The genetic control mechanisms of maltase induction and maltose utilization have been discussed.