Chlorhexidine Cloth Overview for Surgical Infection Prevention.
Infections are one of the most devastating complications that occur after lower extremity total joint arthroplasty or any surgical procedure. As such, it has become a major priority to reduce them through various preoperative strategies. Popular prophylactic antimicrobials include alcohol-based solutions, povidone iodine, as well as combinations of chlorhexidine-based products to address an individual's microbial load on the skin. Chlorhexidine is a broad-spectrum biocide with activity against Gram-positive and Gram-negative bacteria. The use of chlorhexidine cloths may be a choice over solutions, since some studies have shown that they can reduce lower extremity infection rates by greater than two-thirds. In this report, we will describe the scientific basis for the dual application technique of these cloths, as well as our general recommendations for usage for lower extremity arthroplasties and other surgical procedures. Multiple studies have demonstrated their efficacy, with a prospective randomized study of joint arthroplasties demonstrating a 2.9% deep infection rate without their use versus a reduction to 0.4%. In conclusion, we believe that these cloths are appropriate for use in all hip and knee lower extremity arthroplasties as well as other surgical procedures.


A comparative evaluation between real time Roche COBas TAQMAN 48 HCV and bDNA Bayer Versant HCV 3.0.
The HCV virus is a common human pathogen made of a single stranded RNA genome with 9600nt. This work compared two different commercial methods used for HCV viral load, the bDNA Bayer Versant HCV 3.0 and the RealTime Roche COBAS TaqMan 48 HCV. We compared the reproducibility and linearity of the two methods. Seventy-five plasma samples with genotypes 1 to 4, which represent the population (45% genotype 1; 24% genotype 2; 13% genotype 3; 18% genotype 4) were directly processed with the Versanto method based upon signal amplification; the same samples were first extracted (COBAS Ampliprep - TNAI) and then amplified using RealTime PCR (COBAS TaqMan 48). The results obtained indicate the same performance for both methods if they have genotype 1, but in samples with genotypes 2, 3 and 4 the RealTime PCR Roche method gave an underestimation in respect to the Bayer bDNA assay.


Contribution of shared environmental factors to familial aggregation of common cancers: an adoption study in Sweden.
Cancer runs in families, suggesting a heritable component, but the contribution of environmental factors cannot be neglected. Studies on spousal risk can partly disentangle the environmental contribution but miss shared environmental factors during childhood and adolescence. Here, we examined the familial aggregation of common cancers among 80,281 Swedish-born adoptees, identified from the national Swedish Multigeneration Register, and linked them to the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for common cancers (colorectal, lung, breast, prostate, and skin cancers) in the adoptees whose adoptive parents were diagnosed with concordant cancers, compared with the general population. SIRs in adoptees with an affected adoptive parent ranged from 1.00 (breast cancer) to 1.28 (skin cancer), whereas the SIRs in nonadoptees with an affected parent ranged from 1.63 (colorectal cancer) to 2.12 (skin cancer). Environmental factors account for around 0-28% of the familial aggregation. Cancer sites with high environmental contributions were observed for skin and colorectal cancers, which are known to have strong environmental causes.


Acupuncture as Adjuvant Therapy for Sleep Disorders in Parkinson's Disease.
There are few studies which attest the efficacy of acupuncture on treatment of sleep disturbs in Parkinson disease. The aimed of this randomized clinical trial was to evaluate the effects of acupuncture on sleep disturbs of 22 patients with diagnosis of idiopathic Parkinson disease (Hoehn-Yahr 1 to 3) who have assistance on the Pro-Parkinson Program of Clinical Hospital at Federal University of Pernambuco in Brazil. All participants were evaluated by Parkinson Disease Sleep Scale (PDSS) before and after 8 weeks. The experimental group was submitted to 8 sections (once a week) which had duration of 30 minutes. The control group had no intervention. The intervention was executed using the acupuncture points LR3 (Taichong), SP6 (Sanyinjiao), LI4 (Hegu), TE5 (Wai-Guan), HT7 (Shenmen), PC6 (Neiguan), LI11 (Quchi), GB20 (Fengchi). Paired analyses were obtained by Wilcoxon test and independent analyses were made according to Mann-Whitney test. This study presented a potential therapeutic benefit of acupuncture on sleep disturbs of Parkinson's disease patients. This study showed a possible therapeutic benefit through acupuncture in sleep disorders in patients with PD. However, we propose new studies related to the effects of acupuncture on the clinical symptoms and evolution of the disease.


The Wright-Fisher site frequency spectrum as a perturbation of the coalescent's.
The first terms of the Wright-Fisher (WF) site frequency spectrum that follow the coalescent approximation are determined precisely, with a view to understanding the accuracy of the coalescent approximation for large samples. The perturbing terms show that the probability of a single mutant in the sample (singleton probability) is elevated in WF but the rest of the frequency spectrum is lowered. A part of the perturbation can be attributed to a mismatch in rates of merger between WF and the coalescent. The rest of it can be attributed to the difference in the way WF and the coalescent partition children between parents. In particular, the number of children of a parent is approximately Poisson under WF and approximately geometric under the coalescent. Whereas the mismatch in rates raises the probability of singletons under WF, its offspring distribution being approximately Poisson lowers it. The two effects are of opposite sense everywhere except at the tail of the frequency spectrum. The WF frequency spectrum begins to depart from that of the coalescent only for sample sizes that are comparable to the population size. These conclusions are confirmed by a separate analysis that assumes the sample size n to be equal to the population size N. Partly thanks to the canceling effects, the total variation distance of WF minus coalescent is 0.12∕logN for a population sized sample with n=N, which is only 1% for N=2×104. The coalescent remains a good approximation for the site frequency spectrum of-large samples.


[Effect of preoperative radiotherapy as an adjunctive approach on proliferation and apoptosis of cancer cells in rectal cancer].
To investigate the effect of preoperative radiotherapy as an adjunctive approach on proliferation and apoptosis of cancer cells in rectal cancer. Eighty patients with (p)TNM stage II or III rectal cancer were enrolled from April 2000 to December 2002. The patients were divided into two groups, which were group received surgical treatment alone (40 cases) and group received preoperative adjuvant radiotherapy with a radiological dose of 40 G( y ) (40 cases). The expression of Ki- 67 protein in rectal cancer was detected immunohistochemically and apoptosis was detected by TUNEL technique. In radiotherapy group, the tumor volume shrank markedly in 14 cases, partially in 18,slightly in 8 with an overall efficiency rate of 80% .There was significant positive correlation between spontaneous apoptosis and Ki- 69 marker index in cancer tissues before radiotherapy(gamma =0.563P=0.027). The expression of Ki- 67 in rectal cancer tissues was significantly lower after radiotherapy than that before radiotherapy, as well as in the control group(P=0.017 vs. P=0.011).The expression of Ki- 67 in paratumor tissues 2cm from tumor was significantly lower after radiotherapy than that before radiotherapy. Apoptosis index (AI) in rectal cancer tissues was significantly higher after radiotherapy than that before radiotherapy, and that in the control group (P=0.013 vs. P=0.018). Radiotherapy can inhibit proliferation and induce apoptosis of rectal cancer cells. The expression level of Ki- 67 can be considered as a screening index for preoperative radiotherapy.


[Characteristics of working conditions at metallurgy-related plants].
Working conditions at more versus less advanced technology steel plants of the Volgograd Region are analyzed. The working conditions at the less advanced technology plants are referred to as a very high occupational risk. It is necessary to work out measures to lower the poor impact of microclimate, dust, noise, to improve illumination, and to regulate labor at steel plants.


FREQUENCY-DEPENDENT FITNESS IN SILENE VULGARIS, A GYNODIOECIOUS PLANT.
In gynodioecious plants the selective processes that determine the relative number of female and hermaphroditic individuals are often frequency dependent. Frequency-dependent fitness can occur in the two sexes through a variety of mechanisms, especially given pollen limitation and inbreeding depression when hermaphrodites are rare. Frequency dependence in several components of the fitness of female and hermaphroditic Silene vulgaris was tested in experiments in which the relative numbers of the two sexes was varied among 12 artificial populations. In females, the proportion of flowers that set fruit covaried positively among populations with the frequency of hermaphrodites in two separate experiments, whereas the number of flowers/plant covaried negatively in one case. In hermaphrodites, the number of seeds/fruit covaried positively with the frequency of hermaphrodites, whereas the fitness of hermaphrodites estimated through pollen transfer covaried negatively. The results are discussed as they relate to the selective maintenance of gynodioecy in S. vulgaris and in light of a recent model of the effect of population structure on selection in gynodioecious systems.


Cell Type-Specific and Inducible PTEN Gene Silencing by a Tetracycline Transcriptional Activator-Regulated Short Hairpin RNA.
Inducible and reversible gene silencing in desired types of cells is instrumental for deciphering gene functions using cultured cells or in vivo models. However, efficient conditional gene knockdown systems remain to be established. Here, we report the generation of an inducible expression system for short hairpin RNA (shRNA) targeted to PTEN, a well-documented dual-specificity phosphatase involved in tumor suppression and ontogenesis. Upon induction by doxycycline (DOX), the reverse tetracycline transcriptional activator (rtTA) switched on the concomitant expression of GFP and a miR-30 precursor, the subsequent processing of which released the embedded PTEN-targeted shRNA. The efficacy and reversibility of PTEN knockdown by this construct was validated in normal and neoplastic cells, in which PTEN deficiency resulted in accelerated cell proliferation, suppressed apoptosis, and increased invasiveness. Transgenic mice harboring the conditional shRNA-expression cassette were obtained; GFP expression and concurrent PTEN silencing were observed upon ectopic expression of rtTA and induction with Dox. Therefore, this study provides novel tools for the precise dissection of PTEN functions and the generation of PTEN loss of function models in specific subsets of cells during carcinogenesis and ontogenesis.


Magnetic field induced dynamical chaos.
In this article, we have studied the dynamics of a particle having charge in the presence of a magnetic field. The motion of the particle is confined in the x-y plane under a two dimensional nonlinear potential. We have shown that constant magnetic field induced dynamical chaos is possible even for a force which is derived from a simple potential. For a given strength of the magnetic field, initial position, and velocity of the particle, the dynamics may be regular, but it may become chaotic when the field is time dependent. Chaotic dynamics is very often if the field is time dependent. Origin of chaos has been explored using the Hamiltonian function of the dynamics in terms of action and angle variables. Applicability of the present study has been discussed with a few examples.


Segregation-pattern reorientation of a granular mixture on a horizontally oscillating tray.
Reorientation of the segregation pattern of a binary granular mixture on a two-dimensional horizontally oscillating tray is numerically realized. The mixture consists of large and heavy particles and small and light particles, and the segregation pattern shows a transition between a striped pattern perpendicular to the oscillation and one parallel to the oscillating direction according to the change of area fractions of the two types of particle. The transition mechanism is discussed on the basis of a simplified one-dimensional dynamics.


A new technique for determining the distribution of N7-methylguanine using an automated DNA sequencer.
We have developed a method to determine rapidly the sequence specificity of DNA alkylation resulting from chemical treatment. The utility of this approach is demonstrated here in a study of the sequence specificity of alkylation by dimethylsulphate (DMS). The method is independent of the sequence chosen and makes use of the polymerase chain reaction (PCR) to generate a fluorescently labelled DNA target. In this study, a 302 bp segment of the Escherichia coli lacI gene was amplified and the product purified by liquid chromatography on a Mono Q column. This DNA was alkylated with DMS and treated with hot piperidine to produce single-strand breaks at sites of N7 alkylation. The distribution of the break points, and hence the position and extent of alkylation, were determined on an Applied Biosystems 370A automated DNA sequencer.


Modeling and optimizing of the random atomic spin gyroscope drift based on the atomic spin gyroscope.
In order to improve the atom spin gyroscope's operational accuracy and compensate the random error caused by the nonlinear and weak-stability characteristic of the random atomic spin gyroscope (ASG) drift, the hybrid random drift error model based on autoregressive (AR) and genetic programming (GP) + genetic algorithm (GA) technique is established. The time series of random ASG drift is taken as the study object. The time series of random ASG drift is acquired by analyzing and preprocessing the measured data of ASG. The linear section model is established based on AR technique. After that, the nonlinear section model is built based on GP technique and GA is used to optimize the coefficients of the mathematic expression acquired by GP in order to obtain a more accurate model. The simulation result indicates that this hybrid model can effectively reflect the characteristics of the ASG's random drift. The square error of the ASG's random drift is reduced by 92.40%. Comparing with the AR technique and the GP + GA technique, the random drift is reduced by 9.34% and 5.06%, respectively. The hybrid modeling method can effectively compensate the ASG's random drift and improve the stability of the system.


Design and Validation of a Low-Cost Mobile EEG-Based Brain-Computer Interface.
Objective: We designed and validated a wireless, low-cost, easy-to-use, mobile, dry-electrode headset for scalp electroencephalography (EEG) recordings for closed-loop brain-computer (BCI) interface and internet-of-things (IoT) applications. Approach: The EEG-based BCI headset was designed from commercial off-the-shelf (COTS) components using a multi-pronged approach that balanced interoperability, cost, portability, usability, form factor, reliability, and closed-loop operation. Main Results: The adjustable headset was designed to accommodate 90% of the population. A patent-pending self-positioning dry electrode bracket allowed for vertical self-positioning while parting the user's hair to ensure contact of the electrode with the scalp. In the current prototype, five EEG electrodes were incorporated in the electrode bracket spanning the sensorimotor cortices bilaterally, and three skin sensors were included to measure eye movement and blinks. An inertial measurement unit (IMU) provides monitoring of head movements. The EEG amplifier operates with 24-bit resolution up to 500 Hz sampling frequency and can communicate with other devices using 802.11 b/g/n WiFi. It has high signal-to-noise ratio (SNR) and common-mode rejection ratio (CMRR) (121 dB and 110 dB, respectively) and low input noise. In closed-loop BCI mode, the system can operate at 40 Hz, including real-time adaptive noise cancellation and 512 MB of processor memory. It supports LabVIEW as a backend coding language and JavaScript (JS), Cascading Style Sheets (CSS), and HyperText Markup Language (HTML) as front-end coding languages and includes training and optimization of support vector machine (SVM) neural classifiers. Extensive bench testing supports the technical specifications and human-subject pilot testing of a closed-loop BCI application to support upper-limb rehabilitation and provides proof-of-concept validation for the device's use at both the clinic and at home. Significance: The usability, interoperability, portability, reliability, and programmability of the proposed wireless closed-loop BCI system provides a low-cost solution for BCI and neurorehabilitation research and IoT applications.


Alternative therapies for high-risk elderly rheumatic patients.
The main high-risk conditions among elderly rheumatic patients are peptic ulcer, renal or hepatic insufficiencies, and bleeding problems (either spontaneous or iatrogenic). Because the incidence of these conditions is significant, elderly patients should be monitored for them regularly. Although nonsteroidal antiinflammatory drugs (NSAIDs) generally are avoided, these agents can be used in selected patients. High-risk elderly rheumatoid arthritis patients can be given prednisone and a carefully chosen disease-modifying antirheumatic drug. Although analgesics can be used instead of NSAIDs, their efficacy is poor. Local therapy, i.e. intraarticular injections, and even surgery are good alternative resources. In Europe, patients with osteoarthritis are often treated with NSAIDs. High-risk elderly patients may receive sufficient relief with analgesics. If relief is not adequate, hip or knee total prosthesis procedures must be performed earlier than would normally be done.


Gene therapy of the other genome: the challenges of treating mitochondrial DNA defects.
Human mitochondrial DNA is a 16.5 kb circular DNA molecule located inside the mitochondrial matrix. Although accounting for only about 1% of total cellular DNA, defects in mitochondrial DNA have been found to have major effects on human health. A single mtDNA mutation may cause a bewildering variety of clinical symptoms mainly involving the neuromuscular system at any age of onset. Despite significant advances in the understanding of mitochondrial DNA defects at a molecular level, the clinical diagnosis of mtDNA diseases remains a significant challenge and effective therapies for such diseases are as yet unavailable. In contrast to gene therapy for chromosomal DNA defects, mitochondrial gene therapy is a field that is still in its infancy and attempts towards gene therapy of the mitochondrial genome are rare. In this review we outline what we believe are the unique challenges associated with the correction of mtDNA mutations and summarize current approaches to gene therapy for the "other genome".


Unusual complication of internal jugular vein cannulation.
Internal jugular cannulation is a common procedure in the hospitals. We report a rare complication where the guide wire was pushed into the internal jugular vein without threading the catheter through. Complications due to central venous cannulation are also discussed.


HIV-1 infection induces a selective reduction in STAT5 protein expression.
HIV-1 infection is accompanied by qualitative and quantitative defects in CD4+ T lymphocytes. Loss of immune function in HIV patients is usually associated with a profound dysregulation of cytokine production. To investigate whether cytokine signaling defects occur during HIV infection, PHA blasts from healthy human donors were infected with two strains of HIV-1 and screened for the expression of STAT proteins used in cytokine signaling. A selective decrease in STAT5B was seen 8 days after infection with the BZ167 dual-tropic HIV isolate, but not with the Ba-L, M-tropic strain. Based on these findings, purified T cells from HIV-infected patients in different stages of disease were also tested for STAT expression; decreases in STAT5A, STAT5B, and STAT1alpha were observed in all patients. The reduction in STATs seen in vivo and in vitro after HIV infection may contribute to the loss of T cell function in HIV disease.


BMPs, FGF8 and Wnts regulate the differentiation of locus coeruleus noradrenergic neuronal precursors.
In the present study, we investigated the involvement of rhombomere 1 patterning proteins in the regulation of the major noradrenergic centre of the brain, the locus coeruleus. Primary cultures of rat embryonic day 13.5 locus coeruleus were treated with fibroblast growth factor-8, noggin and members of the bone morphogenetic and Wnt protein families. We show that bone morphogenetic proteins 2, 5 and 7 increase and noggin decreases the number of tyrosine hydroxylase-positive locus coeruleus neurons. Interestingly, from all Wnts expressed in the first rhombomere by embryonic day 12.5 in the mice, we only found expression of wnt5a mRNA in the vicinity of the locus coeruleus. In agreement with this finding, from all Wnts studied in vitro, only Wnt5a increased the number of tyrosine hydroxylase-positive neurons in locus coeruleus cultures. Finally, we also found that fibroblast growth factor-8 increased the number of tyrosine hydroxylase-positive cells in locus coeruleus cultures. Neither of the identified factors affected the survival of tyrosine hydroxylase-positive locus coeruleus noradrenergic neurons or the proliferation of their progenitors or neurogenesis. Instead, our results suggest that these patterning signals of rhombomere 1 may work to promote the differentiation of noradrenergic progenitors at later stages of development.


Phototoxic reactions caused by sodium fluorescein.
To report three cases of phototoxic reactions to intravenous fluorescein for retinal angiography and to describe provocative testing in a volunteer. Three patients with phototoxic reactions were interviewed, and one volunteer underwent a controlled challenge test by applying a potent sunscreen and exposing skin areas to direct sunlight before and after fluorescein administration. All patients experienced marked cutaneous erythema, edema, and pain to sun-exposed areas within 1 hour of exposure. The reaction faded during a variable period of time, and one case resulted in mild epidermal desquamation and prolonged discomfort. We noted minimal skin changes in the volunteer who was exposed to the sun before fluorescein administration; however, marked blanching erythema and pain were noted after fluorescein administration and sunlight. Consistent with its in vitro properties as a photodynamic dye, fluorescein may rarely act as a phototoxic agent in humans at doses employed for fluorescein angiography.


Mitochondrial pleomorphy in plant cells is driven by contiguous ER dynamics.
Mitochondria are pleomorphic, double membrane-bound organelles involved in cellular energetics in all eukaryotes. Mitochondria in animal and yeast cells are typically tubular-reticulate structures and several micro-meters long but in green plants they are predominantly observed as 0.2-1.5 μm punctae. While fission and fusion, through the coordinated activity of several conserved proteins, shapes mitochondria, the endoplasmic reticulum (ER) has recently been identified as an additional player in this process in yeast and mammalian cells. The mitochondria-ER relationship in plant cells remains largely uncharacterized. Here, through live-imaging of the entire range of mitochondria pleomorphy we uncover the underlying basis for the predominantly punctate mitochondrial form in plants. We demonstrate that mitochondrial morphology changes in response to light and cytosolic sugar levels in an ER mediated manner. Whereas, large ER polygons and low dynamics under dark conditions favor mitochondrial fusion and elongation, small ER polygons result in increased fission and predominantly small mitochondria. Hypoxia also reduces ER dynamics and increases mitochondrial fusion to produce giant mitochondria. By observing elongated mitochondria in normal plants and fission-impaired Arabidopsis nmt1-2 and drp3a mutants we also establish that thin extensions called matrixules and a beads-on-a-string mitochondrial phenotype are direct consequences of mitochondria-ER interactions.


[Current challenges in the diagnosis and treatment of filamentous mycosis in critically ill patients].
Influenza and coronavirus disease 2019 are independent risk factors for the development of invasive fungal disease (IFD) in critically ill patients in the intensive care unit. IFD, particularly mold infections, have a high mortality rate. The diagnosis and treatment of mold infections is challenging, and early detection and timely treatment are crucial in reducing the mortality of IFD. This review will summarize the latest epidemiology and risk factors for the development of mold infections in critically ill patients, current diagnostic criteria and challenges, as well as the treatment strategies recommended by the international clinical guidelines, aiming to provide some references for the diagnosis and treatment of mold infections in critically ill patients in clinical practice.


Neuroprotective effects of flavonoids on hypoxia-, glutamate-, and oxidative stress-induced retinal ganglion cell death.
This study was conducted to investigate the effect of flavonoids, a major family of antioxidants contained in foods, on retinal ganglion cell (RGC) death induced by hypoxia, excessive glutamate levels, and oxidative stress. Moreover, to assess the structure-activity relationships of flavonoids, three types of flavonoids with different numbers of hydroxyl groups and varieties of sugar chains were studied. Three kinds of flavonoids-nicotiflorin, rutin, and quercitrin-were used. The death of neonatal rat purified RGCs was induced by hypoxic conditions (5% O(2), 5% CO(2), 37 °C) for 12 h, 25 µM glutamate over three days, or oxidative stress by depleting antioxidants from the medium for 24 h. RGC survival rates were calculated under each condition and compared with vehicle cultures. Modification of cell death signaling after stress-induced apoptosis and necrosis by flavonoids was assessed using caspase-3 and calpain immunoreactivity assays. Under hypoxic and glutamate stress, both nicotiflorin and rutin significantly increased the RGC survival rate at 1 nM or higher, while quercitrin increased it at 100 nM or higher. Under oxidative stress, nicotiflorin, rutin, and quercitrin also significantly increased the RGC survival rate at 1 nM, 0.1 nM, and 100 nM or higher, respectively. Rutin significantly inhibited the induction of caspase-3 under both hypoxia and excessive glutamate stress, as well as blocking the induction of calpain during oxidative stress. Nicotiflorin and rutin showed neuroprotective effects on hypoxia-, glutamate- or oxidative stress-induced RGC death at concentrations of 1 nM or higher. The presence of a specific sugar side chain (rutinoside) may enhance neuroprotective activity.


Guanine quadruplexes are formed by specific regions of human transposable elements.
Transposable elements form a significant proportion of eukaryotic genomes. Recently, Lexa et al. (Nucleic Acids Res 42:968-978, 2014) reported that plant long terminal repeat (LTR) retrotransposons often contain potential quadruplex sequences (PQSs) in their LTRs and experimentally confirmed their ability to adopt four-stranded DNA conformations. Here, we searched for PQSs in human retrotransposons and found that PQSs are specifically localized in the 3'-UTR of LINE-1 elements, in LTRs of HERV elements and are strongly accumulated in specific regions of SVA elements. Circular dichroism spectroscopy confirmed that most PQSs had adopted monomolecular or bimolecular guanine quadruplex structures. Evolutionarily young SVA elements contained more PQSs than older elements and their propensity to form quadruplex DNA was higher. Full-length L1 elements contained more PQSs than truncated elements; the highest proportion of PQSs was found inside transpositionally active L1 elements (PA2 and HS families). Conservation of quadruplexes at specific positions of transposable elements implies their importance in their life cycle. The increasing quadruplex presence in evolutionarily young LINE-1 and SVA families makes these elements important contributors toward present genome-wide quadruplex distribution.


Impact of salinity gradient, water pollution and land use types on greenhouse gas emissions from an urbanized estuary.
Estuaries have been recognized as one of the major sources of greenhouse gases (GHGs) in aquatic systems; yet we still lack insights into the impact of both anthropogenic and natural factors on the dynamics of GHG emissions. Here, we assessed the spatiotemporal dynamics and underlying drivers of the GHG emissions from the Scheldt Estuary with a focus on the effects of salinity gradient, water pollution, and land use types, together with their interaction. Overall, we found a negative impact of salinity on carbon dioxide (CO2) and nitrous oxide (N2O) emissions which can be due to the decrease of both salinity and water quality when moving upstream. Stronger impact of water pollution on the GHG emissions was found at the freshwater sites upstream compared to saline sites downstream. In particular, when water quality of the sites reduced from good, mainly located in the mouth and surrounded by arable sites, to polluted, mainly located in the upstream and surrounded by urban sites, CO2 emissions from the sites doubled while N2O emissions tripled. Similarly, the effects of water pollution on methane (CH4) emissions became much stronger in the freshwater sites compared to the saline sites. These decreasing effects from upstream to the mouth were associated with the increase in urbanization as sites surrounded by urban areas released on average almost two times more CO2 and N2O than sites surrounded by nature and industry areas. Applied machine learning methods also revealed that, in addition to salinity effects, nutrient and organic enrichment stimulated the GHG emissions from the Scheldt Estuary. These findings highlight the importance of the interaction between salinity, water pollution, and land use in order to understand their influences on GHG emissions from dynamic estuarine systems.


Phase II study of bortezomib and pegylated liposomal doxorubicin in the treatment of metastatic breast cancer.
Based on preclinical studies and a phase I trial of the combination of bortezomib and pegylated liposomal doxorubicin (PLD), which both showed activity in breast cancer, we conducted a phase II study of this regimen in patients with metastatic breast cancer. Patients received bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of an every-21-day cycle, along with PLD 30 mg/m2 on day 4. The primary objective was to evaluate the response rate of this combination, while secondary objectives were to obtain further safety data about this combination, to evaluate the time to disease progression (TTP), and to evaluate response by the breast cancer subtype. One of 12 evaluable patients had a partial response (8%), while 3 (25%) had stable disease. At 26 months follow-up, the median overall survival was 4.3 months (95% CI, 1.2-26.2) and the median TTP was 1.3 months (95% CI, 0.8-14.0 months). The combination was well tolerated, with the most common events including low-grade nausea and vomiting, neutropenia, and neuropathy, and no cardiac toxicity was seen. Of the 7 tumors subtyped, no association was seen between intrinsic subtype or receptor status and response. The combination of PLD and bortezomib was well tolerated but has minimal activity in heavily pretreated unselected metastatic breast cancer.


Barriers and Facilitators to Palliative Care of Patients with Chronic Heart Failure in Germany: A Study Protocol.
Despite its high prevalence, similar symptoms and symptom burden, people suffering from chronic heart failure receive less palliative care than patients with malignant diseases. Internationally, numerous barriers to palliative care of patients with chronic heart failure are known, however, there are no credible data regarding barriers and facilitators to palliative care of people suffering from chronic heart failure available for Germany. Tripartite study. First part of this study evaluates health care providers' (physicians and nurses) perceived barriers and facilitators to palliative care of patients with chronic heart failure using a qualitative approach. At least 18 persons will be interviewed. In the second part, based on the results of part one, a questionnaire about barriers and facilitators to palliative care of patients with chronic heart failure will be designed and applied to at least 150 physicians and nurses. In the last part a classic Delphi method will be used to develop specific measures to improve the palliative care for chronic heart failure patients. The results of this study will help to understand why patients with heart failure are seldom referred to palliative care and will provide solutions to overcome these barriers. Developed solutions will be the first step to improve palliative care in patients with heart failure in Germany. In addition, the results will help health care providers in other countries to take action to improve palliative care situations for heart failure patients. Significance for public healthPatients with chronic heart failure suffer from similar symptoms and symptom burden than patients with malignant diseases. However, palliative care differs between these groups in a quantitative and qualitative way. This study will help to understand why patients with chronic heart failure receive less palliative care than patients with malignant disease. In addition, measures to overcome barriers and to promote facilitators of palliative care in patients with chronic heart failure will be developed. These recommendations could provide a basis for quality improvement projects or studies aiming at improving symptoms and symptom burden of heart failure patients. The recommended measures could also be used to reduce caregiver burden.


Budding and tubulation in highly oblate vesicles by anchored amphiphilic molecules.
We studied local budding and tubulation induced in highly oblate lipid vesicles by the anchoring of either polymers having a hydrophilic backbone and grafted hydrophobic anchor groups, or by oleoyl-coenzyme A, an amphiphilic molecule important in lipid metabolism. The dynamics of bud formation, shrinkage, and readsorption is consistent with an induced spontaneous curvature coupled with local amphiphile diffusion on the membrane. We report a novel metastable state prior to bud readsorption.


Optimizing everolimus exposure when combined with calcineurin inhibitors in solid organ transplantation.
The mammalian target of rapamycin (mTOR) inhibitor everolimus is a narrow therapeutic index drug for which optimal exposure levels are essential. The consistent pharmacokinetic profile of everolimus allows trough concentration (C0) measurement to be an appropriate and reliable index for therapeutic drug monitoring (TDM). Exposure-response analyses of data from early fixed-dose trials demonstrated that rates of biopsy-proven acute rejection (BPAR) are significantly higher if everolimus C0 declines below 3 ng/mL, an observation confirmed in subsequent concentration-controlled trials. Evidence for the most favorable upper limit is less clear but with reduced-exposure calcineurin inhibitor (CNI) therapy, an upper limit of 8 ng/mL appears to balance efficacy and safety outcomes. The recommended C0 range is 3-8 ng/mL in kidney, liver and heart transplantation patients, based on LC-MS/MS monitoring in whole blood. Randomized clinical trials based on this target range have demonstrated rates of BPAR comparable to a regimen of mycophenolic acid with standard-exposure CNI. Everolimus exhibits moderate intrapatient pharmacokinetic variability, and it can be challenging to maintain stable concentrations within target range in some individuals. Many factors can influence everolimus exposure for a given dose, including hepatic function, activity of the drug efflux pump P-glycoprotein, the rate of everolimus metabolism, drug-drug interactions (predominantly with CYP3A4 and P-glycoprotein inhibitors, including cyclosporine), intake of fatty food, and patient adherence to the prescribed regimen. Trough concentration levels should be monitored 4-5days after the first dose and after any change in everolimus dose, with additional monitoring in response to any change in concomitant medication or other clinical circumstances which could alter everolimus exposure. Although LC-MS/MS is the gold standard for everolimus monitoring, various immunoassays are widely used due to their relative simplicity and lower cost, and results can show considerable discrepancies with reference methods due to issues such as interassay variability and cross-reactivity. Method standardization will be important in the future to improve the consistency and reproducibility of results between centers. In conclusion, based on an extensive program of clinical trials, the optimal exposure range for everolimus in combination with reduced-exposure CNI therapy has been established and can be achieved in most transplant recipients through careful, planned TDM.


The Effect of Clofibrate and Phototherapy on Prolonged Jaundice due to Breast Milk in Full-Term Neonates.
Jaundice is one of the most common problems during infancy. It is believed that breast milk jaundice is one of the reasons for the persistence of jaundice after 14 days of prolonged jaundice. This study evaluates the effect of Clofibrate and phototherapy on prolonged jaundice originating from breast milk in term and healthy neonates. This double-blind clinical trial study was performed on 100 randomly divided neonates in the neonatal ward of Besat Hospital. In addition to phototherapy, the case group received a single dose of edible Clofibrate (50 mg/kg) dissolved in 2 CCs of distilled water. The control group received the same amount of distilled water as the phototherapy group. After treatment, bilirubin change rate, duration of hospitalization, and any association with gender, gestational age, hemoglobin, blood type, and Rh of neonates were determined and compared throughout the 2 groups. Data analysis showed that the bilirubin reduction rate was statistically significantly higher in the case group than in the control group (P < .05). The mean duration of hospitalization and phototherapy in the case group was significantly lower than in the control group (P = .005). The bilirubin reduction rate was not affected significantly by gestational age, blood type, or Rh. This study's results demonstrated that Clofibrate effectively decreased bilirubin levels and shortened the duration of phototherapy and hospitalization in infants with probable breast milk jaundice. IRCT2012092910933N1.


A phase I trial of bortezomib in combination with everolimus for treatment of relapsed/refractory non-Hodgkin lymphoma.
B-cell non-Hodgkin lymphomas (NHL) display dysregulation of pathways controlling cell proliferation and apoptosis. Combined proteasome and mTOR inhibition, demonstrated with bortezomib and everolimus in a preclinical model, thus warrants evaluation in humans. We conducted a phase I study to identify the maximum tolerated dose (MTD) and safety of this combination in relapsed/refractory (r/r) NHL. Twenty-nine patients were enrolled from July 2008 to March, 2015. Toxicities were primarily hematologic, and dose-limiting thrombocytopenia defined the MTD as 5 mg everolimus daily with 1.3 mg/m2 bortezomib d1, 4, 8, and 11 every 21 days. Of 25 response-evaluable patients there was one complete response in a patient with MCL and three partial responses (two MCL, one FL) for an overall response rate of 16%. In conclusion, the combination of everolimus and bortezomib results in dose limiting thrombocytopenia, but is tolerable. This combination has limited clinical activity in heavily pretreated NHL.


Local and systemic Curcumin C3 complex inhibits 4NQO-induced oral tumorigenesis via modulating FGF-2/FGFR-2 activation.
Head and Neck Squamous cell carcinoma (HNSCC) can be characterized by synchronous tumors in the upper aerodigestive tract. Second primary tumors as a result of field cancerization are a significant problem amongst patients with risk factors for HNSCC, indicating a need for chemo preventive agents. We investigated the efficacy of local and systemic Curcumin C3 complex (C3); a purified mixture of Curcumin, bisdemethoxy Curcumin and demethoxy Curcumin as a chemo preventative agent in 4-nitroquinoline-1-oxide (4NQO)-induced tumorigenesis in mice. The effect of local C3 application was compared to C3 administered orally and in combination with systemic administration. C57Bl/6 mice were administered 4NQO (50 µg/ml) in the drinking water for 16 weeks. At 12 weeks, mice were subjected to daily treatment with either vehicle (control), or 15 mg C3 complex by local delivery, gavage, or combined local and gavage for 28 days (16 week time point), and followed up to 22 weeks. Compared to local and oral systemic C3 administration, combination of local and systemic application significantly decreased multiplicity of 4NQO-induced preneoplastic and neoplastic lesions (p<0.05). Treatment with C3 correlated with a decrease in cell proliferation compared to the 4NQO group. Further, pre-treatment with C3 complex significantly attenuated 4NQO induced expression of basic fibroblast growth factor (FGF-2) and its cognate receptor FGFR-2, suggesting an important role of FGF-2/FGFR-2 axis in chemoprevention of HNSCC (p<0.05). Our findings suggest that a combination of local and systemic C3 complex could effectively target proliferation and inhibit 4NQO-induced tumorigenesis via modulation of the FGF-2/FGFR-2 axis as a mechanism for its efficacy.


Synthesis, biophysical, and biochemical properties of PNA-DNA chimeras.
Three PNA-DNA chimeric dimer synthons (tT, upT and uhT, see Sch. 1) have been synthesized in solution and used to make T20-analogue chimeras applying standard solid-phase DNA synthesis protocol. Duplex forming ability of chimeras with dA20 and their hydrolyses by 3'- and 5'-exonucleases (snake venom and bovine spleen phosphodiesterase, respectively) have been investigated.


Lack of evidence on Tai Chi-related effects in patients with type 2 diabetes mellitus: a meta-analysis.
Whether Tai Chi (TC) benefits patients with type 2 diabetes mellitus (T2DM) remains controversial. Thus, we performed a meta-analysis to assess the efficacy of TC in T2DM patients. A computerised search through PubMed and Embase was performed to identify relevant studies. The primary outcomes were fasting blood glucose (FBG), haemoglobin A1c (HbA1c) and insulin resistance (HOMA). Secondary outcomes included total cholesterol, high-density lipoprotein cholesterol (HDL-C) and triglyceride. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated. 4 randomised controlled trials (RCTs) and 5 non-randomised controlled trials (NRCTs) met the inclusion criteria. The pooled WMDs from RCTs were -14.82 mg/dL (95% CI: -49.17 to 19.53; P=0.40) for FBG, -0.19% (95% CI: -0.41 to 0.03; P=0.09) for HbA1c and -0.34 units (95% CI: -3.02 to 2.34; P=0.80) for HOMA. The WMDs from NRCTs were -11.22 mg/dL (95% CI: -18.58 to -3.86; P=0.003) for FBG, -0.41% (95% CI: -0.53 to -0.29; P<0.00001) for HbA1c and -0.60 units (95% CI: -1.46 to 0.25; P=0.16) for HOMA. Furthermore, the pooled results of serum lipids suggest that TC significantly reduced triglyceride (P=0.006) instead of total cholesterol (P=0.77), and failed to improve HDL-C (P=0.12). Sufficient evidence to support the benefits of TC to T2DM patients is lacking. Further large-scale studies are needed to investigate the long-term efficacy of TC.


Molecular Dynamics Simulation of a RNA Aptasensor.
Single-stranded RNA aptamers have emerged as novel biosensor tools. However, the immobilization procedure of the aptamer onto a surface generally induces a loss of affinity. To understand this molecular process, we conducted a complete simulation study for the Flavin mononucleotide aptamer for which experimental data are available. Several molecular dynamics simulations (MD) of the Flavin in complex with its RNA aptamer were conducted in solution, linked with six thymidines (T6) and, finally, immobilized on an hexanol-thiol-functionalized gold surface. First, we demonstrated that our MD computations were able to reproduce the experimental solution structure and to provide a meaningful estimation of the Flavin free energy of binding. We also demonstrated that the T6 linkage, by itself, does not generate a perturbation of the Flavin recognition process. From the simulation of the complete biosensor system, we observed that the aptamer stays oriented parallel to the surface at a distance around 36 Å avoiding, this way, interaction with the surface. We evidenced a structural reorganization of the Flavin aptamer binding mode related to the loss of affinity and induced by an anisotropic distribution of sodium cationic densities. This means that ionic diffusion is different between the surface and the aptamer than above this last one. We suggest that these findings might be extrapolated to other nucleic acids systems for the future design of biosensors with higher efficiency and selectivity.


Vitamin D status among Indonesian elderly women living in institutionalized care units.
to obtain the profile of vitamin D deficiency in Indonesian elderly women. it is a cross-sectional study in 74 elderly women from 4 randomly chosen institutionalized care units in two cities, Jakarta and Bekasi. Data collection included characteristics of subjects, 25(OH)D and PTH, concentration,skin type, nutrient intake including protein, calcium, and vitamin D, and use of sun screen. the prevalence of 25(OH)D deficiency among Indonesian elderly women in institutionalized care is about 35.1%. Most of deficient subjects went out-door only once a week (38.5%). Veil was the most sun protection worn by the subjects and most subjects had length of sun exposure 30-60 minutes a week. The mean daily intake of vitamin D was 0.6 IU, protein was 33.9 gr/day and calcium was 239.9 mg/day,and cut-off of serum 25(OH)D in Indonesian elderly women is (suspected) to be 75.9 nmol/L. we conclude that the prevalence of 25(OH)D deficiency among Indonesian elderly women in institutionalized care is about 35.1% and cut-off of serum 25(OH)Din Indonesian elderly women is (suspected) to be 75.9 nmol/L. Population based study in Indonesia is needed to determine the normal value of 25(OH)D in Indonesian elderly women.


Enlargement of the Optic Chiasm: A Novel Imaging Finding in Glutaric Aciduria Type 1.
Patients with glutaric aciduria type 1, without early diagnosis and initiation of preventive treatment, often develop movement disorders and various degrees of motor disability due to striatal area-specific damage induced by an acute episode of metabolic decompensation. The neuroimaging phenotype of patients with glutaric aciduria type 1 includes characteristic cyst-like bilateral enlargement of the Sylvian fissures and anterior subarachnoid spaces and signal abnormalities including supratentorial white matter and deep gray matter structure T2 hyperintensities, frequently associated with restricted diffusion. In this retrospective study, we add to the neuroimaging spectrum of glutaric aciduria type 1, a novel imaging finding present regardless of a previous metabolic crisis: the enlargement of the optic chiasm associated with signal abnormalities in the anterior intracranial visual structures observed in 6 of 10 patients. These optic pathway abnormalities are suggested as useful diagnostic clues for glutaric aciduria type 1, and possible pathophysiologic mechanisms are discussed.


[Hypothesis of the pathogenesis of renoparenchymal hypertension in chronic kidney failure patients before starting treatment with periodic hemodialysis].
After a brief presentation of the pathogenetic scheme of renoparenchymal hypertension (RPH) in acute glomerulonephritis, of the pathogenesis of not controlled by dialysis and renin-dependent RPH, as well as of the more important causes for origination of arterial hypertension in patients with transplanted kidney, the author suggests the hypothesis, that the RPH in patients with ChRI , prior to the inclusion of the chroniodialysis treatment, originates, is maintained and becomes more frequent and graver , very likely, due to the gradual and progressive accumulation of factors within the patient's organism, elevating the arterial pressure, either by their reduced excretion through the affected kidneys or due to their increased production. In the development of the hypothesis, the author is based on some well known facts from literature and on his own studies, as elevated level of catecholamines in myocardium of patients that died with uremia, decreased elimination of catecholamines in patients with ChRI , elevated level of plasma cortisol in patients with chronic glomerular nephritis and ChRI , elevated levels of somatotropic and of thyreotropic hormone in patients with ChRI , elevated levels of angiotension 2 and of plasma aldosterone in some of the patients with RPH and ChRI , enhanced tendency to sodium and water retention in patients with ChRI , a tendency to increased volume of circulating plasma, increased stroke volume, increased general peripheral resistance, tendency to acidosis and to elevation of the serum level of potassium in advanced ChRI .


Are general practice networks 'ready' for clinical data management?
Australian general practice networks (GPN) are required to report on national performance indicators under the Australian Government Department of Health and Ageing's National Quality Performance System (NQPS). To investigate the extent to which Victorian GPN are 'ready' to manage clinical data from general practice for reporting under the NQPS. A qualitative study using semistructured interviews from a purposive sample of chief executive officers from urban and rural Victorian GPN included those either participating or not participating in the Australian Primary Care Collaboratives Program. Australian Primary Care Collaborative experienced DGP have developed the range of skills and knowledge to undertake clinical data management for quality improvement and NQPS reporting. Trust by local general practices for the provision of clinical data has been developed through the demonstration of benefits to practices and improved patient health. General practice networks without Australian Primary Care Collaborative experience have a range of concerns about clinical data management for NQPS reporting, such as gaining cooperation from their practices, handling privacy issues and finding appropriately skilled staff. Victorian GPN involved in the Australian Primary Care Collaborative appear more 'ready' than GPN without this experience to undertake clinical data management for reporting purposes on the national performance indicators under the NQPS.


Epidemiology-based mortality score in status epilepticus (EMSE).
Status epilepticus (SE) is a neurological emergency with high mortality and often a poor functional outcome amongst survivors. So far, only status epilepticus severity score (STESS) is available to predict individual outcomes. STESS is based on weighted sum scores of age, type of seizure, level of consciousness and history of previous seizures. Weighting factors were based on a priori assumptions. We tested in an explorative, hypothesis generating approach, whether epidemiological data (i.e. mortality rates) can be combined to form a score (Epidemiology-based Mortality score in SE-EMSE), and further, which combination of aetiology, age, comorbidity, EEG, duration and level of consciousness yields highest test performance. Positive and negative predictive value, and correctly classified were compared to STESS (with different cut-off levels: STESS-3, STESS-4). Score points for each parameter, e.g. age, were derived from previously published specific mortality rates. For each combination of parameters, the lowest sum-score of deceased individuals was taken as cut-off. Ninety-two consecutive non-hypoxic patients (age range 20-90 years), with various forms of SE admitted to a tertiary care neurological intensive care unit were investigated retrospectively. EMSE using a combination of aetiology, age, comorbidity and EEG (NPV = 100 %, PPV = 68.8 %, correctly classified 89.1 %) was superior to STESS-3 and STESS-4 (p = 0.0022 or lower). EMSE explained individual mortality in almost 90 % of cases, and performed significantly better than previous scores. This explorative study needs external prospective corroboration. EMSE may be a valuable tool for risk stratification in interventional studies in the future.


[Effects of dicetel on gastrointestinal motility and vegetative dysfunction in patients with duodenal ulcer].
The great majority of patients with duodenal ulcer (DU) given a single oral dose (50 mg) of dicetel (pinaverium bromide)--a selective blocker of calcium channels--showed optimization of vegetative reactivity and vegetative support of physical and mental activities. This contributes to relief of psychovegetative syndrome of the modulation of dysfunctions of proximal gastrointestinal tract (GIT). The addition of dicetel to combined treatment of PH shortened healing of DU, relieved pain, stopped gastric and intestinal dyspepsia, corrected motor-tonic defects of the proximal GIT caused by dysfunction of different links of the regulatory-adaptive system.


Association between EGF, TGF-β1 and TNF-α gene polymorphisms and hepatocellular carcinoma.
Up to present, EGF 61*A/G, TGF-β1 -509*T/C and TNF-α -308*A/G gene polymorphisms have been analysed in other cancer entities than hepatocellular carcinoma (HCC). We here investigated the frequency of these gene polymorphisms among HCC patients. A total of 73 HCC patients and 117 cancer-free healthy people were recruited at the Surgical Department of Zhongshan Hospital. Genomic DNA was isolated from peripheral blood and gene polymorphisms were analyzed by PCR-RFLP. The distribution of EGF 61*G/G homozygotes among HCC patients was more frequent than that in the control group (24.7% vs 11.1%, OR=2.618, 95%CI=1.195-5.738). In parallel, the frequency of the "G" allele in the HCC patient group was also higher than that in the control group (45.9% vs 33.3%, OR= 1.696, 95%CI=1.110-2.592). No difference could be found for the TGF-β1-509 and TNF-α -308 genotypes. EGF 61*G/G genotype and G allele are significantly increased among patients with HCC. TGF-β1-509*T/C and TNF-α -308*A/G gene polymorphisms are not related to this cancer entity.


Near infrared reactance for the estimation of body fatness in regularly exercising individuals.
Near infrared reactance (NIR) is used to measure body fat percentage (BF%), but there is little data on its use in non-obese, regularly exercising individuals. Therefore, this study aimed to examine the limits of agreement between NIR compared to dual x-ray absorptiometry (DXA) for the measurement of BF% in 2 cohorts of regularly exercising individuals. BF% was measured using DXA and NIR in a regular exercising (≥3 sessions/week), healthy active cohort (HA; n=57), and in a regularly exercising and resistance trained (≥2 sessions/week) cohort (RT; n=59). The RT cohort had lower BF% than the HA cohort (15.3±5.5% and 25.8±7.1%, P<0.001). In the HA and RT cohorts, NIR BF% was associated with DXA BF% (R2=0.72, SEE=3.7, p<0.001 and R2=0.50, SEE=4.1 p<0.001, respectively). In the HA cohort, NIR tended to under-predict BF% (mean difference: - 1.3%; 95% limits of agreement (LOA); - 8.8 to 6.2%) whereas in the RT cohort, NIR tended to over-predict BF% compared to DXA (mean difference: 1.1; 95% LOA; - 8.1 to 10.3%). In conclusion, NIR and DXA yield similar average BF% measurements in 2 cohorts of non-obese regularly exercising individuals. However, the rather broad LOA of NIR need to be considered when using NIR to screen for overweight and obesity, or measure and track changes in body composition.


Characterizing integration time and gray-level-related nonlinearities in a NMOS sensor.
We report a nonlinearity effect related to the integration time in a double-beam spectroradiometer equipped with two negative-module metal-oxide semiconductor (NMOS) sensors. This effect can be explained by the addition of photoelectrons produced by the radiant flux on the sensors during the readout phase to the photoelectrons produced during the measurement phase. A new method is proposed to characterize and correct both gray-level and integration-time-related nonlinearities in NMOS sensors. This method is experimentally simple and outperforms other commonly used correction procedures.


Effects of upper ocean sound-speed structure on deep acoustic shadow-zone arrivals at 500- and 1000-km range.
Deep acoustic shadow-zone arrivals observed in the late 1990s in the North Pacific Ocean reveal significant acoustic energy penetrating the geometric shadow. Comparisons of acoustic data obtained from vertical line arrays deployed in conjunction with 250-Hz acoustic sources at ranges of 500 and 1000 km from June to November 2004 in the North Pacific, with simulations incorporating scattering consistent with the Garrett-Munk internal-wave spectrum, are able to describe both the energy contained in and vertical extent of deep shadow-zone arrivals. Incoherent monthly averages of acoustic timefronts indicate that lower cusps associated with acoustic rays with shallow upper turning points (UTPs), where sound-speed structure is most variable and seasonally dependent, deepen from June to October as the summer thermocline develops. Surface-reflected rays, or those with near-surface UTPs, exhibit less scattering due to internal waves than in later months when the UTP deepens. Data collected in November exhibit dramatically more vertical extension than previous months. The depth to which timefronts extend is a complex combination of deterministic changes in the depths of the lower cusps as the range-average profiles evolve with seasonal change and of the amount of scattering, which depends on the mean vertical gradients at the depths of the UTPs.


A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma.
Single-agent doxorubicin has been widely used to treat unresectable hepatocellular carcinoma (HCC), but the response rate is low (< 20%) and there is no convincing evidence for improved survival. Cisplatin, interferon, doxorubicin, and fluorouracil (PIAF) used in combination, by contrast, has shown promise in a phase II study. We compared doxorubicin to PIAF in patients with unresectable HCC in a phase III trial. Patients with histologically confirmed unresectable HCC were randomly assigned to receive either doxorubicin or PIAF every 3 weeks, for up to six cycles. The primary endpoint was overall survival, and secondary endpoints were response rate and toxicity. Survival differences were calculated using the Kaplan-Meier method. Treatment groups were compared for differences in the incidence of adverse events using chi-square tests. All statistical tests were two-sided. The median survival of the doxorubicin and PIAF groups was 6.83 months (95% confidence [CI] = 4.80 to 9.56) and 8.67 months (95% CI = 6.36 to 12.00), respectively (P = 0.83). The hazard ratio for death from any cause in the PIAF compared with the doxorubicin groups was 0.97 (95% CI = 0.71 to 1.32). Eighty-six of the 94 patients receiving doxorubicin and 91 of the 94 receiving PIAF were assessable for response. The overall response rates in the doxorubicin and PIAF groups were 10.5% (95% CI = 3.9% to 16.9%) and 20.9% (95% CI = 12.5% to 29.2%), respectively. Neutropenia, thrombocytopenia, and hypokalemia were statistically significantly more common in patients treated with PIAF than in patients treated with doxorubicin. Although patients on PIAF had a higher overall response rate and better survival than patients on doxorubicin, the differences were not statistically significant. PIAF was also associated with increased treatment-related toxicity. The prognosis of patients with unresectable HCC remains poor.


First-degree relatives with behavioural adverse effects on statins.
Irritability, aggression and other adverse behavioural effects have been associated with the use of statins (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors) and other drug classes. A number of studies have also linked low cholesterol with aggression and violence. This paper presents the cases of two first-degree male relative patients (father and son) identified by self-referral to the University of California in San Diego Statin Effects Study. Both patients experienced behavioural adverse effects on statins including irritability and aggression, however neither patient recognised a significant change in their behaviour. This may be the first report of behavioural adverse effects manifested on statins by first-degree male relatives, which may suggest possible familial/biological predisposition. These cases also highlight the issue of externalisation by patients of the origin of interpersonal discord, which may serve as an obstacle to adverse effects reporting and lead to negative outcomes for patients, and for those around them.


How the storage effect and the number of temporal niches affect biodiversity in stochastic and seasonal environments.
Temporal environmental variations affect diversity in communities of competing populations. In particular, the covariance between competition and environment is known to facilitate invasions of rare species via the storage effect. Here we present a quantitative study of the effects of temporal variations in two-species and in diverse communities. Four scenarios are compared: environmental variations may be either periodic (seasonal) or stochastic, and the dynamics may support the storage effect (global competition) or not (local competition). In two-species communities, coexistence is quantified via the mean time to absorption, and we show that stochastic variations yield shorter persistence time because they allow for rare sequences of bad years. In diverse communities, where the steady-state reflects a colonization-extinction equilibrium, the actual number of temporal niches is shown to play a crucial role. When this number is large, the same trends hold: storage effect and periodic variations increase both species richness and the evenness of the community. Surprisingly, when the number of temporal niches is small global competition acts to decrease species richness and evenness, as it focuses the competition to specific periods, thus increasing the effective fitness differences.


Genetic and environmental influences on risk of death due to infections assessed in Danish twins, 1943-2001.
Genetic differences have been proposed to play a strong role in risk of death from infectious diseases. The study base of 44,005 included all same-sex twin pairs born in 1870-2001, with both twins alive on January 1, 1943, or those born thereafter. Cause of death was obtained from the Danish Cause of Death Register and was available for 18,359 deaths. The authors classified death due to infections by 3 definitions (narrow, broader, and broadest) and calculated concordance rates for same-sex monozygotic and dizygotic twin pairs. Heritability was estimated by using structural equation models. When the 3 definitions were applied, 211 (1.1%), 1,089 (5.9%), and 2,907 (15.8%) deaths, respectively, were due to infections. The probandwise concordance rates for monozygotic twin pairs were consistently higher than for dizygotic twin pairs regardless of the definition (9% vs. 0% (P = 0.04), 10% vs. 3% (P < 0.01), and 19% vs. 15% (P = 0.07), respectively). For the broader and broadest definitions, heritability was 40% (95% confidence interval: 12, 50) and 19% (95% confidence interval: 3, 35), respectively. The concordance rates were generally low, and, although a genetic influence on the risk of death from infectious diseases could be demonstrated, the absolute effect of the genetic component on mortality was small.


Locked bucket-handle tears of both medial and lateral menisci with simultaneous anterior cruciate and medial collateral ligaments injury.
The authors report the case of a 38-year-old male who presented to the accident and emergency department with a locked knee after falling from a height. The knee was locked at 35° of flexion without any signs of instability in clinical examination. The patient was operated within 6 h from injury. During arthroscopy bucket-handle tears of both medial and lateral menisci were found. The bucket-handle fragments were displaced into the intercondylar notch causing the knee to lock. Additionally, tears of the anterior cruciate ligament (ACL) and the medial collateral ligament (MCL) were also found. The patient underwent ACL reconstruction with hamstrings autograft, medial subtotal meniscectomy and lateral meniscus repair. The MCL was treated conservatively. The postoperative period was uneventful and the patient returned to the preinjury level of activity within 8 months. The patient remains asymptomatic 2 years postoperatively.


Fellow and Attending Surgeon Operative Notes are Deficient in Reporting Established Quality Indicators for Roux-en-Y Gastric Bypass: A Preliminary Retrospective Analysis of Operative Dictation.
Introduction Surgeons must dictate the important components of any invasive procedure in a comprehensive, yet concise, operative report. This documentation is vital for communicating operative events and has implications for providing additional healthcare and planning future operations. The quality of surgical care may be impaired in the absence of such communication. Evidence suggests that the quality of reports dictated by trainees and surgeons is poor despite its importance. This investigation analyzed and compared the quality of fellow and staff surgeon Roux-en-Y Gastric Bypass (RYGB) narrative dictations against validated and reliable quality indicators (QIs) for this procedure. Methods A total of 40 bariatric fellow reports and 40 attending RYGB narrative reports were retrospectively analyzed. Results Fellows had a mean completion of 66.4% +/- 3.1% as compared to 61.5% +/- 7.6% for attendings (p<0.0001). Fellows statistically outperformed attendings on all subsections except patient, closure, and postoperative details. Attendings statistically outperformed fellows on closure details only (63.8 +/- 7.5 vs 50.5 +/- 12.0, p=0.002). Conclusions Bariatric surgery trainees outperform attending surgeons in RYGB operative dictation. The clinical significance of this difference is unknown. However, both groups are deficient in reporting at least one-third of items deemed essential to RYGB operative reporting. This indicates a need for further education in RYGB dictation for practicing surgeons and trainees. It also lends interest in exploring alternative forms of operative communication such as synoptic operative reporting in bariatric surgery.


[Incidence of ventricular arrhythmia relative to the QT interval in spontaneous intracranial hemorrhages].
A prospective study was done in 54 patients with acute spontaneous intracranial haemorrhage, 27 of them with subarachnoid bleeding and 27 with primary intracerebral haemorrhage. The frequency of ventricular arrhythmias was registered by continuous long-term ECG and the incidence of QT prolongation by daily standard ECG registration. Prolongation of frequency-corrected QT-interval (QTc) developed in 9 patients with subarachnoid haemorrhage and in 10 with intracerebral haemorrhage. For assessment of time-relation between QT-interval and ventricular arrhythmias the results of corresponding long-term ECG and standard ECG were used and two groups were defined: group A (149 tapes) = QTc less than or equal to 450 ms, group B (43 tapes) = QTc greater than 450 ms. In group B singular frequent ventricular extrasystoles, couplets and non-persistent ventricular tachycardias occurred more frequently though not significantly so. Persistent ventricular tachycardias occurred significantly more frequently in group B (14% vs. 1%, P less than 0.01). In three tapes of group B, all of them with QTc prolongation of more than 550 ms persistent ventricular tachycardias with typical "torsade de pointes " morphology were seen. The results show that QTc prolongation of more than 450 ms occurs in a third and significant ventricular arrhythmia in nearly half of patients with spontaneous intracranial haemorrhage. Persistent ventricular tachycardias occur almost only in cases of QTc-prolongation. Pronounced QTc prolongation of more than 550 ms is rare. However, it can give rise to torsade de pointes and ventricular fibrillation.


Long-term trends in hip arthroplasty use and volume.
We used Medicare administrative data to examine trends in primary and revision total hip arthroplasty (THA) use and hospital volume. Between 1991 and 2005, primary and revision THA use increased by 40.9% and 16.8%, respectively. The percentage of primary THA procedures performed in high-volume hospitals (those in the highest quintile of volume) increased slightly from 58.0% of all procedures in 1991 to 58.7% in 2005 (P < .01). The percentage of revisions performed in high-volume hospitals increased from 60.9% to 62.4% (P < .01). The percentage of primary THA procedures performed by low-volume hospitals remained relatively stable (P = .36), whereas the percentage of revision THA performed by low-volume hospitals declined (P < .001). In aggregate, these results suggest minimal evidence that regionalization of THA is occurring.


Tunability of mobility and conductivity over large ranges in poly(3,3'''-didodecylquaterthiophene)/insulating polymer composites.
Semiconducting polymers are currently being considered as active layers in field-effect transistors, in which high charge carrier mobility and low off conductivity are important. For other applications, such as certain spintronic mechanisms, the opposite characteristics are desirable. Blending such polymers with insulating polymers would be expected to lower the mobility. In this paper, we report that the use of hydrocarbon polymers such as polystyrene as insulators generally raises the mobility when the semiconducting polymer is poly(bisdodecylquaterthiophene). A high mobility value of nearly 0.1 cm(2)/V.s was obtained for an optimal blend. While this is counterintuitive, it is consistent with a few other recent reports. In order to lower the mobility significantly, a much more polar and irregular blending agent is needed. The further addition of tetrafluorotetracyanoquinodimethane as a dopant gave a rare low mobility/high conductivity combination of properties, with a charge carrier density on the order of 10(19) cm(-3). Thus, mobility and conductivity were tuned somewhat independently over 3 and 4 orders of magnitude, respectively.


Autoprocessing: an essential step for expression and purification of enterovirus 71 3C(pro) in Escherichia coli.
A gene encoding the 3BC of human enterovirus 71 (EV71) was cloned and inserted into a derivative of plasmid pET-32a(+) driven by T7 promoter. The expressed 3C protease (3C(pro)) autocatalytically cleaved itself from the recombinant protein Trx-3BC and the mature 3C(pro) partitioned in the soluble fraction of bacterial lysate. The 13-amino-acid peptide substrates with the junction of 3B/3C were used to verify the proteolysis activity of the purified 3C(pro). The EV71 3C(pro) had a Km value of 63 μM (measured by a continuous fluorescence assay). The other solid-phase activity assay of the EV71 3C(pro) was developed using HPLC to analyze the proteolytic products. The combination of two activity assays contributes to promote the identification of the specific inhibitors targeted to the EV71 3C(pro).


The value of newborn urinary proteome analysis in the evaluation and management of ureteropelvic junction obstruction: a cost-effectiveness study.
The cornerstone of management in newborns with ureteropelvic junction obstruction (UPJO) is serial imaging over time. Surgery is undertaken for disease progression. A marker of disease progression would select out those likely to progress for early surgery and diminish the intensity of imaging and follow-up in the remainder. Recently, urinary proteome analysis in the newborn has been reported to fulfill this aim. The objective of this study is to quantitatively evaluate the effect of this matrix of protein biomarkers on the overall cost-effectiveness (C-E) of UPJO evaluation and management. A Markov process decision tree model (Tree Age Pro software, Boston, MA) is created to compare the current strategy (watchful waiting) to one incorporating a urine proteome analysis at birth as a marker of disease progression. The analysis includes the costs of surgery, imaging and office visits based on hospital charge data. We analyze a total of 53 variables. The incorporation of this marker of progression results on the average, in an incremental C-E gain of 8,000 US dollars per quality adjusted life year (QALY) per patient compared to the current strategy of watchful waiting. The results are not sensitive to variation of any of the probabilities including costs and quality of life parameters used for the base-case analysis. The incorporation of urinary proteome analysis in the initial evaluation of UPJO significantly reduces costs and increases the QALYs in this patient population. The test increases the odds of detecting UPJO progression from 1:3 to 1:1, while improving the overall C-E. These findings justify continued research in this area which in addition may have important applications in evaluating treatment outcomes.


Detection of Borrelia burgdorferi sensu lato in ticks: immunofluorescence assay versus polymerase chain reaction.
Immunofluorescence (IFA) and polymerase chain reaction (PCR) were examined as methods for detecting Borrelia burgdorferi sensu lato spirochaetes in unfed Ixodes ricinus nymphs. Although similar results were produced in some cases, a great deal of variation occurred. Furthermore, in both the highly controlled initial laboratory study, involving 252 shared samples, and the study on field-collected ticks (n = 460), the IFA tended to detect more infected ticks than the PCR. The basis for these findings are as yet undetermined. The development of a quality assurance scheme is recommended so that laboratories can validate their methods and a preliminary feasibility study suggested that such a scheme is practical.


Urinary stone disease: a practical guide to metabolic evaluation.
Urolithiasis is the third most common affliction of the urinary tract, after infections and diseases of the prostate. Approximately 10% of the North American population will have at least one urinary calculus by age 70. A thorough history and physical examination will usually confirm the diagnosis of urinary stone disease. A simplified laboratory evaluation may be performed for patients with a single stone episode. A more extensive evaluation is required for patients with recurrent, metabolically active stones and patients at high risk (ie, cystine stone formers and those who develop bladder dysfunction or nephrosclerosis). Intravenous pyelography with tomography remains the gold standard for imaging of the urinary tract to confirm the diagnosis and formulate a treatment plan.


Early- and Long-Term Outcomes of Mitral Valve Repair in a Low-Volume Centre in the Caribbean.
This study examines early- and long-term outcomes of mitral valve repairs in a low-volume cardiac surgery centre in the Caribbean. Ninety-six consecutive patients underwent mitral valve repair from April 2009 to December 2018. Patients were divided into two groups: functional mitral regurgitation requiring simple mitral annuloplasty (FMR, n=63) or structural degenerative mitral regurgitation requiring more complex repair (DMR, n=33). Data collected prospectively were retrospectively analysed from the unit-maintained cardiac surgery database. Thirty-day mortality in the whole series was 2.1%, with 3% in the FMR group and 0% in the DMR group. Early post-operative echocardiography in the FMR group demonstrated 51 patients (83.6%) without mitral regurgitation, 8 patients (13.1%) with trivial to mild regurgitation, and 2 patients (3.3%) with moderate regurgitation. However, at a mean follow-up of 98.2±50.8, only 21 patients (42.8%) were in NYHA class I, with 7 (14.2%) in class II, 16 (32.6%) in class III, and 5 (10.2%) in class IV. There were 9 cardiac-related deaths at final follow-up, with freedom from re-operation and survival of 98% and 75.6%, respectively. In the DMR group, early post-operative echocardiography demonstrated 29 patients (87.9%) without mitral regurgitation, 3 patients (9.1%) with trivial regurgitation and 1 patient (3.0%) with mild regurgitation. At a mean follow-up of 114.1±25.4 months, there was a good functional post-operative status in this group with 93.3% in NYHA class I, and 6.7% in class II. No patient required reintervention, 96.3% of patients had mild or no mitral regurgitation and survival was 90.9%. Despite challenges of maintaining skills in a low-volume centre, mitral valve repair can be performed safely with good early- and long-term results.


Liquid-phase chemical hydrogen storage: catalytic hydrogen generation under ambient conditions.
There is a demand for a sufficient and sustainable energy supply. Hence, the search for applicable hydrogen storage materials is extremely important owing to the diversified merits of hydrogen energy. Lithium and sodium borohydride, ammonia borane, hydrazine, and formic acid have been extensively investigated as promising hydrogen storage materials based on their relatively high hydrogen content. Significant advances, such as hydrogen generation temperatures and reaction kinetics, have been made in the catalytic hydrolysis of aqueous lithium and sodium borohydride and ammonia borane as well as in the catalytic decomposition of hydrous hydrazine and formic acid. In this Minireview we briefly survey the research progresses in catalytic hydrogen generation from these liquid-phase chemical hydrogen storage materials.


Piezoelectric bone surgery: a revolutionary technique for minimally invasive surgery in cranial base and spinal surgery? Technical note.
Piezoelectric surgery represents an innovative, ultrasonic surgery technique for performing a safe and effective osteotomy or osteoplasty that contrasts with the traditional hard and soft tissue management methods with rotating instruments. Because of its physical and mechanical properties, the definitive clinical advantage of piezoelectric bone surgery with regard to precision cutting lies in the sparing of vital neurovascular bundles or general soft tissue and better visualization of the surgical field, thus suggesting its great safety. Piezoelectric bone surgery has been previously described only in oral and maxillofacial operative procedures in adults. Five children between the age of 6 and 84 months were operated on for craniosynostosis, tethered cord, and an extraconal intraorbital tumor. The usefulness of piezoelectric bone surgery during neurosurgical procedures is presented for these cases. This technique is especially recommended when there are anatomic difficulties because of poor intraoperative visibility or the presence of delicate anatomic structures. The present preliminary report (comprising illustrative case reports) demonstrates and introduces for the first time the utility of piezoelectric bone surgery in cranial base and spinal surgery in children. Until now, there has been no documented neurosurgical experience of this technique even in adults.


[Efficacy of Barbed reposition pharyngoplasty combined with Han-Uvulopalatopharyngoplasty for the treatment of OSAHS patients].
Objective: To study the efficacy of Barbed reposition pharyngoplasty (BRP) combined with Han-Uvulopalatopharyngoplasty (H-UPPP) in surgical treatment of OSAHS patients. Methods: OSAHS patients admitted to our department from June 2021 to February 2022 who met the surgical enrollment criteria were divided into two groups by surgical procedure: H-UPPP operation group [Control group, 47 cases, including 42 males and 5 females, aged 18-64 (37.77±11.65)years, and H-UPPP+BRP group [Study group, 48 cases, including 45 males and 3 females, aged 23-60 (39.10±9.86) years]. The surgical efficacy 6 months after operation was retrospectively analyzed. Meanwhile, the relationship between the surgical efficacy and modified Friedman pharyngeal anatomical stages was analyzed. The postoperative pain VAS score at first 3 days and the incidence of foreign body sensation in pharynx after 6 months of operation were compared between the two groups. Statistical analysis was conducted by SPSS 23.0. Results: There were no significant differences in gender, age, BMI, Friedman pharyngeal anatomical stages, ESS score, AHI and LSpO2 between the two groups, preoperatively (P>0.05). There was significant difference between the two groups in ratio of cumulative time of oxygen saturation below 90% to total sleep time(CT90), preoperatively. Surgical efficacy of H-UPPP operation group was 48.9% (23/47), while H-UPPP+BRP operation group was 70.8% (34/48), which was statistically significant (χ2=4.74, P=0.029). H-UPPP+BRP group seemed to have a higher surgical efficacy than H-UPPP group in patients with Friedman Ⅱb (87% vs. 61.9%) and Ⅲ stage (44.4% vs. 15%), but there was no statistically significant difference (P>0.05). H-UPPP+BRP group had a higher pain VAS score in first three days (t=-3.10, P=0.003), also had higher incidence of pharyngeal foreign body sensation after 6 months of operation (χ2=4.727, P=0.030). Conclusions: In the surgical treatment of OSAHS patients, the overall efficacy of BRP combined H-UPPP surgery is higher than that of H-UPPP surgery alone. It may be more suitable for OSAHS patients with modified Friedman type Ⅱb and type Ⅲ stage.


Modelling splice sites with locality-sensitive sequence features.
The splice sites are essential for pre-mRNA maturation and crucial for Splice Site Modelling (SSM); however, there are gaps between the splicing signals and the computationally identified sequence features. In this paper, the Locality Sensitive Features (LSFs) are proposed to reduce the gaps by homogenising their contexts. Under the skewness-kurtosis based statistics and data analysis, SSM attributed with LSFs is fulfilled by double-boundary outlier filters. The LSF-based SSM had been applied to six model organisms of diverse species; by the accuracy and Receiver Operating Characteristic (ROC) analysis, the promising results show the proposed methodology is versatile and robust for the splice-site classification. It is prospective the LSF-based SSM can serve as a new infrastructure for developing effective splice-site prediction methods and have the potential to be applied to other sequence prediction problems.


Rate of cholesterol synthesis in hypo- and hyperthyroid rats.
The rate of cholesterol synthesis, measured by the rate of incorporation of tritium from body water into the cholesterol molecule, was found to be greater than normal in the hyperthyroid rat and below normal in the hypo-thyroid rat.


Microbiology: eukaryotic diversity in Spain's River of Fire.
The Rio Tinto, known by the Phoenicians as 'Ur-yero', or 'River of Fire', because of its deep red colour and high acidity, flows through the world's largest pyritic belt in southwestern Spain. Surprisingly, eukaryotic microbes are the principal contributors of biomass in this hostile river, which has a pH of 2 and contains much higher concentrations of heavy metals than are typically found in fresh waters. Here we show that the Rio Tinto shows an unexpected degree of eukaryotic diversity and includes new lineages that we have identified by sequence analysis of genes encoding small-subunit ribosomal RNAs. The diversity of these eukaryotes is much greater than that of prokaryotes, whose metabolism is responsible for the extreme environment.


[A case of hyperthyroidism combined with thyroid carcinoma].
A 33-year-old woman, with hyperthyroidism combined with thyroid carcinoma is presented. She was given antithyroid medication before the operation, and sub-total thyroidectomy was performed under local anesthesia. Her postoperative course was smooth. Histologically, the resected thyroid was shown to have two small nodular lesions of papillary carcinoma in the diffuse goiter. The current classification, statistics, diagnosis and therapy of this disease are discussed.


Input/output properties of the lateral vestibular nucleus.
This article is a review of work in three species, squirrel monkey, cat, and rat studying the inputs and outputs from the lateral vestibular nucleus (LVN). Different electrophysiological shock paradigms were used to determine the synaptic inputs derived from thick to thin diameter vestibular nerve afferents. Angular and linear mechanical stimulations were used to activate and study the combined and individual contribution of inner ear organs and neck afferents. The spatio-temporal properties of LVN neurons in the decerebrated rat were studied in response to dynamic acceleration inputs using sinusoidal linear translation in the horizontal head plane. Outputs were evaluated using antidromic identification techniques and identified LVN neurons were intracellularly injected with biocytin and their morphology studied.


Accurate diagnosis of lymphoma on whole-slide histopathology images using deep learning.
Histopathological diagnosis of lymphomas represents a challenge requiring either expertise or centralised review, and greatly depends on the technical process of tissue sections. Hence, we developed an innovative deep-learning framework, empowered with a certainty estimation level, designed for haematoxylin and eosin-stained slides analysis, with special focus on follicular lymphoma (FL) diagnosis. Whole-slide images of lymph nodes affected by FL or follicular hyperplasia were used for training, validating, and finally testing Bayesian neural networks (BNN). These BNN provide a diagnostic prediction coupled with an effective certainty estimation, and generate accurate diagnosis with an area under the curve reaching 0.99. Through its uncertainty estimation, our network is also able to detect unfamiliar data such as other small B cell lymphomas or technically heterogeneous cases from external centres. We demonstrate that machine-learning techniques are sensitive to the pre-processing of histopathology slides and require appropriate training to build universal tools to aid diagnosis.


Effect of B. subtilis TRNA(Trp) on readthrough rate at an opal UGA codon.
Bacillus subtilis has been thought to have a high readthrough rate at the UGA stop codon because no opal suppressor tRNA has been isolated so far [Lovett et al. (1991) J. Bacteriol. 173, 1810-1812]. To examine whether a tRNATrp which we have characterized [Matsugi et al. (1992) Nucleic Acids Res. 20, 3514] has the ability to read the UGA codon, in vitro translation was performed with a synthetic mRNA containing a test codon, UGA, UAG, UAA, or UGG, in a reading frame. Addition of Trp-tRNATrp to the system significantly increased the readthrough rate only in the case of UGA. This suggests that this tRNATrp has a dual recognition pattern in B. subtilis, i.e., for the canonical tryptophan codon and for readthrough at the UGA stop codon.


Interleukin-6 may predict survival in extracorporeal membrane oxygenation treatment.
The cytokine network and its association with complement activation during cardiac surgery with cardiopulmonary bypass (CPB) is complex. Extracorporeal membrane oxygenation (ECMO) differs from CPB in duration of days to weeks rather than hours. However, few studies have analyzed the levels of inflammatory mediators during ECMO treatment. Plasma samples from 22 patients [nine neonates, one infant, four children and eight adults (14 males and eight female)] who underwent ECMO treatment were collected prior to, during and after treatment, and analyzed for concentrations of inflammatory and anti-inflammatory cytokines and parameters of complement activation. Seven children were treated for cardiac and seven for pulmonary failure and, in the adult group, four were treated for cardiac and four for pulmonary failure. ECMO was performed with veno-arterial (VA) bypass in all children and five adults, and with veno-venous (VV) bypass in three adults. Fourteen patients survived (64%) and eight (36%) patients died during follow-up. A marked (approximately 99%) and rapid (i.e., within two days) decrease in IL-6 was seen in survivors. The non-survivors were characterized by persistently high IL-6 levels throughout the observation period (i.e., until death). C-reactive protein (CRP) levels showed a similar pattern as the IL-6, with higher levels in non-survivors throughout the observation period. However, in contrast to IL-6, the differences between survivors and non-survivors reached statistical significance, but only at the end of the observation period. It is possible that early measurements of IL-6 in ECMO patients could give prognostic information beyond that of CRP.


[Intrauterine growth in gestational diabetes].
Infants of diabetic tend to have more adipose tissue than normal infants at birth. This is thought to be caused by maternal hyperglycemia and fetal hyperinsulinism. Authors examined 160 newborn infants of mothers with gestational diabetes, to determine whether there is a relation between maternal blood-glucose concentrations and subcutaneous fat in the newborn. Mothers of newborns "large for age" present a mean fasting blood-glucose in third trimester greater than mothers of newborns "adequate for age" (p 0.05). Babies born to mothers who had a mean fasting blood-glucose above 90 mg/100 ml had more subcutaneous fat tissue than newborn infants of mothers with a mean fasting blood-glucose under 90 mg/ml (p less than 0.01). Maternal fasting blood-glucose and mean blood-glucose in the third trimester correlated significantly with neonatal weight, skin-fold thickness, K index and body mass index.


Organization of phosphoribulokinase and ribulose bisphosphate carboxylase/oxygenase genes in Rhodopseudomonas (Rhodobacter) sphaeroides.
A heterologous phosphoribulokinase (PRK) gene probe was used to analyze two recombinant plasmids isolated from a Rhodopseudomonas (Rhodobacter) sphaeroides gene library. These plasmids were previously shown to carry the genes for form I and form II ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBPC/O). Southern blot hybridization analysis indicated that there were two PRK genes linked to the RuBPC/O coding sequences. Restriction mapping showed the arrangement of the duplicate sets of PRK and RuBPC/O to be distinct. Subcloning of the hybridizing PRK sequences downstream of the lac promoter of pUC8 allowed expression of the two PRK enzymes in Escherichia coli. Analysis of the purified proteins by sodium dodecyl sulfate-slab gel electrophoresis revealed polypeptides with molecular weights of 32,000 and 34,000 corresponding to the form I and form II PRKs, respectively. Preliminary experiments on sensitivity to NADH regulation suggested that the two PRK enzymes differ in catalytic properties.


[Cesium-137 residues in food and in persons in areas severely contaminated by the Chernobyl power station accident].
On April 26, 1986, the fourth reactor of the Chernobyl Nuclear Power Station, in the Ukraine, of the former Soviet Union, exploded. Since March in 1991, a group including the author has been performed medical surveys and provided assistance centered mainly in Gomel district of the Republic of Belarus, which contains many severely contaminated areas due to fallout. Ultra sound scanning was performed by the Shinshu University School of Medicine Second Department of surgery on thyroid glands of children in Chechersk region, of Gomel. Twenty-one persons, each with tuberculous echogenic dots in their thyroid glands, were brought to Japan for further examination. The 137Cs residue was measured in these 21 persons, using a whole-body counter (WBC). Subsequently 137Cs was also measured in a range of food items found in the city in which they live. These studies indicate that, although the children live in the same area, differences in life style and in food intake are reflected in the amount of cesium residue in their bodies.


Comparison of pulmonary abnormalities on high-resolution computed tomography in patients with early versus longstanding rheumatoid arthritis.
To identify the predominant radiological abnormalities in the lungs of patients with early rheumatoid arthritis (RA) and in those with longstanding RA. We performed high-resolution computed tomography (HRCT) on a total of 126 patients with early RA (n = 65) and longstanding RA (n = 61). The most likely diagnosis for each case was made on the basis of the predominant HRCT findings and their extent in the lungs. Pulmonary function tests were done for RA patients with parenchymal abnormalities. The most frequent finding was bronchial dilatation (41.3%), followed by ground-glass attenuation (27.0%), parenchymal micronodules (15.1%), subpleural micronodules (15.1%), reticulation (11.9%), bronchial wall thickening (11.9%), nodules (10.3%), honeycombing (8.7%), and airspace consolidation (4%). Parenchymal micronodules and bronchial wall thickening, indicative of small airway diseases, were more prominent in the patients with longstanding RA. There were no significant differences in the frequency of interstitial abnormalities such as ground-glass attenuation, reticulation, honeycombing, or consolidation between the 2 groups. We identified 10 patients with bronchiolitis pattern, 11 with nonspecific interstitial pneumonia (NSIP) pattern, 2 with usual interstitial pneumonia (UIP) pattern, and 2 with organizing pneumonia (OP) pattern. Mean values of FEV1/FVC ratio and FEV25-75 were lower in the patients with the bronchiolitis pattern, and DLCO was decreased in the patients with the NSIP or UIP pattern. Interstitial abnormalities were frequently observed even in patients with early RA, although most of them had no respiratory symptoms. Bronchiolar abnormalities were associated with the duration of RA.


Antidepressant use during pregnancy and serotonin transporter genotype (SLC6A4) affect newborn serum reelin levels.
This study was undertaken to determine whether altered early serotonin signaling either via gestational serotonin reuptake inhibitor (SRI) exposure or genetic variations in the serotonin transporter promoter region (SLC6A4) alters levels of reelin, an important glycoprotein in neurodevelopment, in mothers and their neonates. Serum reelin protein expression was quantified by immunoblot from maternal and neonatal blood collected at delivery from women taking either an SRI during gestation or controls. SRI-exposed mothers had higher levels of one reelin fragment, while SRI-exposed neonates had lower total reelin levels, particularly in females and reelin levels differed with SLC6A4 genotype. Lower neonatal reelin levels predicted less time spent sleeping and more irritability during neonatal behavioral assessment on Day 6 of life. Our results suggest that prenatal SRI exposure and the SLC6A4 genotype influences reelin protein expression in both the mother and newborn and that this may be reflected in neonatal behavior.


Prolonged B cell depletion with rituximab is effective in treating refractory pulmonary granulomatous inflammation in granulomatosis with polyangiitis (GPA).
Pulmonary nodule formation is a frequent feature of granulomatosis with polyangiitis (GPA). Traditional induction therapy includes methotrexate or cyclophosphamide, however, pulmonary nodules generally respond slower than vasculitic components of disease. Efficacy of rituximab (RTX) solely for the treatment of pulmonary nodules has not been assessed. In this observational cohort study, we report patient outcomes with RTX in GPA patients with pulmonary nodules who failed to achieve remission following conventional immunosuppression. Patients (n = 5) with persistent pulmonary nodules were identified from our clinic database and retrospectively evaluated. Systemic manifestations, inflammatory markers, disease activity, concurrent immunosuppression, and absolute B cell numbers were recorded pre-RTX and at 6 monthly intervals following treatment. Chest radiographs at each time point were scored by an experienced radiologist, blinded to clinical details. Five patients with GPA and PR3-ANCA were evaluated (2 male, 3 female), mean age 34 (22-52) years. Pulmonary nodules (median 4, range 2-6), with or without cavitation were present in all patients. RTX induced initial B cell depletion (<5 cells/μL) in all patients but re-population was observed in 3 patients. Repeated RTX treatment in these 3 and persistent B cell depletion in the whole cohort was associated with further significant radiological improvement. Radiographic scoring at each time interval showed reduction in both number of nodules (P = <0.0001) and largest nodule diameter (P = <0.0001) in all patients for at least 18 months following B cell depletion. In summary, RTX therapy induces resolution of pulmonary granulomatous inflammation in GPA following prolonged B cell depletion.