Complex cardiac Nkx2-5 gene expression activated by noggin-sensitive enhancers followed by chamber-specific modules.
We previously reported that an Nkx2-5-GFP bacterial artificial chromosome in transgenic mice recapitulated the endogenous gene activity in the heart. Here, we identified three additional previously uncharacterized distal enhancer modules of Nkx2-5: UH6, which directed transgene expression in the right ventricle, interventricular septum, and atrial ventricular canal; UH5, which directed expression in both atria; and UH4, which directed transgene expression in tongue muscle. Nkx2-5 enhancers drive cardiogenic gene activity from the earliest progenitors to the late-stage embryonic heart, reside within its 27 kb of 5' flanking sequences, organized in a tandem array. Nkx2-5 enhancers involved with stomach-, tongue-, and chamber-restricted expression displayed lacZ transgene activity and chromatin histone acetylation patterns consistent with tissue-specific expression. An examination of Nkx2-5 gene activity in murine embryonic stem cells converted to beating embryoid bodies showed that only the proximal active region 2 and GATA-Smad enhancers were chromatin-remodeled. Chromatin remodeling of active region 2 and GATA-Smad enhancers were blunted by noggin coexpression, which indicated dependence on bone morphogenetic protein signaling for their chromatin activation during activation of Nkx2-5 expression.


Maintaining zebu Maure cattle in a tsetse infested area of Mali.
A study was initiated to evaluate two trypanocidal drugs, the prophylactic isometamidium chloride (Trypamidium) and the curative diminazene aceturate (Berenil) as to their potential for long-term maintenance of zebu cattle in a tsetse infested area of Mali. Trypamidium was administered quarterly and Berenil was administered only as animals were found to be positive for trypanosomes. During the 21-month study trypanosomiasis was the most frequently encountered disease in the cattle in the Berenil treatment group with an average of 5.5 reinfections. The predominant trypanosome species encountered was Trypanosoma vivax and the most important vector was Glossina palpalis gambiensis. The results indicate that, even though the direct costs for drugs under the two maintenance regimens were almost identical, the use of Trypamidium resulted in a significantly greater annual weight gain, prevented death loss due to trypanosomiasis and resulted in a herd with a greater market value.


Difference in formation of carbon cluster cations by laser ablation of graphene and graphene oxide.
The distributions of positive carbon cluster ions produced by laser ablation of graphene (G) and graphene oxide (GO) are found to be quite different. Under a typical experimental condition, narrow distributions of even-numbered clusters from C60+ to C162+ were observed for G, and broad distributions including even-numbered clusters from C100+ to C400+ and odd-numbered clusters from C189+ to C395+ were observed for GO. The threshold of laser energy for G is lower than that of GO. Further results of collision-activated dissociation mass spectrometry indicate that the cluster ions generated from G are structurally similar but are different with those generated from GO or nanodiamonds. It is proposed that the experimentally observed difference can be attributed to the different mechanisms behind the process. A top-down mechanism including both direct transformation of G to fullerene and fragmentation of large-sized fullerenes is suggested for the generation of carbon cluster cations in the process of laser ablation of G. For GO, the experimental results are close to those of nanodiamonds and other materials reported previously and can be explained by the generally accepted bottom-up mechanism.


Cardioprotective effect of calcineurin inhibition in an animal model of renal disease.
Chronic kidney disease is directly associated with cardiovascular complications. Heart remodelling, including fibrosis, hypertrophy, and decreased vascularization, is frequently present in renal diseases. Our objective was to investigate the impact of calcineurin inhibitors (CNI) on cardiac remodelling and function in a rat model of renal disease. Male Sprague Dawley rats were divided into six groups: sham-operated rats, 5/6 nephrectomized rats (Nx) treated with vehicle, CNI (cyclosporine A 5.0 or 7.5, or tacrolimus 0.5 mg/kg/day) or hydralazine (20 mg/kg twice a day) for 14 days, starting on the day of surgery. Creatinine clearance was significantly lower and blood pressure significantly higher in Nx rats when compared with controls. Morphological and echocardiographic analyses revealed increased left ventricular hypertrophy and decreased number of capillaries in Nx rats. Treatment with CNI affected neither the renal function nor the blood pressure, but prevented the development of cardiac hypertrophy and improved vascularization. In addition, regional blood volume improved as confirmed by contrast agent-based echocardiography. Hydralazine treatment did not avoid heart remodelling in this model. Gene expression analysis verified a decrease in hypertrophic genes in the heart of CNI-treated rats, while pro-angiogenic and stem cell-related genes were upregulated. Moreover, mobilization of stem/progenitor cells was increased through manipulation of the CD26/SDF-1 system. We conclude from our studies that CNI-treatment significantly prevented cardiac remodelling and improved heart function in Nx rats without affecting renal function and blood pressure. This sheds new light on possible therapeutic strategies for renal patients at high cardiovascular risk.


Within-category discontinuity interacts with verbal rule complexity in perceptual category learning.
A test of the predicted interaction between within-category discontinuity and verbal rule complexity on information-integration and rule-based category learning was conducted. Within-category discontinuity adversely affected information-integration category learning but not rule-based category learning. Model-based analyses suggested that some information-integration participants improved performance by recruiting more "units" in the discontinuous condition. Verbal rule complexity adversely affected rule-based category learning but not information-integration category learning. Model-based analyses suggested that the rule based effect was on both decision criterion learning and variability in decision criterion placement. These results suggest that within-category discontinuity and decision rule complexity differentially impact information-integration and rule-based category learning and provide information regarding the detailed processing characteristics of these two proposed category learning systems.


Antibody to sigma 32 cross-reacts with DnaK: association of DnaK protein with Escherichia coli RNA polymerase.
A polyclonal antibody to sigma 32, the heat shock sigma factor, has been used to show the presence of low levels of sigma 32 in Escherichia coli RNA polymerase preparations (E sigma 70), which explains the observed in vitro activity of E sigma 70 towards heat shock genes. The sigma 32 antibody cross-reacts with DnaK, and DnaK has been found associated with purified preparations of both E sigma 70 and the heat shock RNA polymerase, E sigma 32.


An unusual presentation of cortical venous thrombosis and its association with typical antipsychotics.
A 41-year-old patient with schizophrenia was admitted to hospital following episodes of unexplained collapse attacks and on and off episodes of frontal headaches for 3 months. After three such episodes of loss of consciousness in 2 weeks duration and subsequent spontaneous recovery, his evaluation which included MRI scan of head revealed extensive cortical venous thrombosis. He was on zuclopenthixol (thioxanthene group) for several months for schizophrenia and was under regular psychiatric evaluation. He was treated for simple lower respiratory infection a week prior to admission. Other causes for any clotting disorders including vasculitic and thrombophilic screen were negative. There was no evidence of focal neurology on examination. Systemic examination was otherwise unremarkable. He was treated initially with unfractionated heparin and subsequently changed to warfarin with target international normalised ratio between two and three for at least 6 months and psychiatrist was advised to stop zuclopenthixol.


Results of a metabolic health clinic at a hostel for homeless men.
People who are homeless have high mortality and morbidity, including from metabolic disorder. The aim of this study was to report on the characteristics and progress of the metabolic health of people attending a metabolic clinic at a homeless men's shelter. Homeless men attending the clinic were assessed by measuring their weight, height, body mass index (BMI), waist circumference, blood pressure, blood lipids, fasting blood glucose and, if indicated, HbA1c. The sample characteristics of people who attended once (one-off clients) were compared to those who attended on more than one occasion (returning clients). Changes in health status were examined among returning clients by comparing baseline results to those at their last clinic visit. Baseline data were recorded on a total of 136 men, of whom 126 had a consultation with a general practitioner and at least one blood test. The 136 clients had a median BMI of 27.4 kg/m2. Forty-three were obese (BMI ≥30 kg/m2), 18 had class II obesity (BMI >35 kg/m2) and seven were underweight (BMI <20 kg/m2). Sixty-five had an intervention for either a newly diagnosed condition or a change to existing medical treatment. Seventy-six returning clients were seen on an average of 2.3 further occasions. Returning clients had significant improvements in measures of metabolic health. Homeless people in Sydney appear to be at a high risk of metabolic disease. The feasibility of a metabolic health clinic was demonstrated, and an encouraging improvement in some health indicators was found.


Molecular understanding of diffusion in confinement.
We introduce a computational method to directly relate diffusivities to the microscopic behavior of the adsorbed molecules. We apply this method to gases in an MFI-type molecular sieve, the reference system in this field. Transitions in the number and nature of adsorption sites result in temporary local increases in the diffusion. This occurs at different loadings in each of the x, y, and z directions, giving rise to the complex loading behavior found experimentally. Our method can be applied to any adsorbent-adsorbate system, and provides a fundamental understanding of diffusion in confinement on a molecular level.


Movement Strategies among Groups of Chronic Ankle Instability, Coper, and Control.
Comprehensive evaluation of movement strategies during functional movement is a difficult undertaking. Because of this challenge, studied movements have been oversimplified. Furthermore, evaluating movement strategies at only a discrete time point(s) provide limited insight into how movement strategies may change or adapt in chronic ankle instability (CAI) patients. This study aimed to identify abnormal movement strategies in individuals with a history of ankle sprain injury during a sports maneuver compared with healthy controls. Sixty-six participants, consisting of 22 CAI patients, 22 ankle sprain copers, and 22 healthy controls, participated in this study. Functional profiles of lower extremity kinematics, kinetics, and EMG activation from initial contact (0% of stance) to toe-off (100% of stance) were collected and analyzed during a jump landing/cutting task using a functional data analysis approach. Compared with copers, CAI patients displayed landing positions of less plantarflexion, less inversion, more knee flexion, more hip flexion, and less hip abduction during the first 25% of stance. However, restricted dorsiflexion angle was observed in both CAI patients and copers relative to controls during the midlanding to mid-side-cutting phase when the ankle and knee reached its peak range of motion (e.g., dorsiflexion and knee flexion). Reduced EMG activation of tibialis anterior, peroneus longus, medial gastrocnemius, and gluteus medius may be due to altered kinematics that reduce muscular demands on the involved muscles. CAI patients displayed altered movement strategies, perhaps in an attempt to avoid perceived positions of risk. Although sagittal joint positions seemed to increase the external torque on the knee and hip extensors, frontal joint positions appeared to reduce the muscular demands on evertor and hip abductor muscles.


Random phase vector for calculating the trace of a large matrix.
We derive an estimate of the statistical error in calculating the trace of a large matrix by using random vectors, and show that the random phase vector gives the results with the smallest statistical error for a given basis set. This result supports use of random phase vectors in the calculation of density of states and linear response functions of large quantum systems.


Highly sensitive and selective detection of mercury ions by using oligonucleotides, DNA intercalators, and conjugated polymers.
In this letter, we demonstrated a practical scheme for the detection of mercury ions in aqueous media at room temperature with high sensitivity and selectivity by using a combination of oligonucleotides, DNA intercalators, and conjugated polymers. This scheme combines the advantages of specific binding interactions between Hg2+ and thymine and optical amplification properties of conjugated polymers. This method is label-free, low cost, and simple to use, and all of the materials are commercially available. It works in a "mix-and-detect" manner. The limit of detection could be improved to 0.27 nM, which is much lower than the maximum level of mercury permitted by the EPA in drinking water. This scheme could also be potentially used as a two-photon sensor for detecting mercury ions in a biological environment where deep penetration is required. A detection limit of as low as approximately 6 nM could be achieved under two-photon excitation.


Vaccination with measles, mumps and rubella vaccine and varicella vaccine: safety, tolerability, immunogenicity, persistence of antibody and duration of protection against varicella in healthy children.
Administration of M-M-R II (Measles, Mumps and Rubella Virus Vaccine, Live) and VARIVAX [Varicella Virus Vaccine Live (Oka/Merck)] given concomitantly at separate injection sites during the same office visit could increase vaccine compliance by reducing the number of health care visits for immunizations. We compared the safety and immunogenicity of M-M-R II and VARIVAX given concomitantly at separate sites (Group A) with administration of the two vaccines 6 weeks apart (Group B) as well as the persistence of varicella antibody and the duration of protection afforded by varicella vaccine. A total of 603 healthy children, ages 12 months to 6 years, with no history of measles, mumps, rubella, varicella and zoster or vaccination against these diseases, were randomized to either Group A or B and were followed for clinical reactions and serologic responses to all four viral components. Children were enrolled from August through December, 1993. Subjects were followed for 5 years to evaluate persistence of varicella antibody and breakthrough varicella rates. We compared breakthrough rates to expected attack rates in unvaccinated children to produce estimates of vaccine efficacy. Both vaccine regimens were generally well-tolerated. There were no significant differences between the groups in the rates of fever, injection site reactions or rashes after vaccination. Seroconversion rates and geometric mean titers for measles, mumps and rubella were not significantly different between groups. The varicella seroconversion rate and percentage with glycoprotein-based ELISA titers > or = 5.0 units were similar between the two groups (99.5 and 92.5% vs. 100 and 94.8% for Groups A and B, respectively), but the geometric mean titers were statistically significantly different (13.2 for Group A and 17.9 for Group B). Varicella antibody persistence rates were >98 to 100% during 6 years of follow-up in both groups. Compared with historical rates, varicella vaccine efficacy during 5 years was estimated to be 90.5% (95% confidence interval, 86.2%, 95.0%) and 88.9% (95% confidence interval, 83.7%, 93.7%) in Groups A and B, respectively. Administration of M-M-R II and VARIVAX concomitantly at separate injection sites or 6 weeks apart was generally well-tolerated and immunogenic in healthy children 12 months to 6 years of age. VARIVAX administered with M-M-R II induced persistent immunity and long-term protection against breakthrough varicella infection.


[Body weight, nutritional factors and physical activity--their influence on prognosis after breast cancer diagnosis].
Numerous studies have examined the association between body weight, nutritional factors, physical activity and the risk for primary breast cancer. Relatively few studies, however, have examined the associations between these issues and the recurrence of the disease and cure of the primary tumor. Today, three areas of focus are actively being researched for breast cancer survivors: body weight, diet composition and physical activity with specific emphasis on the risk for recurrence, survival and quality of life. Increased body weight or BMI (Body Mass Index) at diagnosis was found to be a significant risk factor for recurrent disease, decreased survival, or both. Overall obesity has been shown to adversely affect prognosis. Appropriate weight control may be particularly beneficial for breast cancer survivors. Breast cancer survivors should be encouraged to achieve and maintain a healthy weight. Limiting fat intake can reduce the risk of breast cancer recurrence. Increasing consumption of vegetables and fruits seems to have possible beneficial effects during and after treatments. To date physical activity after breast cancer diagnosis has been found to reduce the risk of death. The greatest benefit occurred in women who performed the equivalent of walking 3-5 hours per week at an average pace. Safe weight loss via increased physical activity and healthful food choices should be encouraged for normal, overweight or obese breast cancer survivors in order to improve survival and life quality.


Blockade of the chemokine receptor CXCR2 ameliorates adjuvant-induced arthritis in rats.
Chemokine receptors CXCR1 and CXCR2 may mediate influx of neutrophils in models of acute and chronic inflammation. The potential benefits of oral administration of a CXCR1/2 inhibitor, DF 2162, in adjuvant-induced polyarthritis (AIA) were investigated. A model of AIA in rats was used to compare the therapeutic effects of the treatment with DF2162, anti-TNF or anti-CINC-1 antibodies on joint inflammation and local production of cytokines and chemokines. DF2162 prevented chemotaxis of rat and human neutrophils induced by chemokines acting on CXCR1/2. DF2162 was orally bioavailable and metabolized to two major metabolites. Only metabolite 1 retained CXCR1/2 blocking activity. Treatment with DF2162 (15 mg kg(-1), twice daily) or metabolite 1, but not metabolite 2, starting on day 10 after arthritis induction diminished histological score, the increase in paw volume, neutrophil influx and local production of TNF, IL-1beta, CCL2 and CCL5. The effects of DF2162 were similar to those of anti-TNF, and more effective than those of anti-CINC-1, antibodies. DF2162 prevented disease progression even when started 13 days after arthritis induction. DF 2162, a novel orally-active non-competitive allosteric inhibitor of CXCR1 and CXCR2, significantly ameliorates AIA in rats, an effect quantitatively and qualitatively similar to those of anti-TNF antibody treatment. These findings highlight the contribution of CXCR2 in the pathophysiology of AIA and suggest that blockade of CXCR1/2 may be a valid therapeutic target for further studies aiming at the development of new drugs for treatment of rheumatoid arthritis.


Bio-fabrication of silver nanoparticles using the leaf extract of an ancient herbal medicine, dandelion (Taraxacum officinale), evaluation of their antioxidant, anticancer potential, and antimicrobial activity against phytopathogens.
In recent years, the use of nanoparticle-based antimicrobials has been increased due to many advantages over conventional agrochemicals. This study investigates the utilization of common medicinal plant dandelion, Taraxacum officinale, for the synthesis of silver nanoparticles (TOL-AgNPs). AgNPs were evaluated for antimicrobial activity against two important phytopathogens, Xanthomonas axonopodis and Pseudomonas syringae. The morphology, size, and structure of TOL-AgNPs were characterized using UV-visible spectroscopy and X-ray diffraction (XRD). Fourier transform infrared spectroscopy (FT-IR) showed the presence of phytochemicals involved during synthesis of NPs. High-resolution transmission electron microscopy (HR-TEM) analysis shed light on the size of monodispersed spherical AgNPs ranging between 5 and 30 nm, with an average particle size of about 15 nm. The TOL-AgNPs (at 20 μg/mL concentration) showed significant antibacterial activity with significant growth inhibition of phytopathogens X. axonopodis (22.0 ± 0.84 mm) and P. syringae (19.5 ± 0.66 mm). The synthesized AgNPs had higher antibacterial activity in comparison with commercial AgNPs. Synergistic assays with standard antibiotics revealed that nanoformulations with tetracycline showed better broad-spectrum efficiency to control phytopathogens. They also possessed significant antioxidant potential in terms of ABTS (IC50 = 45.6 μg/mL), DPPH (IC50 = 56.1 μg/mL), and NO (IC50 = 55.2 μg/mL) free radical scavenging activity. The TOL-AgNPs showed high cytotoxic effect against human liver cancer cells (HepG2). Overall, dandelion-mediated AgNPs synthesis can represent a novel approach to develop effective antimicrobial and anticancer drugs with a cheap and eco-friendly nature.


Individual aptitude in Mandarin lexical tone perception predicts effectiveness of high-variability training.
Although the high-variability training method can enhance learning of non-native speech categories, this can depend on individuals' aptitude. The current study asked how general the effects of perceptual aptitude are by testing whether they occur with training materials spoken by native speakers and whether they depend on the nature of the to-be-learned material. Forty-five native Dutch listeners took part in a 5-day training procedure in which they identified bisyllabic Mandarin pseudowords (e.g., asa) pronounced with different lexical tone combinations. The training materials were presented to different groups of listeners at three levels of variability: low (many repetitions of a limited set of words recorded by a single speaker), medium (fewer repetitions of a more variable set of words recorded by three speakers), and high (similar to medium but with five speakers). Overall, variability did not influence learning performance, but this was due to an interaction with individuals' perceptual aptitude: increasing variability hindered improvements in performance for low-aptitude perceivers while it helped improvements in performance for high-aptitude perceivers. These results show that the previously observed interaction between individuals' aptitude and effects of degree of variability extends to natural tokens of Mandarin speech. This interaction was not found, however, in a closely matched study in which native Dutch listeners were trained on the Japanese geminate/singleton consonant contrast. This may indicate that the effectiveness of high-variability training depends not only on individuals' aptitude in speech perception but also on the nature of the categories being acquired.


Natural Antimicrobial Peptides as Inspiration for Design of a New Generation Antifungal Compounds.
Invasive fungal infections are associated with high mortality rates, despite appropriate antifungal therapy. Limited therapeutic options, resistance development and the high mortality of invasive fungal infections brought about more concern triggering the search for new compounds capable of interfering with fungal viability and virulence. In this context, peptides gained attention as promising candidates for the antimycotics development. Variety of structural and functional characteristics identified for various natural antifungal peptides makes them excellent starting points for design novel drug candidates. Current review provides a brief overview of natural and synthetic antifungal peptides.


Current trends in the use of peritoneal dialysis catheters.
The Tenckhoff catheter was developed in 1968 and has been widely used since for chronic peritoneal dialysis (PD) patients. Variations of the Tenckhoff catheter have been designed over the years in a search for the ideal PD catheter--an access that can provide reliable dialysate flow rates with few complications. Currently, data derived from randomized, controlled, multicenter trials dedicated to testing how catheter design and placement technique influence long-term catheter survival and function are scarce. As a result, no firm guidelines exist at the national or international levels on optimal PD catheter type or implantation technique. Also, no current statistics on the use of PD catheters are available. The last survey was carried out using an audience response system at the Annual Peritoneal Dialysis Conference in Orlando, Florida, in January 1994. The present analysis is based on a new survey done at the 2005 Annual Dialysis Conference in Tampa, Florida. It is a snapshot of preferences in catheter design and implantation technique in 2004 from an international sample of 65 respondent chronic PD centers. The Tenckhoff catheter remains the most widely used catheter, followed closely by the swan-neck catheter in both adult and pediatric respondent centers. Double-cuff catheters continue to be preferred over single-cuff catheters, and coiled intraperitoneal segments are generally preferred over straight intra-peritoneal segments. Surgical implantation technique remains the prevailing placement method in both pediatric and adult respondent centers.


Decreased expression of DNA repair genes (XRCC1, ERCC1, ERCC2, and ERCC4) in squamous intraepithelial lesion and invasive squamous cell carcinoma of the cervix.
Reduced DNA repair might affect the risk of progression from infection with carcinogenic human papillomavirus (HPV), the etiologic agent for cervical cancer (CC), to persistent HPV infection, and hence to cervical pre-cancer and cancer. We assessed the variation in baseline expression of base excision repair gene XRCC1 and three nucleotide excision repair genes ERCC1, ERCC2, and ERCC4 and the risk of developing cervical cancer. A hospital-based case-control study was designed with 50 invasive cervical cancer patients, 40 squamous intraepithelial lesions (SIL) patients and 85 controls subjects. RT-qPCR and Western blotting was used to quantitate in vitro the mRNA and protein levels in fresh CC, SIL and normal cervix tissue. The levels of XRCC1, ERCC2, ERCC4, and ERCC1 transcripts and their respective proteins were lower in cervical cancer and SILs as compared to controls (p ≤ 0.001, 0.001, 0.001, and 0.025, respectively). In multivariate logistic regression analysis (adjusting for parity, age at first child birth, use of oral contraceptives, smoking status), low expression of XRCC1, ERCC2, ERCC4, and ERCC1 was associated with a significant increased risk for CC and SIL. Our results suggest that individuals whose expression of XRCC1, ERCC4, ERCC2, and ERCC1 are reduced may be at a higher risk of developing SIL which eventually leads to invasive cervical carcinoma. Moreover, independently also the reduced expression of these genes can directly lead to cervical cancer progression.


Fracture Strength of Composite Rest Seats: An In Vitro Comparative Study of Different Composite versus Amalgam Restorations.
Occlusal rest provides support for removable partial dentures (RPD). Rest seats are ideally prepared in enamel, but the abutment teeth might be restored or need restorations. This study compared the fracture strength of abutments restored with composite to amalgam restorations after rest seat preparation. Disto-occlusal cavities were prepared in 30 extracted human maxillary premolars. The specimens were allocated in three groups (n = 10) based on the type of restoration. All the specimens were exposed to thermomechanical aging followed by cycling loading. Fracture strength was tested using a universal testing machine, and then, the fracture mode was recorded. The data were analyzed using Kruskal-Wallis test with a significance level set at 0.05. The fracture mode was recorded as catastrophic or non-catastrophic. The fracture strength between all tested groups showed no significant difference. The highest and lowest fracture strength were recorded on amalgam and Tetric N-Ceram groups, respectively. Composite Tetric N-Ceram showed equal distribution of fracture sites on the restorative materials and teeth, it also displayed the highest number of non-catastrophic fractures unlike other groups where the fracture occurred more within the restorations. The fracture strength of composite was comparable to that of amalgam restorations with prepared rest seats.


A Falciformispora senegalensis grain model in Galleria mellonella larvae.
Eumycetoma is a subcutaneous implantation mycosis often found in the foot. One of the hallmarks of eumycetoma is the formation of grains. These grains are either black or white, and the consistency and morphology differs per causative agent. The two most common causative agents of black-grain eumycetoma are Madurella mycetomatis and Falciformispora senegalensis. Since grains cannot be formed in vitro, in vivo models are needed to study grain formation. Here, we used the invertebrate Galleria mellonella to establish an in vivo grain model for F. senegalensis. Three different F. senegalensis strains were selected, and four different inocula were used to infect G. mellonella larvae, ranging from 0.04 mg/larvae to 10 mg/larvae. Larval survival was monitored for 10 days. Grain formation was studied macroscopically and histologically. The efficacy of antifungal therapy was determined for itraconazole, amphotericin B, and terbinafine. A concentration of 10 mg F. senegalensis per larva was lethal for the majority of the larvae within 10 days. At this inoculum, grains were formed within 24 h after infection. The grains produced in the larvae resembled those formed in human patients. Amphotericin B given at 1 mg/kg 4 h, 28 h, and 52 h after infection prolonged larval survival. No enhanced survival was noted for itraconazole or terbinafine. In conclusion, we developed a F. senegalensis grain model in G. mellonella larvae in which grains were formed that were similar to those formed in patients. This model can be used to monitor grain formation over time and study antifungal efficacy.


How Solvent Dynamics Controls the Schlenk Equilibrium of Grignard Reagents: A Computational Study of CH3MgCl in Tetrahydrofuran.
The Schlenk equilibrium is a complex reaction governing the presence of multiple chemical species in solution of Grignard reagents. The full characterization at the molecular level of the transformation of CH3MgCl into MgCl2 and Mg(CH3)2 in tetrahydrofuran (THF) by means of ab initio molecular dynamics simulations with enhanced-sampling metadynamics is presented. The reaction occurs via formation of dinuclear species bridged by chlorine atoms. At room temperature, the different chemical species involved in the reaction accept multiple solvation structures, with two to four THF molecules that can coordinate the Mg atoms. The energy difference between all dinuclear solvated structures is lower than 5 kcal mol-1. The solvent is shown to be a direct key player driving the Schlenk mechanism. In particular, this study illustrates how the most stable symmetrically solvated dinuclear species, (THF)CH3Mg(μ-Cl)2MgCH3(THF) and (THF)CH3Mg(μ-Cl)(μ-CH3)MgCl(THF), need to evolve to less stable asymmetrically solvated species, (THF)CH3Mg(μ-Cl)2MgCH3(THF)2 and (THF)CH3Mg(μ-Cl)(μ-CH3)MgCl(THF)2, in order to yield ligand exchange or product dissociation. In addition, the transferred ligands are always departing from an axial position of a pentacoordinated Mg atom. Thus, solvent dynamics is key to successive Mg-Cl and Mg-CH3 bond cleavages because bond breaking occurs at the most solvated Mg atom and the formation of bonds takes place at the least solvated one. The dynamics of the solvent also contributes to keep relatively flat the free energy profile of the Schlenk equilibrium. These results shed light on one of the most used organometallic reagents whose structure in solvent remains experimentally unresolved. These results may also help to develop a more efficient catalyst for reactions involving these species.


[Idiopathic lymphoid interstitial pneumonia: a report of 3 cases and literature review].
To analyze the clinical, radiological and pathological characteristics of idiopathic lymphoid interstitial pneumonia (idiopathic LIP) and to discuss its diagnosis, treatment and prognosis. Respiratory physicians, pathologists and radiologists together retrospectively analyzed the clinical, chest roentgenogram, computerized tomography, pathological, diagnostic and therapeutic data of 3 patients with idiopathic LIP confirmed by lung biopsy, and reviewed the relevant literatures. The major symptoms of the 3 cases of idiopathic LIP were progressive dyspnea and dry cough. Higher levels of gamma-globulins in serum were found in all the cases. The characteristic radiographic manifestations were bilateral diffuse nodules and cysts. The pathologic feature was diffuse interstitial inflammation with polyclonal lymphocytes infiltration, especially with plasma lymphocytes. Corticosteroids and cytotoxic agents were used and good response to therapy was observed in the cases. Idiopathic LIP has some characteristics on the clinical, radiological and pathological features, but the best diagnostic method depends on a clinical-radiological-pathological approach. The disease usually shows good response to combinative therapy of corticosteroids and cytotoxic agents.


Secondary Metabolites from Deep-Sea Derived Microorganisms.
Microorganisms obtained from the deep sea are a rich source of marine natural products with distinctive chemical structures and bioactivities. In this review, we will provide a retrospective of outstanding research within the scope of deep-sea (≥1000 m) microbial natural products, which has produced up to 442 compounds by the end of 2017. Approximetely, 60% of these structures have demonstrated various biological activities with more than 30% showing cytotoxic function. In this review, we particularly summarize those successful research on secondary metabolites produced by deep-sea derived microorganisms with inclusion of structural characteristics, biological activities, together with biogenetic origins and taxonomic features of the source microorganisms, from which, we expect to provide more comprehensive understanding of small molecules obtained from deep-sea environment and benefit the ongoing scholarly endeavors in the search for novel pharmaceutical agents from the deep-sea derived microorganisms.


How do Parents Manage Symptomatic Children? Social-Distancing Insights for COVID-19 and Seasonal Influenza.
Strategies for controlling pandemics include social distancing. Using data from a 2016 nation-wide survey pertaining to influenza, (generalized) ordered logit models are developed to identify the factors associated with the relative frequency (never/sometimes/always) a household (a) isolates a sick child from others in the household, (b) keeps the sick child out of school/daycare, (c) stops the child's social activities, (d) has a parent stay home to care for the child, and (e) has another adult care for the child. Marital status is non-significant for isolation practices but is significant in caregiving. Married individuals are 25% more likely to report a parent always staying home with a sick child. Males are more likely to report never isolating a sick child (6%, 3%, and 2% for actions a, b, and c, respectively) and 3% more likely to never have a parent stay home. Individuals knowledgeable about the disease are 10% more likely to always keep a sick child home from school/daycare. Parents are 27% more likely to always stay home with an infant. Individuals who had never worn masks (before the survey) are less likely to isolate a child within the household, but do not act significantly differently with respect to school/daycare.


An appraisal of end-of-life care in persons with chronic kidney disease dying in hospital wards.
To review end-of-life care provided by renal healthcare professionals to hospital in-patients with chronic kidney disease, and their carers, over a 12-month period in Northern Ireland. Retrospective review of 100 patients. Mean age at death was 72 years (19-95) and 56% were male. Eighty three percent of patients had a 'Not For Attempted Resuscitation' order during their last admission and this was implemented in 42%. Less than 20% of all patients died in a hospital ward. No patients had an advanced care plan, although 42% had commenced the Liverpool Care Pathway for the Dying Patient. Patients suffered excessive end-of-life symptoms. In addition, there was limited documentation of carer involvement and carer needs were not formally assessed. End-of-life care for patients with advanced chronic renal disease can be enhanced. There is significant variation in the recording of discussions regarding impending death and little preparation. There is poor recording of the patients' wishes regarding death. Those with declining functional status, including those frequently admitted to hospital require holistic assessment regarding end-of-life needs. More effective communication between the patient, family and multi-professional team is required for patients who are dying and those caring for them.


Tracking the toll of kidney disease.
Since the discovery of the Toll-like receptors and their crucial role as modulators of innate immunity, there has been increasing appreciation of their role in human health and disease. Toll-like receptor signaling is critical in defending against invading microorganisms, but sustained receptor activation is also implicated in the pathogenesis of inflammatory diseases. Here we review the role of Toll-like receptors and their endogenous ligands in various renal diseases, particularly their activation in the inflammatory response of ischemic kidney injury, organ transplantation, and immune-mediated glomerulonephritis.


[Surgical treatment of acute conditions of Crohn disease].
A conservative attitude to surgical treatment of Crohn's disease may endanger patients, lives, especially in acute situations. Indications for emergency operation and intraoperative management are subject to special rules. Resection should be minimal but terminated in a marcospically disease-free area. In case of performation, resection is mandatory; mere sewing closed is inadequate. Subtotal colectomy should be performed in cases of toxic megacolon. Abscesses should be drained using a pig-tail catheter; if the abscesses do not heal, surgery is necessary.


Pediatric haematopoiesis and related malignancies.
Survival after acute paediatric (0-14 years), adolescent (15-19 years) and young adult (20-39 years) leukaemia has improved substantially over the last five decades, particularly for acute lymphoblastic leukaemia (ALL) and acute promyelocytic leukaemia. This progress represents one of the most successful achievements in the history of medicine and has been attributed to the development of effective chemotherapy regimens, improvement in supportive care, better risk stratification, use of targeted therapies, and advances in haematopoietic stem cell transplantation. Recent studies have revealed improvement in survival over time for all age groups and subtypes of leukaemia. However, these outcomes varied widely by age and are associated with sociodemographic and clinical factors. The present review concludes that survival and early death after acute leukaemia has greatly improved among young patients. However, inequalities in outcomes remain and are likely a result of multiple factors.


A palladium doped 1T-phase molybdenum disulfide-black phosphorene two-dimensional van der Waals heterostructure for visible-light enhanced electrocatalytic hydrogen evolution.
The electrocatalytic hydrogen evolution reaction (HER) is a green chemistry route for sustainable energy production. Compared to 2H-phase molybdenum disulfide (MoS2), the 1T-phase MoS2 (1T-MoS2) has higher theoretical activity and faster charge transfer kinetics, but the HER performance of 1T-MoS2 is commonly hindered by limited active edge/defect as well as poor structural stability. Herein, we synthesize a well-defined 2D vdW heterostructure composed of Pd doped 1T-MoS2 and black phosphorus (BP) nanosheets via electrostatic self-assembly. The spontaneous Pd doping under mild reaction conditions could introduce catalytically active sulfur vacancies in MoS2 without triggering a wide range of 1T to 2H phase transformation. The hetero-interfacial charge transfer from BP to Pd-1T-MoS2 can effectively improve the intrinsic activity of Pd-1T-MoS2 with a relatively low S vacancy concentration and simultaneously stabilize the 1T-phase structure. Due to the wide-range light absorption of BP nanosheets and the high carrier mobilities of 2D materials, the HER activity of the obtained Pd-1T-MoS2/BP could be further enhanced under ≥420 nm visible light illumination.


Calcium at the cell wall-cytoplast interface.
Attention is given to the role of Ca(2+) at the interface between the cell wall and the cytoplast, especially as seen in pollen tubes. While the cytoplasm directs the synthesis and deposition of the wall, it is less well appreciated that the wall exerts considerable self control and influences activities of the cytoplasm. Ca(2+) participates as a crucial factor in this two way communication. In the cytoplasm, a [Ca(2+)] above 0.1 microM, regulates myriad processes, including secretion of cell wall components. In the cell wall Ca(2+), at 10 microM to 10 mM, binds negative charges on pectins and imparts structural rigidity to the wall. The plasma membrane occupies a pivotal position between these two compartments, where selective channels regulate influx of Ca(2+), and specific carriers pump the ion back into the wall. In addition we draw attention to different factors, which either respond to the wall or are present in the wall, and usually generate elevated [Ca(2+)] in the cytoplasm. These factors include: (i) stretch activated channels; (ii) calmodulin; (iii) annexins; (iv) wall associated kinases; (v) oligogalacturonides; and (vi) extracellular adenosine 5'-triphosphate. Together they provide evidence for a rich and multifaceted system of communication between the cytoplast and cell wall, with Ca(2+) as a carrier of information.


Enhanced in vitro procoagulant and antifibrinolytic potential of superactive variants of recombinant factor VIIa in severe hemophilia A.
Recombinant coagulation factor VIIa (rFVIIa) is generally accepted for treatment of patients with inhibitor-complicated hemophilia. Recently, rFVIIa variants with a specific enhancement of the tissue factor (TF)-independent proteolytic activity have been described. The procoagulant and [thrombin-activatable fibrinolysis inhibitor (TAFI)-dependent] antifibrinolytic potentials of two superactive rFVIIa variants were compared with those of wild-type rFVIIa in a hemophilic setting. Clot lysis assays were performed in plasma from six patients with inhibitor-complicated hemophilia A or in antibody-induced factor VIII-deficient platelet-rich plasma in the presence of different concentrations of the rFVIIa variants. In the plasma model, M298Q-rFVIIa had a moderately increased procoagulant and antifibrinolytic potential, whereas V158D/E296V/M298Q/K337A-rFVIIa had a strongly increased procoagulant and antifibrinolytic activity compared with wild-type rFVIIa. The increased antifibrinolytic potential of the rFVIIa variants was completely dependent on enhancement of TAFI activation. In the platelet-rich plasma model similar results were obtained. The presence of TF was mandatory for clot formation in the absence of exogenous rFVIIa. At lower concentrations of rFVIIa (wild-type or variants), clot formation did occur but was significantly slower when TF activity was blocked. At increasing concentrations of rFVIIa, clotting times were no longer dependent on TF. In conclusion, should a TF-independent mechanism be involved in the efficacy of rFVIIa in patients with hemophilia, the superactive rFVIIa variants studied here might be clinically advantageous, as both procoagulant and antifibrinolytic potencies are significantly enhanced compared with those of wild-type rFVIIa. This ought to result in more efficient cessation of bleeding episodes and reduced risk of rebleeding.


Canopy CO2 enrichment permits tracing the fate of recently assimilated carbon in a mature deciduous forest.
How rapidly newly assimilated carbon (C) is invested into recalcitrant structures of forests, and how closely C pools and fluxes are tied to photosynthesis, is largely unknown. A crane and a purpose-built free-air CO2 enrichment (FACE) system permitted us to label the canopy of a mature deciduous forest with 13C-depleted CO2 for 4 yr and continuously trace the flow of recent C through the forest without disturbance. Potted C4 grasses in the canopy ('isometers') served as a reference for the C-isotope input signal. After four growing seasons, leaves were completely labelled, while newly formed wood (tree rings) still contained 9% old C. Distinct labels were found in fine roots (38%) and sporocarps of mycorrhizal fungi (62%). Soil particles attached to fine roots contained 9% new C, whereas no measurable signal was detected in bulk soil. Soil-air CO2 consisted of 35% new C, indicating that considerable amounts of assimilates were rapidly returned back to the atmosphere. These data illustrate a relatively slow dilution of old mobile C pools in trees, but a pronounced allocation of very recent assimilates to C pools of short residence times.


Estimating completeness of birth registration in South Africa, 1996 - 2011.
To estimate the completeness of live birth registration through South Africa's civil registration and vital statistics system between 1996 and 2011. The number of births registered by the civil registration and vital statistics system was compared with independent estimates of the true number of births derived using: (i) the reverse survival method applied to 2011 census data; (ii) the application of estimated age-specific fertility rates to population estimates from censuses and surveys; and (iii) data from the public-sector district health information system. In 1996, an estimated 25% of births were registered within the calendar year of birth and 33% were registered before the end of the subsequent calendar year. By 2008, 76% of registrations occurred within the calendar year of birth, 84% occurred by the end of the following year and 90% occurred before the child's fifth birthday. These improvements were seen in all provinces and differences in completeness between provinces narrowed markedly. Improvements in the completeness of registration coincided with government efforts to strengthen the system, new legislation on vital registration and the introduction of child support grants, which required birth certificates. Interprovincial migration of children influenced the completeness of registration in affected provinces. There was some terminological confusion among government agencies on defining the timeliness of registration and the year of birth. The completeness of birth registration in South Africa increased rapidly between 1996 and 2004. To allow international comparison, the method for measuring the completeness of birth registration needs to be standardized.


The pathophysiology of brain injury: understanding innovative drug therapies.
The advancement of acute care for persons with brain injury is predicated on the further clarification of the mechanical and biochemical processes that are begun at the time of the injury. Attempts to enhance survival and functional outcome have led to cerebral perfusion and intracranial pressure management techniques. In addition, novel neuroprotective pharmacotherapeutic strategies have been borne from an ever growing knowledge of the degradative biochemical injury that occurs subsequent to the initial insult. The link between the acute and rehabilitation phases of care continues to grow closer, thus compelling the rehabilitationist to be aware of the potential effect these processes and treatments have on outcome.


Perinatal factors and the developmental outcome of preterm infants.
To determine the developmental outcome of sick preterm infants, a retrospective analysis of 101 preterm infant survivors, cared for a teaching hospital's neonatal intensive care unit, was conducted. Information regarding the one-year developmental outcome was compared with significant perinatal factors: birth weight, gestational age, neonatal mortality index, respiratory distress syndrome (RDS) severity, and high-risk pregnancy factors. Eighteen percent of all infants studied had developmental delays indicating an improved prognosis for preterm infants. Severe RDS survivors had the greatest incidence of developmental delays and the most high-risk pregnancy histories.


Lower risk of Alzheimer's disease mortality with exercise, statin, and fruit intake.
Whether lifestyle affects Alzheimer's disease (AD) risk remains controversial. Test whether exercise, diet, or statins affect AD mortality in 153,536 participants of the National Runners' and Walkers' Health Studies. Hazard ratios (HR) and 95% confidence intervals (95% CI) were obtained from Cox proportional hazard analyses for AD mortality versus baseline metabolic equivalent (MET) hours/d of exercise energy expenditure (1 MET equals approximately 1 km run), statin use, and fruit intake when adjusted for age, race, gender, education, and exercise mode. The National Death Index identified 175 subjects who died with AD listed as an underlying (n = 116) or contributing (n = 59) cause of death during 11.6-year average mortality surveillance. Relative to exercising <1.07 MET-hours/d, AD mortality was 6.0% lower for 1.07 to 1.8 MET-hours/d (HR: 0.94, 95% CI: 0.59 to 1.46, p = 0.79), 24.8% lower for 1.8 to 3.6 MET-hours/d (HR: 0.75, 95% CI: 0.50 to 1.13, p = 0.17), and 40.1% lower for ≥3.6 MET-hours/d (HR: 0.60, 95% CI: 0.37 to 0.97, p = 0.04). Relative to non-use, statin use was associated with 61% lower AD mortality (HR: 0.39, 95% CI: 0.15 to 0.82, p = 0.01), whereas use of other cholesterol-lowering medications was not (HR: 0.78, 95% CI: 0.40 to 1.38, p = 0.42). Relative to <1 piece of fruit/day, consuming 2 to 3 pieces daily was associated with 39.7% lower AD mortality (HR: 0.60, 95% CI: 0.39 to 0.91, p = 0.02) and ≥3 pieces/day with 60.7% lower AD mortality (HR: 0.39, 95% CI: 0.22 to 0.67, p = 0.0004). Exercise, statin, and fruit intake were associated with lower risk for AD mortality.


Orlistat: a second look. At best, a minor adjunct to dietary measures.
(1) Treatments for obesity are disappointing, and none has yet shown an effect on morbidity or mortality. Non drug treatments have not been assessed adequately. Long-term maintenance of weight loss requires long-term patient management. (2) Orlistat, a gastrointestinal lipase inhibitor, is licensed in Europe for the treatment of obesity, in combination with a low-calorie diet. (3) The risk-benefit ratio of orlistat could not be estimated from the initial assessment file in 1999. There were fears over a possible increase in the risk of breast cancer. (4) Few new efficacy data have been obtained since. Medium-term trials (12-24 months) show that orlistat (120 mg three times a day), combined with dietary intervention, has a minor supplementary effect on weight loss (-3.5 kg on average). (5) A meta-analysis of three of the four available comparative trials lasting two years failed to conclude that orlistat prevents the onset of type 2 diabetes. Likewise, there is no firm evidence that orlistat lowers cardiovascular morbidity or mortality. (6) Orlistat frequently has gastrointestinal adverse effects, and case reports of hypertension have been published. Orlistat probably interacts with a number of other drugs. (7) Follow-up of nearly 8,000 women for only a few years showed no increase in the incidence of breast cancer on orlistat. (8) In practice, dietary intervention and risk factor management remain the cornerstones in the management of obesity. Orlistat is only a minor, optional and temporary aid, although it appears so far to have no serious adverse effects.


Limbic irritability and chaotic neural response during conflicting stroop task in the patients with unipolar depression.
According to recent findings activation of anterior cingulate cortex (ACC) is related to detecting cognitive conflict. This conflict related activation elicits autonomic responses which can be assessed by psychophysiological measures such as heart rate variability calculated as beat to beat R-R intervals (RRI). Recent findings in neuroscience also suggest that cognitive conflict is related to specific nonlinear chaotic changes of the signal generated by neural systems. The present study used Stroop word-color test as an experimental approach to psychophysiological study of cognitive conflict in connection with RRI measurement, psychometric measurement of limbic irritability (LSCL-33), depression (BDI-II) and calculation of largest Lyapunov exponents in nonlinear data analysis of RRI time series. Significant correlation 0.61 between largest Lyapunov exponents and LSCL-33 found in this study indicate that a defect of neural inhibition during conflicting Stroop task is closely related to limbic irritability. Because limbic irritability is probably closely related to epileptiform abnormalities in the temporolimbic structures, this result might represent useful instrument for indication of anticonvulsant treatment in depressive patients who are resistant to antidepressant medication.


Dose Comparison And Side Effect Profile Of Metformin Extended Release Versus Metformin Immediate Release.
Diabetes Mellitus type 2 is very common worldwide, with majority of cases in Asia Pacific region. Metformin is the first line therapy, along with lifestyle modification for all type 2 diabetics as recommended by ADA. Metformin is available as conventional Metformin Immediate Release (MIR) and Metformin Extended Release (MXR). Metformin XR has better gastrointestinal tolerability and fewer side effects as compared to Metformin IR, with similar efficacy regarding anti-hyperglycaemic effects. The objective of this study was to determine whether metformin XR is as effective as Metformin IR in maintaining glycaemic control at equivalent doses or even at reduced doses; and to compare the side effect profile of the two preparations. This randomized control trial was conducted at Medical and Endocrinology OPD of Jinnah Hospital Lahore. A total of 90 type 2 diabetics of both genders were recruited using nonprobability purposive sampling. Patients were randomized into 3 groups; 30 in each group. Group 1 received Metformin IR 1000 mg twice daily; group 2 received metformin XR 1000 mg twice daily; and group 3 received metformin XR 500 mg twice daily, for a period of three months. HbA1c was done at baseline and after three months of therapy along with fasting blood sugars and random blood sugars weekly. The mean age of patients was 46±9 years, with 54% being males and 46% being females. There was a 1% reduction in HbA1c in group 1, 0.7% reduction in group 2 and only 0.4% reduction in group 3. Similarly, all three therapies were equally effective in reducing blood sugar fasting and blood sugar random at three months. Side effects namely diarrhoea, dyspepsia and flatulence were greatest with Metformin IR (40%) but less than half with Metformin XR at equivalent dose and negligible at half the dose. All three Metformin groups were effective in reduction of HbA1C and glycaemic control clinically and there is no statistical difference in HbA1c reduction among groups at three months.


Data analysis of 36 cases with intraductal papillary mucinous neoplasm of the pancreas for their clinicopathological features, diagnosis, and treatment.
Intraductal papillary mucinous neoplasm (IPMN) is a rare pancreatic cystic neoplasm, accounting for 1% of all exocrine pancreatic neoplasms. This study aimed to summarize the clinicopathological and biological behaviors, as well as the experience in diagnosis and treatment of IPMN. Clinicopathological data were collected from 36 cases with IPMN who were treated in Department of General Surgery, Peking University Third Hospital from May 2001 to July 2011. The 36 cases of IPMN patients included 27 males and 9 females (M:F = 3:1). The age of patients ranged from 52 to 78 years, with an average of 67.3 years. Regarding tumor location, 20 tumors were located in pancreatic head, 3 in pancreatic neck, 10 in pancreatic body and tail, and 3 in the whole pancreas. All the 36 cases underwent surgical treatment, with 13 cases of pancreaticoduodenectomy, 3 cases of middle pancreatectomy, 7 cases of tumor resection plus pancreaticojejunostomy, 3 cases of distal pancreatectomy, 7 cases of distal pancreatectomy plus spleen resection, and 3 cases of total pancreaticoduodenectomy. Of the 36 patients, 9 patients underwent the operations under laparoscopy. The 36 cases included main duct type (14 cases, 38.9%), branch duct type (10 cases, 27.7%), and mixed duct type (12 cases, 33.3%). Pathologically, of the 36 cases, there were 7 IPMN adenomas, 11 borderline IPMNs, 6 IPMN with carcinomas in situ, and 12 IPMNs with invasive carcinomas. All the 36 cases were followed up. During an average of 42 months follow-up period (26-129 months), no recurrence occurred. IPMN, which primarily occurs in male, is a low-grade malignancy which may involve any part of the pancreas, with specific clinicopathological features. IPMN is a different malignancy type from pancreatic ductal carcinoma. Imaging and laboratory examination are helpful for the diagnosis and differential diagnosis. The prediction of invasive IPMN is still difficult. Surgical resection is recommended as the first choice of treatment. Aggressive and proper operation procedure produces better prognosis. Long-term follow-up is necessary for patients after operation. Laparoscopic distal pancreatectomy is a feasible and safe procedure for the indicated patients.


End-to-End versus End-to-Side Microvascular Anastomosis: A Meta-analysis of Free Flap Outcomes.
Background Optimal outcomes in microsurgery have been attributed to a range of factors, with performing of end-to-end (ETE) versus end-to-side (ETS) influencing anastomotic complications and flap outcomes. Methods A systematic review of the literature and meta-analysis was undertaken to evaluate the relative risks of anastomotic complications with ETE versus ETS approaches, for arterial and venous anastomoses looking at risk ratios (RRs) for thrombosis and overall flap failure. Results RRs of thrombosis and flap failure in ETS versus ETE venous anastomosis groups were 1.30 (95% confidence interval [CI]: 0.53-3.21) and 1.50 (95% CI: 0.85-2.67), respectively. The RRs of thrombosis and flap failure in ETS versus ETE arterial anastomosis groups were 1.04 (95% CI: 0.32-3.35) and 1.04 (95% CI: 0.72-1.48), respectively. Conclusion Differences in rates of thrombosis and flap failure between ETE and ETS venous and arterial anastomoses are marginal and nonsignificant. As such, the type of anastomotic technique is best decided on a case-by-case basis, dependent on anatomical, surgical, and patient factors.


Mortality and Cumulative Kidney Score are Associated with Transient and Persistent Acute Kidney Injury in Septic Patients: A Retrospective Study Based on MIMIC-IV.
Acute kidney injury (AKI) is frequently caused by sepsis. Recently, the Acute Disease Quality Initiative (ADQI) workgroup further classified AKI as transient or persistent. Oliguria and increased serum creatinine represent two different kinds of renal impairment. The aim of the study was to assess mortality and cumulative AKI score associated with transient and persistent AKI in septic patients. Septic patients were stratified according to the presence and AKI development (considered persistent when remaining >48 h) were included. An adjusted logistic regression model was used to determine hospital mortality. In addition, we calculated an AKI score by combining both Kidney Disease: Improving Global Outcomes (KDIGO) criteria of urine output and creatinine AKI stages. The relationship between the cumulative AKI score and persistent AKI was further examined using the logistic regression model and receiver operating characteristic (ROC) curve analysis. 12928 septic patients were enrolled in the study. AKI occurred in 73.7% of septic patients, in 39.5% was transient and in 60.5% was persistent. Patients with persistent AKI had higher severity scores and more severe renal dysfunction upon admission. Persistent AKI, but not transient AKI, was associated with increased intensive care units (ICUs) and hospital mortality. Then we found that the cumulative AKI score was associated with an increased risk of persistent AKI. This association was consistent across three original KDIGO severity stages and subgroup analyses. It was found that persistent AKI was independently associated with mortality in septic patients. Furthermore, serum creatinine and urine output criteria had cumulative effects on KDIGO AKI staging and provided more information about the relationship between AKI and outcomes.


Glaucoma Features in an East African Population: A 6-Year Cohort Study of Older Adults in Nakuru, Kenya.
Glaucoma is a leading cause of blindness in people of African descent. Minimal data is available from African population-based cohort studies. The primary aims of this study were to describe the normative distribution of glaucoma features to enable glaucoma classification and to assess risk factors for those with glaucoma at follow-up among people aged 50 years and above in Kenya. Random cluster sampling with probability proportionate to size was used to select a representative cross-sectional sample of adults aged 50 years and above in 2007 to 2008 in Nakuru District, Kenya. A 6-year follow-up was undertaken in 2013 to 2014. Comprehensive ophthalmic examination included visual acuity, digital retinal photography, visual fields, intraocular pressure, optical coherence tomography, and independent grading of optic nerve images. We report glaucoma features, prevalence and predictors for glaucoma based on the International Society for Geographical & Epidemiological Ophthalmology (ISGEO) criteria. Measures were estimated using a Poisson regression model and including inverse-probability weighting for loss to follow-up. At baseline, 4414 participants aged 50 years and above underwent examination. Anterior chamber optical coherence tomography findings: mean anterior chamber angle of 36.6 degrees, mean central corneal thickness of 508.1 μm and a mean anterior chamber depth of 2.67 mm. A total of 2171 participants were examined at follow-up. The vertical cup to disc ratio distribution was 0.7 and 0.8 at the 97.5th and 99.5th percentiles, respectively. A total of 88 (4.3%, 95% confidence interval, 3.5%-5.9%) of participants at follow-up had glaucoma consistent with ISGEO criteria. A relative afferent pupillary defect and raised intraocular pressure were associated with the diagnosis. Glaucoma is a public health challenge in low-resource settings. Research into testing and treatment modalities in Africa is needed.


MYC-driven aggressive B-cell lymphomas: biology, entity, differential diagnosis and clinical management.
MYC, a potent oncogene located at chromosome locus 8q24.21, was identified initially by its involvement in Burkitt lymphoma with t(8;14)(q24;q32). MYC encodes a helix-loop-helix transcription factor that accentuates many cellular functions including proliferation, growth and apoptosis. MYC alterations also have been identified in other mature B-cell neoplasms and are associated with aggressive clinical behavior. There are several regulatory factors and dysregulated signaling that lead to MYC up-regulation in B-cell lymphomas. One typical example is the failure of physiological repressors such as Bcl6 or BLIMP1 to suppress MYC over-expression. In addition, MYC alterations are often developed concurrently with other genetic alterations that counteract the proapoptotic function of MYC. In this review, we discuss the physiologic function of MYC and the role that MYC likely plays in the pathogenesis of B-cell lymphomas. We also summarize the role MYC plays in the diagnosis, prognostication and various strategies to detect MYC rearrangement and expression.


Most older pedestrians are unable to cross the road in time: a cross-sectional study.
to compare walking speed in the UK older population with the speed required to utilise pedestrian crossings (≥1.2 m/s), and determine health and socio-demographic associations with walking impairment. cross-sectional study using Health Survey for England 2005 data. private households in England. random population sample of 3,145 adults (1,444 men) aged ≥65 years. walking speed was assessed by timing a walk of 8 feet at normal pace. Walking impairment was defined as walking speed <1.2 m/s or non-participation in the test due to being unsafe or unable. the mean walking speed was 0.9 m/s in men and 0.8 m/s in women; 84% of men and 93% of women ≥65 years had walking impairment. Female gender, increasing age, lower socio-economic status, poorer health and lower grip strength were predictors of walking impairment. most older adults either cannot walk 8 feet safely or cannot walk fast enough to use a pedestrian crossing in the UK. The health impacts on older adults include limited independence and reduced opportunities for physical activity and social interaction. An assumed normal walking speed for pedestrian crossings of 1.2 m/s is inappropriate for older adults and revision of these timings should be considered.


[Short-term chemotherapy of tuberculosis. Cooperative French trial].
A cooperative french trial in the treatment of pulmonary tuberculosis has compared the efficacy and the tolerance of daily antituberculous regimes, one of short duration of 18 weeks (HRSZ/HRZ), the other of standard duration of 9 months (HRE). Of 204 patients included in the trial 180 were analysed. No significant difference was found between the two regimes regarding either biological tolerance or clinical outcome. Four relapses were seen within 24 months of the onset of treatment, two in each regime, which shows that 18 weeks treatment is ethically acceptable. Such short course therapy is useful in those patients who would sometimes find prolonged therapy difficult or would be likely to abandon treatment prematurely.


Matrix metalloproteinase 9 activity enhances host susceptibility to pulmonary infection with type A and B strains of Francisella tularensis.
A striking feature of pulmonary infection with the Gram-negative intracellular bacterium Francisella tularensis, a category A biological threat agent, is an intense accumulation of inflammatory cells, particularly neutrophils and macrophages, at sites of bacterial replication. Given the essential role played by host matrix metalloproteinases (MMPs) in modulating leukocyte recruitment and the potentially indiscriminate destructive capacity of these cells, we investigated whether MMP-9, an important member of this protease family released by neutrophils and activated macrophages, plays a role in the pathogenesis of respiratory tularemia. We found that F. tularensis induced expression of MMP-9 in FVB/NJ mice and that the action of this protease is associated with higher bacterial burdens in pulmonary and extrapulmonary tissues, development of more extensive histopathology predominated by neutrophils, and increased morbidity and mortality compared with mice lacking MMP-9 (MMP-9(-/-)). Moreover, MMP-9(-/-) mice were able to resolve infection with either the virulence-attenuated type B (live vaccine strain) or the highly virulent type A (SchuS4) strain of F. tularensis. Disease resolution was accompanied by diminished leukocyte recruitment and reductions in both bacterial burden and proinflammatory cytokine production. Notably, neutrophilic infiltrates were significantly reduced in MMP-9(-/-) mice, owing perhaps to limited release of Pro-Gly-Pro, a potent neutrophil chemotactic tripeptide released from extracellular matrix through the action of MMP-9. Collectively, these results suggest that MMP-9 activity plays a central role in modulating the clinical course and severity of respiratory tularemia and identifies MMPs as novel targets for therapeutic intervention as a means of modulating neutrophil recruitment.


Adaptive Natural Killer Cells Integrate Interleukin-18 during Target-Cell Encounter.
Human cytomegalovirus (HCMV) infection induces adaptations in the natural killer (NK)-cell compartment. Expanded subsets of adaptive NK cells display potent effector functions against cellular targets, despite their apparent unresponsiveness to stimulation with classical dendritic cell-derived cytokines interleukin (IL)-12 and IL-18. However, it remains unclear whether adaptive NK cells have completely lost their ability to sense inflammation via IL-12 and IL-18 or whether these pro-inflammatory signals can be functionally integrated into defined contexts. Here, we demonstrate that adaptive NKG2C+ NK cells can be costimulated by the presence of pro-inflammatory cytokines during target cell-induced activation. Cytokine costimulation of adaptive NK cells resulted in elevated interferon (IFN)-gamma and tumor necrosis factor (TNF) production, which promoted protein expression of HLA class I and adhesion molecules as well as transcription of genes involved in antigen processing and antiviral states in endothelial bystander cells in vitro. We further show that IL-18 drove costimulation in functional assays and was sufficient for elevated cytokine production in the absence of IL-12. Hence, adaptive NKG2C+ NK cells-although poorly responsive to IL-12 and IL-18 as an isolated stimulus-integrate IL-18 as a costimulatory signal during target-cell encounter.


Hand-held echocardiography during complex electrophysiologic procedures.
Complex electrophysiologic (EP) procedures are time consuming and open to complications. Accurate and rapid recognition of cardiac pathologies is essential before, during, and immediately after such procedures. In this study, we aimed to compare hand-held echocardiography (HHE) with standard echocardiography (SE) to determine whether HHE can be used as a practical and reliable diagnostic tool during such procedures. One hundred consecutive patients undergoing complex EP procedures and catheter ablation were included in the study. All patients were evaluated with SE or HHE in terms of main cardiac pathologies at the beginning and immediately after the procedure. The diagnostic accuracy and evaluation time of both methods were compared at the beginning and after the procedure. The agreement between both methods was calculated. At the beginning and after the procedure, opening and evaluation times with HHE were significantly shorter than with SE (P<0.001 for all). There was significant agreement between the two methods in the diagnosis of cardiac pathologies (Agreement was 95% for minimal mild aortic regurgitation (AR), 99% for moderate/ severe AR, 93% for minimal/ mild mitral regurgitation (MR), 95% for moderate/ severe MR, 100% for pericardial effusion, and 100% for left ventricular thrombus at the beginning of the procedure). With the use of HHE during complex EP procedures, cardiac pathologies can be diagnosed with similar accuracy as SE. In addition, HHE has a significant advantage over SE in terms of time to diagnosis.


On the pleasantness of a haptic stimulation: how different textures can be recognized through heart rate variability nonlinear analysis.
The hedonic attributes of cutaneous elicitation play a crucial role in everyday life, influencing our behavior and psychophysical state. However, the correlation between such a hedonic aspect of touch and the Autonomic Nervous System (ANS)-related physiological response, which is intimately connected to emotions, still needs to be deeply investigated. This study reports on caress-like stimuli conveyed to the forearm of 32 healthy subjects through different fabrics actuated by a haptic device, which can control both the strength (i.e. the normal force exerted by the fabric) and the velocity of the elicitation. The mimicked caresses were elicited with a fixed force of 6 N, two levels of velocity of 9.4 mm/sec and 65 mm/sec, and four different fabrics with different textures: burlap, hemp, velvet and silk. Participants were asked to score the caress-like stimuli in terms of arousal and valence through a self-assessment questionnaire. Heartbeat data related to the perceived most pleasant (silk) and unpleasant (burlap) fabrics were used as an input to an automatic pattern recognition procedure. Accordingly, considering gender differences, support vector machines using features extracted from linear and nonlinear heartbeat dynamics showed a recognition accuracy of 84.38% (men) and 78.13% (women) while discerning between burlap and silk elicitations at the higher velocity. Results suggest that the fabrics used for the caress-like stimulation significantly affect the nonlinear cardiovascular dynamics, also showing differences according to gender.


Identification of the TFII-I family target genes in the vertebrate genome.
GTF2I and GTF2IRD1 encode members of the TFII-I transcription factor family and are prime candidates in the Williams syndrome, a complex neurodevelopmental disorder. Our previous expression microarray studies implicated TFII-I proteins in the regulation of a number of genes critical in various aspects of cell physiology. Here, we combined bioinformatics and microarray results to identify TFII-I downstream targets in the vertebrate genome. These results were validated by chromatin immunoprecipitation and siRNA analysis. The collected evidence revealed the complexity of TFII-I-mediated processes that involve distinct regulatory networks. Altogether, these results lead to a better understanding of specific molecular events, some of which may be responsible for the Williams syndrome phenotype.


Coronal sealing ability of three sectional obturation techniques--SimpliFill, Thermafil and warm vertical compaction--compared with cold lateral condensation and post space preparation.
The purpose of this study was to evaluate the effect post space preparation has on the coronal seal of root canals obturated with cold lateral condensation of gutta-percha compared with the corsonal sealing ability of three sectional obturation techniques not requiring post space preparation. Sixty-eight human maxillary central incisors were divided equally into four groups: cold lateral condensation (Group I), SimpliFill (Group II), Thermafil (Group III) and warm vertical compaction (Group IV). After coronal flaring, all four groups were cleaned and shaped with Lightspeed rotary instruments to a size 60 master apical rotary. After obturation Peeso Reamers were used to create a post space for Group I, while Groups 2, 3 and 4 incorporated the post space in the obturation (sectional technique) and did not require making a post space after obturation. The teeth were then stored in 100% humidity for 1 week and then kept in rhodamine B fluorescent dye for 3 weeks. The teeth were then split open, and the linear dye penetration from a coronal to apical direction (coronal seal) was evaluated with a fluorescent light microscope. Statistical analysis showed that Group I (cold lateral condensation followed by post space made with Peeso Reamers) leaked significantly more (P < 0.05) than the remaining three sectional obturation groups. It was concluded that stresses generated during post space preparation might be detrimental to the seal obtained by the obturation. Sectional obturations with their superior sealing ability offer a viable alternative.


Optimal climate for large trees at high elevations drives patterns of biomass in remote forests of Papua New Guinea.
Our ability to model global carbon fluxes depends on understanding how terrestrial carbon stocks respond to varying environmental conditions. Tropical forests contain the bulk of the biosphere's carbon. However, there is a lack of consensus as to how gradients in environmental conditions affect tropical forest carbon. Papua New Guinea (PNG) lies within one of the largest areas of contiguous tropical forest and is characterized by environmental gradients driven by altitude; yet, the region has been grossly understudied. Here, we present the first field assessment of aboveground biomass (AGB) across three main forest types of PNG using 193 plots stratified across 3,100-m elevation gradient. Unexpectedly, AGB had no direct relationship to rainfall, temperature, soil, or topography. Instead, natural disturbances explained most variation in AGB. While large trees (diameter at breast height > 50 cm) drove altitudinal patterns of AGB, resulting in a major peak in AGB (2,200-3,100 m) and some of the most carbon-rich forests at these altitudes anywhere. Large trees were correlated to a set of climatic variables following a hump-shaped curve. The set of "optimal" climatic conditions found in montane cloud forests is similar to that of maritime temperate areas that harbor the largest trees in the world: high ratio of precipitation to evapotranspiration (2.8), moderate mean annual temperature (13.7°C), and low intra-annual temperature range (7.5°C). At extreme altitudes (2,800-3,100 m), where tree diversity elsewhere is usually low and large trees are generally rare or absent, specimens from 18 families had girths >70 cm diameter and maximum heights 20-41 m. These findings indicate that simple AGB-climate-edaphic models may not be suitable for estimating carbon storage in forests where optimal climate niches exist. Our study, conducted in a very remote area, suggests that tropical montane forests may contain greater AGB than previously thought and the importance of securing their future under a changing climate is therefore enhanced.


Tissue polypeptide antigen and carcinoembryonic antigen as tumor markers in lung cancer.
Simultaneous measurements of serum tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA) were conducted on 106 patients with bronchogenic carcinoma and 19 patients with inflammatory pulmonary disease. The distribution of cell types was 63 with adenocarcinoma, 26 with epidermoid carcinoma, 9 with small cell carcinoma, 4 with large cell carcinoma and 4 with adenosquamous carcinoma. There were 20 patients in stage 1, 6 in stage 2, 38 in stage 3 and 42 in stage 4 of their disease. The cut-off values of TPA and CEA were 110 U/L and 3 ng/ml, respectively. The diagnostic sensitivity of TPA and CEA was 61% (65/106) and 47% (50/106), respectively. The diagnostic specificity of TPA and CEA was 90% (17/19) and 95% (18/19), respectively. In combination with TPA and CEA the diagnostic sensitivity and specificity to indicate at least one positive result was 73% and 84%, respectively. Both TPA and CEA revealed significantly higher mean serum levels in stage 4 patients than in stage 1 patients. The intermarker correlation between the serum levels of TPA and CEA was low in this study. Serial measurements of serum TPA after surgical resection were found to be useful in the monitoring of recurrence of tumors.


Comparative evaluation of conventional versus endoscopic septoplasty for limited septal deviation and spur.
To compare the procedure, results and complications of conventional septoplasty with those of endoscopic septoplasty, in cases of limited septal deviation and septal spurs. Prospective study; interventional type; randomised block design; comparative clinical trial. We included in the study 80 patients presenting with limited septal deviation, septal spur with nasal obstruction, or deviated septum with septal correction was required in order to access the ostio-meatal complex (OMC) for functional endoscopic sinus surgery. Of these 12 were children with septal deviation producing significant nasal obstruction. All patients were divided into two groups- with one undergoing conventional and the other endoscopic septoplasty. Post-operative assessment was carried out one month, three months and one to two years after the procedure. Post-operative complications such as haemorrhage, infraorbital oedema, nasal pain and in-patient hospital was slightly more in the conventional septoplasty group. No statistically significant difference was found between the conventional and endoscopic septoplasty groups, as assessed by subjective and objective evaluation.


Altered cortical gyrification patterns in panic disorder: deficits and potential compensation.
Abnormal gyrification patterns may reflect aberrant cortical connectivity during an early period of brain maturation. We here investigated anatomical distribution of cortical gyrification deficits underlying panic disorder and the relationships of these potential neurodevelopmental markers with panic symptom severity. High-resolution three-dimensional T1-weighted structural images were obtained from 23 patients with panic disorder and 33 matched healthy individuals. Local gyrification indices were measured in each genetically-based parcellated cortical subregion and regional gyrification patterns were compared between groups. Cortical areas in which gyrification patterns were associated with panic symptom severity were also determined. Significant reductions in cortical gyrification were observed in panic patients compared with healthy individuals, which were mainly distributed in the lateral brain extending from the fronto-parietal to the temporal areas. In contrast, hyper-gyrification in the posteromedial cortical regions which exert interconnecting roles in the default mode network, was associated with less severe panic symptoms. Post-hoc analysis for the inter-regional covariance of local gyrification indices revealed that interconnections of the posteromedial cortical regions with other cortical areas which belong to the default mode network were reduced in panic patients with severe symptoms relative to either less severe patients or healthy individuals. Our findings suggest not only substantial perturbation in cortical gyrification patterns in panic disorder but also potential contribution of integrated cortical folding pattern of the default mode network to alleviated panic severity.


Promoting research-based nursing: the nurse administrator's role.
As the practice of research increasingly becomes a part of the nursing profession, nurses must develop their ability to evaluate and incorporate the findings gained through the research process. This article reports the results of a survey aimed at determining problem areas existing among nursing staffs in understanding, accepting, and incorporating research findings. The report will help nursing administrators identify specific factors that inhibit the use of research findings and improve the conditions for incorporating research in their facilities.


In vivo photoacoustic monitoring using 700-nm region Raman source for targeting Prussian blue nanoparticles in mouse tumor model.
Photoacoustic imaging (PAI) is a noninvasive imaging tool to visualize optical absorbing contrast agents. Due to high ultrasonic resolution and superior optical sensitivity, PAI can be used to monitor nanoparticle-mediated cancer therapy. The current study synthesized Food and Drug Administration-approved Prussian blue (PB) in the form of nanoparticles (NPs) with the peak absorption at 712 nm for photoacoustically imaging tumor-bearing mouse models. To monitor PB NPs from the background tissue in vivo, we also developed a new 700-nm-region stimulated Raman scattering (SRS) source (pulse energy up to 200 nJ and repetition rate up to 50 kHz) and implemented optical-resolution photoacoustic microscopy (OR-PAM). The SRS-assisted OR-PAM system was able to monitor PB NPs in the tumor model with micrometer resolution. Due to strong light absorption at 712 nm, the developed SRS light yielded a two-fold higher contrast from PB NPs, in comparison with a 532-nm pumping source. The proposed laser source involved cost-effective and simple system implementation along with high compatibility with the fiber-based OR-PAM system. The study highlights the OR-PAM system in conjunction with the tunable-color SRS light source as a feasible tool to assist NP-mediated cancer therapy.


Computed tomography of neuraxis aspergillosis.
Aspergillosis of the neuraxis is a relatively rare entity. It is being encountered with increasing frequency due to the improved care and longevity of immunocompromised patients. Although there are more than 80 cases in the literature, we are aware of only five patients with reported computed tomographic (CT) findings. We report the CT findings of two additional cases.


Copper doped ceria porous nanostructures towards a highly efficient bifunctional catalyst for carbon monoxide and nitric oxide elimination.
Copper doped ceria porous nanostructures with a tunable BET surface area were prepared using an efficient and general metal-organic-framework-driven, self-template route. The XRD, SEM and TEM results indicate that Cu2+ was successfully substituted into the CeO2 lattice and well dispersed in the CeO2:Cu2+ nanocrystals. The CeO2:Cu2+ nanocrystals exhibit a superior bifunctional catalytic performance for CO oxidation and selective catalytic reduction of NO. Interestingly, CO oxidation reactivity over the CeO2:Cu2+ nanocrystals was found to be dependent on the Cu2+ dopants and BET surface area. By tuning the content of Cu2+ and BET surface area through choosing different organic ligands, the 100% conversion temperature of CO over CeO2:Cu2+ nanocrystals obtained from thermolysis of CeCu-BPDC nanocrystals can be decreased to 110 °C. The porous nanomaterials show a high CO conversion rate without any loss in activity even after five cycles. Furthermore, the activity of the catalysts for NO reduction increased with the increase of BET surface, which is in accordance with the results of CO oxidation.


Oxygen equilibrium studies on carp-human hybrid hemoglobins.
Hybrid hemoglobins have been made in which one chain is derived from human hemoglobin and the other from carp hemoglobin. Both hybrid hemoglobins show low cooperativity in oxygen binding. Hybrid I (alpha carp: beta human) has a very small Bohr effect, whereas hybrid II (alpha human: beta carp) has a Bohr effect nearly as large as that for human hemoglobin. Both hemoglobins have P50's more closely resembling carp hemoglobin than human hemoglobin in the region of pH 7, and for both hybrids, as for carp, cooperativity virtually disappears at acid and alkaline pHs. Since both hybrids are formed from chains derived from cooperative parent hemoglobins, it is difficult to account for the low cooperativity in terms only of the T-state salt bridges and the alpha 1-beta 2 contacts involved in the R-T switch region. We suggest that the F9 Ser in the carp beta-chain as well as alpha 1-beta 1 interactions is important in controlling the allosteric transitions in these hybrids.


Successful treatment of pneumatosis intestinalis with associated pneumoperitoneum and ileus with hyperbaric oxygen therapy.
Pneumatosis intestinalis (PI), or the presence of air in the bowel wall, is a rare disorder that is associated with a variety of underlying diseases, including connective tissue disorders. PI presents on a spectrum from asymptomatic to bowel obstruction and acute abdomen. In general, treatment of PI consists of treating the underlying disease. Both normobaric and hyperbaric oxygen have been used to treat PI directly. Here we report a symptomatic scleroderma-related case of PI that responded clinically to hyperbaric oxygen therapy. This report adds to a growing body of literature supporting a role for hyperbaric oxygen therapy in symptomatic PI.


Outcome of direct restorations placed within the general dental services in England and Wales (Part 1): variation by type of restoration and re-intervention.
It is the aim of this paper to consider the dental factors associated with the need for re-intervention on a restoration, such as the tooth position, size of cavity, and restoration material. Patients whose data were included in this study were those whose birthdays were included within a set of randomly selected dates, one of which was chosen in each possible year of birth. The restoration records consisted of all those records containing directly placed restorations which related to courses of treatment of patients 18 years or older with last date on the claim form after 31st December 1990, and with date of acceptance after September 1990 and before January 2002. For each tooth treated with a direct restoration the subsequent history of intervention on that tooth was consulted, and the next date of intervention, if any could be found in the extended data set, was obtained. Thus a data set was created of direct restorations with their dates of placement and their dates, if any, of re-intervention. Data for over 80,000 different adult patients were analyzed, of whom 46% were male and 54% female. A total of 503,965 tooth restoration occasions were obtained from the data over a period of eleven years. Single surface amalgam restorations were found to have the longest survival --58% at 10 years, and glass ionomer the shortest 38% at 10 years. Factors which were found to reduce restoration outcome included involvement of the incisal angle in composite restorations--this resulted in a reduction in median survival of around two years--and the placement of pins in a restoration. The presence of a root filling was also found to reduce the survival of restorations in the crown of the root filled tooth. Small amalgam restorations have longer survival times before re-intervention than large amalgam restorations such as MOD. Composite and glass ionomer restorations perform less well than amalgam restorations. Pin placement and root filling reduce the survival time of restorations.


TEMPO-Mediated Catalysis of the Sterically Hindered Hydrogen Atom Transfer Reaction between (C5Ph5)Cr(CO)3H and a Trityl Radical.
We have demonstrated the ability of TEMPO to catalyze H· transfer from (C5Ph5)Cr(CO)3H to a trityl radical (tris( p- tert-butylphenyl)methyl radical). We have measured the rate constant and activation parameters for the direct reaction, and for each step in the catalytic process: H· transfer from (C5Ph5)Cr(CO)3H to TEMPO and H· transfer from TEMPO-H to the trityl radical. We have compared the measured rate constants with the differences in bond strength, and with the changes in the Global Electrophilicity Index determined with high accuracy for each radical using state of the art quantum chemical methods. We conclude that neither is a major factor in determining the rates of these H· transfer reactions and that the effectiveness of TEMPO as a catalyst is largely the result of its relative lack of steric congestion compared to the trityl radical.


A new copper(II) complex based on 1-[(1H-benzotriazol-1-yl)meth-yl]-1H-1,2,4-triazole.
The title complex, tetra-aqua-{1-[(1H-benzotriazol-1-yl)meth-yl]-1H-1,2,4-triazole-κN(4)}(sulfato-κO)copper(II) sesquihydrate, [Cu(SO(4))(C(9)H(8)N(6))(H(2)O)(4)]·1.5H(2)O, is composed of one copper atom, one 1-[(2H-benzotriazol-1-yl)meth-yl]-1-H-1,2,4-triazole (bmt) ligand, one sulfate ligand, four coordin-ated water mol-ecules and one and a half uncoordinated water mol-ecules. The Cu(II) atom is six-coordinated by one N atom from a bmt ligand and five O atoms from the monodentate sulfate ligand and four water mol-ecules in a distorted octa-hedral geometry. In the crystal, adjacent mol-ecules are linked through O-H⋯O and O-H⋯N hydrogen bonds involving the sulfate anion and the coordin-ated and uncoordinated water mol-ecules into a three-dimensional network.


Understanding the mechanisms in accelerated drug reactions.
The purpose is to understand the underlying mechanisms of accelerated allergic reactions to drugs, defined here as reactions occurring between 1 and 24 h after drug intake. Recent publications have shown that accelerated reactions are T cell-mediated, although an IgE mechanism cannot be ruled out in some cases. Classification of allergic reactions to drugs is complex. Based on the time interval between drug administration and appearance of the clinical reaction, as well as the type of clinical symptoms, they can be classified as: immediate, typically appearing from less than 1 to 6 h after the last drug administration and nonimmediate, occurring at any time from 1 h after drug administration. Therefore, overlap exists in what the Levine classification defined as accelerated reactions, where clinical symptoms are mainly urticaria and less often exanthema and serum sickness-like reactions. The immunological mechanisms involved suggest that they are T cell-mediated reactions with a Th1 pattern, comprising increased production of IFNγ, TNFα, the chemokine CXCL9 and its corresponding receptor CXCR3. In most cases an IgE-mediated response is ruled out because of negative immediate skin test results, no detection of serum-specific IgE antibodies or tryptase, and no skin-secreted tryptase. However, an IgE-mediated response can be demonstrated in exceptional situations. Finally, serum sickness-like reactions have been reported as an immune complex-mediated accelerated reaction. However, the exact mechanism has not been confirmed.


Chromosome analysis in a human hepato-blastoma cell line producing alpha-fetoprotein.
Analysis of the chromosomes of a cloned human hepato-blastoma cell line, HUH-6-clone 5 by Q-, G- and C-banding revealed numerical and structural chromosome aberrations. The modal number of chromosomes was 49. Trisomies #12 and 20 were present in most of the cells, and 8q isochromosome was detected in all of the cells analyzed. High levels of alpha-fetoprotein production by this cell strain were also demonstrated.


Attempted Suicide Triggers in Thai Adolescent Perspectives.
The study goal was to describe attempted suicide triggers in Thai adolescents. A descriptive exploratory qualitative study approach was used utilizing in-depth interviews with twelve adolescents who had attempted suicide and six of their parents. Content analysis was conducted. Attempted suicide triggers were (1) severe verbal criticisms and expulsion to die by a significant family member, (2) disappointed and unwanted by boyfriend in first serious relationship, (3) unwanted pregnancy, and (4) mental illness leading to intense emotions and irresistible impulses. These attempted suicide triggers should be of concern and brought into suicide prevention management programs such as emotional management, effective communication for adolescents and family.


Absence of effects of contralateral group I muscle afferents on presynaptic inhibition of Ia terminals in humans and cats.
Crossed effects from group I afferents on reflex excitability and their mechanisms of action are not yet well understood. The current view is that the influence is weak and takes place indirectly via oligosynaptic pathways. We examined possible contralateral effects from group I afferents on presynaptic inhibition of Ia terminals in humans and cats. In resting and seated human subjects the soleus (SO) H-reflex was conditioned by an electrical stimulus to the ipsilateral common peroneal nerve (CPN) to assess the level of presynaptic inhibition (PSI_control). A brief conditioning vibratory stimulus was applied to the triceps surae tendon at the contralateral side (to activate preferentially Ia muscle afferents). The amplitude of the resulting H-reflex response (PSI_conditioned) was compared to the H-reflex under PSI_control, i.e., without the vibration. The interstimulus interval between the brief vibratory stimulus and the electrical shock to the CPN was -60 to 60 ms. The H-reflex conditioned by both stimuli did not differ from that conditioned exclusively by the ipsilateral CPN stimulation. In anesthetized cats, bilateral monosynaptic reflexes (MSRs) in the left and right L(7) ventral roots were recorded simultaneously. Conditioning stimulation applied to the contralateral group I posterior biceps and semitendinosus (PBSt) afferents at different time intervals (0-120 ms) did not have an effect on the ipsilateral gastrocnemius/soleus (GS) MSR. An additional experimental paradigm in the cat using contralateral tendon vibration, similar to that conducted in humans, was also performed. No significant differences between GS-MSRs conditioned by ipsilateral PBSt stimulus alone and those conditioned by both ipsilateral PBSt stimulus and contralateral tendon vibration were detected. The present results strongly suggest an absence of effects from contralateral group I fibers on the presynaptic mechanism of MSR modulation in relaxed humans and anesthetized cats.


Combined use of ultrasound and computed tomography in evaluation of intraabdominal pregnancy and fetal demise.
The ultrasonographic and CT findings in a case of intraabdominal pregnancy with fetal demise are presented. To our knowledge, this is the first published report of CT evaluation of intraabdominal fetal demise. The complementary role of CT and ultrasound in diagnosing intraabdominal fetal demise are discussed.