Shared and distinct alterations of white matter tracts in remitted and nonremitted patients with schizophrenia.
Patients with schizophrenia do not usually achieve remission state even after adequate antipsychotics treatment. Previous studies found significant difference in white matter integrity between patients with good outcomes and those with poor outcomes, but difference is still unclear at individual tract level. This study aimed to use a systematic approach to identify the tracts that were associated with remission state in patients with schizophrenia. We evaluated 91 patients with schizophrenia (remitted, 50; nonremitted, 41) and 50 healthy controls through diffusion spectrum imaging. White matter tract integrity was assessed through an automatic tract-specific analysis method to determine the mean generalized fractional anisotropy (GFA) values of the 76 white matter tract bundles in each participant. Analysis of covariance among the 3 groups revealed 12 tracts that were significantly different in GFA values. Post-hoc analysis showed that compared with the healthy controls, the nonremission group had reduced integrity in all 12 tracts, whereas the remission group had reduced integrity in only 4 tracts. Comparison between the remission and nonremission groups revealed 4 tracts with significant difference (i.e., the right fornix, bilateral uncinate fasciculi, and callosal fibers connecting the temporal poles) even after adjusting age, sex, education year, illness duration, and medication dose. Furthermore, all the 4 tracts were correlated with negative symptoms scores of the positive and negative syndrome scale. In conclusion, our study identified the tracts that were associated with remission state of schizophrenia. These tracts might be a potential prognostic marker for the symptomatic remission in patients with schizophrenia.


Comparison of toxicokinetic and tissue distribution of triptolide-loaded solid lipid nanoparticles vs free triptolide in rats.
The traditional Chinese medicine Tripterygium wilfordii Hook F (TWHF) is used clinically to treat some autoimmune and inflammatory disorders including rheumatoid arthritis, systemic lupus erythematosus, and skin diseases. However TWHF has a high potential for toxicity, so its clinical use is limited. Solid lipid nanoparticle (SLN) delivery systems are reported to have remarkable advantages over conventional formulations of bioactive plant extracts, such as enhancing solubility and bioavailability, offering protection from toxicity, and enhancing pharmacological activity. We reported previously that a tripterygium glycoside (TG) solid lipid nanoparticle (TG-SLN) delivery system had a protective effect against TG-induced male reproductive toxicity. To better understand this issue, we used triptolide (TP) as a model drug in a comparative study of the toxicokinetic and tissue distribution of TP-SLN and free TP in rats, allowing us to observing the in vivo behavior of this nanoformulation and to assess mechanisms of SLN-related toxicity. A fast and sensitive HPLC-APCI-MS/MS method was developed for the determination of triptolide in rat plasma. Fourteen rats were divided randomly into two groups of 7 rats each for toxicokinetic analysis, with one group receiving free TP (450μg/kg) and the other receiving the TP-SLN formulation (450μg/kg). Blood was obtained before dosing and 0.083, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3 and 4h after drug administration. Thirty-six rats were divided randomly into six equal groups for a tissue-distribution study. Half of the rats received intragastric administration of TP (450μg/kg) and the other half received TP-SLN (450μg/kg). At 15, 45, and 90min after dosing, samples of blood, liver, kidney, spleen, lung, and testicular tissue were taken. TP concentration in the samples was determined by LC-APCI-MS-MS. The toxicokinetic results for the nanoformulation showed a significant increase the area under the curve (AUC) (P<0.05), significantly longer T(max) and mean retention times (MRTs) (0-t) (P<0.05), significantly decreased C(max) (P<0.05). The nanoformulation promoted absorption with a slow release character, indicating that toxicokinetic changes may be the most important mechanism for the enhanced efficacy of nanoformulations. Tissue-distribution results suggest a tendency for TP concentrations in the lung and spleen to increase, while TP concentrations in plasma, liver, kidney, and testes tended to decrease in the TP-SLN group. At multiple time points, testicular tissue TP concentrations were lower in the TP-SLN group than in free TP group. This provides an important clue for the decreased reproductive toxicity observed with TP-SLN.


Forecastable and Guidable Bubble-Propelled Microplate Motors for Cell Transport.
Cell transport is important to renew body functions and organs with stem cells, or to attack cancer cells with immune cells. The main hindrances of this method are the lack of understanding of cell motion as well as proper transport systems. In this publication, bubble-propelled polyelectrolyte microplates are used for controlled transport and guidance of HeLa cells. Cells survive attachment on the microplates and up to 22 min in 5% hydrogen peroxide solution. They can be guided by a magnetic field whereby increased friction of cells attached to microplates decreases the speed by 90% compared to pristine microplates. The motion direction of the cell-motor system is easier to predict due to the cell being opposite to the bubbles.


Controlling the liberation rate of the in situ release of a chemical fuel for the operationally autonomous motions of molecular machines.
Second-order rate constants of the aminolysis of 2-cyano-2-phenylpropanoic anhydride 3 by a series of N-methylanilines differently substituted in the aromatic moiety (4a-d) were measured in dichloromethane. The common reaction product of aminolysis is 2-cyano-2-phenylpropanoic acid 1, which is known to be an effective fuel for acid-base driven molecular machines, but cannot be used in molar excess with respect to the machine. The motivation behind the kinetic study has been the prospect of using the aminolysis of 3 to supply the machine with fuel at a rate that is never so high as to overfeed the system, thus avoiding the malfunction of the machine with concomitant waste of fuel. Knowledge of the kinetic parameters dictated the choice of 4c as the best nucleophile in the lot for feeding acid 1 into a catenane-based molecular machine at a rate that ensured a correct operation.


Percutaneous cardioplegia delivery using the miniport in minimally invasive mitral valve surgery.
Minimally invasive cardiac surgery involves limited exposure of cardiac structures. Extracorporeal circulation is usually conducted by peripheral cannulation. Cross-clamp can be achieved by remote ways of either balloon endoclamp or transthoracic clamp. Effective delivery of cardioplegic solution is somewhat more difficult than those above mentioned tasks. In order to prevent additional expenses, we sought to deliver cardioplegic solution in a simple, reproducible, and cost-effective way. The miniport is used for this application. The procedures are reported in detail.


Climate change should drive mammal defaunation in tropical dry forests.
Human-induced climate change has intensified negative impacts on socioeconomic factors, the environment, and biodiversity, including changes in rainfall patterns and an increase in global average temperatures. Drylands are particularly at risk, with projections suggesting they will become hotter, drier, and less suitable for a significant portion of their species, potentially leading to mammal defaunation. We use ecological niche modelling and community ecology biodiversity metrics to examine potential geographical range shifts of non-volant mammal species in the largest Neotropical dryland, the Caatinga, and evaluate impacts of climate change on mammal assemblages. According to projections, 85% of the mammal species will lose suitable habitats, with one quarter of species projected to completely lose suitable habitats by 2060. This will result in a decrease in species richness for more than 90% of assemblages and an increase in compositional similarity to nearby assemblages (i.e., reduction in spatial beta diversity) for 70% of the assemblages. Small-sized mammals will be the most impacted and lose most of their suitable habitats, especially in highlands. The scenario is even worse in the eastern half of Caatinga where habitat destruction already prevails, compounding the threats faced by species there. While species-specific responses can vary with respect to dispersal, behavior, and energy requirements, our findings indicate that climate change can drive mammal assemblages to biotic homogenization and species loss, with drastic changes in assemblage trophic structure. For successful long-term socioenvironmental policy and conservation planning, it is critical that findings from biodiversity forecasts are considered.


Cystitis glandularis: Management and challenges in a renal transplant recipient.
Cystitis cystica or glandularis is a clinical and pathological entity of the bladder mucosa occurring secondary to inflammation or chronic obstruction. Its premalignant nature remains controversial, especially in an immunocompromised transplant recipient. We present a rare case where a chronic kidney disease patient was found to have cystitis glandularis while being worked up for living-related donor renal transplant and describe its subsequent management.


Eosinophil apoptosis and clearance in asthma.
Asthma is an increasingly common respiratory condition characterized by reversible airway obstruction, bronchial hyper-responsiveness and airway inflammation with a clear unmet need for more effective therapy. Eosinophilic asthma is a phenotype of the condition that features increased blood or sputum eosinophils whose numbers correlate with disease severity. Several lines of evidence are now emerging, which implicate increased persistence of eosinophils in the lungs of patients with asthma as a consequence of inhibition of and defects in the apoptotic process, together with impaired apoptotic cell removal mechanisms. This article will update our knowledge of the mechanisms controlling eosinophil apoptosis and clearance, together with evidence implicating defects in apoptosis and pro-inflammatory cell removal in asthma. Recent developments in novel therapies for asthma that target eosinophil apoptotic and/or clearance pathways will also be discussed.


The 4-flap Jester's Hat Technique for Nipple Reduction.
Macrothelia, or nipple hypertrophy, is a condition that may cause severe psychological distress to those who suffer from it. Although effective in their primary goal of reducing nipple diameter and projection, previously reported techniques in nipple reduction suffer from imperfect aesthetic outcomes with noticeable scarring patterns, anatomically anomalous shape, and a smoothing of the natural ruffles of the nipple. We propose a simple technique to nipple reduction that improves upon previous techniques and creates a more naturally appearing nipple. A 4-flap technique resembling a jester's hat is described whereby suture lines are concealed within the central nipple to recreate the naturally ruffled appearance of a native nipple. Four patients have undergone this technique at a single institution with 100% patient satisfaction and no postoperative complications. Nipple sensation was maintained in all patients postoperatively. A 4-flap nipple reduction technique is a viable alternative to previously described techniques, which may offer more anatomically congruent results.


Reflexivity and metapositions: strategies for appraisal of clinical evidence.
According to Sackett, evidence-based medicine is the conscientious, explicit and judicious use of current best evidence in making decisions about the care of the individual patient. In this article, clinical reasoning is depicted as multilayered processes of evidence construction by means of social interaction and human interpretation. A basic set of knowledge is the doctors initial capital at the onset of the individual encounter. This is a necessary, but insufficient, presumption for the elaboration of clinical knowledge required to solve the particular problem. A diagnostic conclusion may appear to constitute the most obvious part of knowledge. Yet the formulation of hypotheses and the choice of adequate strategies for the pursuit of evidence are perhaps even more significant dimensions of clinical knowledge. Potential biases affect the ways in which evidence is gathered and used. When clinicians are not committed to appraising the evidence constituting the foundations of their enterprise, quality assessment of clinical practice becomes casual and unreliable. Reflexivity implies having a self-conscious account of the production of knowledge as it is being produced. From metapositions, critical questions can be asked and sometimes answered. Evidence-based practice in the original sense requires that doctors reflect upon their own positions as knowers, in the process of situated knowing, where certain rhetorical spaces rule.


Lack of activities of amikacin and sulphamethoxazole against Mycobacterium avium-intracellulare.
Twenty clinical isolates of Mycobacterium avium-intracellulare were tested with amikacin and sulphamethoxazole for in-vitro susceptibilities. The MICs and MBCs of the former drug ranged from 8 to > 64 mg/L (median MIC: 64 mg/L, median MBC: > 64 mg/L). The MICs and MBCs of the latter drug were found to be > 256 mg/L. Each of eight patients with invasive pulmonary disease due to these organisms was treated with amikacin for six months and with cotrimoxazole (sulphamethoxazole-trimethoprim) for one year. Only one patient had sustained bacteriological conversion. Three patients showed a transient reduction of bacillary load during the period of amikacin administration. The rest all failed to show response. Thus sulphamethoxazole was found to have no activity against Mycobacterium avium-intracellulare, and amikacin has doubtful activity when used alone in treatment of M. avium-intracellulare infection.


Investigation of a vapor-deposited thin silica film: morphological and spectral characterization.
Surface modification reactions by organosilicon compounds have demonstrated great success in a wide variety of applications. However, they are of limited usefulness in that they only proceed appreciably on surfaces that have an abundance of reactive hydroxyl groups, thus preventing their application to some materials of technological relevance, such as plastics and polymers. A process capable of depositing a surface rich in reactive hydroxyl groups onto a wide variety of substrates could potentially enable the extension of organosilane surface modification reactions to new materials, but conventional processes for depositing oxide layers require temperatures that are too high for most polymers and plastics. It has been shown that silica layers can be deposited from the vapor-phase hydrolysis of tetrachlorosilane at room temperature, but little if any work has been done to characterize the resulting films. In this work, ellipsometry, atomic force microscopy, and Fourier transform infrared spectroscopy are employed to study the characteristics of films formed from this process. Interestingly, very different film morphologies can be obtained by changing key processing parameters. Furthermore, isotopic exchange experiments and dehydration studies show that the surfaces of the silica films obtained by this method are composed entirely of hydrogen-bonded silanol groups and do not exhibit any freely vibrating surface silanol groups, a result that is in contrast with conventionally prepared silica materials. Still, this layer has been shown to behave very similarly to conventional silica materials with respect to surface reactions. Finally, infrared spectral data and contact angle data demonstrate that this method can be employed to deposit silica layers onto poly(methyl methacrylate) and polystyrene surfaces.


CT-guided injection of the stellate ganglion: description of technique and efficacy of sympathetic blockade.
Stellate ganglion blockade, typically performed by using palpable osseous landmarks, is an accepted method in the diagnosis and treatment of sympathetically maintained pain and other conditions. The authors present the results of stellate ganglion injection performed with computed tomographic (CT) guidance. Thirteen CT-guided procedures were performed in seven patients. Lidocaine, bupivacaine, and buprenorphine were used to achieve the blockade. Successful blocks were achieved in all 13 cases as evidenced by production of Horner syndrome and ipsilateral hand temperature elevations. The average ipsilateral and contralateral hand temperature changes following the procedure were 7.5 degrees C and 0.5 degrees C. The ipsilateral hand temperature changes and the differences between the ipsilateral and contralateral hand temperature changes exceeded 1.5 degrees C in every case. Five patients preferred the CT-guided procedure over the conventional technique, and two patients noted no substantial difference between the approaches. With the CT-guided technique, a highly effective sympathetic block is achieved with a substantially reduced volume of anesthetic compared with the conventional approach.


Nanoengineered polymer capsules: tools for detection, controlled delivery, and site-specific manipulation.
We present the concept of multifunctional nanoengineered polymer capsules and outline their applications as new drug delivery systems or supramolecular toolboxes containing, for example, enzymes capable of converting nontoxic prodrugs into toxic drugs at a designated location. Such functionalized nanocontainers offer a wide range of applications including enzymatic catalysis, controlled release, and directed drug delivery in medicine due to their multifunctionality. The unique advantage of capsules in comparison to other systems is that they can be functionalized or loaded simultaneously with the above-mentioned components, thus permitting multifunctional processes in single cells.


Rare-Earth Elements in Tektites.
The rare-earth element content of three tektites has been determined by neutron activation analysis. The relative abundance patterns are all nearly alike and are identical to the pattern characteristic of well-differentiated terrestrial sediments. Possible consequences of finding this pattern in truly extraterrestrial matter are considered.


Facilitating a transition from compulsory detention of people who use drugs towards voluntary community-based drug dependence treatment and support services in Asia.
Evidence indicates that detention of people who use drugs in compulsory centers in the name of treatment is common in Cambodia, China, Indonesia, Lao PDR, Malaysia, Myanmar, Philippines, Thailand, and Vietnam. The expansion of such practices has been costly, has not generated positive health outcomes, and has not reduced supply or demand for illicit drugs. United Nations agencies have convened several consultations with government and civil society stakeholders in order to facilitate a transition to voluntary evidence- and community-based drug dependence treatment and support services. In an effort to support such efforts, an informal group of experts proposes a three-step process to initiate and accelerate national-level transitions. Specifically, the working group recommends the establishment of a national multisectoral decision-making committee to oversee the development of national transition plans, drug policy reform to eliminate barriers to community-based drug dependence treatment and support services, and the integration of community-based drug dependence treatment in existing national health and social service systems.In parallel, the working group recommends that national-level transitions should be guided by overarching principles, including ethics, human rights, meaningful involvement of affected communities, and client safety, as well as good governance, transparency, and accountability. The transition also represents an opportunity to review the roles and responsibilities of various agencies across the public health and public security sectors in order to balance the workload and ensure positive results. The need to accelerate national-level transitions to voluntary community-based drug dependence treatment and support services is compelling--on economic, medical, sustainable community development, and ethical grounds--as extensively documented in the literature. In this context, the expert working group fully endorses initiation of a transition towards voluntary evidence- and community-based drug dependence treatment and support services across the region, as well as the steady scale-down of compulsory centers for drug users.Components of voluntary community-based drug dependence treatment and support services are being implemented in Cambodia, China, Indonesia, Malaysia, and Thailand. However, significant technical and financial support will be required to be allocated from national budgets and by international development agencies in order to complete the transition and reduce the reliance on detention of people who use drugs in Asia.


Design and implementation of electronic health record integrated clinical prediction rules (iCPR): a randomized trial in diverse primary care settings.
Clinical prediction rules (CPRs) represent a method of determining individual patient risk to help providers make more accurate decisions at the point of care. Well-validated CPRs are underutilized but may decrease antibiotic overuse for acute respiratory infections. The integrated clinical prediction rules (iCPR) study builds on a previous single clinic study to integrate two CPRs into the electronic health record and assess their impact on practice. This article discusses study design and implementation of a multicenter cluster randomized control trial of the iCPR clinical decision support system, including the tool adaptation, usability testing, staff training, and implementation study to disseminate iCPR at multiple clinical sites across two health care systems. The iCPR tool is based on two well-validated CPRs, one for strep pharyngitis and one for pneumonia. The iCPR tool uses the reason for visit to trigger a risk calculator. Provider completion of the risk calculator provides a risk score, which is linked to an order set. Order sets guide evidence-based care and include progress note documentation, tests, prescription medications, and patient instructions. The iCPR tool was refined based on interviews with providers, medical assistants, and clinic managers, and two rounds of usability testing. "Near live" usability testing with simulated patients was used to ensure that iCPR fit into providers' clinical workflows. Thirty-three Family Medicine and General Internal Medicine primary care clinics were recruited at two institutions. Clinics were randomized to academic detailing about strep pharyngitis and pneumonia diagnosis and treatment (control) or academic detailing plus use of the iCPR tool (intervention). The primary outcome is the difference in antibiotic prescribing rates between the intervention and control groups with secondary outcomes of difference in rapid strep and chest x-ray ordering. Use of the components of the iCPR will also be assessed. The iCPR study uses a strong user-centered design and builds on the previous initial study, to assess whether CPRs integrated in the electronic health record can change provider behavior and improve evidence-based care in a broad range of primary care clinics. Clinicaltrials.gov ( NCT02534987 ).


Intravenous administration of mesenchymal stem cells prevents angiotensin II-induced aortic aneurysm formation in apolipoprotein E-deficient mouse.
Mesenchymal stem cells (MSCs) are known to be capable of suppressing inflammatory responses. We previously reported that intra-abdominal implantation of bone marrow-derived MSCs (BM-MSCs) sheet by laparotomy attenuated angiotensin II (AngII)-induced aortic aneurysm (AA) growth in apolipoprotein E-deficient (apoE-/-) mice through anti-inflammation effects. However, cell delivery by laparotomy is invasive; we here demonstrated the effects of multiple intravenous administrations of BM-MSCs on AngII-induced AA formation. BM-MSCs were isolated from femurs and tibiae of male apoE-/- mice. Experimental AA was induced by AngII infusion for 28 days in apoE-/- mice. Mice received weekly intravenous administration of BM-MSCs (n=12) or saline (n=10). After 4 weeks, AA formation incidence, aortic diameter, macrophage accumulation, matrix metalloproteinase (MMP)' activity, elastin content, and cytokines were evaluated. AngII induced AA formation in 100% of the mice in the saline group and 50% in the BM-MSCs treatment group (P < 0.05). A significant decrease of aortic diameter was observed in the BM-MSCs treatment group at ascending and infrarenal levels, which was associated with decreased macrophage infiltration and suppressed activities of MMP-2 and MMP-9 in aortic tissues, as well as a preservation of elastin content of aortic tissues. In addition, interleukin (IL)-1β, IL-6, and monocyte chemotactic protein-1 significantly decreased while insulin-like growth factor-1 and tissue inhibitor of metalloproteinases-2 increased in the aortic tissues of BM-MSCs treatment group. Multiple intravenous administrations of BM-MSCs attenuated the development of AngII-induced AA in apoE-/- mice and may become a promising alternative therapeutic strategy for AA progression.


Apoptosis-independent poor morphology of bovine embryos produced by multiple ovulation.
In multiple ovulation and embryo transfer (MOET) programmes in cattle, a considerable number of morphologically poor-quality embryos continue to be produced; this is one of the limiting factors of the technique. Apoptosis has often been implicated in developmental arrest and fragmentation; these are regarded as poor traits of embryonic quality in mammalian pre-implantation embryos. In the present study, apoptosis was assessed in morphologically poor-quality embryos in comparison with good-quality embryos that were recovered from a MOET programme. Retarded embryos (two to 16 cell stage), morulae with severe fragmentation and morphologically good-quality morulae recovered from superstimulated cows at day 7 post-insemination were subjected to TdT-mediated dUTP nick-end labelling (TUNEL) and Hoechst staining. Cell nuclei that showed both TUNEL staining and apoptotic morphology were considered to be apoptotic. Apoptotic index (AI) was calculated as the percentage of apoptotic cells per embryo. Fifteen of 17 retarded embryos and 10 of 15 morphologically poor-quality morulae did not show signs of apoptosis. The mean AIs in the morphologically poor-quality embryos (two to 16 cell stage, 2.2%; poor morulae, 1.3%) were as low as that in the good-quality embryos (2.9%). These results suggest that another mode of developmental arrest and/or fragmentation that is independent of apoptosis occurs in morphologically poor-quality embryos recovered from MOET programmes.


FAILED PSYCHIATRIC CLINIC APPOINTMENTS. RELATIONSHIP TO SOCIAL CLASS.
A study was made to determine what factors might be related to failure of patients to keep appointments at a county hospital psychiatric clinic. The hypothesis that the lowest status groups would have the poorest appointment records was substantiated in that they had the highest proportion of broken appointments without notification. Contrary to expectations, however, the highest status groups had poorer records than those in the central status groups-the skilled or semi-skilled workers and those with high school education. Marital status was also found to be related to appointment status, with divorced and separated persons displaying the greatest likelihood of breaking appointments without notifying the clinic.


Neuroprotective agents in acute ischemic stroke.
The concept of neuroprotection relies on the principle that delayed neuronal injury occurs after ischemia. The phenomenon of the "ischemic cascade" has been described, and each step along this cascade provides a target for therapeutic intervention. A wide variety of drugs have been studied in humans. Ten classes of neuroprotective agents have reached phase III efficacy trials but have shown mixed results. They included calcium channel antagonists, NMDA receptor antagonists, lubeluzole, CDP-choline, the free radical scavenger tirilazad and ebselen, enlimomab, GABA agonist clomethiazole, the sodium channel antagonist fosphenytoin, magnesium, glycine site antagonist GV150526 and piracetam. Furthermore, the mechanisms that underlie the development of focal ischemic injury continue to be discovered, opening new therapeutic perspective for neuroprotection that might clinically be applicable in the future.


First-line autologous stem cell transplantation in primary CNS lymphoma.
The treatment of primary central nervous system lymphoma (PCNSL) has been considerably improved over recent years. In this article, we report six cases of PCNSL treated by first-line induction chemotherapy followed by intensive chemotherapy and autologous stem cell transplantation (ASCT). Six immunocompetent patients presenting with a PCNSL, confirmed by thoraco-abdomino-pelvic computer tomography scan and bone marrow biopsy, were treated with induction chemotherapy followed by BEAM intensive chemotherapy and ASCT and radiotherapy. At the end of the treatment, all the patients were in complete remission. After a median follow-up of 41.5 months (17-70 months), four patients were alive without signs of relapse (median survival: 35.5 months). Two patients died from relapse at 19 and 23 months. The neurotoxicity was low with epilepsy in one patient and persistent left side dysesthesia in another one. These results are fairly encouraging. Other studies with greater numbers of patients and longer follow-up are needed to confirm this study.


Outcome of metformin-facilitated reinitiation of oral diabetic therapy in insulin-treated patients with non-insulin-dependent diabetes mellitus.
To test the feasibility of reimplementation of oral diabetic therapy in insulin-treated patients with non-insulin-dependent diabetes mellitus (NIDDM) and to determine the characteristics of patients in whom such conversion was successful. We attempted reinitiation of combination oral therapy with metformin and a sulfonylurea in 55 consecutive C-peptide-positive patients who had had NIDDM for less than 30 years and had received insulin therapy for less than 10 years. Reinitiation of oral therapy was successful in 42 patients and unsuccessful in 13. Reinitiation of oral therapy was unsuccessful because of lack of diabetic control in nine patients and gastrointestinal side effects in four patients. The successful group had a lower insulin requirement (P = 0.004), a shorter duration of insulin therapy (P = 0.013), and a lower body mass index (P = 0.014). Baseline glycosylated hemoglobin, C-peptide level, age, and duration of diabetes were not significant predictive factors. Glycosylated hemoglobin levels were significantly lower (mean, 1.3%; P = 0.0001) after successful reinitiation of oral therapy in comparison with before. Both groups of patients (those with successful and those with unsuccessful conversion to oral therapy) lost weight. The group of patients with NIDDM in whom reinitiation of combination oral therapy is most likely to be successful are those with a shorter duration of insulin therapy, lower insulin requirements, and lower body mass index. Successful conversion to oral diabetic therapy significantly decreases the glycosylated hemoglobin level.


Atomic force microscopy of chronic lymphatic leukaemia cells activation induced by Staphylococcus aureus.
Activation of lymphatic cells is associated with changes in morphology, ultrastructure and adhesion force. We have investigated the activation efficiency of Staphylococcus aureus (SAC) on B-cell chronic lymphatic leukaemia (B-CLL) cells using atomic force microscopy (AFM), and found changes in the above properties. Cell viability and proliferation were measured using Cell Counting Kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA). AFM clearly showed that the volume and nuclear-cytoplasm ratio of cells increased significantly with activated time. It also showed that pseudopodia and immunological synapses began to appear at 24 h. In the activation process, nano-structures of the cell surface became aggregated, and adhesion increased. In conclusion, the results indicate a close relationship between membrane reconstruction and multiplication process of B-CLL cells.


[Activity and isoenzyme spectra of lactate dehydrogenase of plateau zokor (Myospalax baileyi) in different season].
To explore the adapting metabolic mechanisms of the plateau zokors to the hypoxic-hypercapnic environment. The activities of lactate dehydrogenase in serum and tissues, and the content of lactate in serum of plateau zokors in spring, summer and autumn were determined by using method of enzyme analysis. The spectrums of lactate dehydrogenase isoenzymes in serum and tissues of plateau zokors in spring, summer and autumn were analyzed by using method of the discontinuous systemic poly-acrylamide perpendicular plank gel electrophoresis. The activities of lactate dehydrogenase in serum had obvious seasonally difference that were higher in spring and lower in autumn, and the content of lactate in serum showed same changing pattern. The spectrums of lactate dehydrogenase isoenzymes in serum showed five bands that were LDH1, LDH2, LDH3, LDH4 and LDH5 from positive pole to negative pole respectively, it showed clearly two bands in serum of summer that were LDH4 and LDH5 and one band in serum of autumn that was LDH5. The activities of LDH in tissues of skeleton muscle, cardiac muscle and brain were higher compared with the other tissues, it decreased markedly from spring to summer to autumn. In tissues of liver, kidney and lungs, activities of LDH were lower. Activities of LDH in livers, were significantly higher in spring compared that in summer and autumn, which had no obvious difference between summer and autumn. Activities of LDH in kidneys and lungs, showed no obviously difference between spring and summer, which decreased markedly in autumn. The spectrums of lactate dehydrogenase isoenzymes in tissues of cardiac muscle, liver, lungs, kidney, brain and skeleton muscle showed five bands, the spectrums were obvious different in different tissues, and the content of LDH isoenzymes showed seasonal changes in different tissues. Glycolysis levels in plateau zokors had obvious seasonally change which increased in spring and decreased in autumn significantly. It related to the activity of plateau zokors in different seasons and seasonal fluctuation of oxygen and carbon dioxide in burrows of plateau zokors.


Endoplasmic reticulum factor ERLIN2 regulates cytosolic lipid content in cancer cells.
Increased de novo lipogenesis is a hallmark of aggressive cancers. Lipid droplets, the major form of cytosolic lipid storage, have been implicated in cancer cell proliferation and tumorigenesis. Recently, we identified the ERLIN2 [ER (endoplasmic reticulum) lipid raft-associated 2) gene that is amplified and overexpressed in aggressive human breast cancer. Previous studies demonstrated that ERLIN2 plays a supporting oncogenic role by facilitating the transformation of human breast cancer cells. In the present study, we found that ERLIN2 supports cancer cell growth by regulating cytosolic lipid droplet production. ERLIN2 is preferably expressed in human breast cancer cells or hepatoma cells and is inducible by insulin signalling or when cells are cultured in lipoprotein-deficient medium. Increased expression of ERLIN2 promotes the accumulation of cytosolic lipid droplets in breast cancer cells or hepatoma cells in response to insulin or overload of unsaturated fatty acids. ERLIN2 regulates activation of SREBP (sterol regulatory element-binding protein) 1c, the key regulator of de novo lipogenesis, in cancer cells. ERLIN2 was found to bind to INSIG1 (insulin-induced gene 1), a key ER membrane protein that blocks SREBP activation. Consistent with the role of ERLIN2 in regulating cytosolic lipid content, down-regulation of ERLIN2 in breast cancer or hepatoma cells led to lower cell proliferation rates. The present study revealed a novel role for ERLIN2 in supporting cancer cell growth by promoting the activation of the key lipogenic regulator SREBP1c and the production of cytosolic lipid droplets. The identification of ERLIN2 as a regulator of cytosolic lipid content in cancer cells has important implications for understanding the molecular basis of tumorigenesis and the treatment of cancer.


[Clinical picture and morphology of orbital rhabdomyosarcomas in children].
The clinical course of orbital rhabdomyosarcoma is described in seven male children. A survey of the literature on the subject is given. Particular attention is paid to certain diagnostic problems of this most frequent orbital malignant primary in childhood. An adequate combination therapy which results in cure in more than half of the patients should be employed provided that an exact morphological diagnosis is made; this still causes often great difficulty. Electron microscopy is of great value in distinguishing this type of tumor from other malignancies, including the so-called reticulosarcoma. In comparison with the case material of other authors, there was a relatively high rate of late deaths in our patients.


Fundamentals and Challenges of Engineering Charge Polarized Active Sites for CO2 Photoreduction toward C2 Products.
ConspectusGlobal warming and climatic deterioration are partly caused by carbon dioxide (CO2) emission. Given this, CO2 reduction into valuable carbonaceous fuels is a win-win route to simultaneously alleviate the greenhouse effect and the energy crisis, where CO2 reduction into hydrocarbon fuels by solar energy may be a potential strategy. Up to now, most of the current photocatalysts photoconvert CO2 to C1 products. It is extremely difficult to achieve production of C2 products, which have higher economic value and energy density, due to the kinetic challenge of C-C coupling of the C1 intermediates. Therefore, to realize CO2 photoreduction to C2 fuels, design of high-activity photocatalysts to expedite the C-C coupling is significant. Besides, the current mechanism for CO2 photoreduction toward C2 fuels is usually uncertain, which is possibly attributed to the following two reasons: (1) It is arduous to determine the actual catalytic sites for the C-C coupling step. (2) It is hard to monitor the low-concentration active intermediates during the multielectron transfer step.Most traditional metal-based photocatalysts usually possess charge balanced active sites that have the same charge density. In this aspect, the neighboring C1 intermediates may also show the same charge distribution, which would lead to dipole-dipole repulsion, thus preventing C-C coupling for producing C2 fuels. By contrast, photocatalysts with charge polarized active sites possess obviously different charge distributions in the adjacent C1 intermediates, which can effectively suppress the electrostatic repulsion to steer the C-C coupling. Based on this analysis, higher asymmetric charge density on the active sites would be more beneficial to anchoring between the adjacent intermediates and active atoms in catalysts, which can boost C-C coupling.In this Account, we summarize various strategies, including vacancy engineering, doping engineering, loading engineering, and heterojunction engineering, for tailoring charge polarized active sites to boost the C-C coupling for the first time. Also, we overview diverse in situ characterization technologies, such as in situ X-ray photoelectron spectroscopy, in situ Raman spectroscopy, and in situ Fourier transform infrared spectroscopy, for determining charge polarized active sites and monitoring reaction intermediates, helping to reveal the internal catalytic mechanism of CO2 photoreduction toward C2 products. We hope this Account may help readers to understand the crucial function of charge polarized active sites during CO2 photoreduction toward C2 products and provide guidance for designing and preparing highly active catalysts for photocatalytic CO2 reduction.


Nutritional losses and gains during processing: future problems and issues.
Developments in food technology and nutrition today are shaping our food supply in an unprecedented way. They have not only helped produce a variety of foods with varying taste and texture but also optimally retain the nutritional quality of food. Increased use of novel ingredients in the future manufacture of foods is likely to reduce the amount of micronutrients available in our diet. To combat this, food fortification may be more widely used. Collaboration between food technologists and nutritionists is imperative if we are to see the continued manufacture of wholesome food.


Atrophy of the basal ganglia as the initial diagnostic sign of germinoma in the basal ganglia.
Germ-cell tumors of the central nervous system generally develop in the midline, but the tumors can also occur in the basal ganglia and/or thalamus. However, MR images have rarely been documented in the early stage of the tumor in these regions. We retrospectively reviewed MR images obtained on admission and approximately 3 years earlier in two patients with germinoma in the basal ganglia, and compared them with CT. In addition to hyperdensity on CT, both hyperintensity on T1-weighted images and a small hyperintense lesion on T2-weighted images were commonly seen in the basal ganglia. These findings may be early MRI signs of germinoma in this region, and the earliest and most characteristic diagnostic feature on MRI was atrophy of the basal ganglia, which was recognizable before development of hemiparesis.


Studies of the toxicological potential of capsinoids: VIII. A 13-week toxicity study of commercial-grade dihydrocapsiate in rats.
Dihydrocapsiate, (4-hydroxy-3-methoxybenzyl 8-methylnona- noate; CAS No. 205687-03-2) is a naturally occurring capsinoid compound found in nonpungent chili peppers. Although the safety of synthetically produced dihydrocapsiate has been previously evaluated, the purpose of this 13-week gavage toxicity study is to evaluate dihydrocapsiate produced with a slightly modified manufacturing process. Sprague-Dawley rats, 10 rats/sex/group, 6 weeks of age at study initiation, were administered the dihydrocapsiate daily by gavage at dose levels of 0 (vehicle), 100, 300, or 1000 mg/kg/day. The rats were observed for antimortem and postmortem signs of toxicity, including changes in clinical signs, body weights, food consumption, water intake, ophthalmology, clinical pathology (clinical chemistry, hematology, urinalysis), tissue findings (macroscopic and microscopic examination), as well as organ weights. There were no changes observed in clinical signs, body weight, food consumption, water intake, ophthalmology, urinalysis, hematology, or blood chemistry that were attributable to the administration of dihydrocapsiate. The only change observed attributable to the dihydrocapsiate administration involved the liver and that change occurred only at the high dose (1000 mg/kg). Both sexes had an increase in organ weights, but this increase correlated with a change in histopathology (i.e., hepatocyte hypertrophy) only in the males. No dihydrocapsiate-related histopathological changes were observed in males at doses < or = 300 mg/kg or in females at any of the doses tested (< or = 1000 mg/kg). It was concluded that the no observed adverse effect level (NOAEL) of dihydrocapsiate was 300 mg/kg/day for male rats and 1000 mg/kg/day for female rats in this 13 week gavage study.


The share of ultra-processed foods determines the overall nutritional quality of diets in Brazil.
To estimate the dietary share of ultra-processed foods and to determine its association with the overall nutritional quality of diets in Brazil. Cross-sectional. Brazil. A representative sample of 32 898 Brazilians aged ≥10 years was studied. Food intake data were collected. We calculated the average dietary content of individual nutrients and compared them across quintiles of energy share of ultra-processed foods. Then we identified nutrient-based dietary patterns, and evaluated the association between quintiles of dietary share of ultra-processed foods and the patterns' scores. The mean per capita daily dietary energy intake was 7933 kJ (1896 kcal), with 58·1 % from unprocessed or minimally processed foods, 10·9 % from processed culinary ingredients, 10·6 % from processed foods and 20·4 % from ultra-processed foods. Consumption of ultra-processed foods was directly associated with high consumption of free sugars and total, saturated and trans fats, and with low consumption of protein, dietary fibre, and most of the assessed vitamins and minerals. Four nutrient-based dietary patterns were identified. 'Healthy pattern 1' carried more protein and micronutrients, and less free sugars. 'Healthy pattern 2' carried more vitamins. 'Healthy pattern 3' carried more dietary fibre and minerals and less free sugars. 'Unhealthy pattern' carried more total, saturated and trans fats, and less dietary fibre. The dietary share of ultra-processed foods was inversely associated with 'healthy pattern 1' (-0·16; 95 % CI -0·17, -0·15) and 'healthy pattern 3' (-0·18; 95 % CI -0·19, -0·17), and directly associated with 'unhealthy pattern' (0·17; 95 % CI 0·15, 0·18). Dietary share of ultra-processed foods determines the overall nutritional quality of diets in Brazil.


Distinct genomic organization, mRNA expression and cellular localization of members of two amastin sub-families present in Trypanosoma cruzi.
Amastins are surface glycoproteins (approximately 180 residues long) initially described in Trypanosoma cruzi as particularly abundant during the amastigote stage of this protozoan parasite. Subsequently, they have been found to be encoded by large gene families also present in the genomes of several species of Leishmania and in other Trypanosomatids. Although most amastin genes are organized in clusters associated with tuzin genes and are up-regulated in the intracellular stage of T. cruzi and Leishmania spp, distinct genomic organizations and mRNA expression patterns have also been reported. Based on the analysis of the complete genome sequences of two T. cruzi strains, we identified a total of 14 copies of amastin genes in T. cruzi and showed that they belong to two of the four previously described amastin subfamilies. Whereas δ-amastin genes are organized in two or more clusters with alternating copies of tuzin genes, the two copies of β-amastins are linked together in a distinct chromosome. Most T. cruzi amastins have similar surface localization as determined by confocal microscopy and western blot analyses. Transcript levels for δ-amastins were found to be up-regulated in amastigotes from several T. cruzi strains, except in the G strain, which is known to have low infection capacity. In contrast, in all strains analysed, β-amastin transcripts are more abundant in epimastigotes, the stage found in the insect vector. Here we showed that not only the number and diversity of T. cruzi amastin genes is larger than what has been predicted, but also their mode of expression during the parasite life cycle is more complex. Although most T. cruzi amastins have a similar surface localization, only δ-amastin genes have their expression up-regulated in amastigotes. The results showing that a sub-group of this family is up-regulated in epimastigotes, suggest that, in addition of their role in intracellular amastigotes, T. cruzi amastins may also serve important functions during the insect stage of the parasite life cycle. Most importantly, evidence for their role as virulence factors was also unveiled from the data showing that δ-amastin expression is down regulated in a strain presenting low infection capacity.


Postinfection intravesical femoral head resulting in a vesicocutaneous fistula: A bizarre presentation and outcome.
Vesicocutaneous fistula can occur secondary to numerous factors. We present a case of 14-year-old girl who presented with a discharging sinus beside her labia majora with bony ankylosis of her left hip secondary to infection. Investigations revealed the femoral head protruding into the urinary bladder, resulting in a vesicocutaneous fistula. This case highlights the bizarre presentation of infection in the hip and the difficulty in diagnosis of a resultant vesicocutaneous fistula.


P-wave dispersion doesn't increase in patients with epilepsy.
Epileptic seizures have occasionally been associated with cardiac conditions as atrioventricular blocks, long QT syndrome etc. P-wave dispersion (PWD), which is the difference between the longest (P max) and shortest P-wave duration (P min), is considered as a forerunner of atrial fibrillation. In this study, we investigated P-wave dispersion (PWD) in epileptic patients; based on the hypothesis that microthromboembolism may occur in atrial fibrillation. Seventy five patients with mixed types of epilepsy and 50 age and sex matched healthy individuals were included into the study. P max, P min and PWD values were calculated for each subject from an ECG. The mean age of subjects in the epilepsy group and control group were similar (p>0.05). P max in patients with epilepsy was 125.1±0.7 ms, P min was 67.3±10.3 ms, and PWD was 57.6±8.3 ms while these values in the control group were 116.8±11.0 ms, 66.5±5.5 ms and 46.8±7.1 ms, respectively. There were no statistically significant difference between two groups (p>0.05). PWD does not increase in patients with mixed types of epilepsy. Therefore we believe that microthromboembolism due to atrial fibrillation can't cause epileptic seizures in patients with no structural heart disease.


Mycobacterium tuberculosis heat shock proteins use diverse Toll-like receptor pathways to activate pro-inflammatory signals.
Although the Toll-like receptors used by Mycobacterium tuberculosis membrane and secreted factors are known, the pathways activated by M. tuberculosis heat shock proteins are not. An efficient immune response against the intracellular pathogen M. tuberculosis is critically dependent on rapid detection of the invading pathogen by the innate immune system and coordinated activation of the adaptive immune response. Macrophage phagocytosis of M. tuberculosis is accompanied by activation of the transcription factor NF-kappaB and secretion of inflammatory mediators that play an important role in granuloma formation and immune protection during M. tuberculosis infection. The interaction between M. tuberculosis and the various Toll-like receptors is complex, and it appears that distinct mycobacterial components may interact with different members of the Toll-like receptor family. Here we show that recombinant, purified, mycobacterial heat shock proteins 65 and 70 induce NF-kappaB activity in a dose-dependent manner in human endothelial cells. Furthermore, we show that whereas mycobacterial heat shock protein 65 signals exclusively through Toll-like receptor 4, heat shock protein 70 also signals through Toll-like receptor 2. Mycobacterial heat shock protein 65-induced NF-kappaB activation was MyD88-, TIRAP-, TRIF-, and TRAM-dependent and required the presence of MD-2. A better understanding of the recognition of mycobacterial heat shock proteins and their role in the host immune response to the pathogen may open the way to a better understanding of the immunological processes induced by this important human pathogen and the host-pathogen interactions and may help in the rational design of more effective vaccines or vaccine adjuvants.


6-Shogaol reduced chronic inflammatory response in the knees of rats treated with complete Freund's adjuvant.
6-Shogaol is one of the major compounds in the ginger rhizome that may contribute to its anti-inflammatory properties. Confirmation of this contribution was sought in this study in Sprague- Dawley rats (200-250 g) treated with a single injection (0.5 ml of 1 mg/ml) of a commercial preparation of complete Freund's Adjuvant (CFA) to induce monoarthritis in the right knee over a period of 28 days. During this development of arthritis, each rat received a daily oral dose of either peanut oil (0.2 ml-control) or 6-shogaol (6.2 mg/Kg in 0.2 ml peanut oil). Within 2 days of CFA injection, the control group produced maximum edematous swelling of the knee that was sustained up to the end of the investigation period. But, in the 6-shogaol treated group, significantly lower magnitudes of unsustained swelling of the knees (from 5.1 +/- 0.2 mm to 1.0 +/- 0.2 mm, p < 0.002, n = 6) were produced during the investigation period. Unsustained swelling of the knees (from 3.2 +/- 0.6 mm to 0.8 +/- 1.1 mm, p < 0.00008, n = 6) was also produced after 3 days of treatment with indomethacin (2 mg/Kg/day) as a standard anti-inflammatory drug, but during the first 2 days of drug treatment swelling of the knees was significantly larger (11.6 +/- 2.0 mm, p < 0.0002, n = 6) than either the controls or the 6-shogaol treated group of rats. This exaggerated effect in the early stage of indomethacin treatment was inhibited by montelukast, a cysteinyl leukotriene receptor antagonist. Also, 6-shogaol and indomethacin were most effective in reducing swelling of the knees on day 28 when the controls still had maximum swelling. The effect of 6-shogaol compared to the controls was associated with significantly lower concentration of soluble vascular cell adhesion molecule-1 (VCAM-1) in the blood and infiltration of leukocytes, including lymphocytes and monocytes/macrophages, into the synovial cavity of the knee. There was also preservation of the morphological integrity of the cartilage lining the femur compared to damage to this tissue in the peanut oil treated control group of rats. From these results, it is concluded that 6-shogaol reduced the inflammatory response and protected the femoral cartilage from damage produced in a CFA monoarthritic model of the knee joint of rats.


Core-Sheath Fiber-Based Triboelectric Nanogenerators for Energy Harvesting and Self-Powered Straight-Arm Sit-Up Sensing.
Fiber-based triboelectric nanogenerators (F-TENGs), a green and sustainable energy-harvesting and transformation technology, hold great potential in the areas of portable energy harvesters and smart wearable sensors. Herein, the core-sheath structure F-TENGs (CF-TENGs) are developed by using continuous production equipment. The CF-TENGs, consisting of an elastic conductive fiber (core layer) and silicone rubber (sheath layer), can simultaneously accomplish stable reversible strain and excellent electrical output performance. High outputs (an open-circuit voltage of 17.5 V and a short-circuit current of 0.1 μA at a frequency of 1 Hz) can be attained when the CF-TENGs (a length of 5 cm) are contacted with a nylon fabric. The CF-TENGs not only act as self-powered sensors for applications in motion monitoring but also efficiently transfer mechanical energy into electric energy. As self-powered wearable sensors, the CF-TENGs can accurately indicate various human physiological movements. Moreover, they can be applied on straight-arm sit-up sensing to achieve standardized sport testing. Importantly, a CF-TENG-based weaved fabric presents high electrical performance to meet requirements as an energy harvester. These CF-TENGs provide a significant insight to facilitate the development of fiber-based triboelectric applications.


Evaluation of a modified Karnofsky score to assess physical and psychological wellbeing of cats in a hospital setting.
Objectives The Karnofsky score (KS) modified for cats, a scoring system to rate health and quality of life (QOL) in cats, is used in clinical trials, but its reliability and validity are yet to be determined. The present study aims to evaluate the scientific robustness of the KS when adapted for use in a hospital setting. Methods A list of variables to consider during the physical examination, which informs the clinician's score (CS) part of the KS, was added and clinicians were allowed to choose a score anywhere between 0 and 50. The Karnofsky QOL questionnaire was adapted for use in a hospital setting. F-tests with Bonferroni correction and Spearman rank correlation coefficients were used to evaluate reliability and validity of the KS to assess the health and wellbeing of cats in a hospital setting. The records of 54 feline immunodeficiency virus-positive cats, which were recruited for a clinical trial and hospitalised for 6 weeks, were reviewed. Four veterinarians scored the CS, and one veterinarian and a veterinary nurse assessed the QOL score. Results Mean absolute difference between observers was significantly larger for the CS than for the QOL score ( P <0.001) and two veterinarians scored significantly higher than the remaining two veterinarians ( P <0.001). Inter-observer correlation ranged from 0.45-0.75 for the CS. For the QOL score, the absolute difference between observers was small, no significant difference was found between observers and a high degree of inter-observer correlation was noted (r = 0.91). Conclusions and relevance The results indicate low inter-observer reliability for the CS, requiring additional modifications to this part of the KS. The QOL score seems more reliable, and the questionnaire may serve as a reliable tool in the assessment of QOL in cats in a hospital setting. Consequently, further adaptation of the KS is mandatory when simultaneous assessment of both the cat's clinical health and perceived wellbeing is required.


MD simulations and multivariate studies for modeling the antileishmanial activity of peptides.
Leishmaniasis, a protozoan-caused disease, requires alternative treatments with minimized side-effects and less prone to resistance development. Antimicrobial peptides represent a possible choice to be developed. We report on the prospection of structural parameters of 23 helical antimicrobial and leishmanicidal peptides as a tool for modeling and predicting the activity of new peptides. This investigation is based on molecular dynamic simulations (MD) in mimetic membrane environment, as most of these peptides share the feature of interacting with phospholipid bilayers. To overcome the lack of experimental data on peptides' structures, we started simulations from designed 100% α-helices. This procedure was validated through comparisons with NMR data and the determination of the structure of Decoralin-amide. From physicochemical features and MD results, descriptors were raised and statistically related to the minimum inhibitory concentration against Leishmania by the multivariate data analysis technique. This statistical procedure confirmed five descriptors combined by different loadings in five principal components. The leishmanicidal activity depends on peptides' charge, backbone solvation, volume, and solvent-accessible surface area. The generated model possesses good predictability (q2 = 0.715, r2 = 0.898) and is indicative for the most and the least active peptides. This is a novel theoretical path for structure-activity studies combining computational methods that identify and prioritize the promising peptide candidates.


An introduction: oxidative phosphorylation diseases.
Oxidative phosphorylation (OXPHOS) is responsible for producing much of the adenosine triphosphate that is required by cells. The OXPHOS pathway incorporates over 100 polypeptides whose genes are located in either the nuclear DNA or the mitochondrial DNA (mtDNA). The expression of these genes and the assembly of the five OXPHOS enzyme complexes (complexes I to V) is a highly ordered and coordinated process. A broad array of human diseases result from mutations in either the nuclear or mtDNA genes or even in the systems that coordinate their interactions. Consequently, OXPHOS diseases can have complex inheritance patterns and a wide spectrum of clinical presentations.


New optical technologies for earlier endoscopic diagnosis of premalignant gastrointestinal lesions.
Gastrointestinal malignancies continue to be the second leading cause of cancer-related deaths in the developed world. The early detection and treatment of gastrointestinal preneoplasms has been demonstrated to significantly improve patient survival. Conventional screening tools include standard white light endoscopy (WLE) and frequent surveillance with biopsy. Well-defined endoscopic surveillance biopsy protocols aimed at early detection of dysplasia and malignancy have been undertaken for groups at high risk. Unfortunately, the poor sensitivity associated with WLE is a significant limitation. In this regard, major efforts continue in the development and evaluation of alternative diagnostic techniques. This review will focus on notable developments made at the forefront of research in modern gastrointestinal endoscopy based on novel optical endoscopic modalities, which rely on the interactions of light with tissues. Here we present the 'state-of-the-art' in fluorescence endoscopic imaging and spectroscopy, Raman spectroscopy, optical coherence tomography, light scattering spectroscopy, chromoendoscopy, confocal fluorescence endoscopy, and immunofluorescence endoscopy. These new developments may offer significant improvements in the diagnosis of early lesions by allowing for targeted mucosal excisional biopsies, and perhaps may even provide 'optical biopsies' of equivalent histological accuracy. This enhancement of the endoscopist's ability to detect subtle preneoplastic changes in the gastrointestional mucosa in real time and improved staging of lesions could lead to curative endoscopic ablation of these lesions and, in the long term, improve patient survival and quality of life.


Functional and physical characterization of the cell cycle ubiquitin-conjugating enzyme CDC34 (UBC3). Identification of a functional determinant within the tail that facilitates CDC34 self-association.
Like several other ubiquitin-conjugating enzymes, the yeast cell cycle enzyme CDC34 (UBC3) has a carboxyl-terminal extension or tail. These tails appear to carry out unique functions that can vary from one ubiquitin-conjugating enzyme to the next. Using biophysical techniques we have determined that the tail of CDC34 constitutes a highly structured and extended domain. Although the tail of CDC34 is the largest tail identified to date (125 residues), we have found that only 39 residues lying adjacent to the catalytic domain are necessary and sufficient for full cell cycle function and that this region fulfills a novel function that may be common to the tails of other ubiquitin-conjugating enzymes. Cross-linking studies demonstrate that this region facilitates a physical interaction between CDC34 monomers in vitro. Furthermore, phenotypic analysis of various CDC34 derivatives expressed in different cdc34 mutant strains indicates that this region facilitates the same interaction in vivo. Based on these findings, it appears that the cell cycle function of CDC34 is dependent upon the ability of CDC34 monomers to interact with one another and that this interaction is mediated by a small region of the CDC34 tail. The similarity of this region with sequences contained within the tails of the UBC1 and UBC6 enzymes suggests that these tails may function in a similar manner.


Risk Stratification for Early-onset Colorectal Cancer Screening: Are We Ready for Implementation?
Early-onset colorectal cancer (EOCRC) is increasing at alarming rates and identifying risk factors is a high priority. There is a need to develop risk stratification approaches for colorectal cancer screening among younger populations. Although there is a growing body of evidence identifying risk factors for EOCRC, including the report by Imperiale and colleagues in this issue, risk stratification for EOCRC screening has not been implemented into practice. This publication highlights how essential it is to bring research findings into practice and bridge the gaps between developing risk prediction modeling in epidemiology and implementation science. While encouraging, we are still a long way off from having a clinically applicable risk prediction tool. See related article by Imperiale et al., p. 513.


Scale-Limited Lagrange Stability and Finite-Time Synchronization for Memristive Recurrent Neural Networks on Time Scales.
The existed results of Lagrange stability and finite-time synchronization for memristive recurrent neural networks (MRNNs) are scale-free on time evolvement, and some restrictions appear naturally. In this paper, two novel scale-limited comparison principles are established by means of inequality techniques and induction principle on time scales. Then the results concerning Lagrange stability and global finite-time synchronization of MRNNs on time scales are obtained. Scaled-limited Lagrange stability criteria are derived, in detail, via nonsmooth analysis and theory of time scales. Moreover, novel criteria for achieving the global finite-time synchronization are acquired. In addition, the derived method can also be used to study global finite-time stabilization. The proposed results extend or improve the existed ones in the literatures. Two numerical examples are chosen to show the effectiveness of the obtained results.


Genome-wide non-invasive prenatal testing in single- and multiple-pregnancies at any risk: Identification of maternal polymorphisms to reduce the number of unnecessary invasive confirmation testing.
Non-invasive prenatal testing by targeted or genome-wide copy number profiling (cnNIPT) has the potential to outperform standard NIPT targeting the common trisomies 13, 18, and 21, only. Nevertheless, prospective results and outcome data on cnNIPT are still scarce and there is increasing evidence for maternal copy number variants (CNVs) interfering with results of both, standard and cnNIPT. We assessed the performance of cnNIPT in 3053 prospective and 116 retrospective cases with special consideration of maternal CNVs in singleton and multiple gestational pregnancies at any risk, as well as comprehensive follow-up. A result was achieved in 2998 (98.2%) of total prospective cases (89.2% analyzed genome-wide). Confirmed fetal chromosomal abnormalities were detected in 45 (1.5%) cases, of which five (11%) would have remained undetected in standard NIPTs. Additionally, we observed 4 likely fetal trisomies without follow-up and a likely phenotype associated placental partial trisomy 16. Moreover, we observed clinically relevant confirmed maternal CNVs in 9 (0.3%) cases and likely maternal clonal hematopoiesis in 3 (0.1%). For common fetal trisomies we prospectively observed a very high sensitivity (100% [95% CI: 91.96-100%]) and specificity (>99.9% [95% CI: 99.8-100%]), and positive predictive value (PPV) (97.8% [95% CI: 86.1-99.7%]), but our retrospective control cases demonstrated that due to cases of fetal restricted mosaicism the true sensitivity of NIPT is lower. After showing that 97.3% of small CNVs prospectively observed in 8.3% of genome-wide tests were mostly benign maternal variants, sensitivity (75.0% [95% CI: 19.4%-99.4%]), specificity (99.7% [99.5%-99.9%]) and PPV (30.0% [14.5%-52.1%]) for relevant fetal CNVs were relatively high, too. Maternal autoimmune disorders and medication, such as dalteparin, seem to impair assay quality. When maternal CNVs are recognized as such, cnNIPT showed a very high sensitivity, specificity and PPV for common trisomies in single and multiple pregnancies at any risk and very good values genome-wide. We found that the resolution for segmental aberrations is generally comparable to standard karyotyping, and exceeds the latter if the fetal fraction is above 10%, which allows detection of the 2.5 Mb 22q11.2 microdeletion associated with the velocardiofacial syndrome, even if the mother is not a carrier.


[Translation of chicken interferon messenger in a cell-free protein synthesis system and in a cell culture].
A highly effective cell-free system for protein synthesis was obtained from rabbit reticulocytes and for the first time used for synthesis of biologically active chicken interferon. The optimal conditions for translation of its mRNA were developed. The translation efficacy in the cell-free system was 10-50 times higher than that in the culture of heterologous cells. The higher the purity level of RNA, the higher the translation level. With respect to poly (A+) RNA sedimenting in the sucrose gradient 9S the efficacy reached 2560 units per 1 microgram of RNA. By the content of poly (A), sequences and rate of the sedimentation, mRNA of the chicken interferon was similar to that of the human fibroblast cell interferon. The possible translation of mRNA of the chicken interferon at low concentrations of exogenic potassium ions in the cell-free system is explained by production of interferon in infected cells where the concentration of the intracellular potassium significantly decreases which is indicative of the mRNA interferon similarity with virus templates. It was found that only albino New Zealand rabbits, but also chinchilla may be used for preparation of the cell-free protein synthesizing system. Various exogenic templates in the mRNA-dependent cell-free system prepared from reticulocyte nonfractionated lysate by treatment with micrococcal nuclease stimulated the protein synthesis by 7-15 times.


To dimerize or not: para-aminothiophenol on a bismuth heterostructure.
Surface enhanced Raman spectroscopy (SERS) of p-aminothiophenol (PATP) was investigated on β-Bi2O3/Bi2O2CO3 nanoparticles, a novel bismuth based metal substrate with the lowest limit of detection of 1 mM. Unlike on noble metal surfaces where PATP gets converted to p,p'-dimercaptoazobenzene (DMAB) due to photocatalytic coupling, no such transformation of PATP was observed on β-Bi2O3/Bi2O2CO3 nanoparticles. Density functional theory (DFT) calculations at the PW91PW91/LANL2DZ/6-311+G(d,p) level of theory supported the experimental results exceedingly well. Also, the charge transfer direction from PATP to β-Bi2O3/Bi2O2CO3 nanoparticles was revealed by the projected density of states calculation.


Case report: portal and systemic venous gas in a patient with perforated duodenal ulcer: CT findings.
Gas within the portal circulation has been known to be associated with a number of conditions most commonly mesenteric ischemia and necrosis. Systemic venous gas is described with few conditions and is mostly iatrogenic in nature. We describe a case of combined portal and systemic venous gas detected by computed tomography in a patient with perforated duodenal ulcer.


[Comparative evaluation of non-invasive methods of determining the minute blood volume].
Comparative value of minute flow volume measurement by radiocardiography, echocardiography, tetrapolar chest rheography and ultrasonic impulse doppler flowmetry was assessed in 30 individuals. Radiocardiography was often associated with overstated values and could not be used for minute volume monitoring. Tetrapolar chest rheography was also associated with overstated values in cases of left-ventricular insufficiency, and inadequately overstated values in 6% of normal subjects and understated values in 1%. Ultrasonic impulse doppler flowmetry was not possible in 8% of the cases because of poor echo. Ultrasonic impulse doppler flowmetry and echocardiography were found to be the most promising and clinically suitable procedures.


Isokinetic gradient sedimentation of normal human bone marrow cells: a simple method for isolation of proliferative granulocytic and erythroid elements.
Proliferative granulocytes and erythroid precursors were isolated from cell suspensions of human normal bone marrow by sedimentation on an isokinetic gradient of continuous low-density Ficoll. A fivefold enrichment with a 70% recovery of the proliferative granulocyte cohort and of early erythroid elements was achieved, as determined by differential morphology and tritiated thymidine incorporation. Viability and in vitro proliferative capacity following gradient centrifugation remained intact. This method of cell separation, based on differences in cell diameter, affords a simple and rapid means for the purification of specific cell populations from heterologous human normal bone marrow.


"Open door" operation to raise the vertebral arch in myelopathy due to cervical spondylosis.
The authors discuss the various operations used in the treatment of myelopathy caused by cervical spondylosis. Recently they have used the so-called "open door" operation, which raises the posterior vertebral arch, in place of laminectomy, hemilaminectomy and anterior interbody fusion. The "open door" operation is less radical, less traumatizing and safer, and ensures considerable enlargement of the vertebral canal. This enlargement can be clearly demonstrated by tomography as well as by the traditional radiological methods.


Attitudes Toward COVID-19 Vaccination Among Behavioral Health Service Clients.
The authors examined attitudes toward and uptake of COVID-19 vaccination among individuals with serious mental illness or substance use disorder. Clients of a community mental health center in Texas (N=50) participated in semistructured, in-person interviews regarding their COVID-19 vaccination decision. Thematic analysis was used to analyze interview data. Most participants (68%) reported receipt of at least one COVID-19 vaccine dose. Participants were motivated to get vaccinated mostly by a desire to protect themselves or others. Convenience of vaccination location and access to free vaccination facilitated vaccine uptake. However, concerns about the COVID-19 vaccine were common among both vaccinated and unvaccinated participants and could be reinforced or overcome by social network influences. Fear, uncertainty, and conflicting vaccine information were common themes in the COVID-19 vaccination decisions of behavioral health service clients. Improving access to information from trusted sources, including health care providers, could help to overcome vaccine concerns in this population.


Prognostic impact of left ventricular global longitudinal strain in atrial mitral regurgitation.
Left atrial (LA) and left ventricular (LV) mechanics are impaired in patients with atrial functional mitral regurgitation (AFMR), but their prognostic value in this subset of patients remains unknown. The present study aimed to evaluate the association between LA and LV longitudinal strain and clinical outcomes in patients with AFMR. A total of 197 patients (mean age 73±10 years, 44% men) with at least moderate AFMR were retrospectively identified. LV global longitudinal strain (GLS) and left atrial reservoir strain (LAS) were calculated by two-dimensional speckle tracking echocardiography. All-cause mortality was the primary endpoint of the study. The threshold value of LV GLS (≤16.3%) to identify impaired LV mechanics was defined based on the risk excess of the primary endpoint described with a spline curve analysis. Impaired LV GLS (≤16.3%) was found in 89 (45%) patients. During a median follow-up of 69 months, 45 (23%) subjects experienced the primary endpoint. Patients with impaired LV GLS (≤16.3%) had a significantly lower cumulative survival rate at 5 years, as compared with patients with LV GLS (>16.3%) (74% vs 93%, p<0.001). On multivariable Cox regression analysis, LV GLS expressed as continuous variable was independently associated with the occurrence of all-cause mortality (HR 0.856, 95% CI 0.763 to 0.960; p=0.008) after adjustment for age, LAS, pulmonary artery systolic pressure and severe tricuspid regurgitation. Conversely, LAS was not significantly associated with patients' outcome. In patients with significant AFMR, the impairment of LV GLS was independently associated with worse outcomes.


Oropharyngeal teratoma, a rare cause of airway obstruction in neonates.
Oropharyngeal teratomas are extremely rare congenital tumours, and because of their location in the upper airway they represent one of the most unusual causes of airway obstruction during the neonatal period. We report a 2-month-old girl who presented with repeated vomiting, failure to thrive and recurrent bouts of stridor and cyanosis since birth. On examination there was a mass originating from the oropharynx. The mass was excised under general anaesthesia by CO(2) laser. Histopathological examination revealed a teratoma of the oropharynx. We discuss the clinical presentation, diagnosis and treatment of this case as well as a review of the literature.


Screening Youth Soccer Players by Means of Cognitive Function and Agility Testing.
Talent identification in sports is a heavily debated topic. Previous studies have separately explored either executive functions or gross motor skills to predict the success of top-level soccer players or, more generally, to characterize elite performance in soccer. However, at mid-childhood, the possibility to scope sport-specific requirements remains elusive. We aimed in this study to investigate a valid and simple method of testing for a unique combination of cognitive and speed abilities for identifying promising soccer players at mid-childhood. We measured cognitive functions by means of a Stroop smartphone application and agility with a T-Drill Ball-success test, in two groups of (a) elite- (n = 31) and (b) low-division (n = 37) Italian 7-year-old male soccer players. We administered the tests in a randomized order to both groups. We found better inhibitory control, cognitive flexibility and soccer-specific agility in high-division versus low-division players (p < .001). Inhibitory response and agility were positively associated with the augmented quality of the performance from low-division players to high-division players (r = .55; p = .0001). These results suggest that, even at an early age, cognitive control together with soccer-specific skills is associated with better performance.


Are incident gallstones associated to sex-dependent changes with age? A cohort study.
Age and female sex have repeatedly been identified as gallstone determinants but the underlying mechanisms are not clarified. The objectives of this study were to determine if changes with age in physiology, lifestyle, or reproductive hormones were associated with incident gallstones. A cohort study of a general population random sample (N = 2366) aged 30-60 years was performed. Participants were ultrasound screened for gallstones in 1982-84 and again in 1993-94. Lifestyle data and blood samples were obtained and re-analyzed in 2004. Changes with age in physiology (body mass index, blood pressure, blood lipids, self-rated health), lifestyle (smoking, alcohol and coffee consumption, dietary habits, physical activity level), and indices of reproductive function (number of births, oral contraceptive use, hormone replacement therapy, male reproductive hormones) were explored in females and males separately. Adjusted logistic regression analyses were performed. Incident gallstones (gallstones and cholecystectomy) at ultrasound examination in participants initially free of gallstones at baseline occurred in 9.9% of the study population. In females, increasing alcohol consumption (odds ratio (OR) 0.94, 95% confidence interval (CI) [0.90; 0.98]) and the cessation of hormone replacement therapy (OR 0.29, 95% CI [0.10; 0.83]) inversely determined incident gallstones. In males, increasing levels of SHBG (OR 0.97, 95% CI [0.94; 0.998]) inversely determined incident gallstones. Other changes with age in physiology, lifestyle, or reproductive hormones were not associated. High baseline free testosterone determined incident gallstones in males (OR 1.15, 95% CI [1.02; 1.30]). To conclude, changes with age in alcohol consumption in females and in reproductive hormones determined incident gallstones. Male reproductive hormones seem to have an impact on incident gallstones. Sex differences should be explored further in future studies.


Mitochondrial network structure homeostasis and cell death.
Mitochondria are the major cellular energy-producing organelles and intracellular source of reactive oxygen species. These organelles are responsible for driving cell life and death through mitochondrial network structure homeostasis, which is determined by a balance of fission and fusion. Recent advances revealed that a number of components of the fission and fusion machinery, including dynamin-related protein 1 (Drp1), mitofusin1/2 (Mfn1/2) and Optic atrophy 1 (OPA1), that have been implicated in mitochondrial shape changes are indispensible for autophagy, apoptosis and necroptosis. Drp1 is the main regulator of mitochondrial fission and has become a key point of contention. The controversy focuses on whether Drp1 is directly involved in the regulation of cell death and, if involved, whether is it a stimulator or a negative regulator of cell death. Here, we examine the relevance of the homeostasis of the mitochondrial network structure in 3 different types of cell death, including autophagy, apoptosis and necroptosis. Furthermore, a variety of cancers often exhibit a fragmented mitochondrial phenotype. Thus, the fragmented ratio can reflect tumor progression that predicts prognosis and therapeutic response. In addition, we investigate whether the targeting of the mitochondrial fission protein Drp1 could be a novel therapeutic approach.


Patient Characterization Protocols for Psychophysiological Studies of Traumatic Brain Injury and Post-TBI Psychiatric Disorders.
Psychophysiological investigations of traumatic brain injury (TBI) are being conducted for several reasons, including the objective of learning more about the underlying physiological mechanisms of the pathological processes that can be initiated by a head injury. Additional goals include the development of objective physiologically based measures that can be used to monitor the response to treatment and to identify minimally symptomatic individuals who are at risk of delayed-onset neuropsychiatric disorders following injury. Research programs studying TBI search for relationships between psychophysiological measures, particularly ERP (event-related potential) component properties (e.g., timing, amplitude, scalp distribution), and a participant's clinical condition. Moreover, the complex relationships between brain injury and psychiatric disorders are receiving increased research attention, and ERP technologies are making contributions to this effort. This review has two objectives supporting such research efforts. The first is to review evidence indicating that TBI is a significant risk factor for post-injury neuropsychiatric disorders. The second objective is to introduce ERP researchers who are not familiar with neuropsychiatric assessment to the instruments that are available for characterizing TBI, post-concussion syndrome, and psychiatric disorders. Specific recommendations within this very large literature are made. We have proceeded on the assumption that, as is typically the case in an ERP laboratory, the investigators are not clinically qualified and that they will not have access to participant medical records.


The effects of oral and combined parenteral/oral immunization against an experimental Escherichia coli urinary tract infection in mice.
A double oral immunization (PO/PO) with an outer membrane protein (OMP) from a human uropathogenic strain of Escherichia coli, resulted in the partial protection of mice infected per urethrally with the same strain. Complete protection was achieved by immunizing with OMP in Freund's complete adjuvant (FCA), intramuscularly (i.m.), followed by an oral boost (i.m./PO). The PO/PO protocol stimulated mainly local urinary antibody synthesis, particularly IgA, whilst the i.m./PO regimen resulted in the appearance of both serum and urine antibodies. A single dose of OMP, 6 days after infection, rendered the mice resistant to reinfection, in contrast to non-immunized mice, and led to a significant increase in urine, serum and bile IgA anti-OMP levels. Our results confirm previous reports that the urinary tract forms part of the common mucosal immune system and provides further evidence for immunological memory in mucosal immunity. These results also demonstrate that our OMP preparation is a highly effective immunizing antigen, and that such preparations may be suitable as oral vaccines against urinary tract infection in humans.


[Gap junctions in the human urinary bladder].
Gap junctions are intercellular contacts important for the synchronization of muscle cell activity through electrical coupling. Since the role of gap junctions for the function of smooth bladder muscle is still a matter of debate, we investigated the occurrence of gap junctions and the gap junctional protein connexin (Cx) 45 in the detrusor of the nonobstructed stable human bladder. Detrusor biopsies from 6 patients aged 64 (55-72) years with stable nonobstructed bladders were investigated for the occurrence of gap junctions by electron microscopy, molecular biological techniques and immunohistochemistry. Transmission electron microscopy and freeze fracture showed the presence of gap junction at plasma membranes of detrusor smooth muscle cells. By reverse transcriptase (RT) polymerase chain reaction (PCR) and in situ hybridization, we found an expression of Cx45 in the detrusor. These data were confirmed by immunolocalization of Cx45 on smooth muscle cells. This study provides morphological as well as molecular biological and immunohistochemical evidence that bladder smooth muscle cells are electrically coupled.


The Medical versus Zoological Concept of Outflow Tract Valves of the Vertebrate Heart.
The anatomical elements that in humans prevent blood backflow from the aorta and pulmonary artery to the left and right ventriclesare the aortic and pulmonary valves, respectively. Each valve regularly consists of three leaflets (cusps), each supported by its valvular sinus. From the medical viewpoint, each set of three leaflets and sinuses is regarded as a morpho-functional unit. This notion also applies to birds and non-human mammals. However, the structures that prevent the return of blood to the heart in other vertebrates are notably different. This has led to discrepancies between physicians and zoologists in defining what a cardiac outflow tract valve is. The aim here is to compare the gross anatomy of the outflow tract valvular system among several groups of vertebrates in order to understand the conceptual and nomenclature controversies in the field.


First principles centroid molecular dynamics simulation of hydride in nanoporous C12A7:H.
Hydrides in nanoporous [Ca24Al28O64]4+(H-)4 (C12A7:H-) were investigated via first principles centroid molecular dynamics (CMD). The quality of our CMD simulations was assessed by examining the temperature dependence of the distribution of hydrides in the cages constituting the C12A7 framework. The vibrational states of C12A7:H- were analyzed by using the trajectories of the centroids generated in our CMD simulations. We find that the rattling motions of H- and D- behave qualitatively differently, resulting in non-trivial isotope effects, which are suggested to be detectable by using infrared and Raman spectroscopy.


[The effect of nitroglycerin on the Ca2+ ion level in the cytoplasm of human lymphocytes].
Fluorescence was used to examine the effects of nitroglycerin (60 microM) on basal and mitogen-induced (ConA, 25 micrograms/ml) Ca2+ levels in the human lymphocytic cytoplasm. Calcium-blocking effect of nitroglycerin was markedly shown in the medium containing 1 mM CaCl2 and virtually absent in calcium-free buffer. It is concluded that nitroglycerin affects cellular Ca2+ entry. A 120-minute preincubation led to a complete loss of the inhibitory effects of the drug on mitogen-induced Ca2+ responses of lymphocytes. Human lymphocytes are proposed as an experimental model for investigating the effects of nitrates and the mechanisms of their tolerance development.


Confinement of pure-electron plasmas in a toroidal magnetic-surface configuration.
A pure-electron plasma has been confined in a toroidal magnetic-surface configuration for as long as classical diffusion time due to neutral collisions. By controlling the potential of the internal conductor, long-term stable confinement of electrons has been achieved in a toroidal geometry.


Concurrent NP-HPTLC Determination of Shikonin and β,β-Dimethylacryl Shikonin in Arnebia benthamii.
Naphthoquinones are important class of molecules found as a natural red color pigments in roots of Arnebia benthamii (Wall. ex G. Don) L M. Johnston. The aim of present investigation is to develop and validates a simple, cost-effective and reliable method for quantification of these compounds. Therefore, a normal phase-high performance thin-layer chromatography (NP-HPTLC) method for concurrent determination of shikonin and β,β-dimethylacryl shikonin in A. benthamii was established. Method development of naphthoquinones in the methanol extract was done using hexane-ethyl acetate-methanol (40:7.5:2.5, v/v/v) solvent system at 520 nm. The developed method showed good band separation for shikonin (Rf, 0.37) and β,β-dimethylacryl shikonin (Rf, 0.58). The linearity ranged between 100 and 8,000 ng spot(-1) with an average recovery of >97% in both cases. The results showed reproducible intraday and interday precision (<2.0% RSD) in quantification of naphthoquinones. The limits of detection are 12.96 and 14.65 ng spot(-1) while the limits of quantification are 39.27 and 44.39 ng spot(-1) for shikonin and β,β-dimethylacryl shikonin, respectively. The developed method is reliable, fast, easy to follow and economic in concurrent assessment of shikonin and β,β-dimethylacryl shikonin in A. benthamii root samples. In addition, it seems to be first report for identification and quantification of β,β-dimethylacryl shikonin from the A. benthamii.


Determining the contents of protein and amino acids in peanuts using near-infrared reflectance spectroscopy.
The protein and amino acid contents of peanuts play a key role in determining their quality and value. Therefore, accurate, nondestructive, quick, and automated measurement of these components would be valuable in a commercial environment. This study explored the feasibility of determining the contents of protein and amino acids in peanuts using near infrared-reflectance spectroscopy (NIRS). 141 peanut samples were collected from 12 provinces in China. The spectra were scanned and obtained with an NIRS system. The determination coefficient and the ratio of the standard deviation in the validation set to the standard error of validation corresponded to 0.99 and 6.53 for protein, 0.88 and 2.52 for Asp, 0.83 and 3.00 for Thr, 0.86 and 2.40 for Ser, 0.87 and 2.57 for Glu, 0.88 and 2.36 for Gly, 0.88 and 3.00 for Leu, 0.89 and 2.88 for Arg, and 0.96 and 7.50 for Cys. NIRS combined with multivariate calibration has significant potential in determining the protein and amino acid contents of peanuts. This method is suitable for use in an industrial setting owing to its ease of use as well as the relatively low cost of obtaining and running the necessary equipment.


Unexplained syncope: diagnostic value of tilt-table testing.
Vasovagal syncope is a common syncope in patients who have no structural heart disease and occurs more often in young adults. It typically occurs in the erect posture, either standing or sitting. Upon recognition of the prodrome associated with NCS, subjects may avert syncope by lying down or putting the head between the knees. Use of head-up tilting is a recognized diagnostic tool and widely used for the evaluation of vasovagal syncope. However, cardiac diagnostic tests are not 100% accurate. This fact was recently underscored by what occurred in the recent tragic loss, due to ventricular fibrillation, of basketball star Reggie Lewis of the Boston Celtics. It is alleged that the tilt-table test was positive but that he also had structural heart disease. The most important diagnostic tool is the physician's clinical judgment.


The effect of dopamine on renal function during aortic cross clamping.
Eighteen male patients undergoing elective surgical reconstruction of the abdominal aorta were divided into two groups. Patients in Group I (nine) were given dopamine intravenously, in a dose of 2 micrograms/kg/min, during the first half of the period of cross-clamping, whilst those in Group II received dopamine during the second half. Each patient acted as his own control and for each, three periods were examined, namely: pre-clamp, clamping with dopamine and clamping without dopamine. Dopamine infusion during aortic clamping caused a significant rise in sodium output (P less than 0.01), potassium output (P less than 0.05), creatinine clearance (P less than 0.05) and urine output (P less than 0.05). We conclude that dopamine infusion during aortic clamping helps to protect the kidney from any deleterious effect of clamping.


Dynamics of the pi(-)p-->pi(0)pi(0)n reaction for p(pi(-))<750 MeV/c.
Data are presented for the reaction pi(-)p-->pi(0)pi(0)n in the range from threshold to p(pi(-))=750 MeV/c. The systematics of the data and multipole analyses are examined for sensitivity to a f(0)(600) ("sigma") meson. A one-pion-exchange mechanism is found to be very weak, or absent. The reaction appears to become dominated by sequential pi(0) decays through the Delta(1232) resonance as the beam momentum increases, along with substantial interference effects from several competing mechanisms.


Designing Studies Acceptable for Abstraction and Inclusion in Evidence-Based Laboratory Practice Guidelines.
Expansion of technologies, changing infrastructure, and dwindling resources have produced the need for health care reform and changes in clinical laboratories. The health care model will have to shift increasingly from a fee-for-service model to a value-based model. Laboratories will have to focus more on evidence-based outcome studies evaluating the effects of their preanalytical and postanalytical practices on real patient outcomes. Although well-designed clinical trials and multicenter studies are needed to determine the effects of laboratory processes on outcomes, there has been concern that too few well-designed studies have been published. To help improve the quality of study design and to facilitate reporting transparency, several method statements have been developed. The Standards for Reporting of Diagnostic Accuracy Studies (STARD) initiative was recently updated, listing 30 items deemed crucial for transparent reporting of studies, thereby allowing the creation of a robust database for clinical practice guidelines. Three methods describing the assessment of the quality of data on which to base recommendations for such guidelines are also available. Close attention must be given to study design so that parameters ensuring study quality are met, thereby allowing inclusion of the study data in the formulation of evidence-based laboratory best practices guidelines.


Localization of the binding site on plasma kallikrein for high-molecular-weight kininogen to both apple 1 and apple 4 domains of the heavy chain.
The C-terminal end of the heavy chain of human plasma prekallikrein or kallikrein contains a binding site for high-molecular-weight kininogen, the nonenzymatic procofactor of contact activation. To further map this binding site, a series of overlapping peptides were synthesized. The amount of kallikrein that bound to kininogen-coated microtiter plate wells in the presence of increasing concentrations of each peptide was determined by kallikrein amidolytic activity. A peptide encompassing Lys266-Gly295 of kallikrein, conformationally constrained by a disulfide bond, displayed the lowest Kd value (approximately 67 microM). The linear peptide, Leu262-Gly295, displayed lower affinity (129 microM). N-terminal or C-terminal truncation/extension peptides of this sequence diminished binding activity. Since the closely related protein, factor XI, has been shown to bind kininogen, a kallikrein-based peptide (Phe56-Gly86) homologous to the binding domain of FXI, was examined and found to possess less, but significant, binding affinity for kininogen (Kd 530 microM). Isothermal titration calorimetry was used to assess binding between the kallikrein-based peptides and a peptide encompassing the kallikrein binding domain in kininogen (Ser565-Lys595). Leu262-Gly295 possesses potent binding activity (Kd 52 microM), while Phe56-Gly86 displays poorer binding activity (Kd 400 microM). These interactions are endothermic and entropically favored, suggesting that a conformational rearrangement takes place upon binding. We conclude that the binding site for kininogen within prekallikrein is composed of discontinuous linear segments that form a contiguous surface in the folded protein.


Potential role of fractional anisotropy derived from diffusion tensor imaging in differentiating high-grade gliomas from low-grade gliomas: a meta-analysis.
It is crucial to accurately differentiate high-grade gliomas (HGGs) from low-grade gliomas (LGGs) preoperatively, as treatment strategies vary. So we performed a meta-analysis to assess the sensitivity and specificity of fractional anisotropy (FA) value derived from diffusion tensor imaging (DTI) in differentiating HGGs from LGGs. Between January 2005 and June 2014, relevant articles were searched from the Embase and Medline databases for analysis. Statistical analyses were performed using Meta-Disc 1.4. A total of 221 patients included in the FA analysis: 127 with HGGs and 94 LGGs. The pooled sensitivity, specificity and diagnostic odds ratio (DOR) for differentiating HGGs from LGGs were 93% (95% CI 0.87-0.97), 85% (95% CI 0.76-0.92), and 55.41 (95% CI 16.77-183.07), respectively. And computation of heterogeneity metrics revealed an acceptable level of the between-study heterogeneity of DOR (I(2)=30.9%). The results of our meta-analysis present that the FA derived from DTI act as a useful diagnostic marker could be used in distinguishing the HGGs from LGGs in the preoperative and the clinical application values are to be confirmed by further larger case-control studies.